201102_israel journal of psychiatry and related sciences

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In schizophrenia, how do you get from here

Vol. 48 - Number 2 2011

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Rates of Expressed Emotions in Pakistani Relatives of Patients with Schizophrenia Aisha Ikram et al.

Volume 48, Number 2, 2011 Israel Journal of Psychiatry and Related Sciences

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Xeplion®, a new once-monthly injectable schizophrenia therapy,1 significantly reduces relapse.2 With early onset of efficacy3,4 and good tolerability,1–6 Xeplion can help your patients shape a future in a way that they wish.

Preventive Pharmacological Treatment – an Evolving new Concept in Schizophrenia Rony Sabbag et al.

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Virtual Reality Exposure versus Cognitive Restructuring for Treatment of Public Speaking Anxiety Helene S. Wallach et al.

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Social Cognition in Social Anxiety: First Evidence for Increased Empathic Abilities Yasmin Tibi-Elhanany et al.

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Responsibility of the Therapist for the Patients' Actions (Tarasoff Rules) Yuval Melamed et al.

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ICD-10 Psychosocial Categories and Psychiatric Diagnosis Silvana Fennig et al.

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Family variables related to behavioral problems in childhood Antonio Félix Raya et al.

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Relationship between Personality and Disability in Patients with Major Depressive Disorder Medine Yazıcı Gűleç, Çiçek Hocaoğlu

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Tachyphylaxis/ Tolerance to Preventing relapse, enabling futures

Antidepressive Medications: A Review

Gregory Katz

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References: 1. Xeplion prescribing information. 2. Hough D et al. Schiz Res 2010; 116: 107-117.

3. Pandina GJ et al. J Clin Psychopharmacol 2010; 30: 235-244. 4. Kramer M et al. Int J Neuropsychopharmacol 2010; 13: 635-647. 5. Gopal S et al. J Psychopharmacol Online First, published on July 8, 2010 as doi:10.1177/0269881110372817. 6. Hoy SM et al. CNS Drug Rev 2010; 24(3): 227-244.

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Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Rates of Expressed Emotions in Pakistani Relatives of Patients with Schizophrenia Aisha Ikram, MPhil,1 Kausar Suhail, PhD,1 Sadaf Zara Jafery, MPhil,1 and Swaran Singh, MD, FRCPsych2 1

Department of Psychology, GC University, Lahore, Pakistan Health Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.

2

ABSTRACT Background: Studies have reported substantial crosscultural variations in rates of Expressed Emotions (EE) in relatives of patients with schizophrenia. As a first attempt from Pakistan, this study aimed to measure the components of EE among relatives of patients with schizophrenia in a different socio-cultural set-up.

Method: Thirty-two key family members were interviewed using the Camberwell Family Interview (CFI) and Five Minute Speech Sample (FMSS).

Results: Seventy-five percent of the family members appeared to be high EE with the majority (59%) rated so on the basis of hostility alone. Moreover, symptomatic behavior of the patient contributed more to the rating of relatives’ hostility. Pakistani relatives showed higher levels of emotional over-involvement and hostility as compared to many other cultures. In comparison to CFI, the FMSS showed lower sensitivity for identifying high EE relatives, thus it may not be very suitable to use on its own in Pakistan for cultural reasons.

Limitations: Lack of follow-up data and small sample size limit the scope of the study.

Conclusions: Pakistani relatives appeared to be more hostile yet emotionally over-involved and warm toward their sick relatives as compared to the households reported in many previous studies. Psycho-educational programs need to be initiated for the concerned families to reduce their level of hostility. Outcome studies are also warranted in order to understand any link between high EE and relapse of schizophrenia in Pakistan.

Expressed emotions (EE) refers to a global index of particular emotions, attitudes and behaviors expressed by relatives toward a family member. Expressed emotions are known to have harmful effects and often ignite psychiatric relapse (1). The assessment of EE is usually made through an interview schedule known as the Camberwell Family Interview (2) which is traditionally a tape recorded interview which is rated along five dimensions of emotions, namely criticism, hostility, emotional over-involvement (EOI), positive remarks, and warmth.

However, the rating of EE is derived only from the scores on the first three scales.

Despite a general consensus about the link between relapse and EE (3-5) studies have shown a wide and varying range of EE index in different cultures (6, 7).

Overall, studies conducted in a western cultural context (8) have shown higher rates of EE as compared to those reported from nonwestern cultures (9, 10). However, the lower rates of EE are not consistently reported from all nonwestern cultures. For example, considerably higher rates of EE have been found in Egypt (11), Israel (3), Japan (4), and China (12).

Nonetheless, it may be concluded that relatives’ emotional responses to an ill family member are determined by how a culture defines family life and what behavior patterns are considered appropriate for interpersonal interactions in kin relationships. For example, displacement of hostility, ridicule, protection, and devotion may vary according to individual family dynamics (13). In Mexican-American families, for instance, a high degree of involvement in the family affairs by the household relatives is culturally conventional (14). A similar observation was made for Pakistani relatives living in Britain (6) and native Pakistanis (15). This also seems true for other components of EE. For example, anger is readily shown in Israel and

Address for Correspondence: Professor Kausar Suhail, PhD, Department of Psychology, GC University, Kechery Road, Lahore, 54000, Pakistan.   kausarsuhail@gmail.com

74

Aisha Ikram et al.

failure to show one’s anger is considered a sign of weakness (3). Thus criticism and hostility may bring false-positives from Israel and emotional over-involvement from Pakistani, Mexican or some other cultures. This may lead to the conclusion that the normative levels of overt expressions of emotions may differ between cultures and that the impact of these emotions varies for different cultural groups. For example, as compared to western studies, Egyptian patients were more likely to tolerate higher levels of criticism before relapse (11). Similar observations were made for EOI, when conventional criteria of high EE were predictive of relapse in white families but not in Pakistani families living in the U.K. (6). These studies suggest that there are culturally acceptable levels of overt emotions that an individual can tolerate or expect in a given culture, and therefore the ratings of EE must be adjusted in relation to the norms of the culture under study (3).

To the best of our knowledge, no study has attempted so far to measure rates of EE in Pakistan using standardized methodology. Previously two studies have measured EE in Pakistani families using self-constructed measures (15, 16) the reliability of which was not known. Moreover, the results generated from these studies are not comparable with the studies conducted in other countries because of methodological differences. The only study with Pakistani families using CFI was conducted in Britain more than a decade ago. In that study families with Pakistani origin showed higher levels of hostility and EOI compared to British Sikh and white families (6). However, no attempt has been made so far to assess the prevalence of EE in local Pakistanis using standard methodology. The current work was undertaken to fill this gap in EE literature and aimed to investigate the rates of EE among relatives of patients with schizophrenia in Pakistan and compare the results to those obtained from other countries. Considering the conceptualization of over-involvement, it appears quite likely that the Pakistani relatives with elaborate family orientations and close-knit familial ties will show more of such behaviors in their social interactions with family members. It was hypothesized that Pakistani relatives will show a great deal of emotional over-involvement. A previous community survey also provided some evidence that many kinds of sacrificing and over-involved behaviors considered pathological in family relations are culturally appropriate in Pakistan (17). The study also aimed to assess whether a higher incidence of hostility observed in British-Pakistanis (6) was a consequence of some stress of living in a “foreign� culture or may be considered a characteristic of socialization in Pakistani culture.

Method Phase I: Translation and Training Phase

The CFI (2) was translated into Urdu by two bilingual speakers. An attempt was made to translate the conceptual, rather than literal, meaning of all items of the CFI. The second author (KS) then compared the two translations and the original English version, and picked up the Urdu items best matched with those in English. Those English items which did not convey meaning appropriately in Urdu language were again translated into Urdu by two different bilingual speakers, and the process was repeated until all items were satisfactorily translated.

The translated version was shown to five psychologists for indicating problems of understanding in any of the items, whether linguistic or cultural. The experts did not point out any problem. The CFI is a semi-structured interview schedule and relies mostly on the detailed information as described by the interviewee. Moreover, the main items are simple enough to understand and are not specific to any culture. Hence, the CFI was considered safe to use with Pakistani families.

The second author (KS), who had acquired official training to use and rate CFI from the University of California at Los Angeles, trained the first (AI) and third (SZJ) authors to conduct CFI interviews and then rate different components associated with EE. This training was conducted with CFI interviews used in another study. Interviewing in the second phase was started after both trainees (AI & SZJ) obtained sufficient inter-rater reliability indices with the second author on all main components of EE, i.e., .80 or higher. The interrater reliability was obtained in about 25 interviews.

Phase II: Rating of EE

Sample Patients consecutively admitted to two psychiatric units of Lahore, provincial capital of Pakistan, during January to December 2007 inclusive with a diagnosis of schizophrenia were initially recruited to assess expressed emotions in their key family members. The inclusion criteria for the patients were: a clinical diagnosis of schizophrenia by the consultant psychiatrist; age range of 18-60 years; the patient lived with at least one key member of his or her family.

Thirty-seven patients satisfying these criteria were referred by the consulting psychiatrists. Both patients and their relatives were contacted to seek their permission to carry out this study. The refusal rate was 8% which included refusals from one patient and two relatives. Two patients were 75

Expressed Emotions in Pakistan

excluded later as further questioning revealed that they had not sufficient contact with any family member and used to live at different places before the current admissions.

The remaining 32 patients were assessed through DSMIV-TR for broadly defined schizophrenia criteria (295.30, 295.10, 295.20, 295.90, 295.60, 295.40, 295.70, 297.1, 298.8, & 297.3 [18]) which all patients fulfilled. The inclusion criteria for the key relative were that s/he must be 18 years old or above and should have face-to-face interaction of 35 hours or more per week with the patient for at least three months before the current admission. In Pakistan, the majority of the patients live with their extended family, hence the criterion of face-to-face interaction of sufficient duration was not difficult to fulfill. An attempt was made to interview that relative in each case who was involved in the day-to-day care of the patient. However, in a few cases, the relative having the maximum contact was not available or willing for some reason. In that case the next relative with the maximum contact was taken. The criterion of at least 35 contact hours per week was nevertheless retained in all cases. The mean ages of patients and relatives were 33.84 (SD= 8.75; age range = 20-53) and 46.69 (SD= 14.88; age range = 18-70) respectively. Sixty-five percent of both patients and relatives were educated up to 12th grade, with 20% patients and 25% relatives being educated up to graduate level. Majority of the patients were unmarried (72%), whereas 75% of the relatives were married. Only 15% of the patients used to work before the current admission, and 45% of the relatives were housewives. Majority of the carers were mothers (n=14, 44%), followed by brothers (n=8, 25%), sisters and fathers (n= 4 each, 12.5%), and then husbands (n=2, 6%).

Instruments Camberwell Family Interview The Camberwell Family Interview was used to extract family emotions. It is a semi-structured interview schedule which is used to obtain information about circumstances in the home, three months preceding a patient’s admission to hospital for an acute, psychotic episode, and also to observe a relative’s behavior in the interview situation. The CFI consists of five scales: criticism, hostility, over-involvement, warmth and positive remarks. High EE is defined on the basis of six or more critical comments, presence of hostility, or a score of three or above on EOI. Five Minute Speech Sample (FMSS) The Five Minute Speech Sample (FMSS) is a brief measure of EE in which a relative is asked to speak for five 76

minutes uninterruptedly about the patient and how the two of them get along (19). The FMSS requires much less time and energy as compared to the CFI. In the current study, the FMSS was used to assess the extent of correlation between both measures on EE indicators so that FMSS could be used as a substitute for the CFI in future large scale studies, in case both measures correlate well.

High EE was rated on FMSS when a respondent made at least one critical comment anywhere in the speech sample; presence of all three or any two components from the statements of attitude, use of excessive details, and five positive remarks; and presence of hostility. The comparison between FMSS and CFI was made on the basis of the number of relatives identified as high or low EE on both measures assessed through kappa correlation as a measure of extent of agreement between both.

Procedure Families of the patients were contacted through the hospital administration. The study was explained to the patients and relatives as an investigation to look at the family interactions to understand the course of illness in the patients. Before taking interviews, written informed consent describing the purpose of the study and participants’ rights was obtained from all the participants. Other ethical issues concerning confidentiality and privacy were carefully handled throughout the course of the research.

All interviews were conducted on the hospital premises.

Relatives were informed that their conversation with the interviewer will be audio-recorded. Both first (AI) and third (SZJ) authors conducted CFI and FMSS interviews.

Each interview was completed in approximately one and half hours on average, while the scoring of the same usually took three hours. The FMSS was administered first followed by the CFI. Both interviewers as well as the second author independently transcribed and rated CFI and FMSS interviews. Reasonably high coefficients of interrater reliabilities were obtained for the CFI (K= .90) and FMSS (K= .86). The EE ratings used in this study were decided after discussions held among three authors to reach consensus ratings for each interview.

Results The results of this study were analyzed using SPSS Version 10.00. Table 1 displays the rates of EE derived from the current data as well as those from studies conducted in other parts of the world. This cross-cultural comparison indicates higher levels of overall index of EE in Pakistani

Aisha Ikram et al.

as compared to the rates reported from many other counInter-correlations between different components of tries. Analysis on individual components of EE again EE are illustrated in Table 3. The scores on EOI showed showed the higher rates of hostility and EOI as compared significant positive correlations with warmth scores to many other countries. However, the current rate of and the number of positive remarks, however, only EOI was very consistent with 55% high EOI relatives the former association reached statistical significance. reported in the only study conducted with Pakistanis livSimilarly, scores on hostility correlated significantly ing in Britain (6). Mean CC score of Pakistani relatives was with the number of critical comments. All other intercomparable to that found in Chinese (20), and lower than correlations were non-significant. those observed in British-Pakistanis, British-Sikhs and white British (6), and Mexican-Americans (21). Table 2. Types of High Expressed Emotion Relatives and However, like other components of EE, it remained Components of High EE (N=32) higher than the mean score of CC in Indian families EOI(10). As far as nonclinical scales of CFI are concerned, EE Component CC ≥ 6 Hostility Conventional EOI – Pak Relative (n, %) n (%) N (%) n (%) n (%) Pakistani relatives appeared to be slightly higher in Mother (14, 43.75) 3 (21.43) 8 (57.14) 11 (78.58) 5 (35.71) their rating on warmth with the average rating being Father (4, 12.50) 1 (25.00) 2 (50.00) 2 (50.00) 1 (25.00) 3.33. In contrast to the display of warmth, Pakistani families expressed fewer positive remarks on average Sister (4, 12.50) 1 (25.00) 3 (75.00) 1 (25.00) 0 as compared to those expressed by families in Britain Brother (8, 25) 2 (25.00) 6 (75.00) 2 (25.00) 1 (12.50) (6, 22), India (10), and China (20).

Husband (2, 6.25) 0 0 1 (50.00) 1 (50.00) Table 2 presents breakdown of the sample accordTotal 7 (21.87) 19 (59.37) 17 (53.38) 8 (25) ing to their EE levels. Among all relatives, mothers were more emotionally over-involved. There was a disAs CFI has been identified as a standardized and reliable proportionate number of all relatives, although these difmeasure of EE across studies, it was considered as the criferences do not contribute much to the conclusions. This terion measure for comparison with the ratings obtained Table also shows the rating of EOI using both Pakistani on the FMSS. The relatives’ five minute speech samples (17) and conventional (23) criteria. As a result, the numwere transcribed and rated on all five components of CFI. ber of high EOI relatives was dropped from 17 (53%) to 8 Kappa coefficient between the CFI and FMSS produced a (25%) with the Pakistani criteria. A rather dramatic change low agreement on the rating of high and low EE relatives occurred in the rating of high EOI for women (66% vs.

(K=.30, p ≤.11) and the FMSS could only detect 37% of all 28%) as compared to men (36% vs. 21%), which suggests high EE relatives as identified on the CFI. However, the that Pakistani culture expects more sacrificing and devoted FMSS could accurately identify all low EE relatives. behavior from female family members.

Table 1. Distribution of EE Components Among Pakistani Relatives and Those from other Cultures Location

Population (N)

Critical Comments/ %

Hostility (%)

Warmth

Positive Remarks

EOI %

High EE %

Lahore (current study)

Pakistani (22)

3.8

59

3.33

1.17

53

75

Birmingham [6]

British-white (20)

6.05

15

3.15

3.20

25

45

British-Sikh (20)

5.0

20

3.20

2.35

10

30

2.25

55

80

26, 50*

56

British-Pakistani (20)

6.65

25

2.85

Iran [28]

Iranian (97)

21%

41, 80*

-

Hong Kong [5]

Chinese (33)

24%

06

-

-

21

45

China [20]

Chinese (71)

3.93

16

2.14

1.72

8.5

28

London [2]

White

8.40

18

2.30

2.60

36

54

Los Angeles [21]

Mexican-Americans (69)

6.86

28

-

-

30

67

India [10]

Indians (104)

1.9

16

2.00

0.80

4.0

23

Denmark [17]

Danish (28)

4.5

21

2.50

3.10

56

54

*rates derived for only high EE group

77

Expressed Emotions in Pakistan

Table 3. Intercorrelations among all Subscales of CFI (N=32) Components

Critical Comments

Hostility

EOI

Warmth

Critical Comments

--

.37*

-.23

-.22

Hostility EOI Warmth

--

.14

-.34

--

.39* --

Positive Remarks *p<.05

Discussion The results of this work indicated higher levels of EE (75%) in Pakistani as compared to those reported from many other countries (see Table 1). However, this finding is in reasonable accordance with those of a minority of studies, for example, 74% in Los Angeles (8), 66% in France (24) and 80% in the only study conducted in Britain with British Pakistanis (6). The current high rates of EE are not congruent with the Chandigarh study (10) conducted in a cultural setting very similar to that in Pakistan. The researchers found relatively few households in Chandigarh which were high in EE (23%) and, in contrast to previous studies, no relative scored high on the EOI factor. They suggested that the low incidence of EE in India may be due to a lesser proportion of the Indians living in nuclear households, where emotions generated by having a relative with a psychotic disorder might be distributed throughout the network of an extended family.

The protecting factor of extended families also applied to Pakistan (68% of current families lived in joint family system), which indicates that some specific cultural factors may be responsible for these opposing results from similar cultures.. Since Lahore is an urban center it may be more appropriate to make the comparison with Chandigarh city, which had 30% high EE relatives compared with 8% in rural areas. Although this slightly narrows the gap between the ratings obtained from India and Pakistan, it does not exclude the possibility of involvement of some peculiar socio-cultural differences between both.

Cultural factors also appeared to influence the rating of emotional over-involvement; 34% of Pakistani relatives were markedly over-involved (i.e., scored 4 or 5 on the 6-point scale). A high rating of EOI in both native and British-Pakistanis (6) suggests that emotional overinvolvement may be a fundamental feature of kin relationships in Pakistani families which remains intact even after moving to another cultural setting. Hashemi and 78

Cochrane (6) concluded that the early socialization and up-bringing of a child in Pakistan is Positive done in a way that is very likely to increase closeremarks ness and sacrificing behaviors toward immedi-.24 ate family members. The authors also explain a 0 lower level of EOI in Indian relatives (10) by sug.33 gesting that most of the Indian relatives did not .18 socially isolate themselves because of the patient -and continued their social interaction which was missing in Pakistani caregivers.

The conceptualization of EOI also makes it more likely to be higher in close-knit societies like Pakistan. These family patterns are true of many cultures, including Mexican-Americans (25) and Egyptians (11).

Significant positive correlation between scores on EOI and warmth also suggests that in Pakistan emotional overinvolvement is a culturally distinct feature of concern for the relative and is expected in family relationships.

Among 17 high EOI relatives, the majority were females (n =12) who all were mothers except one sister. This observation has been made in earlier (26) and later EE studies (20). The finding of high EOI among women and mothers is not surprising given the cultural dimensions it taps, such as caretaking and affective attachments ideally relegated to women (13). The presence of more mothers in this sample nevertheless increases the probability of more mothers in any category of high EE. However, Pakistani mothers exhibited all characteristics of high EOI; though many of such behaviors are considered a norm in Pakistan if displayed by a mother. Jafri (17) measured the cultural validity of EOI construct in a community survey in Pakistan and showed that many of the behaviors, which are taken as evidence of high EOI according to the conventional criteria, were expected in Pakistan and such expectations were mainly from female relatives. Gender differences in rating of EOI on both conventional and Pakistani criteria in the current investigation also suggest that Pakistani culture expects more sacrificing and devoted behavior from female family members. This emphasizes the need to validate the construct of EOI across cultures. It has been suggested earlier that because of diverse acceptable degrees of protection and care for the patient in different cultures, EOI has not always been associated with relapse in schizophrenia (6). However, outcome studies are warranted to elucidate these connections in Pakistan.

Hostility appeared to be the most prominent component of interpersonal relations in Pakistani families with a psychiatric patient at home. Although 59% of the total sample showed the presence of hostility, 79% of the high

Aisha Ikram et al.

EE relatives exhibited hostility and thus hostility appeared to be the most common component that contributed to the rating of high EE. This figure is closer to a previous finding reported from Iran, where 80% of the high EE relatives expressed hostile comments about their sick family members (27). The current families appeared to be higher in hostility compared to those in other cultures, as shown in Table 1. The higher frequency of hostility in Pakistani caregivers may be attributed to the following factors.

Firstly, Pakistani families’ concern about the family name and honor may be one reason of this hostility. Secondly, lack of self-control in patients may have caused hostility in the relatives considering the general observation that self-control is appreciated here as a personality trait.

Ajmal (29) pointed out that most Pakistani households start preaching the virtue of self-restraint and self-control from the very beginning, and that is how a child learns through socialization that it is wicked to lose control over oneself. Consistently, a large-scale survey showed that not being able to control one’s symptomatic behavior in psychosis was considered as weakness of character by a sizeable proportion of people in Pakistan (30). The perception of the family that the patient is capable of controlling the symptomatic behavior associated with psychosis but is not making much effort to do so may enhance hostility in the care-taker. A recent study with Mexican-American families showed that high-EE caregivers perceive the expression of symptoms as caused by ill relative’s agency more frequently than low-EE caregivers (8, 30). Thirdly, the societal attitude toward deviant behavior will also determine the reaction toward a mentally sick person. There is some indication that psychiatric illness is stigmatized in Pakistan due to which appropriate treatment is not sought for it (31). In case of such interpretations, negative affective reactions of relatives toward mentally sick may be expected. Fourthly, the higher rate of hostility may also be a particular feature of the current Pakistani society, with its tremendous amount of political, economic and social instability, the outcome of which may be a change in emotional climate of the family. Lastly, lack of awareness about the causes and treatment of psychosis in Pakistan (30) may be another reason of hostility toward the symptomatic behavior of patients suffering from psychosis. In recent years a few incidents have been disclosed in Pakistan where mental patients were tied with chains by their families for many years because they thought that the afflicted people were “mad” or possessed and thus could be dangerous if left free. Consultation with any mental health professional was never considered as the problem seemed incurable

to them. Some evidence for this can also be found from the lack of objectivity shown by the relatives. Although a majority of the relatives were empathic and considered that the symptoms of the patient were due to the illness, some attributed the illness to paranormal agents, such as black magic, bad spells and evil eye.

To understand the association between criticism and hostility, critical comments contributing to the rating of hostility were examined separately. This analysis revealed that symptomatic behaviors of the patient (e.g., derailed, disorganized, lack of will-power, lethargic, and “everything wrong”) contributed most to the relatives’ hostility followed by not doing household work/chores and then a disrespectful attitude toward parents. This analysis also suggests that lack of awareness about mental health problems may be one of the main reasons creating interpersonal discords between family members and patients.

The current findings are not very consistent with those of many previous studies where verbal criticism appeared to be the most salient component of high-EE (11, 13, 20, 32). In previous British and American studies (6, 21) hostility always occurred in the context of excessive criticism conjunction, whereas in Pakistan 74% of the hostile relatives scored below the threshold of critical comments for high criticism (6 or above). Consistent with this, 29% of Chandigarh relatives making hostile comments scored below this level of criticism. A higher proportion of hostile but moderately critical relatives in Pakistan may lead to the speculation that people may be more inhibited in expressing criticism toward family members due to the cultural importance and teaching of self-restraint and self-control (28), although unintentional criticism may still reflect in the form of hostility.

The impact of culture was also evident on the target of criticism. Pakistani relatives primarily focused on socially embarrassing behavior (38.79%), followed by faulty personality traits (26.72%), symptomatic behaviors (21.12%), and then work-related behaviors of the patient (13.36%).

Families were more intolerant of behaviors which cause harm to the family reputation and were very concerned what “others” would say. This attitude is largely attributed to the stigma attached to mental illness (33, 34), which may risk damaging the family name. Consistent with this, Mexican Americans (25) and Chinese households in Hong Kong (5) criticized disrespectful and disruptive behaviors of the patients. On the contrary, British and Anglo-American relatives considered the negatively valued personality traits and psychotic symptoms more problematic (21, 22) because of the cultural significance of certain 79

Expressed Emotions in Pakistan

values, such as, independence, autonomy and taking initiative. A few families in Pakistan (13.36%) also criticized the patients for not doing any work. Men were criticized more for not earning and women for not doing household work and taking care of parents, consistent with the cultural roles of both genders. Thus, culture determines whether criticism will be a prominent feature of the familial emotional climate and what will be the content of criticism.

Three scales of CFI, criticism, EOI and hostility, are used to rate high or low EE, although there is some evidence that if a family shows high levels of warmth concurrently, it may lead to a good outcome for the patient by neutralizing the effect of negative emotions (35). Pakistani relatives appeared to be slightly higher in their rating on warmth. In the present study most of the respondents scored either 3 or 4 (37.5% each), which corresponds with moderate and moderately high warmth respectively.

In contrast to the display of warmth, Pakistani families expressed fewer positive remarks on average as compared to those reported in many previous studies, which indicates that Pakistani people generally make less use of positive comments in their social interactions with mental patients. This may partly be possible because of the poor health care facilities and resulting burden of care on the families in Pakistan. However, the overall lower proportion of positive remarks in comparison with critical comments across studies may be because of the specific format and structure of CFI which encourages reporting of negative behavior of the patient. Another explanation for the excess of criticism in comparison to positive remarks is that the typical psychotic behavior of schizophrenia patients may induce relatives to express verbal criticism more frequently.

Consistent with the previous studies (36) the FMSS showed a moderate correlation with the CFI which indicated that the FMSS may be used as an adjunct measure with the CFI but it should not be employed alone for the cross-cultural assessment of EE. In particular, the FMSS failed to assess hostility and criticism in relativesâ&#x20AC;&#x2122; statements in the limited time available for their talk. It may seem logical to speculate that due to cultural reasons Pakistani families were reluctant to share their private familial matters and family disputes with an â&#x20AC;&#x153;outsiderâ&#x20AC;? (researcher). The FMSS showed lower sensitivity for identifying high EE relatives, but low EE families were identified with 100% accuracy. This lower sensitivity was also mentioned by Shimodera and colleagues (36) who suggested that the borderline low-EE subjects may have to be included in the high-EE group to improve its sensitivity.

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As the first attempt to rate expressed emotions in Pakistani relatives using standardized methodology, this study made it possible to compare findings across cultures.

However, certain methodological weaknesses should be kept in mind while generalizing from the results obtained from this study. Firstly, lack of follow-up data limits the scope of the study and thus no association can be made between family EE and relapse in the patients. Secondly, only one relative having maximum contact with the patient was interviewed from each household. The ideal situation would be that as many key relatives as possible would be interviewed from each household, which not only would provide an overall idea of the emotional climate of the family but also would indicate the maximum levels of all EE components in a particular family. Thirdly, the Urdu version of CFI may not have been able to pick up elements of EE as accurately as it does in the English language. Anyway, an attempt was made to resolve this problem and EE ratings for each interview were determined by independent transcriptions and ratings by the raters who were trained to rate EE according to criteria employed in previous studies (23). Fourthly, the sample size was rather small to draw unequivocal conclusions. Moreover, the key relatives were predominantly mothers, but that reflects the natural distribution of carers in Pakistan. As a pioneering attempt this study nevertheless provided a ground for future investigations which may be conducted with relatively large samples and a rich mix of all relations.

The clinical significance of present findings can only be established by the outcome studies in Pakistan which are required to determine whether hostility as the most prominent component of interpersonal relations and emotional over-involvement in family relations are pathological or shall be considered a part of culture. Moreover, the cut-off scores for qualifying as high for any component of EE need to be determined in relation to outcome of the disorder. Meanwhile, the current findings can be used as a strong base to initiate psycho-education programs in hospitals for families to create awareness about the psychosis and the related symptomatic behavior of the patient. These programs may be able to reduce the level of hostility among the relatives hypothesized to be caused by the ignorance about severe mental health problems.

Conclusions The current findings provided important information regarding the prevalence of EE in Pakistani relatives of patients with schizophrenia. The results of this work sug-

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gest that the components of EE are not culture specific and are observable in Pakistan with the similar features observed in other cultures. The findings of this work also yielded some differences. The Pakistani relatives appeared to be more hostile yet emotionally over-involved and warm toward their sick relatives as compared to the households reported in many previous studies. The present findings have strong implications for mental health professionals who can initiate psycho-education programs for the families to reduce their level of hostility.

Outcome studies are nevertheless warranted in Pakistan to determine whether hostility, as the most prominent component of interpersonal relations and emotional over-involvement in kin relations, is pathological or to be considered a part of the culture.

Acknowledgements

The authors are very obliged to British Council for providing financial support to carry out this work (PMI2 Connect Award No. RC PK 32). They also wish to acknowledge the contribution of families who very willingly shared their experiences with the research team.

References 1. Hooley JM, Hoffman PD. Expressed emotion and clinical outcome in borderline personality disorder. Am J Psychiatry 1999;56:1557-1562.

2. Vaughn CE, Leff JP. The measurement of expressed emotion in the families of psychiatric patients. Br J Soc Clin Psychol 1976;15:157-165.

3. Heresco-Levy U, Greenberg D, Dasberg H. Family expressed emotion: Concepts, dilemmas and Israeli perspectives. Isr J Psychiatry 1990;27:204-215.

4. Mino Y, Inoue S, Tanaka S, Tsuda T. Expressed emotion among families and course of schizophrenia in Japan: A 2-year cohort study. Schizophr Res 1997;24:333-339.

5. Ng RMK, Mui J, Cheung HK, Leung SP. Expressed emotion and relapse of schizophrenia in Hong Kong. Hong Kong J Psychiatry 2001;11:4-11.

6. Hashemi AH, Cochrane R. Expressed emotion and schizophrenia: A review of studies across cultures. Int Rev Psychiatry 1999;11:219-224.

7. Moline RA, Singh S, Morris A, Meltzer HY. Family expressed emotion and relapse in schizophrenia in 24 urban American patients. Am J Psychiatry 1985;142:1078-1081.

8. Nuechterlien KH, Synder KS, Dawson ME, Rappe S, Gitlin M, Fogelson MD. Expressed emotion, fixed dose fluphenazine decanoate maintenance, and relapse in recent onset schizophrenia.

Psychopharmacol Bull 1986;22:633-639.

9. Azhar MZ, Varma SL. Relationship of expressed emotion with relapse of schizophrenia patients in Kelantan. Singapore Med J 1996;37:82-85.

10. Wig NN, Menon DK, Bedi H, Leff J, Kuipers L, Ghosh A, et al. Expressed emotion and schizophrenia in north India. II. Distribution of expressed emotion components among relatives of schizophrenic patients in Aarhus and Chandigarh. Br J Psychiatry 1987;151:160-165.

11. Kamal A. Variables in expressed emotion associated with relapse: A comparison between depressed and schizophrenic samples in an Egyptian community. Curr Psychiatry 1995;2:211-216.

12. Philips MR, Xiong W. Expressed emotion in mainland China: Chinese families with schizophrenic patients. Int J Ment Health 1995;24:54-75.

13. Jenkins JH, Karno M. The meaning of expressed emotion: Theoretical issues raised by cross-cultural research. Am J of Psychiatry 1992;149:9-21.

14. Jenkins JH. Too close for comfort: Schizophrenia and emotional

over-involvement among Mexicano families. In: Gaines AD, editor.

Ethnopsychiatry: The cultural construction of professional and folk psychiatries. Albany, N.Y.: SUNY, 1992: pp. 203-221.

15. Ishfaq K. Parental expressed emotions and schizophrenia. Unpublished MPhil thesis, University of the Punjab, Lahore, Pakistan, 2003.

16. Mahmood A, Niaz S, Rashid U, Chaudhry HR. Expressed emotions and schizophrenia in Pakistan. Pak J Med Sci 2006;22:424-428.

17. Jafri SZ. Cultural analysis of expressed emotion construct. Unpublished M.Phil. thesis, GC University, Lahore, Pakistan, 2007.

18. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric, 2000.

19. Maga単a AB, Goldstein MJ, Karno M, Miklowitz DJ, Jenkins J, Falloon IRH. A brief method for assessing expressed emotion in relatives of psychiatric patients. Psychiatr Res 1986;17:203-212.

20. Ran MS, Leff J, Hou ZJ, Xiang MZ, Wan CLW. The characteristics of expressed emotion among relatives of patients with schizophrenia in Chengdu, China. Cult Med Psychiatry 2003;27:95-106.

21. Vaughn CE, Snyder KS, Jones S, Freeman WB, Falloon IRH. Family factors in schizophrenic relapse: Replication in California of British research on expressed emotion. Arch Gen Psychiatry 1984;4:1169-1177.

22. Vaughn CE, Leff JP. The influence of family and social factors on the course of psychiatric illness: A comparison of schizophrenic and depressed neurotic patients. Br J Psychiatry 1976;129:125-137.

23. Leff J, Vaughn CE. Expressed emotion in families: Its significance for mental illness. New York: Guilford, 1985.

24. Barrelet L, Ferrero F, Szigethy L, Giddey C, Pellizzer G. Expressed emotion and first-admission schizophrenia: Nine-month follow-up in a French cultural environment. Br J Psychiatry 1990;156:357-362.

25. Karno M, Jenkins JH, de la Selva A, Santana F, Telles C, Lopez S, et al. Expressed emotion and schizophrenic outcome among Mexican American families. J Nerv Ment Dis 1987;175:143-151.

26. Brown GW, Carstairs M, Monck E, Birley JLT, Wing JK. Influence of family life on the course of schizophrenic illness: A replication. Br J Psychiatry 1972;121:241-258.

27. Leff J, Vaughn CE. Expressed emotion in families: Its significance for mental illness. New York: Guilford, 1985.

28. Mottaghipour Y, Pourmand D, Maleki H, Davidian L. Expressed emotion and the course of schizophrenia in Iran. Soc Psychiatry Psychiatr Epidemiol 2001;36:195-199.

29. Ajmal M. Cultural presuppositions and mental disease. Psychol Q 1969;3:25-29.

30. Suhail K. A study investigating mental health literacy in Pakistan. J Ment Health 2004;14:167-182.

31. Breitborde NJK, Lopez SR, Nuechterlein KH. Expressed emotion, human agency, and schizophrenia: Toward a new model for the EE relapse association. Cult Med Psychiatry 2009;33:41-60.

32. Qidwai W, Azam SI. Psychiatric morbidity and perceptions on psychiatric illness among patients presenting to family physicians in April 2001 at a teaching hospital in Karachi. Asia Pac Fam Med J 2002;2/3:79-82.

33. Bebbington PS, Kuipers L. The predictive utility of expressed emotion in schizophrenia: An aggregate analysis. Psychol Med 1994;24:707-718.

34. Suhail K, Ajmal MA. Counseling in Pakistan: An Eastern Muslim perspective. In: Gerstein LH, Heppner PP, Egisdottir SS, Leung MA, Norsworthy KL, editors. International Handbook of Cross-Cultural Counseling. New York: Sage, 2009: pp. 237-250.

35. Suhail K, Anjum S. Stigma towards help-seeking behavior and mental health problems. Bangladesh Psychol Stud 2004;14:55-70.

36. Shimodera S, Mino Y, Inoue S, Izumoto Y, Kishi Y, Tanaka S. Validity of a five minute speech sample in measuring emotion in the families of patients with schizophrenia in Japan. Cult Med Psychiatry 1999;27:95-106.

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Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Preventive Pharmacological Treatment – an Evolving new Concept in Schizophrenia Rony Sabbag, BMedSc,1 Raz Levin, MSc,2,3 Shany Edelman, MSc,2,3 and Uriel Heresco-Levy, MD1,2 1

Hadassah Medical School, Hebrew University, Jerusalem, Israel Psychiatry Department, Herzog Memorial Hospital, Jerusalem, Israel 3 Neurobiology Department, Hebrew University, Jerusalem, Israel 2

ABSTRACT Treatment for schizophrenia remains one of the major challenges of modern medicine. The development of innovative pharmacological approaches for this disorder can potentially alleviate tremendous human suffering and revolutionize mental health delivery systems. While current treatment guidelines for schizophrenia refer to the post-psychosis onset phase of illness, presently there is a strong resurgent interest in secondary prevention intervention applied during schizophrenia prodrome. This development stems largely from the recognition that neurobiological deficit processes associated with schizophrenia severity and chronicity are already active by the time clinical onset is recognized. Proposed preventive treatments include presently used medications and experimental compounds that hypothetically may influence ongoing pathophysiological processes earlier in their development. The future establishment of the early recognition and intervention concept in schizophrenia is critically dependent on the outcome of ongoing research assessing the feasibility of prodrome diagnosis, the efficacy of specific medications and the alleviation of the risks associated with early pharmacological treatment.

INTRODUCTION Schizophrenia, long considered the most chronic, debilitating and costly mental illness, is one of the most devastating human diseases, ranking among the top 10 causes of disability in developed countries worldwide (1). It Address for Correspondence:

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affects ~1% of the world’s population and generally is diagnosed in late adolescence or early adulthood following the appearance of florid psychotic symptoms.

Currently, the pharmacological treatment of schizophrenia relies on the use of conventional (1st generation) and newer, atypical (2nd generation) antipsychotics. The fundamental paradigms followed by these medications consist of attenuation, in various degrees, of dopamine D2 receptor function, combined, in the case of atypical antipsychotics, with blockade or inverse agonism of serotonin 5-HT2 receptors. Recently, two landmark studies, the Clinical Antipsychotic Trials of Intervention Efficacy (CATIE) (2) and the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS) (3) compared the effectiveness and tolerability of 1st and 2nd generation antipsychotics and indicated once more that there is no satisfactory treatment for schizophrenia in terms of efficacy or tolerability (4). Very few differences in effectiveness between 1st and 2nd generation antipsychotics were found and the majority of patients in each drug group discontinued their assigned treatments owing to inefficacy, intolerable side effects or for other reasons. Treatment resistance in schizophrenia remains thus a complex mental health problem. Despite optimal available treatments, the majority of affected individuals have substantial lifelong impairment and more than one half require continuous support, whether living in the community or in long-term institutions. Patients with persistent positive symptoms still account for 20-30% of schizophrenia patients (5). Furthermore, the limited clinical effectiveness of available treatments against negative and cognitive symptoms undermines efforts to rehabilitate the patients and limit chronicity. Neurocognitive impairment is associated with key features of schizophrenia, such as the inability to acquire skills, poor social problem solving, and poor community functioning and

Rony Sabbag, 6/7 Hatibonim St., Jerusalem 92386, Israel

ronysabbag@gmail.com

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may actually represent a stronger correlate of poor outcome than any other symptom domain (6).

In view of the limitations of existing treatment paradigms and given the recent developments in the understanding of pathophysiological processes associated with schizophrenia, current research in the therapeutics of this disorder is exploring two intertwined issues: 1) the possibility that early pharmacological treatment applied as “preventive” intervention, or at least as rapidly as possible following the appearance of florid symptoms, may attenuate, delay or even prevent schizophrenia development, and 2) the assessment of the therapeutic potential of novel compounds characterized by mechanisms of action different from those of presently available medications.

SCHIZOPHRENIA PREVENTION: OLD CONCEPTS – NEW EMPHASES a. The Caplan model and the “risk reduction” approach In 1964, Dr. Gerald Caplan, a child psychiatrist, reconceptualized the prevention of mental illness as a public health issue involving primary, secondary and tertiary levels of prevention (7). Primary prevention aims at reducing the incidence of new cases (i.e., preventing healthy individuals from acquiring the disorder); secondary prevention aims at reducing prevalence of the disorder by early intervention (i.e., preventing individuals with early signs of illness becoming more seriously ill); tertiary prevention aims at preventing those individuals with the disorder from being incapacitated by the illness.

An alternative approach to the prevention of mental illness, termed “risk reduction,” was advocated by Mrazek and Haggerty (8). The “risk reduction” approach distinguishes between two types of prevention that would be considered primary or on the primary-secondary border under the Caplan model. Universal preventive interventions are targeted to the general public or to a whole population group for whom individual risks for mental disorders have not yet been identified. Selective preventive interventions are targeted to individuals or subgroups of the population whose risk for developing a mental disorder is significantly higher than average. b. Schizophrenia phases Schizophrenia can be viewed as a disorder characterized by three main phases: premorbid, prodromal and psychotic. The premorbid phase may contribute to the vulnerability to schizophrenia. This phase encompasses

the prenatal and perinatal developmental periods as well as early childhood, and may include the occurrence of perinatal complications such as obstetrical trauma, distorted mother-child bonding and maladaptive learning or abnormal family communication patterns (9).

A history of delayed developmental milestones in the areas of sitting, standing, walking and talking and the presence of minor physical anomalies (e.g., malformed ears, dermatoglyphic abnormalities) may represent indirect evidence of abnormal prenatal development.

Moreover, there have also been reports of premorbid cognitive, personality and social functioning deficits in patients with schizophrenia (10).

The prodromal phase is characterized by a decline from premorbid functioning and extends up to the time of onset of frank psychotic symptoms. The average length of the prodromal phase is two to five years, and during this phase subjects experience substantial impairment in psychosocial functioning. Common early prodromal features include nonspecific symptoms, such as sleep disturbance, anxiety, irritability, depressed mood, poor concentration and fatigue. Characteristic subsyndromal symptoms include “oddness,” social isolation, impaired perception and thought processes.

Retrospective studies also suggest that much of the functional decline associated with schizophrenia occurs during the prodromal stage (11). Full blown positive symptoms, ideas of reference and marked suspiciousness usually develop later and herald the imminent onset of psychosis (12).

An emotionally charged event and/or a stressful environment may precipitate the psychotic episode. The psychotic stage of early schizophrenia can be seen as progressing through an acute phase, an early recovery phase and a late recovery phase. The acute phase refers to the presence of florid psychotic features such as delusions, hallucinations and formal thought disorder. The early recovery phase refers to the first 6 months following acute treatment. The late recovery phase refers to the subsequent 6 to 18-month period. The period following recovery from a first episode of psychosis and extending for up to five years has been termed “the critical period” (10). This is because most follow-up studies have shown that up to 80% of patients will relapse within this 5-year period.

As mentioned earlier, the “Caplan model” and the “risk reduction” approach can be applied on these progressing phases. Primary prevention in schizophrenia would be considered universal prevention since the prevention efforts would be made prior to the emergence of evident 83

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risk factors (i.e., during the premorbid phase). The aim of secondary prevention would be to reduce the proportion of patients making a full transition to schizophrenia through intervention during the prodromal phase of the disorder. Tertiary prevention of schizophrenia aims to reduce the mortality and morbidity of the disease, and ultimately its future progression. The current treatment of schizophrenia represents in fact tertiary prevention, and is the only form of intervention that is presently applied in the treatment of this disorder. c. Secondary prevention Secondary prevention of schizophrenia is potentially the most cost-effective form of preventive intervention.

Primary prevention requires strategies that target the entire population, hence it requires strong sociopolitical support and implies a heavy economic burden. Since schizophrenia is a relatively rare occurrence, large-scale screening of the general population for identification of asymptomatic individuals at higher risk does not appear practical at present time (9, 12). In contrast, secondary prevention is considered potentially feasible. Theoretically, the notion of early pharmacological intervention during the prodromal phase of schizophrenia has a dual aim: 1) to treat active prodromal symptoms, and 2) to prevent further deterioration and progression toward chronicity.

Overall, it raises the possibility of preventing, delaying, or ameliorating the onset of the diagnosable disorder. This type of intervention, although already in use in other medical branches and potentially groundbreaking for mental health treatment delivery systems, has not been systematically assessed until recently. The main factors contributing to this delay have been: 1) the difficulty in achieving, at an early stage of the disease, sufficient sensitivity and specificity for correctly predicting subsequent chronic psychosis (true positive), 2) the lack of specific and ethically acceptable treatments for this stage of illness, and 3) the danger of unnecessarily exposing to treatments associated with disabling side effects (e.g., antipsychotic drugs) individuals who may not ultimately develop schizophrenia or other chronic psychoses (false positive) or for whom, overall, the early “psychiatric labeling” and/or installment of psychotropic treatment may be detrimental.

DIAGNOSIS OF SCHIZOPHRENIA PRODROME It is widely accepted that interactions between a genetically mediated neurobiological vulnerability and nongenetic “second hits” or stressors may lead to the develop84

ment of schizophrenia. While family studies stress the importance of defining genetic high-risk groups, it also appears that schizophrenia is a highly polygenic disorder.

Consequently, significant difficulties still remain in the exact mapping of genes or combinations of genes (i.e., oligogenetic interactions) that create the heritable trait that precedes schizophrenia onset. At present, we are unable to identify which individuals within the genetic high-risk group will eventually develop schizophrenia with sufficient positive predictive value (10). Moreover, an approach that focuses exclusively on genetic risk is characterized by low sensitivity, as >80% of individuals with schizophrenia have no affected first-degree relatives and >60% have completely negative family histories (13). a. Prospective identification based on current symptoms Prior to the last decade, there was little support for the feasibility of identifying prodromal individuals on a prospective basis. DSM-III-R attempted to describe schizophrenia prodrome in terms of a behavioral checklist. This list was subsequently withdrawn from DSM-IV because the reliability and validity of the listed prodromal symptoms have never been established (14). Most of the literature on the prodromal phase had been based on detailed retrospective reconstruction of the prodrome (15) and/ or the relapse prodrome (i.e., the prodrome preceding an exacerbation of known/diagnosed psychotic illness).

However, such approaches are methodologically problematic. The accuracy of recall of prodromal symptoms is questionable in the first approach and in the latter, the relapse prodrome, may not be an accurate reflection of the prodrome preceding the first psychotic episode, as it might be modified by the disease process itself and by the ongoing pharmacological and psychosocial treatment.

During the past decade, substantial progress has been made in the prospective identification of the prodromal phase, based on current symptoms. McGorry and colleagues (15) have developed a set of criteria for identifying prodromal individuals using a “close-in” strategy. This approach takes into account recent-onset functional decline plus genetic risk (a first-degree relative diagnosed with a psychotic disorder or with schizotypal personality disorder) and onset of attenuated (subthreshold) positive psychotic symptoms, or brief limited intermittent psychotic symptoms too short in duration to meet DSM criteria for psychosis. A structured interview, the Comprehensive Assessment of At Risk Mental States (CAARMS), is used to determine

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whether these criteria are met (an online version of this questionnaire is available on: www.nimhe.csip.org.uk/ silo/files/sofas-caarms-july-2006-1.doc).

Two additional instruments for rating and tracking prodromal phenomena cross-sectionally and over time were developed at the Prevention through Risk Identification Management and Education (PRIME) Clinic (New Haven, Connecticut, U.S.A.). These instruments are the Structured Interview for Prodromal Syndromes (SIPS) (16) which includes the Scale of Prodromal Symptoms (SOPS) (17). The SIPS is a structured diagnostic interview used to diagnose the prodromal syndrome and may be thought of as analogous to the Structured Clinical Interview for DSM-IV (SCID) or other structured diagnostic interviews. The SIPS includes the SOPS, the Schizotypal Personality Disorder Checklist (18), a family history questionnaire (19) and a well-anchored version of the Global Assessment of Functioning Scale (GAF) (20) The SOPS is a 19-item scale designed to measure the severity of prodromal symptoms and their change over time. It may be conceptualized as analogous to the Positive and Negative Syndrome Scale, the Brief Psychiatric Rating Scale, and other established symptom severity rating scales for patients who are fully psychotic. The SOPS contains four subscales for positive, negative, disorganization, and general symptoms domains. Both SIPS and SOPS have demonstrated excellent reliability (21).

Notwithstanding their high reliability, the accuracy of screening instruments such as CAARMS or SIPS is reliant to some extent on the population being screened; that is, if these instruments are applied to a population with fewer at-risk cases, a much higher rate of false-positive diagnoses will result. This group of false-positive cases may be as high as 60% with current instruments and in the populations in which they are currently being used (10). Considering these drawbacks, additional research and the integration of newer concepts is clearly needed in order to increase the accuracy of these instruments and reach a more reliable diagnosis of schizophrenia prodromal phase. b. Imaging findings Based on postmortem observations of reductions of dendritic branching and spine and synapse density in schizophrenia (22), many schizophrenia researchers now believe that disruptions in cellular connectivity are involved broadly in the pathophysiology of this disorder.

Reduced cortical connectivity is likely to be present, at

least in part, in some cases from birth, representing a lifelong biological vulnerability but may progress beyond a threshold critical for expression of psychotic symptoms as a function of normal neuromaturational events (i.e., synaptic pruning) during adolescence (23). In other cases, reductions in cortical connectivity may emerge during adolescence due to aberrant neurodevelopmental processes (i.e., abnormal pruning) and/or environmental insults (e.g., elevated cortisol levels leading to dendritic atrophy). The contributions of early (prenatal and perinatal) and later (adolescent) brain developmental processes to psychosis risk are not mutually exclusive, and both sets of processes may be operative in some cases (reviewed in 16, 24, 25). Relevant to the neurodevelopmental hypothesis, radiologically detectable volumetric abnormalities in schizophrenia may be apparent at the onset time of frank psychosis (25, 26). Whether these changes progress over time has been a more contentious issue, but recent longitudinal MRI studies suggest that progressive reductions in global and regional gray matter volume can be identified (25, 27). Additionally, there is some evidence that progressive changes may occur before the onset of psychosis. In subjects at ultra-high risk for developing psychosis and who subsequently developed psychosis, a longitudinal reduction in gray matter volume in the inferior frontal, medial temporal and cingulate cortices was found between baseline and follow-up scans (28).

These changes were not evident in individuals who were at ultra-high risk but did not develop psychosis at follow-up. A recent study (29) reported progressive gray matter reduction of the superior temporal gyrus (STG) during the prodromal phase and after the onset of frank psychosis in a high-risk cohort. Morphologic abnormalities of the STG and its functionally relevant subregions, such as the primary auditory cortex and planum temporale, a neocortical language region, have been repeatedly described in schizophrenia. Volumetric reductions of these regions, especially in the left hemisphere, have been found to correlate with auditory hallucinations or thought disorder (30). These findings support the naturalistic observations of schizophrenia deterioration that commences two to three years before the onset of psychosis and appears to diminish in activity during the first few years after illness onset.

Another study (31) expanded this research and attempted to assess whether there were white matter abnormalities in people at ultra-high risk of psychosis and whether these were associated with the subsequent development of psychosis. This study found that relative 85

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to individuals who did not later develop psychosis, the subgroup that subsequently developed psychosis had a larger volume of white matter in an area subjacent to the left premotor cortex, close to the superior frontooccipital fasciculus, with a trend for a greater volume in a homologous region of white matter in the right hemisphere. Furthermore, longitudinal comparison of data revealed a reduction in white matter volume in the region of the left fronto-occipital fasciculus in individuals who developed psychosis.

Overall, these accumulating new data suggest that regressive developmental processes active during late adolescence and early adulthood, that are likely to result in reduced cellular connectivity (such as synaptic pruning and disrupted white matter development), may underlie the emergence and early course of psychotic symptoms. Furthermore, they represent an important milestone on the way of coping with the diagnosis difficulties mentioned earlier, as they may greatly improve the ability to distinguish between patients who may subsequently develop psychosis and those who may not. c. Multifactorial diagnosis Recent data stemming from the eight centers – North American Prodrome Longitudinal Study (NAPLS) – indicate that the development of multivariate risk prediction algorithms may significantly improve accuracy in the prediction of development of schizophrenia or other psychotic disorders. In a collaborative analysis (32) with 2-year follow-up of 291 prospectively identified treatment-seeking patients meeting SIPS criteria, the risk of conversion to psychosis was 35%, with a decelerating rate of transition during the 2 1/2-year follow-up. Five features assessed at baseline contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse.

Prediction algorithms combining two or three of these variables resulted in dramatic increases in positive predictive power (i.e., 68%-80%) compared with the prodromal criteria alone. These findings demonstrate that prospective ascertainment of individuals at risk for psychosis is feasible, with a level of predictive accuracy comparable to that in other areas of preventive medicine. Moreover, the future inclusion of imaging parameters in risk prediction algorithms holds promise for an additional accuracy increase.

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Overall, in view of these encouraging findings, the concept of early detection in schizophrenia is increasingly appealing. Presently, the DSM-V Psychotic Disorders Work group is debating whether available data may justify the establishment of psychosis risk as a specific diagnostic class within the next edition of this influential classification system.

PHARMACOLOGICAL INTERVENTION DURING THE PRODROMAL PHASE The interventional measures for prodromal patients studied to date, such as antipsychotic medication and cognitive behavioral therapy, are viewed essentially as a modification of the existing standard treatment for established schizophrenia (10). A critical question concerning the utility of the prodromal syndrome definition refers to the modes of pharmacological intervention that are theoretically predicted to reduce prodromal symptomatology and eventually prevent progression from a prodromal to a full psychotic state. Presently, the proposed pharmacological treatments for secondary prevention include medications, mainly atypical antipsychotics and antidepressants, presently used in neuropsychiatric disorders and novel treatments suggested by neurodevelopmental considerations (Table 1).

Table 1. Pharmacological treatments proposed for secondary prevention intervention in schizophrenia Medications used routinely in neuropsychiatric disorders • Atypical antipsychotics • Risperidone • Olanzapine • Amisulpride • Aripiprazole • Antidepressants • Anxiolitics • Low dose lithium carbonate Medications suggested by neurodevelopmental considerations • Antioxidants • Essential fatty acids • Estrogens • Glutamatergic neurotransmission modulators

a. Currently used medications The case for testing antipsychotic drugs as prophylactic measures rests entirely on their empirically proven efficacy in decreasing the severity of positive psychotic symptoms among patients with established illness. The results of the first clinical trials, involving risperidone (33), olanzapine (34, 35) amisulpride (36) and aripip-

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razole (37) treatment, have been recently reported and additional prodromal intervention studies using antipsychotics are presently ongoing. These studies indicate that, overall, pharmacological intervention may result in reduced prodromal symptom intensity in particular as far as positive symptoms are concerned. However, initial applications of these agents have produced discouraging results on the primary question of preventive effectiveness (25). Furthermore, as evidenced by the significant weight gain observed in the olanzapine study (34, 35), they confirmed the concern for worrisome side effects associated with antipsychotic drugs, many of which could be more prominent in adolescent prodromal individuals than in adult patients (38).

An additional course of action presently explored is antidepressant treatment. The concept of using antidepressants in the prodromal phase is based on the notion that early interventions should be as benign as possible, especially with respect to stigma, immediate side effects and long-term health consequences. Nevertheless, potential exacerbation of psychotic symptoms represents a significant drawback limiting the use of this type of medication with prodromal patients. So far, one prospective naturalistic treatment study of adolescents considered to be in the prodromal phase suggested successful results with the use of antidepressants (39). In general, adolescents were more likely to be noncompliant to 2nd generation antipsychotics than to antidepressants; therefore, it was suggested that in some cases it might be preferable to begin treatment with antidepressants and progress to antipsychotics once symptoms intensify. Presently, this line of investigation is being further explored. b. Neurodevelopmental treatments From both efficacy and safety perspectives, the concept of assessing medications specifically relevant to prodromal stages is presently gaining ground. In this context, the demonstrated role of glutamatergic dysfunction in the pathogenesis of schizophrenia raises the possibility of using modulators of glutamatergic neurotransmission as early pharmacological intervention (40).

Most of the excitatory transmission in the brain is mediated by the endogenous amino acids glutamate (GLU), and aspartate. The action of GLU and its congeners is mediated at three subtypes of ionotropic receptors: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDAR), and at two distinct families of metabotrophic G proteincouples receptors. Several lines of evidence suggest that

NMDAR hypoactivity could be implicated in the progressive developmental pathophysiology of schizophrenia and in the related symptoms and deficits progression seen during the pre-psychotic phase. NMDARs play a crucial role in regulating neuronal migration, neurite outgrowth, activity dependent synaptogenesis, and the “pruning” of supernumerary neurons by apoptosis (reviewed in 41, 42).

Furthermore, there is increasing evidence of reinforcing interactions between NMDAR and trophic factors such as brain-derived neurotrophic factor (BDNF). Activation of NMDAR induces the expression of BDNF as this is prevented in an activity-dependent model in which NMDAR subunit epsilon has been inactivated by a null mutation (reviewed in 43). It is hypothesized that, in schizophrenia, genetic factors may predispose to an excess synaptic elimination, increased neuronal apoptosis, decreased cell somal size, or a combination of these processes already during pre-psychotic stages. Such changes might result from altered expression of genes that are critical for neurodevelopmental processes such as glutamatergic NMDAR/ AMPA expression (44) and brain-derived neurotrophic factor levels. Recent studies suggest that polymorphisms in GLU-related genes that would be predicted to alter NMDAR function are associated with schizophrenia.

These polymorphisms include neuregulins (NRGs), which may influence the insertion of NMDAR subunits into the membrane, and d-amino acid oxidase (DAAO) and G72 proteins that interact to metabolize D-serine (DSR) which acts as a NMDAR co-agonist (reviewed in 45, 46). The discovery of the association between schizophrenia and DAAO and G72 genes highlights the NMDAR hypofunction hypothesis and draws further attention to the potential role of NMDR agonists.

Furthermore, during the last decade, a first generation of controlled clinical trials have demonstrated that adjuvant treatment with NMDAR glycine (GLY) site modulators (e.g., GLY, DSR, sarcosine) may results in symptom alleviation in established treatment-refractory schizophrenia patients (reviewed in 40, 47, 48). Presently, these types of compounds are assessed in multicenter controlled trials as secondary preventive intervention for individuals at risk for developing this disorder.

SECONDARY PREVENTION: INCENTIVES AND RISKS Although extensive research on early detection and pharmacological intervention in schizophrenia has been recently conducted on a large international scale, 87

Preventive Pharmacological Treatment – an Evolving new Concept in Schizophrenia

these issues remain controversial. On one hand, there clearly are important scientific and economic incentives for developing this line of investigation; on the other, additional data is necessary for alleviating the concerns and risks associated with the preventive intervention concept (Table 2).

Table 2. Secondary prevention intervention in schizophrenia: Incentives and risks Incentives: • Economic • Neurobiological deficit processes already present when onset is recognized • Duration of untreated psychosis (DUP) - prognosis correlation • Introduction of antipsychotics with reduced side effects • Prodromal patients are highly symptomatic, functionally and cognitively impaired and treatment-seeking.

Risks: • "Psychiatric case" classification, stigmatization, demoralization, depression.

• Lack of validated diagnostic criteria.

• False-positive cases (up to 60%) • Adverse events of antipsychotic medications, increased vulnerability in young patients • Competency issues in children/ adolescents

Successful intervention during the prodromal phase would be cost-effective for the health systems and revolutionary in terms of illness prognosis. There is evidence suggesting that early treatment could result in a significant reduction in morbidity and better quality of life for patients with schizophrenia and their families (49), thus reducing the high costs of current treatment.

Identifying patients before the first psychotic episode may prevent progression of neurobiological deficit processes that have been associated with severity and chronicity of schizophrenia and are already present at the time of the first psychotic episode (25, 49). Moreover, short duration of untreated psychosis (DUP) seems to be correlated with better prognosis (50). DUP is defined as the time between the onset of the first psychotic symptoms and the first adequate treatment. A longer DUP has been found to be associated with poor premorbid functioning, an insidious onset of psychosis and the presence of negative symptoms (10). Patients with longer DUP were reported to have decreased hippocampus volumes, implying that psychosis may have toxic effects upon the brain and may contribute to cognitive deterioration (10, 51).

Finally, prodromal symptoms are relatively severe compared with other symptoms that are generally perceived as requiring psychiatric treatment. Indeed, pro88

dromal patients were shown to have lower quality of life than a group of treated first episode psychosis patients (10), and retrospectively, most prodromal patients have previously sought and received psychiatric treatment, including psychotropic medications.

As far as risks are concerned, first and foremost, there is concern that participation in early intervention programs would classify an individual as a “psychiatric case” (10, 39). The patient may then face stigmatization by others or experience self-stigmatization resulting in demoralization and depression. Furthermore, using present diagnostic criteria, many individuals who are labeled as prodromal will never develop schizophrenia.

If false-positive cases are treated with medication, these individuals will be exposed to the risk of adverse effects with little or no opportunity to benefit. These dangers are particularly relevant for children and adolescents judged to be in a prodromal state but who may not be competent to give informed consent for treatment administration. Obtaining consent for a highly experimental and debatable form of intervention from parents and guardians remains an ethical issue that requires careful consideration (52).

Balanced against these risks is the fact that close monitoring and frequent assessments may help clarify schizophrenia risk and shed light on what might have initially contributed to patients’ prodromal symptomatology. Without early intervention and treatment, it is also possible that individuals who convert to psychosis will experience ultimately more severe stigmatization once the psychosis evolves and starts to affect their thoughts and behaviors.

More general concerns are expressed in regard to: 1) whether “time has come” to formally endorse preventive intervention recommendations, 2) possible legal vulnerabilities, 3) wide use of medications resulting in more harm than good and 4) diagnostic processes and danger that at the present level of knowledge non-experts, including primary care doctors and pediatricians, may be unable to make reliable and valid diagnoses.

CONCLUSIONS Preventive pharmacological treatment is a new evolving concept in schizophrenia that may improve present treatment paradigms and result in significant clinical and economic benefits. Despite recently achieved progress, significant issues, such as improved prodrome phase diagnosis and definition of specific pharmaco-

Rony Sabbag et al.

logical treatments, need further assessments. Successful advancement of this research field holds the promise for reducing the legitimate concerns associated with the risks implied by the preventive intervention concept.

Presently, research and treatment networks focusing on early diagnosis and intervention are already operating in developed countries (e.g., Australia, Germany, United States, England) and it seems likely that in the near future we will witness the establishment of pharmacological interventions with proven efficacy for secondary prevention of schizophrenia.

References 1. Gross CP, Anderson GF, Powe NR. The relation between funding by the National Institutes of Health and the burden of disease. N Eng J Med 1999; 340:1881-1887.

2. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA. Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209-1223.

3. Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, et al.

Randomized controlled trial of the effect on quality of life of secondvs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study (CUtLASS 1).

Arch Gen Psychiatry 2006; 63:1079-1087.

4. Mintz J, Kopelowicz A. CUtLASS confirms CATIE. Arch Gen Psychiatry 2007;64:978.

5. Conley RR, Buchanan RW. Evaluation of treatment-resistant schizophrenia. Schizophr Bull 1997; 23:663-674.

6. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996; 153:321-330.

7. Caplan G. Principles of preventive psychiatry. New York: Basic Books, 1964.

8. Mrazek PJ, Haggerty RJ, editors. Reducing risks for mental disorders: Frontiers for preventive intervention research. Washington, DC: National Academy, 1994.

9. Olin SC, Mednick SA. Risk factors of psychosis: Identifying vulnerable populations premorbidly. Schizophr Bull 1996; 22: 223-240.

10. Lee C, McGlashan TH, Woods SW. Prevention of schizophrenia: can it be achieved? CNS Drugs 2005; 19:193-206.

11. Perkins DO, Leserman J, Jarskog LF, Graham K, Kazmer J, Lieberman JA. Characterizing and dating the onset of symptoms in psychotic illness: The Symptom Onset in Schizophrenia (SOS) inventory. Schizophr Res 2000; 44:1-10.

12. Yung AR, McGorry PD. The prodromal phase of first-episode psychosis: Past and current conceptualizations. Schizophr Bull 1996; 22: 353-370.

13. Jablensky A. Schizophrenia: The epidemiological horizon. In: Hirsch SR, Weinberger DR, editors. Schizophrenia. Oxford: Blackwell Science, 1995: pp. 206-256.

14. Jackson HJ, McGorry PD, McKenzie D. The reliability of DSM-III prodromal symptoms in first-episode psychotic patients. Acta Psychiatr Scand 1994; 90:375-378.

15. McGorry PD, Yung AR, Phillips LJ. Closing in: What features predict the onset of first-episode psychosis within an ultra-high-risk group?

In: Zipursky RB, Schulz SC, editors. The early stages of schizophrenia.

Washington DC: American Psychiatric, 2002: pp. 3-32.

16. McGlashan, TH, Miller TJ, Woods SW, Hoffman RE, Davidson LA. Scale for the assessment of prodromal symptoms and states. In: Miller TJ, Mednick SA, McGlashan TH, Liberger J, Johannessen JO, editors.

Early intervention in psychotic disorders. Dordrecht, The Netherlands: Kluwer, 2001: pp.135-149.

17. Miller TJ, McGlashan TH, Woods SW, Stein K, Driesen N, Corcoran, CM, et al. Symptom assessment in schizophrenic prodromal states.

Psychiatr Q 1999; 70:273-287.

18. DSM-IV. Diagnostic and statistical manual of mental disorders. 4th ed.

Washington, DC: American Psychiatric Association, 1994.

19. Andreasen NC, Endicott J, Spitzer RL, Winokur G. The family history method using diagnostic criteria: Reliability and validity. Arch Gen Psychiatry 1977; 34:1229-1235.

20. Hall RC. Global Assessment of Functioning: A modified scale.

Psychosomatics 1995; 36:267-275.

21. Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: Predictive validity, interrater reliability, and training to reliability. Schizophr Bull 2003; 29:703- 715.

22. Glantz LA, Lewis DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 2000; 57:65-73.

23. McGlashan TH, Hoffman RE. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Arch Gen Psychiatry 2000; 57:637-648.

24. Cannon TD, van Erp TG, Bearden CE, Loewy R, Thompson P, Toga AW, et al. Early and late neurodevelopmental influences in the prodrome to schizophrenia: Contributions of genes, environment, and their interactions. Schizophr Bull 2003; 29:653-669.

25. Cannon TD. Neurodevelopment and the transition from schizophrenia prodrome to schizophrenia: Research imperatives. Biol Psychiatry 2008; 64:737-738.

26. Shenton M, Dickey C, Frumin M, McCarley R. A review on MRI findings in schizophrenia. Schizophr Res 2001; 49:1-52.

27. Van Haren NE, Hulshoff Pol HE, Schnack HG, Cahn W, Mandl RC, Collins DL, et al. Focal gray matter changes in schizophrenia across the course of the illness: A 5-year follow-up study.

Neuropsychopharmacology 2007; 32: 2057-2066.

28. Pantelis C, Velakoulis D, McGorry PD, Wood SJ, Suckling J, Phillips LJ, et al. Neuroanatomical abnormalities before and after onset of psychosis: A cross-sectional and longitudinal MRI comparison. Lancet 2003; 361: 281-288.

29. Takahashi T, Wood SJ, Yung AR, Soulsby B, McGorry PD, Suzuki M, et al. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch Gen Psychiatry 2009; 66:366-376.

30. Takahashi T, Suzuki M, Zhou SY, Tanino R, Hagino H, Kawasaki Y, et al. Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum. Schizophr Res 2006; 83:131-143.

31. Walterfang M, McGuire PK, Yung AR, Phillips LJ, Velakoulis D, Wood SJ, et al. White matter volume changes in people who develop psychosis.

Br J Psychiatry 2008; 193:210-215.

32. Cannon TD, Cadenhead KS, Cornblatt B, Woods S, Addington J, Walker EF, et al. Prediction of psychosis in youth at high clinical risk: A multi-site longitudinal study in North America. Arch Gen Psychiatry 2008; 65:28-37.

33. McGorry PD, Yung AR, Phillips LJ, Yuen HP, Francey S, Cosgrave EM et al. Randomized controlled trial of interventions designed to reduce the risk of progression to first episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 2002; 59:921-928.

34. Woods SW, Breier A, Zipursky RB, Perkins DO, Addington J, Miller TJ, et al. Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome. Biol Psychiatry 2003; 54:453-464.

35. McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller T, Woods SW, et al. Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry 2006; 163:790- 799.

36. Ruhrmann S, Bechdolf A, K端hn KU, Wagner M, Schultze-Lutter F,

89

Preventive Pharmacological Treatment â&#x20AC;&#x201C; an Evolving new Concept in Schizophrenia

Janssen B, et al. Acute effects of treatment for prodromal symptoms for people putatively in a late initial prodromal state of psychosis. Br J Psychiatry Suppl 2007; 51:s88-s95.

37. Woods SW, Tully EM, Walsh BC, Hawkins KA, Callahan JL, Cohen SJ, et al. Aripiprazole in the treatment of the psychosis prodrome: An openlabel pilot study. Br J Psychiatry Suppl 2007; 51: s96-s101.

38. Kelly Dl, Conley RR, Love RC, Horn DS, Ushchack CM. Weight gain in adolescents treated with risperidone and conventional antipsychotics over six months. J Child Adolesc Psychopharmacol 1998; 8:151-159.

39. Cornblatt BA, Lencz T, Smith CW, Olsen R, Auther AM, Nakayama E, et al. Can antidepressants be used to treat the schizophrenia prodrome?

Results of a prospective, naturalistic treatment study of adolescents. J Clin Psychiatry 2007; 68:546-557.

40. Heresco-Levy U. Glutamatergic neurotransmission modulators as preventive pharmacological intervention in schizophrenia. In: HerescoLevy U., Javitt DC, editors. Glutamate in neuropsychiatric disorders.

Research Signpost, Kerala, India, 2008: pp. 157-177.

41. Ulas J, Cotman CW. Excitatory amino acid receptors in schizophrenia.

Schizophr Bull 1993; 19:105-117.

42. Newcomer JW, Krystal JH. NMDA receptor regulation of memory and behaviour in humans. Hippocampus 2001; 11:529-542.

43. Coyle JT, Tsai G. NMDA receptor function, neuroplasticity and the pathophysiology of schizophrenia. Int Rev Neurobiol 2004; 59:491-515.

44. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia.

90

Arch Gen Psychiatry 1995; 52:998-1007.

45. Falls DL. Neuregulins: Functions, forms and signaling strategies. Exp Cell Res 2003; 284:14-30.

46. Boks MP, Rietkerk T, von de Beek MH, Sommer IE, de Koning TJ, Kahn RS. Reviewing the role of the genes G72 and DAAO in glutamate neurotransmission in schizophrenia. Eur Neuropsychopharm 2007; 17: 567-572.

47. Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev 2006; 19:CD003730.

48. Heresco-Levy U. Glutamatergic neurotransmission modulators as emerging new drugs for schizophrenia. Expert Opin Emerg Drugs 2005; 10:827- 844.

49. McGlashan TH, Johannessen JO. Early detection and intervention with schizophrenia: Rationale. Schizophr Bull 1996; 22:201-222.

50. Melle I, Larsen TK, Haahr U, Friis S, Johannessen JO, Opjordsmoen S, et al. Reducing the duration of untreated first-episode psychosis: Effects on clinical presentation. Arch Gen Psychiatry 2004;61:143-145.

51. Penttila MS, Lauronen E, Koponen HJ, Miettunen J, Isohanni MK. Duration of untreated psychosis and changes of brain structure in schizophrenia within the Northern Finland 1966 birth cohort.

Schizophr Res Suppl 2008; 98: s10-s11.

52. Heinssen RK, Perkins DO, Appelbaum PS, Fenton WS. Informed consent in early psychosis research: National Institute of Mental Health workshop, November 15, 2000. Schizopher Bull 2001; 27: 571-584.

Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Helene S. Wallach et al.

Virtual Reality Exposure versus Cognitive Restructuring for Treatment of Public Speaking Anxiety: A Pilot Study Helene S. Wallach, PhD, 1 Marilyn P. Safir, PhD, 1 and Margalit Bar-Zvi, MD2 1

Department of Psychology, University of Haifa, Haifa, Israel Out-Patient Psychiatry, Ziv Hospital, Safed, Israel

2

ABSTRACT Objectives: To determine the utility of Virtual Reality Exposure Therapy (VRE) in comparison with Cognitive Therapy (CT) and with Cognitive-Behavior Therapy (CBT).

Method: Subjects suffering from public speaking anxiety (PSA) were randomly allocated to VRE and CT, and received 12 therapy sessions, employing standardized treatment manuals. Outcome (questionnaires, observer and self ratings of a behavioral task) was compared to results of subjects in a previous study CBT and Wait List Controls who were not significantly different on demographic data.

Results: CT was not superior to VRE on cognitive measures, but was superior to VRE on one behavioral measure (LSAS fear). VRE was superior to CT on one behavioral measure (fear reduction on a behavioral task). No differences were found between either CT, or VRE, and CBT and all were superior to WL. Limitations: Subject group was small and homogeneous.

It appeared advisable to increase number of therapy sessions.

Conclusions: VRE and CT proved to be equally effective to CBT in reducing PSA relative to a control group, with minimal differential effects between them. Therefore, employing either one may be satisfactory and sufficient.

The gold standard treatment for phobias is Cognitive Behavior Therapy (CBT) which combines both behavioral and cognitive elements (1-4). Although numerous studies have been conducted to examine the necessity of employing both cognitive and behavioral elements in therapy, it remains unclear whether it is sufficient to deliver cognitive therapy (CT) alone, behavior therapy (BT) alone or if both need to be employed (5-8). In recent years, Virtual Reality Exposure (VRE) has been utilized for the BT (exposure) component of CBT. Therefore, for this pilot study, we compared VRE to CT in an attempt to examine the relative efficacy of each component independently, and in comparison with the combined treatment.

Social Phobias

Social phobia is defined as a fear of and desire to avoid a situation in which the individual may come under scrutiny by others and fears he/she may act in ways that may be humiliating or embarrassing (9). Social phobia affects school performance, ability to create social networks and intimate relationships as well as work performance, is the most common anxiety disorder, and the third most common psychiatric disorder (10, 11). In the present study we focused on a non-generalized social phobia - public speaking anxiety. Public speaking anxiety (PSA) is the most common social phobia, afflicting 40% of all those who suffer from social phobia (11).

Virtual Reality Exposure (VRE) for Social Phobia

Exposure is presumed to extinguish maladaptive conditioning (phobic object = fear) through anxiety reduction, and to shape new conditioned responses (neutral or adaptive responses to the formally phobic object).

Address for Correspondence:

Helene S. Wallach PhD, Department of Psychology, University of Haifa, Haifa, 31905, Israel

â&#x20AC;&#x2020; helenwa@yahoo.com

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Virtual Reality Exposure versus Cognitive Restructuring

This occurs as the client experiences both a reduction in anxiety during the exposure (habituation) and the absence of the catastrophic event he/she anticipated (extinction) (1, 12, 13). VR is defined as a situation in which sensory information is generated by a computer rather than by the natural environment (e.g., 14).

During the exposure stage in VR, the client puts on a helmet which is connected to a computer. The helmet provides both visual and audio input. The therapist employs a special computer program enabling her/ him to change various elements in the virtual environment, thus providing the client with gradual exposure to aversive stimuli. The therapist views exactly what the client views in the helmet, on the computer screen. The client’s head movements change the environment, just as they would in the real world, hence increasing the sense of immersion. The therapist monitors the client’s Subjective Units of Discomfort (SUD) and thus controls the fear level of the environment. Thus, VRE is superior to conventional exposure for people who have difficulty imagining situations vividly, for those who avoid remaining in the imagined fearful situation, and for those who are unable to control their imagination and flood themselves with higher levels of anxiety than are produced by the hierarchy. In addition, the drop-out rate from VRE has been found to be much lower than the drop-out rate from traditional BT (15, 16).

Cognitive Therapy for Social Phobia

Cognitive factors are especially obvious in social phobia (6, 17, 18). Socially anxious individuals over-estimate the threat of public criticism, scrutiny or embarrassment (17). They also have negative and distorted images of how others view them (19, 20). In addition, clients exaggerate the “social cost” of their performance (21). This leads to the perception of social situations as dangerous, to an increase in anxiety relevant physical sensations when encountering feared situations, to hyper vigilance to the environment and to bodily sensations and to avoidance of feared social situations or the use of “safety” behaviors. Therefore, faulty cognitions develop, maintain and increase social phobia (18, 20). However, therapy that challenges these cognitions was found to be beneficial and crucial in the treatment of PSA (2, 22, 23).

Cognitive-Behavior Therapy for Phobias

The combination of Cognitive and Behavior Therapies (CBT) has been reported to be the treatment of choice for phobias (e.g., 23-25). Thus this pilot attempted to 92

compare VRE to both CT and to the gold standard treatment for PSA, namely CBT. Methods and Experimental Design Participants

Twenty subjects who suffered from PSA were recruited for this study. Candidates suffering from a psychotic disorder, drug or alcohol abuse, or epilepsy, or who were in psychotherapy for this problem, or were taking psychotropic medication were excluded. Epilepsy may be aggravated by the use of VR, and therefore this served as an exclusion criteria. Subjects were young (average age 28), were mostly Jewish (85%) and single (75%) (Table 1). In addition, their results were compared with data from a recent study that employed CBT (28 participants) for PSA using similar protocols and a wait list control (WL) (30 participants) condition (16). Subjects in the previous study were also primarily Jewish (89%, 90%), young (average age 28, 25) and single (75%, 93%) and not significantly different on these variables from the subjects in the present study (Table 1).

Table 1. Demographic Variables

N

Age M Sd

Family situation Single Other

Sex MF

Ethnicity Maj.a Min.b

VRE

10

27.50

7.85

5

5

9

1

8

2

CT

10

28.11

1.69

4

6

6

4

9

1

CBT

28

28.18

7.97

5

23

21

7

25

3

WL

30

25.29

2.62

9

21

28

2

27

3

Note. aMaj=Majority; bMin=Minority

Measures

1. Liebowitz Social Anxiety Scale (LSAS) (26) includes 24 questions. For each question, the participant rates the amount of fear experienced (answered on a 4-point Likert scale from 0 – “not at all” to 3 – “very much”) and the amount of avoidance experienced (rated on a 4-point Likert scale from 0 – “never, 0%” to 3 – “usually, 68%-100%”). This scale has high reliability (Cronbach α .90-.95). It also has good validity (high correlations with other anxiety measures, e.g., Social Interaction Anxiety Scale – fear scale .72, avoidance scale .68; Social Phobia Scale – fear scale .64, avoidance scale .59).

2. Self Statements During Public Speaking (SSPS) (27).

This 10-item measure assesses fearful thoughts during public speaking. It consists of two subscales: posi-

Helene S. Wallach et al.

tive and negative self-statements. This scale has high reliability (.78-0.80 & .80-.86, respectively). It also has good validity (discriminates between social phobics and the general population; correlates with other anxiety scales: e.g., Personal Report of Confidence as a Speaker .67; Fear of Negative Evaluation .49; Social Phobia and Anxiety Inventory .48. For the positive scale, higher scores indicate less anxiety.

3. Fear of Negative Evaluation (FNE) (28) includes 30 yes/no questions. The questions relate to cognitive aspects of the phobic experience – fear of criticism or negative evaluation. FNE has high reliability (.78.94), and good validity (e.g., correlations with Taylor’s Manifest Anxiety -.60, social and evaluative parts of the Endler-Hunt S-R -.47).

4. Behavioral Task: Upon completion of treatment, participants presented a 10-minute talk on a topic they choose (standing, and without notes) in front of a live audience composed of four or five staff members who served as observers, and were unaware of treatment group placement. Participants were rated on 10 anxiety indicators. Nine indicators were rated on a 5-point Likert type scale from “very much” to “not at all” (e.g., eye contact, stuttering), and one was a global fear assessment rated on a 0-10 scale from 0 – “not at all anxious” to 10 – “very anxious.” Prior to rating the subjects, all observers underwent a brief training session in order to insure high inter-rater reliability. In addition, subjects rated their anxiety at various points (waiting outside the room, giving the lecture, etc.) on 5-point Likert type scales.

Procedure

Subjects were recruited through advertisements on the university website, in campus newspapers and strategically placed flyers on campus. Those interested in participating were interviewed by a research assistant, signed an informed consent form, completed pre-treatment questionnaires, and were randomly assigned by the research assistant by order of arrival to one of two groups: VRE or CT. Random assignment was performed before scoring of the questionnaires was undertaken.

Data compiled from subjects that participated in a previous study was employed for the CBT treatment and the WL groups (16). Recruitment and exclusion criteria were similar for that study.

Due to technical, logistic and budgetary constraints no formal diagnosis of PSA or of psychiatric co-morbidity was undertaken. Therefore, we cannot be certain

our subjects met the formal criterion for PSA. However, they volunteered for this study, reporting that they suffered from PSA, and would like treatment. Additionally their pre-therapy scores were similar to those of individuals suffering from social phobia in previous studies. For example, mean LSAS Fear scores ranged from 28.18-34.80 in this study which is higher than mean scores found in a previous studies (18.92 and 24.9), mean LSAS Avoidance scores ranged from 24.46-27.97 in this study which is also higher than 18.20 and 16.7 found in a previous studies (29, 30). Mean FNE scores ranged from 20.07-21.80 in this study which is similar to mean FNE scores (23.14-25.04) found in previous studies (29, 31). Mean SSPS positive scores ranged from 10.18-13.90 in this study similar to the score of 9.4 found in a previous study, while mean SSPS negative scores ranged from 11.64-13.10 in this study compared to mean of 15.80 in a previous study (32).

Subjects in both treatment groups (VRE and CT) in this study and in the CBT treatment group in the previous study received 12 individual one-hour treatment sessions administered according to protocols designed for both studies. Therapists (graduate psychology students in the final stages of their clinical training) were given extensive training in application of the treatment protocols, and supervised throughout the study by senior Clinical Psychologists to ensure that they were actually following treatment protocols. The WLC group filled out questionnaires at the beginning and end of a 12-week wait period, after which they were randomly assigned to CBT (first study).

All subjects performed the behavioral task at the end of treatment or wait period.

Treatment Protocols:

Cognitive treatment protocol: The cognitive aspects of the treatment outlined by Heimberg and Becker (22) were utilized in this research. They included: presentation and discussion of the cognitive model of social phobia and the rational for cognitive treatment, training in cognitive restructuring (identification of automatic thoughts, identification of thinking errors, learning to correct thinking errors and to replace automatic thoughts with rational responses). Cognitive restructuring was practiced during sessions through role play and in homework assignments as well. No behavioral homework was given and role-play in the sessions was limited to cognitive disputation without behavioral exposure.

Virtual reality exposure treatment components: 93

Virtual Reality Exposure versus Cognitive Restructuring

The behavioral aspects of the treatment outlined by Heimberg and Becker (22) were also utilized in this research. They included: presentation and discussion of the behavioral model of social phobia and the rationale for behavioral treatment, graded in-session behavioral exposure in virtual environments using SUDS ratings, and graded homework assignment. No cognitive homework assignments were given, and no discussion of cognitions occurred during in session exposures.

VR was employed for the exposure. VR components consisted of software and hardware (computer, headmounted display – HMD). The software package was purchased from Virtually Better, Inc. It provides scenes in which the subject is required to read from text, which appears on a podium in the virtual world, in front of a large audience in various situations (audience clapping, asking questions, appearing hostile, etc.). The subjects provided the text, but the scenes were controlled by the therapist, according to the hierarchy which was developed for each subject prior to exposure. The computer used was Intel Pentium 4 with 1 GB Ram and 120 GB hard disk with Windows XP operating system, NVIDEA 6600 256MB PCI-E graphics card and Integrated SoundMAX Cadenza +Internal Mono Speaker audio card. The HMD was VFX3D from Interactive Imaging Systems, Inc. This HMD has a 3D stereoscopic Smart Visor, 35 degree field of view, fixed focus at 11 feet, 100% stereo overlap, requires no IPD and can be worn over eyeglasses. It has two 0.7 inch color LCD displays with 360,000 pixel resolution, virtual orientation system tracking with pitch and roll sensitivity 70 degrees and yaw sensitivity 360 degrees.

Results Demographic Variables

The two treatment groups composed of subjects solicited for this pilot study (CT, VRE) were compared on demographic variables (Table 1) using Wilcoxon Two Sample Test for age, and χ2 for group status, family status and gender. No significant differences were found on majority/minority group status, family status, or percentages of males and females. A significant difference was found on age (p≤0.05). The CT group participants were slightly older (28.11) than VRE group participants (27.5). The three treatment groups were then compared (CT, VRE, and CBT) on demographic variables (Table 1). No significant differences were found on age, majority/minority group, family status, or percentages of males and females. In addition, the two treatment 94

groups were compared on demographic variables to the WL group from the former study (Table 1). Here again, no significant differences were found on majority/ minority group, family status, or percentages of males and females. A significant difference was found on age using the Wilcoxon two sample test, Z=2.04, p≤0.05.

The WL group participants were younger (25.29) than the treatment group participants (27.79).

Pre-therapy measures

We compared the two treatment groups from this study, CT and VRE to the WL control group from the previous study on pre-treatment clinical measures. None of the comparisons were significant: LSAS fear F(2,50)=.48, n.s.; LSAS avoidance F(2,50)=.16, n.s.; SSPS positive F(2,50)=1.17, n.s.; SSPS negative F(2,50)=.02, n.s.; FNE F(2,50)=.23, n.s. Therefore, the groups did not differ significantly prior to treatment.

Differential utility of VRE in comparison with CT

We compared CT to VRE on both cognitive (FNE, SSPS positive, SSPS negative), and behavioral (self and observer ratings of global fear, LSAS ratings of fear and avoidance) measures (Tables 2 & 3). As our primary goal was to differentiate between CT and VRE, and not in their interaction, comparisons were made using difference scores employing alpha correction for multiple analyses. In addition, we calculated effect sizes for the difference between these two groups using the Mann-Whitney statistic. No significant differences were found between CT and VRE on FNE, SSPS positive, SSPS negative, therefore, CT was not superior to VRE on cognitive measures. Effect sizes for these comparisons were 0.665 for FNE, 0.615 for SSPS positive, 0.575 for SSPS negative. For comparison, effect size for FNE in a previous study was 0.68 (29). Nor was a significant difference found between CT and VRE on LSAS avoidance. Effect size for this comparison was 0.620.

However, a significant difference was found between them on the LSAS fear, t(18)=-2.88, p≤0.01, after performing alpha correction: p≤0.049). Effect size for this comparison was 0.845. For comparison, effect size in a previous study was 0.12-0.34 for LSAS fear and 0.320.51 for LSAS avoidance (29). Contrary to predictions, the CT group showed larger reductions in fear than the VRE group. Comparing the treatment groups on self ratings of global fear (Table 3), only one measure (level of fear while standing in front of the audience) was significant, S=80, p≤0.05. As predicted the VRE

Helene S. Wallach et al.

Table 2. Pre- and Post-Anxiety Measures FNE M Sd

LSAS Fear M Sd

LSAS Avoidance M Sd

SSPS Positive M Sd

SSPS Negative M Sd

VRE Pre Post Change

21.80 18.90 2.90

3.58 5.02 4.48

30.80 28.4 2.40**

12.24 12.03 6.06

25.30 18.70 6.60***

10.15 10.08 3.86

13.80 17.20 -3.40*

4.47 3.36 4.97

12.50 9.40 3.10

4.99 4.20 5.78

CT Pre Post Change

20.50 19.50 1.00

4.95 4.48 6.18

34.80 23.60 11.20**

11.18 8.67 7.54

27.30 16.80 10.50***

14.14 10.04 8.32

10.90 15.00 -4.10*

6.19 5.42 3.63

12.60 11.30 1.30

4.62 4.24 4.90

CBT Pre Post Change

20.07 16.36 3.71

6.89 7.86 9.00

28.18 19.39 8.79

11.17 8.31 13.81

24.46 14.86 9.60

13.65 8.34 13.29

10.18 16.68 -6.50

5.57 6.22 6.90

11.64 9.89 1.75

6.49 6.24 6.98

WL Pre Post Change

21.70 20.97 0.73

5.70 6.48 4.03

30.93 29.83 1.10*

11.29 12.94 8.89

27.97 29.13 -1.16***

12.10 11.47 9.16

11.10 12.10 -1.00*

5.20 5.83 5.22

13.10 13.07 0.03*

5.33 6.61 4.66

Note. * p ≤ 0.05; **p≤0.01; *** p≤0.0005

Comparing CT and VRE to WL

Table 3. Ratings of Behavioral Task (lecture) SG1a SG2 SG3 SG4 Mean Sd Mean Sd Mean Sd Mean Sd VRE 6.10 2.42 4.40 1.17 CT

5.90 2.73 7.40* 1.07

7.00 2.98 4.40 2.41 7.10 3.35

SG5 Mean Sd

SGt Mean Sd

7.80 1.03

6.32 0.78

8.40* 1.84 7.30 1.77

6.84 1.79

Note. aSG-self grading (1-preparing for the lecture, 2-listening to instructions, 3-waiting for turn, 4-standing in front of the audience, 5-giving the talk, t-total) * p ≤ 0.05

group reported feeling less anxious than the CT group.

However, no significant differences were found when they were compared on observer ratings.

Are CT and VRE Effective?

Examining changes from pre to post therapy in each treatment group

For each therapy group, post-therapy scores were compared to pre-therapy scores using t-tests. The VRE group improved significantly on LSAS avoidance t(9)=5.40, p≤0.0005, after alpha correction, p≤0.005, and on SSPS positive t(9)=2.16, p≤0.05, but not after alpha correction, p≤0.264. The changes on LSAS fear t(9)=1,25; SSPS negative t(9)=1.70; and FNE t(9)=2.05 were not significant. The CT group improved significantly on LSAS fear t(9)=4.70, p≤0.001, after alpha correction p≤0.005; LSAS avoidance t(9)=3.99, p≤0.005, after alpha correction p≤0.01; and SSPS positive t(9)=3.57, p≤0.01, after alpha correction p≤0.05. The changes on SSPS negative t(9)=0.84 and on FNE t(9)=0.51 were not significant.

As the two treatment groups did not differ significantly on most of the measures and the groups were so small, we combined the two treatment groups from this pilot study (VRE, CT) and compared them to the WL participants. We found significant differences on three of the five questionnaires (Table 2). LSAS fear, t (48)=2.31, p≤0.05, however, this difference disappeared after alpha correction p≤0.12. The combined treatment group improved significantly more (reducing their fear by 6.80) than the WL group (who reduced their fear by 1.10). The effect size of this comparison was 0.67. LSAS avoidance, t(48)=4.08, p≤0.0005, after alpha correction p≤0.001. The treatment group also significantly reduced their avoidance (8.55) more than the WL group (-1.16). Effect size for this comparison was 1.21. SSPS positive, t(48)=-1.96, p≤0.05, however, this difference disappeared following alpha correction p≤0.25. The treatment group improved more (increased by 3.75) than the WL group (increased by -1.00). Effect size for this comparison was 0.58. No significant results were found on the FNE, t(48)=0.92, n.s. (effect size 0.26) or on the SSPS negative, t(48)=-1.52, n.s. (effect size 0.43).

Is CBT superior to CT and to VRE? Comparing CBT to CT and to VRE

No significant differences were found between the three treatment groups (VRE and CT from this pilot study, CBT from the previous study) (Table 2). Using the Kruskal-Wallis test, LSAS fear, χ2(2)=5.21, n.s.; LSAS avoidance, χ2(2)=0.64, n.s.; SSPS positive, χ2(2)=1.24, 95

Virtual Reality Exposure versus Cognitive Restructuring

n.s.; SSPS negative, χ2(2)=0.42, n.s.; FNE, χ2(2)=1.56, n.s.

Therefore, CBT was not superior to either CT or VRE. Discussion VR has only been employed in therapy for public speaking anxiety in a few studies (14, 32, 33). Although VR was found to reduce anxiety in these studies, random assignment with a control group and comparative statistical analyses were not used. One randomized study using VR with public speaking anxiety (16) found that VR was equally effective as CBT without VR, and that both were superior to WL control group. The present pilot study was designed to compare the effectiveness of Virtual Reality Exposure (i.e., exposure without the cognitive component) in comparison with Cognitive Therapy (i.e., the cognitive component without exposure) and with Cognitive-Behavior Therapy (i.e., both the cognitive and the exposure components) for individuals who suffer from public speaking anxiety.

Both CT and VRE significantly reduced anxiety from pre to post treatment. CT was not superior to VRE on cognitive measures, and VRE was superior to CT on only one aspect of self observation (fear while standing in front of the audience), but CT was superior to VRE on LSAS fear reduction, which is a behavioral measure.

No other differences were found between CT and VRE. In addition, no differences were found between either CT or VRE and CBT. All three active treatments (CT, VRE and CBT) were superior to the WL. Previous studies (treating various phobias other than public speaking anxiety) failed to find significant lasting differences between CT and BT. Similarly, using a new technology, namely Virtual Reality, for the exposure rendered similar findings whereby using either CT or VRE alone is satisfactory, and probably sufficient.

In accordance with the literature, both CT and VRE changed maladaptive cognitions and reduced fear levels, even though operating through different modalities.

Although our conclusions parallel those of previous studies (e.g., 1, 3), it is premature to conclude that VRE and CT do not differ in their impact on specific aspects of the phobia. We found large, but insignificant differences between them. Because of our small sample size, statistical analyses were not powerful. Therefore, we plan to replicate this study utilizing larger sample sizes in order to further investigate this important question.

In addition, it should be noted that our participants cannot be considered representative – they were young, 96

female and unmarried, as well as extremely compliant.

It is necessary to repeat this study with a larger, more heterogeneous sample. We accepted self identified PSA participants and did not formally diagnose public speaking anxiety, nor did we examine for psychiatric co-morbidity. This may also have affected our results. Therefore, we recommended employing clinical interviews to derive formal diagnoses for future research participants. Lastly, although we closely supervised our graduate student therapists, we did not have the means to tape therapist performance in order to ensure treatment fidelity. It is important in future research to do this.

Acknowledgements The authors wish to thank Sharon Dvir and Nadav Harris, who served as the therapists, and Hadas Kleider, who assisted in running the project.

This research project was made possible by the aid of an excellence research grant by the Research Authority of the University of Haifa.

References 1. Craske MG. Anxiety disorders: psychological approaches to theory and treatment. Boulder, Colorado: Westview, 1999.

2. Beck JS. Cognitive therapy: Basics and beyond. New York: Guilford, 1995.

3. Feske U, Chambless DL. Cognitive behavioral versus exposure only treatment for social phobia: A meta-analysis. Behav Ther 1995; 26: 695720.

4. Hofmann SG. Cognitive mediation of treatment change in social phobia. J Consult Clin Psychol 2004; 72: 393-399.

5. Butler AC, Chapman JE, Forman EM, Beck AT. The empirical status of cognitive-behavioral therapy: A review of meta-analyses. Clin Psychol Rev 2006; 26: 17-31.

6. Oakley ME, Padesky CA. Cognitive therapy for anxiety disorders.

In: Hersen M, Eisler RM, Miller P, editors. Progress in Behavior Modification (Vol. 25). Thousand Oaks, Cal.: Sage, 1990: pp. 11-46.

7. Abramowitz JS, Franklin ME, Foa EB. Empirical status of cognitivebehavioral therapy for obsessive-compulsive disorder: A meta-analytic review. Rom J Cogn Behav Psychother 2002; 2: 89-104.

8. Fama J, Wilhelm S. Reply to Kozak and Coles: Expanding the conceptualization of Cognitive Therapy and its therapeutic potential.

In: Abramowitz JS, Houts AC, editors. Concepts and controversies in Obsessive-Compulsive disorder. New York: Springer Science + Business Media, 2005: pp. 305-310.

9. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed)(Text rev.). Washington, DC: Author, 2000.

10. Pollack MH. Social anxiety disorder: Designing a pharmacologic treatment strategy. J Clin Psychiatry 1999; 60: 20-26.

11. Ruscio AM, Brown TA, Chiu WT, Sareen J, Stein MB, Kessler RC. Social fears and social phobia in the USA: Results from the National Comorbidity Survey Replication. Psychol Med 2008; 38: 15-28.

12. Wolitzky-Taylor KB, Horowitz JD, Powers MB, Telch MJ. Psychological approaches in the treatment of specific phobias: A meta-analysis. Clin Psychol Rev 2008; 28: 1021-1037.

13. Goldberg J, Zwibel A, Safir MP, Merbaum M. Mediating factors in the modification of smoking behavior. J Behav Ther Exp Psychiatry 1983; 14: 325‑330.

14. Wiederhold BK, Wiederhold MD. Virtual Reality therapy for anxiety disorders: Advances in evaluation and treatment. Washington, DC:

Helene S. Wallach et al.

American Psychological Association, 2005.

15. Garcia-Palacios A, Botella C, Hoffman H, Fabregat S. Comparing acceptance and refusal rates of Virtual Reality exposure vs. In Vivo exposure by patients with specific phobias. Cyberpsychol Behav 2007; 10: 722-724.

16. Wallach HS, Safir MP, Bar-Zvi M. Virtual Reality Cognitive Behavior Therapy for public speaking anxiety: A randomized clinical trial. Behav Modif 2009; 33: 314-338.

17. Stopa L, Clark DM. Social phobia and interpretation of social events.

Behav Res Ther 2000; 38: 273-283.

18. Heimberg RG, Becker RE. Cognitive-Behavioral group therapy for Social Phobia: Basic mechanisms and clinical strategies. New York: Guilford, 2002.

19. Freeman A, Pretzer J, Fleming B, Simon KM. Clinical applications of Cognitive Therapy (2nd ed.). New York: Kluwer Academic, 2004.

20. Wells A, Clark DM. Social phobia: A cognitive approach. In: Davey GCL, editor. Phobias â&#x20AC;&#x201C; a handbook of theory, research and treatment.

New York: John Wiley, 1997: pp. 3-26.

21. Foa EB, Franklin ME, Perry KJ, Herbert JD. Cognitive biases in generalized social phobia. J Abnorm Psychol 1996; 105: 433â&#x20AC;&#x201C;439.

22. Beck AT, Emery G. Anxiety disorders and phobias: A cognitive perspective. New York: Basic Books, 1985.

23. Hope DA, Heimberg RG. Social phobia and social anxiety. In: Barlow DH, editor. Clinical handbook of psychological disorders (2nd ed). New York: Guilford, 1993: pp. 99-136.

24. Otto MW. Cognitive-behavioral therapy for social anxiety disorder:

Model, methods and outcome. J Clin Psychiatry 1999; 60: 14-19.

25. Smits JAJ, Hofmann SG. A meta-analytic review of the effects of psychotherapy control conditions for anxiety disorders. Psychol Med 2008; 38: 1-11.

26. Fresco DM, Coles ME, Heimberg RG, et al. The Liebowitz Social Anxiety Scale: A comparison of the psychometric properties of self-report and clinician-administered formats. Psychol Med 2001; 31: 1025-1035.

27. Hofmann SG, DiBartolo PM. An instrument to assess self-statements during public speaking: Scale development and preliminary psychometric properties. Behav Ther 2000; 31: 499-515.

28. Watson D, Friend R. Measurement of social-evaluative anxiety. J Consult Clin Psychol 1969; 33: 448-457.

29. Cox BJ, Ross L, Swinson RP, Direnfeld DM. A comparison of social phobia outcome measures in cognitive-behavioral group therapy. Behav Modif 1998; 22; 285-297.

30. Klinger E, Bouchard S, Legeron P, Roy S, Lauer F, Chemin I, Nugues P. Virtual reality therapy versus cognitive behavior therapy for social phobia: A preliminary controlled study. Cyberpsychology Behav 2005; 8; 76-88.

31. Clark DM, Ehlers A, Hackmann A, McManus F, Fennell M. Cognitive therapy versus exposure and applied relaxation in social phobia: A randomized controlled trial. J Consult Clin Psychol 2006; 74; 568-578.

32. Anderson PL, Zimand E, Hodges LF, Rothbaum BO. Cognitive behavioral therapy for public-speaking anxiety using virtual reality for exposure. Depress Anxiety 2005; 22; 156-158.

33. Harris SR, Kemmerling Rl, North MM. Brief virtual reality therapy for public speaking anxiety. Cyberpsychol Behav 2002; 5; 543-550.

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Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Social Cognition in Social Anxiety: First Evidence for Increased Empathic Abilities Yasmin Tibi-Elhanany, MA, and Simone G. Shamay-Tsoory, PhD Department of Psychology, University of Haifa, Haifa, Israel

Introduction

ABSTRACT Background: Individuals with social phobia (SP) show sensitivity and attentiveness to other people’s states of mind. Although cognitive processes in SP have been extensively studied, these individuals’ social cognition characteristics have never been examined before. We hypothesized that high socially anxious individuals (HSA) may exhibit elevated mentalizing and empathic abilities.

Methods: Empathy was assessed using self-rating scales in HSA individuals (n=21) and low socially anxious (LSA) individuals (n=22), based on their score on the Liebowitz social anxiety scale. A computerized task was used to assess the ability to judge first and second order affective vs. cognitive mental state attributions.

Results: HSA individuals exhibited elevated affective empathy tendencies. However, controlling for the general anxiety variable revealed that social anxiety was related to cognitive empathy measures, rather than affective empathy. In addition, compared with LSA participants, HSA participants exhibited higher accuracy levels on the affective mental state attribution conditions, but were less accurate than LSA individuals on the parallel cognitive mental state attribution conditions.

Limitations: Additional research with larger samples and clinically diagnosed individuals is required.

Conclusions: Results support the hypothesis that high socially anxious individuals may demonstrate a unique social-cognitive abilities profile with elevated cognitive empathy tendencies and high accuracy in affective mental state attributions.

Address for Correspondence: sshamay@psy.haifa.ac.il

98

Attention processes such as hypervigilance to threatening social information and self-focused attention are assumed to play an important role in the maintenance of social phobia (SP) (1, 2). Although cognitive biases in SP have been extensively documented in the literature (3-6), these individuals’ social cognition capacities have never been examined before. Individuals with SP are preoccupied with the impression they make, and place fundamental importance to being positively appraised by others. As a result of their social concerns, they may ambivalently tune themselves to obtain insight into others’ state of mind, displaying heightened self-awareness and excessive alertness to social signals. These (internal and external) attentional biases which influence the perceptiveness of social stimuli in SP may overall be manifested in a unique social-cognitive abilities profile.

One cardinal aspect of social cognition is the ability to empathize (7). Empathy, in its broadest sense, refers to the reactions of one individual to the observed experiences of another (8). While some investigators have emphasized empathy as the ability to engage in the cognitive process of adopting another’s psychological point of view (“cognitive empathy”), others stressed its emotional facets (“affective empathy”), referring to the capacity to experience a vicarious response to another person (9).

In addition to the cognitive perspective taking component of empathy, another perspective taking type is referred to as visual perspective taking; the ability to take an others’ perspective visually (10). Interestingly, the state of visually taking an observer perspective is a common imagery phenomenon in SP (2, 11-13). The assumption that self-focused attention and social evaluative concerns increase the likelihood to adopt an observer perspective has gained support in non-anxious (14, 15) and socially anxious individuals as well (12, 13, 16).

Simone Shamay-Tsoory, PhD, Department of Psychology, University of Haifa, Haifa 31905, Israel

Yasmin Tibi-Elhanany and Simone G. Shamay-Tsoory

It had been suggested that the visual perspective ability may not be restricted to adopting an external viewpoint, but it may be related to the capacity to adopt mental perspectives in healthy subjects (17) and schizotypic individuals (18). Considering their vigilance with regard to social cues, increased other-awareness and self-monitoring in social situations, it was speculated that individuals with SP will show increased empathic tendencies.

Empathy is thought to require not only adequate social perception (19), but also entails the capacity to comprehend complex mental states (20). Taking the others’ external vantage point in SP might also indicate increased mentalizing abilities.

Theory of Mind (ToM), the ability to make inferences regarding the mental state, desires and intentions of other individuals, is another major component of social cognition (21). This ability to infer others’ mental states (mentalizing) is closely linked to the ability of empathizing, since failure to represent other persons’ beliefs and intentions may result in failure to see things from another person’s perspective and, thus, interfere with the empathic response (20, 22).

Similarly to empathy, a dual feature of cognitive and affective ToM has been suggested. The first emphasizes the capacity to represent mental states of others that are manifested in their thoughts and beliefs (23), whereas the affective aspect of ToM includes the inferences one makes regarding others’ emotional states and feelings.

Abu-Akel (24) has suggested that mentalizing deficits in developmental and psychiatric populations may be viewed as lying on a continuum, in which at one end ToM deficits stem from lack the awareness of others’ mental state (e.g., people with autistic spectrum disorders), whereas the other end of this range includes individuals whose abnormal ToM abilities are the consequence of a tendency to over attribute mental states to others (e.g., people with paranoid thinking). Although they were not placed on this ToM range, the basic ability of individuals with SP to represent others’ mental states is manifested in their concern about others’ attitudes towards them. However, their excessive alertness to the social world and the sense their worries are being “seen through” by others (11) might be associated with a tendency to over attribute mental states to others.

Although empathic and ToM abilities have been extensively documented in several disorders such as antisocial personality disorders (25), autism (26), Asperger’s syndrome (27), and schizophrenia (28, 29), no reported study has explored these abilities in individuals with

social anxiety disorder. Taken together, the purpose of the present study was to examine the hypothesis that socially anxious individuals may exhibit elevated empathic tendencies and emotional ToM abilities, based on their sensitivity and attentiveness to others’ state of mind.

The first goal of the present study was to characterize the relationship between cognitive and affective empathy and social anxiety in sub-clinical socially anxious individuals. The second goal was to compare mentalizing abilities of individuals with low and high social anxiety. Finally, the relative contribution of trait/general anxiety on empathy was also examined to assess the specificity of the contribution of the social component in social anxiety as compared with the general tendency of participants to be anxious.

Method Subjects

Subjects were 87 volunteers (age ranged from 19 to 53) who responded to an advertisement. A trained clinical psychologist administered a demographic and clinical questionnaire which included questions regarding demographic details as well as physical and mental health questions. Individuals suffering from neurological problems or a major physical illness, alcohol or substance abuse were excluded from the study. All participants completed the self-report format of the Liebowitz Social Anxiety Scale (LSAS) (30). This version of the LSAS translated into Hebrew was reported to demonstrate high test-retest reliability in a sample of patients with SP (r=0.87 and r= 0.91 for the LSAS anxiety and avoidance scales respectively). In addition, the LSAS also demonstrated high internal consistency for both the anxiety and avoidance subscales, and good treatment sensitivity (31). In our sample, scores ranged from 0 to 84, Mean= 35.75, SD=18.19. All participants were fluent in Hebrew, and testing was conducted individually in two sessions.

Clinical assessment

Additionally to the LSAS, participants completed the Beck Anxiety Inventory (BAI) (32) and the Trait version (will be referred to as trait anxiety inventory; TAI) of the State-Trait Anxiety Inventory (33).

Subjects were further assigned to either low or high social anxiety (LSA, HSA) groups according to their total LSAS scores. The LSA group consisted of subjects who scored lower than 25 (lower quartile) on the LSAS 99

Social Cognition in Social Anxiety: First Evidence for Increased Empathic Abilities

(n= 22; 12 males, 10 females), whereas the HSA group included subjects who scored higher than 45 (upper quartile) on the LSAS (n=21; 6 males, 15 females).

Assessment of empathic abilities Two self-report scales were used to assess empathic abilities. Affective empathy was evaluated by the Questionnaire Measure of Emotional Empathy (QMEE) (34) – a widely utilized instrument that evaluates the affective role taking ability, tapping the likelihood of the tendency to react emotionally to the observed experiences of other people in a variety of contexts.

Both affective and cognitive empathy were further assessed using the Interpersonal Reactive Index (IRI) (35). This instrument consists of four seven-item subscales each tapping a separate component of empathy.

The perspective taking scale (PT) measures the reported tendency to spontaneously adopt the psychological point of view of others in everyday life. The fantasy scale (FS) measures the tendency to imaginatively transpose oneself into fictional situations. Those two scales are considered to tap the cognitive facet of empathy. On the other hand the two other empathy scales measure an affective facet of empathy: the empathic concern (EC) scale assesses the tendency to experience feelings of sympathy and compassion for others and the personal distress scale (PD) taps the tendency to experience distress and discomfort in response of others’ observed distress. It has been suggested that while the PT and the FS subscales of the IRI assess cognitive empathy, the PD and EC subscales tap affective empathy. Therefore we used the sum of the PT and FS as a cognitive empathy index and the sum of the PD and EC as affective empathy indexes.

The selection of the IRI scales was based on a pretest designed to evaluate the Hebrew version of these instruments, reliability analysis of the Hebrew versions of these empathy scales yielded high reliability coefficients for both the cognitive empathy scale (Alpha=0.79) and the affective empathy scale (Alpha = 0.82) (36).

ing to a single category (e.g., fruits, chairs) or faces, one in each corner of the computer screen. The subject’s task is to point to the correct answer (the image Yoni is referring to), based on a sentence that appears at the top of the screen and available cues such as Yoni’s eye gaze, Yoni’s facial expression or the face’s (the one Yoni is referring to) eye gaze and facial expression (Figure 1). There are three main conditions: “cognitive” (24 trials), “affective” (24 trials) and “physical” (16 trials), each requiring either a 1st (32 trials) or a 2nd (32 trials) order inference. The cognitive and the affective conditions involve mental inferences whereas the physical condition requires a choice based on a physical attribute of the character (thus serving as a control condition, to ensure that the subject understands the task).

In the first order cognitive conditions (Figure 1a), both Yoni’s facial expression and the verbal cue are neutral, whereas in the affective conditions Figure 1a), both cues provide affective (For example: Yoni is thinking of ___ [Cog 1. condition] vs. Yoni loves___ [Aff 1. condition]).

Each ToM condition had a control physical condition to control for errors made due to attention and working memory deficits. The control physical conditions also served as a test of the ability to understand the instructions and follow the task demands and assess basic visual scanning abilities.

In the 2nd order condition (Cog2, Aff2, Phy2) the four stimuli consist of face images and the choice of the correct response requires understanding of the interaction between each of these figures and Yoni’s mental state Figure 1b). In 70% of the 2nd trials Yoni’s eye gaze is directed at one of the four faces stimuli (the correct answer) and in 30% trials Yoni’s gaze is directed straight ahead. (This was done after a pilot study that demonstrated that some subjects responded automatically to the stimuli to which the Yoni’s gaze was directed and avoided reading the sentences.) When Yoni’s gaze is directed straight ahead the decision must be based on the verbal cue and the face’s gaze. Subject’s performance was rated for accuracy and reaction time.

ToM Task: Cognitive and affective mental inference and a mentalistic significance of eye direction: This computerized task (programmed using E-prime) is based on a task described previously by Baron-Cohen (37) and involves the ability to judge mental states based on verbal and eye gaze cues. The task consists of 64 trials, each showing a cartoon outline of a face (named Yoni) and four colored pictures of either objects belong-

Results As Table 1 shows, the two groups did not differ in terms of age [t (40) < 1, ns], education [t (39) < 1, ns], or gender [t (42) = 1.75, ns].

Significant group main effects were evident on all social anxiety measures: LSAS- total [t (31)=15.45, p<0.0005], fear [t (33)=14.38, p<0.0005] and avoidance

Materials

100

Yasmin Tibi-Elhanany and Simone G. Shamay-Tsoory

Figure 1. Sample of Items: Figure 1a first order ToM; Figure 1b second order ToM

Table 1. Means and standard deviations of demographic variables and symptomatology measures Low Social Anxiety (N=22)

High Social Anxiety (N=21)

LSAS-total Mean (SD)

14.59 (6.72)

61.00 (12.09)*

LSAS- fear Mean (SD)

7.45 (4.05)

31.48 (6.55)*

LSAS- avoidance Mean (SD)

7.14 (5.28)

29.52 (8.31)*

12 10

6 15

Age (y) Mean (SD)

25 (7.24)

25.33 (7.47)

Education (y) Mean (SD)

13 (1.22)

13 (1.49)

BAI Mean (SD)

6.71 (3.86)

14. 9 (7.08)*

STAI-trait Mean (SD)

32.71 (5.4)

46.2 (10.86)*

Z general anxiety

-0.68 (0.41)

0.47 (0.69)

Gender Male Female

Figure 1a

*Level of significance was set at p<0.05 (2-tailed)

Figure 1b

[t (34)=10.49, p<0.0005] as well as on measures of general anxiety: BAI [t (15)= 2.77, p=0.01] and TAI [t (14)= 3.37, p=0.005], and on a combined measure of general anxiety that is constructed from z-scores of the BAI and TAI: z-general anxiety [t (15)= -3.90), p= 0.001].

Cognitive and Affective Empathy

Raw empathy scores were transformed into z scores, to allow direct comparison between cognitive and affective empathy scales. As shown in Figure 2, an independent t-test analysis revealed significant differences between social anxiety groups, in the QMEE [t (40) =2.13,

p=0.04], the IRI total scores [t (41) = 2.08, p=0.04], IRI affective [t (41) = 2.61, p=0.01] and the personal distress scale of the IRI [t (41) = 3.02, p=0.004]. In all of these empathy measures, HSA individuals scored higher than individuals in the LSA group. No differences between groups were evident in the IRI cognitive [t (41)<1, ns], the perspective taking, fantasy and empathic concern scales of the IRI [all t (41)<1, ns].

A paired t-test analysis was conducted with the cognitive and affective components of the IRI. Results indicated a significant difference between the cognitive and affective IRI components in the low social anxiety group [t (21) = 3.47, p=0.002], suggesting they had significantly higher scores on the cognitive rather than affective empathy measures. However, the high SA group did not demonstrate any significant difference between the affective and cognitive components of the IRI [t (20) =1.34, ns] (Figure 3, 4).

Relations between social anxiety, general anxiety and empathy

The relation between social anxiety (measured by LSAStotal) and empathy was further emphasized by correlation analysis, which indicates that social anxiety positively correlated with empathy measures, particularly with measurements of affective empathy (Table 2).

101

Social Cognition in Social Anxiety: First Evidence for Increased Empathic Abilities

Figure 2. Empathy measures coded into z-scores, of individuals in the HSA group compared with individuals in the LSA group. Independent t-tests: QMEE [t (40) =2.13, p=0.04]; IRI [t (41)= 2.08, p=0.04]; IRI cognitive [t (41)<1, ns]; IRI affective [t (41) = 2.61, p=0.01]. Individuals with high social anxiety (High SA) scored higher than individuals with low social anxiety (Low SA) on the QMEE, IRI and IRI affective scales.

Empathy z scores of SA groups

0.6

Low SA

*

IRI COG

IRI AFF

*

12

*

10

IRI score

z scores

Cognitive and Affective IRI (mean) with general anxiety as covariate

14

0.2 0

18 16

High SA

0.4 *

Figure 4. Cognitive and affective IRI scores in individuals with high social anxiety (High SA) and low social anxiety (Low SA), with trait anxiety scores measured by the STAI-T, as a covariate. A univariate analysis of variance: A significant difference between the groups emerged for the IRI-cog [F (1,14)= 6.61, p=0.02], but not for the IRI-aff [F (1,14)<1, ns].

QMEE

IRI

IRI cog

IRI aff

8 6 4

-0.2

2 -0.4

0 Low SA

High SA

-0.6

Table 2. Correlations between social and general anxiety and empathy

-0.8

Figure 3. Cognitive and affective IRI scores, in individuals with high social anxiety (High SA) and low social anxiety (Low SA).

Paired t-tests: LSA group [t (21) = 3.47, p=0.002]; HSA group [t (20) =1.34, ns]. Low SA individuals had significantly higher scores on the cognitive rather than the affective component of IRI. No differences between the IRI components were found in high SA individuals.

12

Cognitive and Affective IRI in SA IRI COG

IRI AFF

10

IRI score

*

LSAS general

LSAS fear

LSAS avoidance

QMEE (n=84)

0.27**

0.32**

Ns

IRI-total scores (n=86)

0.25**

0.31**

Ns

IRI affective (n=86)

0.29**

0.34**

Ns

IRI cognitive (n=86)

Ns

ns

Ns

Perspective Taking(n=86)

Ns

ns

Ns

Fantasy Scale (n=86)

Ns

0.24*

Ns

Empathic Concern (n=86)

Ns

ns

Ns

Personal Distress (n=86)

0.31**

0.37**

0.21*

TAI (n=30)

0.48**

0.44**

0.49**

BAI (n=30)

Ns

ns

Ns

8

** Correlation is significant at the 0.01 level (2-tailed) * Correlation is significant at the 0.05 level (2-tailed)

6

As clearly observed in Table 2, a positive correlation between social anxiety and general anxiety, measured by the TAI, was also evident. In addition, the TAI measure of general anxiety was correlated significantly with the personal distress subscale (r=0.36, p= 0.05). It is important to mention here that while the TAI measure correlated with measures of social anxiety, surprisingly, the BAI measure of general anxiety did not correlate with any measure of social anxiety and therefore it was not used for further analysis.

4

2

0 Low SA

102

High SA

Yasmin Tibi-Elhanany and Simone G. Shamay-Tsoory

Correlation and between-groups Analysis Controlling for General Anxiety

To control for the relative contribution of general anxiety, a partial correlation analysis was conducted.

Pearson correlation analysis controlling for general anxiety (TAI) revealed elimination of correlations between social anxiety and affective empathy. However, positive correlations between cognitive empathy (measured by the cognitive component of the IRI) and social anxiety were evident: LSAS-total (r=0.32, p=0.04, n=28); fear subscale (r= 0.35, p=0.03, n=28).

To further investigate the possibility that the betweengroups difference in empathy could be due to individual differences in propensity to anxiety in general, empathy analysis was reanalyzed with general anxiety (TAI) measures as covariate. A univariate ANOVA of IRI-cognitive indicated that general anxiety measured by the TAI did not have a significant effect on empathy [F(1,14)=3.62, ns], and significant differences between SA groups [F (1,14)= 6.61, p=0.02] were evident (Figure 4). HSA individuals had higher scores than LSA individuals on the IRI-cognitive measure. Further analysis revealed that the above reported finding of the IRI-cognitive appears to stem from the fantasy scale and not the perspective taking scale that construct the IRI-cognitive. Univariate ANOVA indicated of significant differences between high and low SA individuals on the fantasy scale [F (1,14)=15.21, p=0.002] with the TAI as a covariate, but not on the perspective taking scale [F (1,14)<1, ns].

This was not the case for the affective empathy component of the IRI (IRI-affective), as results indicated that there was no differential effect between the SA groups in this affective empathy measure while general anxiety had a significant effect [F (1,14)<1, ns].

accurate in the affective ToM conditions (Mean=1.88, SD=0.13) as compared to the cognitive ToM conditions (Mean=1.75, SD=0.21). A significant group by type (interaction) effect [F(1,25)=8.62, p=0.007] indicated that the pattern of accuracy of types (cognitive, affective) differed between groups. Individuals with HSA were better at the affective ToM condition while individuals with LSA were better at the cognitive ToM condition. Nonetheless, follow-up t-tests indicated that the two groups did not differ significantly from each other in the affective [t (25)=1.56, ns] and cognitive conditions [t (25)= 1.07, ns].

Finally we reanalyzed the data with the control physical condition as a covariate to control for potential impairments in basic visual scanning and task comprehension. Repeated measures analysis was additionally conducted with the total physical condition serving as a covariate, to examine whether the SA groups differed significantly from each other on cognitive and affective response accuracy. This analysis indicated that the accuracy in the physical condition did not have a significant effect [Hotelling’s Trace; F(1,24)<1,ns] on affective and cognitive ToM accurcy. In addition, as observed in Figure 5, there was a significant group by type effect [Hotelling’s Trace; F(1,24)=8.19 ,p=0.009] indicating that even when controlling for the physical condition, the HAS group was particularly better in the affective ToM condition.

Figure 5. Response accuracy scores at the combined first and second-order cognitive and affective ToM conditions in individuals with high social anxiety (High SA) and low social anxiety (Low SA). A repeated measures analysis with the combined first and second-order physical condition served as a covariate: a significant group (Low SA, High SA) by type (Cognitive ToM, Affective ToM) interaction effect emerged [Hotelling’s Trace; F(1,24)=8.19, p=0.009].

Theory of Mind

Response Accuracy

As presented above, the task involved three main conditions: “cognitive,” “affective” and “physical” and therefore, the primary variable of interest was the type of judgment. The first and the second order conditions (cognitive, affective, and physical) were summed into measures of total accuracy. In order to obtain measures of the trends and interactions over the different types of judgment, a repeated measures analysis of variance was conducted, with type as the within-subjects factor and group as the between-subjects factor. This analysis revealed a significant type effect [F(1,25)=20.43, p<0.005], indicating a significant difference in accuracy between types (cognitive, affective): subjects were more

1.05 1

Cognitive and Affective ToM IRI COG

IRI AFF

0.95 0.9 0.85 0.8 0.75 0.7

Cognitive ToM

Affective ToM

103

Social Cognition in Social Anxiety: First Evidence for Increased Empathic Abilities

Discussion In accordance with our hypothesis, overall, HSA individuals demonstrated elevated empathic tendencies compared to LSA individuals. The relation between social anxiety and empathy was further emphasized by correlation analysis which indicated that social anxiety positively correlated with empathy measures, particularly with measures of affective empathy. Measures of social and trait anxiety were also moderately correlated (ranged from 0.44 to 0.49) and HSA subjects displayed elevated trait anxiety compared to LSA ones. Overall, HSA individuals exhibited elevated affective empathy tendencies. However, controlling for general anxiety revealed that social anxiety was related to cognitive empathy measures, rather than affective empathy: HSA individuals depicted elevated scores on cognitive, but not affective empathy measures.

Elevated performance of HSA individuals on the cognitive empathy scale aligns with data regarding their attentional biases towards signals of social disapproval or criticism (38) as well as their enhanced vigilance towards social stimuli (5). Although HSA individuals demonstrated elevated cognitive empathy, their perspective taking score indicated of a lower non significant trend compared to LSA individuals. In addition, the perspective taking scores did not correlate with any of the social anxiety measures.

Yet, controlling for general anxiety had revealed that on the second cognitive IRI component, the fantasy scale, HSA individuals had higher scores compared to LSA individuals. The essence of the fantasy scale is the tendency to imagine oneself in the circumstances of another, hence its role taking relevance (9). However, its uniqueness is that the objects of the role taking process are fictitious characters appearing in books and movies. It is possible that the differentiation reported here between perspective taking of real as opposed to imaginary people stems from the social fear and avoidance. These obstacles most likely do not exist in fictional characters and therefore, the actual role taking tendency of social anxious individuals may manifest itself in this particular scale.

Another interesting result indicated that the social anxiety component, rather than the avoidant behavior, is related with enhanced social cognition. Fear, but not avoidance (measured by LSAS) correlated with empathy measures. Avoidance scores positively correlated only with the personal distress subscale and general anxiety.

This dissociation between fear and avoidance might imply 104

that anxiety-related biases (excessive vigilance or selective allocation of attention) but not its behavioral consequence (avoidance) are related to empathy abilities.

One may wonder how the process of being empathically tuned to others co-occurs with the known difficulty that HSA individuals have in the interpretation of others’ signs (39). This dissonance could be resolved based on the distinction between empathic disposition and accuracy. According to Davis (9), cognitive IRI scales evaluate the likelihood to engage in the process of attempting to reflect on the point of view of others; they do not inquire about the outcome of that process (accuracy or social insight). Although empathically accurate perceivers are good at “reading” others’ thoughts and feelings (20), empathy inaccuracy does not necessarily indicate minimal role taking effort. Therefore, it may be speculated that although socially anxious individuals tend to negatively misinterpret others’ feedback, they may exhibit a facilitated tendency to adopt the psychological point of view of others. Although taking the others’ external vantage point in SP may appear self-centered motivated as it stems from heighten self-consciousness, socially anxious individuals in fact vigorously engage in mentalizing activities. Considering their tuned senses with regard to social cues as well as increased other-awareness and self-monitoring in social situations, it is possible that individuals with SP will show increased empathic tendencies, particularly in the cognitive perspective domain, but decreased empathic accuracy.

Indeed, HSA individuals displayed elevated cognitive empathy scores; however they tended to be less accurate than LSA individuals on the cognitive mindreading task.

It is possible that in “real-life” situations, for all their mentalizing attempts, their social perception is inaccurate because of their propensity to “over-mentalize.”

It has been suggested that empathy depends on otherawareness (40), which might be achieved by using one’s own knowledge as the primary basis for understanding others (41). This “self-orientation in service of the other” is consistent with the “simulation” theory (42) according to which we mentally attempt to mimic others’ thought processes and feelings, using our own mental state as a model of theirs. It may be hypothesized that socially anxious individuals are prone to engage in simulation.

For example, it has been reported that socially anxious individuals tend to use their own knowledge as a primary basis to gain insight into others’ thoughts (43).

It was suggested that increased sensitivity to the subtle social cues is required to make theory of mind judg-

Yasmin Tibi-Elhanany and Simone G. Shamay-Tsoory

ments (44). This may be the case with socially anxious individuals which are characterized with exaggerated sensitivity to the implied threat in others’ faces (45).

Indeed, our results indicated a differentiated ToM accuracy pattern since HSA participants exhibited higher accuracy levels than LSA participants on the affective condition, but were less accurate than the LSA group on the cognitive condition. Although not formulated in terms of social cognition, mindreading abilities have been viewed as central to the development of SP, but the focus was on a self-consciousness construct of how they think they appear to other people (13) not on ToM in its broadest sense. Socially anxious people assume that others will have the same negative views of them as they construct about themselves (11). Indeed, this tendency to use one’s own knowledge as a primary basis to gain insight into others’ thoughts that was mentioned before characterizes SP (43).

Although we did not directly examine those relations, we found both cognitive empathy and affective mindreading to co-characterize HSA individuals. It seems that making inferences regarding one’s emotional state (affective ToM) requires the involvement of processes which are cognitive by nature such as adopting another person’s point of view (cognitive empathy). These results are in concordance with Shamay-Tsoory, et al. (46), who reported significant correlations between cognitive empathy (measured by the IRI) and “affective ToM” (measured by a faux pas task) in patients with frontal brain lesions.

To sum up, individuals with SP are preoccupied with the impression they make, and place fundamental importance on being positively appraised by others. They may be especially sensitive to social stimuli, but in real-life social situations, while bombarded with social information, the accuracy of their analysis of those stimuli is negatively affected. Thus, the mode of processing the external social environment as well as the tendency to self focus in SP may influence their perceptiveness of social stimuli, which overall may be manifested in a unique social-cognitive abilities profile.

Finally, it should be noted that although the study included individuals with sub-clinical social anxiety, their measured social anxiety levels were almost as high as scores obtained from social phobic individuals in the clinical literature (for example, 31, 47) which indicates that they experienced significant levels of social anxiety. Nonetheless, it seems worthwhile to further explore social cognitive abilities in clinical samples of social

phobic individuals, and maybe compare the general and more limited type.

References 1. Bogels SM, Mansell W. Attention processes in the maintenance and treatment of social phobia: Hypervigilance, avoidance and self-focused attention. Clin Psychol Rev 2004; 24: 827-856.

2. Spurr JM, Stopa L. Self-focused attention in social phobia and social anxiety. Clin Psychol Rev 2002; 22: 947-975.

3. Musa CZ, Lepine JP. Cognitive aspects of social phobia: A review of theories and experimental research. Eur Psychiatry 2000; 15: 59-66.

4. Amir N, Foa EB. Cognitive basis in social phobia. In Hofmann SG, DiBartolo PM, editors. From social anxiety to social phobia: Multiple perspectives. Needham Heights: Allyn & Bacon, 2001: pp. 254-267.

5. Heinrichs N, Hofmann SG. Information processing in social phobia: A critical review. Clin Psychol Rev 2001; 21: 751-770.

6. Hirsch CR, Clark DM. Information-processing bias in social phobia.

Clin Psychol Rev 2004; 24: 799-825.

7. Lee KH, Farrow TF, Spence SA, Woodruff PW. Social cognition, brain networks and schizophrenia. Psychol Med 2004; 34: 391-400.

8. Davis MH. A multidimensional approach to individual differences in empathy. JSAS 1980; 10: 85.

9. Davis MH. Empathy: A social psychological approach. Madison, Wisconsin: Brown and Benchmark, 1994.

10. Eisenberg N, Murphy BC, Shepard S. The development of empathic accuracy. In Ickes W, editor. Empathic accuracy. New York: Guilford, 1997: pp. 73-116.

11. Clark DM, Wells A. A cognitive model of social phobia. In Heimberg RG, Liebowitz MR, Hope DA, Schneier FR, editors. Social phobia: Diagnosis, assessment, and treatment. New York: Guilford, 1995: pp.

69-133.

12. Spurr JM, Stopa L. The observer perspective: Effects on social anxiety and performance. Behav Res Ther 2003; 41: 1009-1029.

13. Wells A, Clark DM, Ahmad S. How do I look with my mind’s eye: Perspective taking in social phobic imagery. Behav Res Ther 1998; 36: 631-634.

14. Hass RG. Perspective taking and self-awareness: Draw an “E” on your forehead. J Pers Soc 1984; 46: 788-798.

15. Stephenson B, Wicklund RA. Self-directed attention and taking the other’s perspective. J Exp Soc Psychol 1983; 19: 58-77.

16. Wells A, Papageorgiou C. The observer perspective: Biased imagery in social phobia, agoraphobia, and blood/ injury phobia. Behav Res Ther 1999; 37: 653-658.

17. Hodges SD, Wegner DM. Automatic and controlled empathy. In Ickes W, editor. Empathic accuracy. New York: Guilford, 1997: pp. 311-341.

18. Langdon R, Coltheart M. Visual perspective-taking and schizotypy: Evidence for a simulation-based account of mentalizing in normal adults. Cognition 2001; 82: 1-26.

19. Pelphrey KA, Morris JP, McCarthy G. Grasping the intentions of others: The perceived intentionality of an action influences activity in the superior temporal sulcus during social perception. J Cogn Neurosci 2004; 16: 1706-1716.

20. Ickes W, editor. Empathic accuracy. New York: Guilford, 1997.

21. Premack D, Woodruff G. Chimpanzee problem-solving: A test for comprehension. Science 1978; 202: 532-535.

22. Shamay-Tsoory SG, Tomer R, Berger BD, Aharon-Peretz J. Characterization of empathy deficits following prefrontal brain damage: The role of the right entromedial prefrontal cortex. J Cog Neurosci 2003; 15: 324-337.

23. Brothers L, Ring B. A neuroethological framework for the representation of minds. J Cog Neurosci 1992; 4: 107-118.

105

Social Cognition in Social Anxiety: First Evidence for Increased Empathic Abilities

24. Abu-Akel A. A neurobiological mapping of theory of mind. Brain Res Rev 2003; 43: 29-40.

25. Blair RJR. Neurocognitive models of aggression, the antisocial personality disorders, and psychopathy. J Neurol Neurosur Ps 2001; 71: 727-731.

26. Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: Implications for explaining autism. Science 2005; 310: 819-823.

27. Shamay-Tsoory SG, Tomer R, Yaniv S, Aharon-Peretz J. Empathy deficits in Asperger syndrome: A cognitive profile. Neurocase 2002; 8: 245-252.

28. Shamay-Tsoory SG, Shur S, Barcai-Goodman L, Medlovich S, Harari H, Levkovitz Y. Dissociation of cognitive from affective components of theory of mind in schizophrenia. Psychiat Res 2007; 149: 11-23.

29. Lee KH, Farrow TF, Spence SA, Woodruff PW. Social cognition, brain networks and schizophrenia. Psychol Med 2004; 34: 391-400.

30. Liebowitz MR. Social phobia. Mod Probl Pharm 1987; 22: 141-173.

31. Levin JB, Marom S, Gur S, Wechter D, Hermesh H. Psychometric properties and three proposed subscales of a self-report version of the Liebowitz social anxiety scale translated into Hebrew. Depress Anxiety 2002; 16:143-151.

32. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol 1988; 56: 893-897.

33. Spielberger DC, Gorsuch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the state-trait anxiety inventory. Palo Alto, Cal.: Consulting Psychologists, 1983.

34. Mehrabian A, Epstein N. A measure of emotional empathy. J Pers 1972; 40: 525-543.

35. Davis MH. Measuring individual differences in empathy: Evidence for a multidimensional approach. J Pers Soc 1983; 44: 113–126.

36. Shamay-Tsoory SG, Tomer R, Goldsher D, Berger BD, Aharon-Peretz

106

J. Impairment in cognitive and affective empathy in patients with brain lesions: Anatomical and cognitive correlates. J Clin Exp Neuropsychol 2004; 26: 1113–1127.

37. Baron-Cohen S. Mindblindness: An essay on autism and theory of mind. Cambridge, Mass.: MIT, 1995.

38. Rapee RM, Heimberg RG. A cognitive-behavioral model of anxiety in social phobia. Behav Res Ther 1997; 35: 741-756.

39. Stopa L, Clark DM. Social phobia and interpretation of social events.

Behav Res Ther 2000; 38: 273-283.

40. Decety J, Jackson PL. The functional architecture of human empathy.

Behav Cogn Neurosci Rev 2004; 3: 71-100.

41. Harris PL. Understanding emotion. In: Lewi M, Haviland-Jones JM editors. Handbook of emotions. New York: Guilford, 2000: pp. 281-292.

42. Gallese V, Goldman A. Mirror neurons and the simulation theory of mind-reading. Trends Cogn Sci 1998; 2: 493-501.

43. Gilbert P, Trower P. Evolution and process in social anxiety. In: Crozier WR Alden LE, editors. International book of social anxiety: Concepts, research and interventions relating to the self and shyness. West Sussex: John Wiley & Sons, 2001: pp. 259-279.

44. Harkness K, Sabbagh M, Jacobson J, Chowdrey N, Chen T. Enhanced accuracy of mental state decoding in dysphoric college students.

Cognition Emotion 2005; 19: 999-1027.

45. Horley K, Williams LM, Gonsalvez C, Gordon E. Face to face: Visual scanpath evidence for abnormal processing of facial expressions in social phobia. J Psychiatr Res 2004; 127: 43-53.

46. Shamay-Tsoory SG, Tomer R, Berger BD, Goldsher D, Aharon-Peretz J. Impaired “affective theory of mind” is associated with right ventromedial prefrontal damage. Cogn Behav Neurol 2005; 18: 1-12.

47. Gilboa-Schechtman E, Presburger G, Marom S, Hermesh H. The effects of social anxiety and depression on the evaluation of facial crowds.

Behav Res Ther 2005; 43: 467-474.

Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Yuval Melamed et al.

Responsibility of the Therapist for the Patients' Actions (Tarasoff Rules): Position of the Psychiatrists Yuval Melamed, MD, MHA,1,2 Yevgenia Or, MD,1 Dimitri Rudinski, MD,1 Shlomit Cohen, MD,3 Marc Gelkopf, PhD,1,4 Arturo Lerner, MD,1,2 and Avi Bleich, MD, MPA1,2 1

Lev Hasharon Mental Health Center, Netanya, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 3 Abarbanel Mental Health Center, Bat Yam, Israel 4 Department of Community Mental Health and Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel 2

ABSTRACT Background and aims: Patient confidentiality and the therapist's responsibility to society may present a challenge in the therapeutic relationship between the psychiatrist and the patient. We examined the attitudes of Israeli psychiatrists concerning the duty to warn and protect according to the Tarasoff Rule.

Methods: Questionnaires to examine psychiatrists’ opinions concerning the implementation of the Tarasoff Rule in Israel were sent to senior psychiatrists involved in forensic psychiatry for anonymous completion.

Results: 108 (64%) questionnaires were returned. 61 (57%) replied that they encountered similar situations.

Conclusions: Thorough understanding of the Tarasoff Rule, clarification of the patient's potential dangerousness, and timely deliberation of the issues will assist the therapist. Investigation of the medical consensus of senior physicians, as performed in our study, is also a point of reference for formulating an opinion.

Background The responsibility of the therapist for the actions of the patient is a historical dilemma. The patient-doctor relationship is unique and demands safeguarding medical confidentiality. The essence of the therapist’s comAddress for Correspondence: ymelamed@post.tau.ac.il

mitment is to the patient (Hippocratic Oath), and in the past, society’s needs were not taken into account.

However, the family was included in the circle of confidence, as they were concerned with the patient’s health and welfare. With time, the physician became society’s representative and society naturally expected that the physician would promote its interests.

It is easy to fulfill this duty when the interests coincide: Improved health of the patient also improves the health of society, but confidentiality and the responsibility to society may potentially clash in the therapeutic relationship with the patient (1).

The “Tarasoff Rule”(2) as discussed in the courts in the United States, is generally accepted by consensus among specialists in Israel. The Tarasoff case in California affected the obligations of the therapist and extended the borders of the catalyst for malpractice in the United States. Prosenjit Poddar, a University of California at Berkeley student, dated a co-ed, Tatiana Tarasoff, and after he realized that Tanya was dating other men, he had a severe mental breakdown, went for psychiatric care, and revealed his intentions to commit murder (3). The therapist notified campus security of Poddar’s intentions, the police then interviewed Poddar and decided that he did not represent an immediate danger (he denied wanting to harm anyone). However, he stopped psychiatric therapy and later, in 1969, Prosenjit Poddar killed Tatiana Tarasoff. Tarasoff’s parents filed a damages claim against the university and against the therapists.

In 1974 the Supreme Court of California ruled that the therapists were legally responsible for not hav-

Dr. Yuval Melamed, Lev Hasharon Mental Health Center, POB 90000, Netanya 42100, Israel

107

Therapists' responsibility for patients' actions

ing warned the victim (4). Duty to warn refers to the responsibility of a counselor or therapist to breach confidentiality if an identifiable person is in clear danger.

He must determine the degree of seriousness of the threat and notify the person in danger and others who are in a position to protect that person (5, 6).

In their second ruling (4), the court released the police from liability without explanation and more broadly formulated the duty of therapists, imposing a duty to use reasonable care to protect third parties against dangers posed by patients (7).

The case of Tarasoff v. Regents of the University of California (1976) imposed an affirmative duty on therapists to warn a potential victim of intended harm by the client, stating that the right to confidentiality ends when public peril begins.

The Tarasoff Rule thus creates a moral dilemma, between maintaining patient confidentiality and the obligation to maintain public safety. Quite often, the therapist cannot know there is indeed a real threat.

There are no rules or guidelines to diagnose a threat, and each case is unique. The therapist’s role in therapy is to treat the patient.

There is no ideal solution for the dilemma of maintaining medical confidentiality versus the duty to warn and/or protect. Patient confidentiality is a legal responsibility, and breaching that responsibility is a criminal act, a civil wrong involving damages, and a catalyst for legal sanctions (8).

In the case of a patient who is in a psychotic state and threatens others, the conditions for a hospitalization order are fulfilled, and he/she will be hospitalized, and thus the danger will be averted. What happens when the individual is not psychotic?

In England (W. v. Egdell) (9) a psychiatrist was sued by a patient he had examined, for a private expert opinion, because the psychiatrist passed the information concerning his dangerousness to the supervisor of the hospital where he was hospitalized. The prosecution was denied because the duty to protect the public overrides the issue of confidentiality in such a case.

This issue is not unique for mental health, as general physicians are also faced with similar situations (10).

It seems that there is an obligation to protect the third party when communicable diseases such as HIV (11, 12) are involved, and child abuse.

The family physician faces an even greater dilemma if the spouse is also his patient, or the child of the abusive parent (13).

108

It is easy to see the undesirable results of excessive intervention, and unnecessary warnings (14, 15). This may cause unnecessary harm to the patients – loss of license to carry a weapon, loss of employment, family relations, etc. There is a considerable difference between a person who is in the process of divorce and is angry with his wife, and threatens her (the wife is in danger) and one who raises the issue in treatment and as a result of therapy the threat is removed. “Unnecessary” notification to the police in this type of case could lead to a police complaint and the opening of a police record with all that it entails, while in fact, it becomes clear that the complaint was based on the expression of anger. In terms of public interest, it is preferable that individuals seek therapy and go on with their lives rather than proceed without emotional help. Thus, public interest is also in conflict: protection of society vs. the individual’s right to confidentiality, as a social interest.

It is often assumed that the duty to warn and the obligation to protect is the responsibility of the police.

The therapist fulfills his responsibility by passing the information to the police; it is difficult to imagine how the therapist would have access to contact information for all potential victims.

The objective of this study was to examine the attitudes of psychiatrists concerning the duty to warn and protect according to the Tarasoff Rule.

Methods Questionnaires were sent by post to senior psychiatrists with an explanation of the survey and request to complete the forms anonymously in the return envelopes provided. The survey was performed among senior psychiatrists involved in forensic psychiatry, did not involve specific patient information, and responses were anonymous, thus Helsinki approval was not sought.

Completion and return of the forms was considered consent to participate in the survey.

The following questionnaire was used: The Tarasoff Rule is well known in the United States.

According to the Tarasoff Rule, if a patient in therapy threatens to harm another individual the therapists must warn the potential victim. To the best of our knowledge, the Tarasoff Rule was never discussed in the courts in Israel. We would appreciate if you could note your position, for the purposes of this survey: Do you recall a similar case in your practice, and how did you respond?

Yuval Melamed et al.

Contacted the District Psychiatrist Contacted the police Contacted the person threatened All of the above A different combination, please describe Other, please describe Please related to the following case: David, age 32, in the process of divorce, was in private psychotherapy, once a week. He was in a reactive depressive crises. He was very angry with his wife, who in his words “destroyed my life, disrupts my relationship with my daughters and demands very high alimony.” After a calm period in therapy and development of a therapeutic relationship, he arrived in a stormy state, and described how his wife did not allow him to meet with his daughters on the holiday, in contradiction to the agreement between them and told him that he will never see his daughters again.

During the session, he angrily told the therapist that he will kill her, and finally left the session before it was over, claiming that the therapist also does not understand him.

Contact the District Psychiatrist Contact the Police Contact the person threatened Contact the person in therapy All of the above A different combination, please describe Other, please describe

tice. Their methods for dealing with the issues included: contacting the regional psychiatrists for consultation or hospitalization orders 43/61(70.49%), contacting the police 38/61 (62.29%), contacting the potential victim 31/61(50.81%), other responses 15/61 (24.59%) (15%).

Many responders gave combined responses, indicating that they made two or more contacts, thus 61 respondents provided a total of 127 responses.

Concerning the case presented: the following replies were received: Of the 108 responders, 60 reported that they would have contacted the potential victim (55.55%), contacted the police 48 (44.44%), and involved the District Psychiatrist 25 (23.14%), reported to the welfare department 4 (3.70%), discussed with the patient 45 (41.66%), other 15 (13.88%). Most responders would have made more than one contact, thus a total of 197 responses were received.

Discussion Physicians have long been aware of the dilemma between maintaining patient confidentiality and the duty to protect society. With the help of the law, ethics and a system of checks and balances there is usually an appropriate balance. Patients generally do not avoid coming for treatment for fear of lack of medical discretion, and physicians do not generally breach confidentiality.

The Tarasoff Rule takes the dilemma one step forward, to where the treating physician deliberates between maintaining confidentiality and the duty to report to the authorities, and/or additional persons, i.e., the potential victim, family, or others.

The second Tarasoff ruling places the therapist in a more difficult situation (16).

In our study, we found awareness of the issue, and most physicians had even encountered cases involving the “Tarasoff dilemma” (64%), which do not include

Study sample:

The questionnaire was sent to 170 specialists in psychiatry with at least five years experience in the field, and active in the field of forensic psychiatry.

Results 108 (64%) questionnaires were returned.

In response to the first question: 61 (57%) replied that they had encountered this type of dilemma in their pracTable 1. Israeli Forensic Psychiatrists' responses to Tarasoff Rule Police N (%)

District Psychiatrist N (%)

Potential Victim N (%)

Social Services N (%)

Patient in therapy N (%)

Other

Had patients that threatened to harm a 3 party N = 61 Total responses = 127

38 (62.29%)

43 (70.49%)

19 (31.14%)

-

-

15 (24.59%)

Responders to hypothetical case N=108 Total responses = 197

48 (44.44%)

25 (23.14%)

60 (55.55%)

4 (3.70%)

45 (41.66%)

15 (13.88%)

Contact rd

Responders were allowed more than one response thus the answers do not total 100%.

109

Therapists' responsibility for patients' actions

all cases that involved the duty to report, which has become routine for physicians.

It should be noted that in Israel, the Tarasoff Rule has never been discussed in court, though the position of the State is that this rule applies to therapists either by expecting them to warn the third party, or those close to the third party or by contacting the police (17).

The dilemma presented in our study involved psychotherapy with a non-psychotic patient. Some responses concerned notifying the potential victims, and others contacted the District Psychiatrists.

This indicates a change; in the past, in times of danger, the therapists contacted the police, and it seems there has been a shift in awareness regarding the duty to warn the potential victim.

It is difficult to understand the message from the original Tarasoff case, according to which the therapist was at fault, though he passed detailed information on to the police, who certainly had the wherewithal to prevent a tragedy, and they were obligated to investigate the matter with the victim. Perhaps the message is that society passes responsibility to the caregiver, since s/he may know when to operate outside of the treatment room.

In actual fact, we are not dealing with an all encompassing breach of patient confidentiality, and implementation of the rule is done sparingly (18).

In addition, the therapist cannot always be confident that warning will cause less harm than not warning (19).

The therapist is obligated to evaluate all aspects of his patients’ condition, including a careful evaluation of potential risk, in routine examinations, especially during the first patient interview (20).

The dilemma of the Tarasoff Rule has no easy solution, but deeper understanding of the rule, clarification of the patient’s potential dangerousness, and timely deliberation of the issues will assist the therapist.

Investigation of the medical consensus of senior physicians, as performed in our study, is also a point of reference for formalizing an opinion.

110

References 1. Livman, LA. (1996). Maintaining patient confidentiality or the duty to warn others of danger – the physician’s dilemma. Unpublished MA dissertation, Department of Law, Hebrew University, Jerusalem, Israel (Hebrew).

2. Tarasoff v. Regents of University of California, 17 Cal.3d 425; 551 P.2d 334; 131 Cal. Rptr. 14 [1976].

3. Buckner F., Fireston, M. (2000). Where the public peril begins: 25 years after Tarasoff. J Leg Med 21:187-222.

4. Tarasoff v Regents of University of California (1974). 13 Cal 3d 177, 118 Cal Rptr 129, 529 P2d 553.

5. Herlighy B, Sheeley VL. Counselor liability and the duty to warn: Selected cases, statutory trends, and implications for practice. Counselor Education and Supervision 1988; 27: 203-215.

6. Pate RH, Jr. Are you liable? American Counselor 1992; 1: 15-19.

7. Keith-Spiegel P, Koocher GP. Ethics in psychology: Professional standards and cases. New York: Random House, 1985.

8. Pettis RW. Tarasoff and the dangerous driver: A look at the driving cases. Bull Am Acad Psychiatry Law 1992; 20:427-437.

9. Frampton A. Reporting of gunshot wounds by doctors in emergency departments: A duty or a right? Some legal and ethical issues surrounding breaking patient confidentiality. Emerg Med J 2005; 22: 84-86.

10. McGuire J, Nieri D, Abbott D, et al. Do Tarasoff principles apply in AIDS-related psychotherapy? Ethical decision making and the role of therapist homophobia and perceived client dangerousness. Prof Psychol Res Pr 1995; 26:608-611.

11. Givelber D. The legal obligation to prevent harm: The Tarasoff rule and its limits. Mt Sinai J Med 1996; 63:77-81.

12. Huprich SK, Fuller KM, Schneider RB. Divergent ethical perspectives on the duty-to-warn principle with HIV patients. Ethics Behav 2003; 13:263-278.

13. Oppenheimer K, Swanson G. Duty to warn: When should confidentiality be breached? J Fam Pract 1990; 30:179-184.

14. Melamed Y. . Summary of workshop on “Therapist’s responsibility for the patient’s actions.” Michtav LeHaver 2000: p. 65 (Hebrew).

15. Perlin ML. Tarasoff and the dilemma of the dangerous patient: New directions for the 1990’s. Law Psychol Rev 1992; 16:29-63.

16. Weil F. Releasing the treating psychiatrist from confidentiality. Medicine Law 1993; 12:249-255.

17. Expert opinion, Legal advisor of the Ministry of Health, 2000.

18. McNiel DE, Binder RL, Fulton FM. Management of threats of violence under California’s duty-to-protect statute. Am J Psychiatry 1998; 155:1097-1101; Erratum in: Am J Psychiatry 1998;155:1465.

19. Herbert PB. The duty to warn: A reconsideration and critique. J Am Acad Psychiatry Law 2002; 30:417-424.

20. Bauer A, Rosca P, Grinshpoon A, et al. Risk versus confidentiality: The therapist’s responsibility for his psychiatric patient’s acts. Harefuah 2003; 142:304-308, 316, 315 (Hebrew).

Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Silvana Fennig et al.

Relationship between ICD-10 Psychosocial Categories and Psychiatric Diagnosis in Israeli Adolescents Silvana Fennig, MD, 1,2,3 Alan Apter, MD,1,2,3 Netta Horesh,PhD,1,2,3 Ruth Arzi, MA,1,2,3 Gil Zalsman, MD,1,2,3 Avi Weizman, MD,3,4 and Shmuel Fennig, MD,3,5 1

The Feinberg Child Study Center, Schneider Children’s Medical Center of Israel, Beilinson Campus, Petach Tikva, Israel Department of Psychological Medicine, Schneider Children’s Medical Center of Israel, Beilinson Campus, Petach Tikva, Israel 3 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 4 Geha Psychiatric Center, Beilinson Campus, Petach Tikva, Israel 5 Shalvata Mental Health Center, Hod Hasharon, Israel 2

ABSTRACT Aim: The study examined the relationship between psychosocial categories obtained by WHO-developed semistructured interviews (ICD-10 Axis V) and clinical Axis I psychiatric diagnoses in psychiatrically hospitalized adolescents.

Methods: The sample included 71 consecutive patients admitted to an adolescent unit and their mothers.

Mothers completed a semi-structured interview derived from the criteria for each psychosocial category (Axis V), and the adolescents were diagnosed by experienced psychiatrists using the Schedule for Affective Disorders for School Age Children (K-SADS-P).

Results: Anorexia nervosa and conduct disorder were associated with a psychosocial category of “abnormal qualities of upbringing,” and conduct disorder and schizophrenia were associated with a psychosocial category of “events brought about by the child’s own behavior.”

Conclusions: The systematic assessment of psychosocial categories add specific information to the validity of the Axis I diagnosis.

Introduction The established role of psychosocial stress as a risk factor for psychiatric disorders in adults led to its investigation in the development of child and adolescent mental disorders (1) and to its association in the course of mental disorders and in the response to treatment (2). Research on psychopathology in this age group highlighted the problems of reliability of the different sources of information and how to resolve those differences (3-5).

These findings suggested that psychopathology should be approached from a developmental perspective with assessments of family, peer, school, and their environmental relationships, thereby obviating the need for a structured and systematic psychosocial diagnsosis.

In 1990, a work group of the World Health Organization (WHO) specified criteria for abnormal psychosocial situation in a similar fashion to the clinical Axis I psychiatric disorders in the research version of ICD-10 and the DSM-IV (6). The tenth revision of the ICD-10 adopted these recommendations in the form of the new nine-category qualitative classification for children based on previous studies (7). This axis suggests a way to code abnormal psychosocial conditions based on the developmental age of the child and his past history. The categories were chosen based on their ability to validate significant risk factors even if they were not considered a direct etiological factor (8, 9). Clear operational criteria were developed for each category, and two semistructured interviews, one for children and one for their parents, were constructed. The

Address for Correspondence: Silvana Fennig, MD, Schneider Children’s Medical Center of Israel, Beilinson Campus, Petach Tikva, Israel 49202 l silvanaf@clalit.org.il

111

ICD-10 psychosocial diagnosis

psychosocial categories form the fifth axis of the five-part multiaxial classification of childhood psychiatric disorders (7). We found as part of the present study that all of the psychosocial categories of Axis V were common and relevant to a population of inpatient adolescents and we conclude, based on our findings, that it is possible to make reliable and relevant diagnoses in severely ill adolescents (10).

In the present paper we aimed to further investigate the specific links between the psychiatric diagnosis and the psychosocial categories.

Sarason et al. (11) claim that there is a correlation between specific life events and specific psychiatric disorders. It is widely accepted that depression and mania are associated with life events and the ability to adjust to them.

Specific life events like loss, divorce of parents and traumatic events in the parent are associated with higher rates of mood disorders later in life, especially if those events occur during childhood (12, 13). Abnormal family relationship and rearing practices have been related to eating disorders for many years (14). However, when anorexic patients are studied separately from those with other eating disorders the results of controlled studies are conflicting (15). In a recent study women with bulimia nervosa tended to report more troubled childhood expriences than did women from a non-morbid comparison group.

In this respect they resembled those with major depression. In contrast, those with anorexia nervosa resembled the non-morbid women rather than the other psychiatric groups (16). Some authors claim that family factors are related to short-term outcomes (17). The research on life events and schizophrenia had been subject to the usual methodological problems of retrospective case-control designs and have had difficulties in outlining predispositional factors in schizophrenia (18). In a review, Holmes et al. (19) concluded that in addition to temperament and psychiatric comorbidity, psychosocial factors influence the development of conduct disorder. A child’s family experience is one of the most influential environmental factors contributing to conduct disorder beginning at birth and continuing throughout childhood and adolescence.

Familial factors related to the development of conduct disorder are inconsistent supervision interspersed with harsh punishment, large family size, institutional living early in life, parental rejection, inconsistent parental figures and the presence of an alcoholic father (20).

Many of the studies on psychosocial correlates and severe mental illness have shown overlapping and nonspecific stressors as preceding or contributing to the 112

development of mental illness. However, considering our limited resources, we found it very important, especially with adolescents, to reach a more specific psychosocial category, so that we could more effectively direct our psychosocial interventions.

The purpose of the present study was to determine the specificity of the Axis V categories against the Axis I diagnoses by applying systematically specific criteria for the psychosocial categories using a semi-structured interview. We hypothesized that there is a specific relationship between the psychosocial category and the Axis I diagnosis. We expected subjects with mood disorders to have problems in the categories of acute life events and social stressors; those with conduct disorder to have problems in the categories of family relationship and societal stress; those with anorexia nervosa to have problems in the category of abnormal upbringing; and subjects with schizophrenia to have more problems in the category of the consequences of their illness on the family and on their life. No specific hypothesis was raised regarding OCD. Methods Subjects: Fifty-five mothers of patients, consecutively admitted to the Adolescent Unit of a university-affiliated psychiatric hospital, were interviewed. The choice of the mothers as the source of information was because we thought that mothers were usually more aware of their children's upbringing and to minimize the effect of gender and role in the family on our findings. Mean age was 16.04±1.7 years; most were of middle socioeconomic class, 23 boys (41.8%) and 32 girls (58.2%). Axis I diagnoses according to the ICD-10 were as follows: schizophrenia, 14 patients (25.5%); mood disorder, 10 (18.2%); conduct disorder, 20 (36.4%); obsessivecompulsive disorder, 6 (10.9%), and anorexia nervosa restrictive type, 5 (9.1%). The study was approved by the Geha Hospital Review Board, and written informed consent was obtained from all subjects and their parents after the nature of the study was fully explained.

Instruments: The parents completed the parent version of the semistructured interview of the ICD psychosocial axis which rates 9 psychosocial categories on a 3-point scale: 0 – the item is not present; 1 – possibly present; 2 – definitively present; 9 – not enough data to decide (WHO, Parent Interview Schedule, 8). Each main category included 1-7 subcategories (total of 39 sub-categories). Categories 1 through 5 relate to unusual family environments: 1 – abnormal intrafamilial relationship like

Silvana Fennig et al.

lack of interest and/or concern from parents, physical and sexual abuse; 2 – mental disorder, deviance or handicap in the child’s primary care support group; 3 – inadequate or distorted intra-familial communication; 4 – abnormal qualities of upbringing; 5 - abnormal immediate environment (e.g., institutional upbringing); 6 – acute stressful life events like death in the family, sexual abuse, birth of a sibling; 7 – societal stressors like those associated with immigration or moving to a different geographical region; 8 – chronic interpersonal stress associated with school or work; 9 – stressful events/situations resulting from the child’s own disorder/disability. We present for example one of the sub-categorizations of Category 4 and one of the sub-categorizations of Category 9: Category 4 consists of four different subcategories and the sum on all these subcategories represent the means presented in the table: 4.3 – inappropriate parental pressures: 4.3.0 inappropriate parental pressures regarding gender; high score on this item means – encouraging the child for inappropriate gender behavior, e.g., encouraging the girl to develop masculine behavior; 4.3.1 – inappropriate parental pressures regarding the child's chronological age; high score on this item means – putting pressure on the child to behave in a way that is incompatible with his age, his developmental stage or his will, e.g., parents involve the child with their intimate problems, child is functioning as a “parental child.” Category 9 has four subcategories: 9.0 – institutional upbringing: the child was put out of his family and hospitalized or was sent to a treatment facility because of his illness for at least 3 months; 9.1 – removal from home carrying significant contextual threat; 9.2 – events resulting in loss of self-esteem as a result of the child’s disorder, and 9.8 other. All psychosocial diagnoses refer to the 6 months prior to admission. For each sub-category there were detailed instructions for coding as provided by the manual: 2 = definitely present, 1 = present but not in the required severity, 0 = absent, normal, 8 = not applicable, 9 = not enough information. The interview takes about 90 minutes to complete. For the present study, the interview schedules were translated into Hebrew and retranslated back into English by two clinicians. The methodology used was described in an earlier study (10). Inter-rater reliability for the psychosocial diagnoses was moderate to high (k=0.83 to 1.0) for all nine categories. All patients were evaluated psychiatrically and received DSM-IV Axis I and II diagnoses (21). They also completed the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-P). The Hebrew version of the K-SADS-P was validated on the unit’s population

(22). The psychiatrists who made the final diagnoses were blinded to the results of the psychosocial questionnaires.

In addition, data were gathered from the families and from clinical observations during hospitalization. The psychosocial interview was conducted by two experienced psychiatric social workers specially trained by the unit director (A.A.) with 15 subjects (not included in the study) for two months. Differences in interpretation were discussed until a consensus was reached.

Procedure: All study interviews were conducted 2 to 4 weeks after admission. To measure inter-rater reliability, 55 patients were rated concurrently by the two interviewers using the child version of the semistructured interview, and their mothers were rated with the parent version.

Statistical Analysis

We summarize the sums of items given on each category and means for each category and for each diagnosis were calculated. Kruskal-Wallis (χ2) test was used for nonparametric comparisons of more than two groups; Mann Whitney (U) analyses were used to compare two groups.

Non-parametric analyses were done because the distribution of the scores on the items deviated from normality.

Results Comparison of the means of the psychosocial categories by Kruskal-Wallis test (χ2) showed statistically significant differences for categories 4 (abnormal qualities of upbringing) and 9 (stressful life events resulting from child’s behavior or disorder). To find the source of these differences, we analyzed the data with the Mann-Whitney test for pairs of categories. For category 4, there was a statistically significant difference between patients with schizophrenia and conduct disorder (U=57.5, p < .01) and between patients with schizophrenia and anorexia nervosa (U=17.5, p < .05). The highest mean scores for category 4 were noted for the patients with conduct disorder and with anorexia nervosa (Table 1). Regarding category 9, there was a statistically significant difference between patients with schizophrenia and with anorexia nervosa (U=16.0, p <. 05), between patients with affective disorder and conduct disorder (U=64.5, p < .05), and between patients with schizophrenia and affective disorder (U=23.0, p <.

01). To rule out the possible effect of the two small groups (anorexia nervosa, n=6 and obsessive compulsive disorder, n=5), we conducted a non-parametric analysis of the three larger groups. As shown in Table 2, the results were similar to those achieved by comparing the five Axis 1 diagnos113

ICD-10 psychosocial diagnosis

Table 1. Means* of Axis V Categories and Clinical Axis I Diagnoses (n=55) Axis I diagnoses Axis V Diagnoses

Schizophrenia N=14

Mood N=10

Conduct N=20

Anorexia N=6

OCD N=5

χ2

1. Abnormal intrafamilial relationship (6 subcategories)

26.75

27.05

30.23

27.00

25.70

.63

2. Mental disorder, deviance or handicap in child’s primary support group (4 subcategories)

24.96

29.00

28.48

28.08

32.50

.95

3. Inadequate or distorted familial communication (1 subcategories)

25.27

25.30

28.42

25.17

26.80

.48

4. Abnormal qualities of upbringing (5 subcategories)

18.54

26.30

34.80

33.17

25.40

9.43*

5. Abnormal environment (5 subcategories)

26.96

28.70

30.52

21.25

27.50

1.64

6. Acute life events (7 subcategories)

26.61

29.70

28.45

30.25

24.00

.66

7. Societal stressors (3 subcategories)

25.50

33.95

28.15

25.50

25.50

1.99

8. Chronic interpersonal stress associated with schoolwork (4 subcategories)

28.15

24.10

28.53

20.33

26.75

1.74

9. Stressful life events resulting from child’s disorder (4 subcategories)

37.21

18.90

28.80

20.75

25.90

9.22*

p<.05 * Means of sums of each category includes sums of all subcategories Category 9 – Stressful events/situations resulting from the child’s own disorder disability and includes 9.0 institutional upbringing; 9.1 removal from home carrying significant contextual threat and 9.2 – events resulting in loss of self-esteem as a result of the child’s behavior Category 4: 4.0 – parental overprotecting; 4.1 – inadequate parental supervision/control; 4.2- experiential deprivation; 4.3 inappropriate parental pressures on child to behave not according to gender or chronological age; 4.8 – other

Table 2. Comparison of mean scores on three main Axis I diagnoses and Axis V categories (N=44) Axis I diagnoses Axis V diagnoses

Schizophrenia N=14

Mood N=10

Conduct N=20

χ2

1. Abnormal intrafamilial relationship

21.50

24.00

21.07

.53

2. Mental disorder, deviance or handicap in the child’s primary support group

23.75

23.27

20.50

.63

3. Inadequate or distorted familial communication

19.95

22.36

19.92

.58

4. Abnormal qualities of upbringing

15.61

20.8

28.17

8.47*

5. Abnormal environment

22.15

23.73

21.00

1.64

6. Acute life events

23.75

22.75

21.25

.24

7. Societal stressors

20.0

26.8

22.1

5.50*

8. Chronic interpersonal stress associated with schoolwork

18.90

23.39

22.19

0.69

9. Stressful life events resulting from child’s disorder

28.86

14.25

22.17

8.29*

P <.05* * Means of sums of each category includes sums of all subcategories Category 4: 4.0 – parental overprotecting; 4.1 – inadequate parental supervision/ control; 4.2- experiential deprivation; 4.3 inappropriate parental pressures on child to behave not according to gender or chronological age; 4.8 – other Category 7: Societal Stressors: 7.0 persecution or adverse discrimination; 7.1 migration or social transplantation and 7.8 - other Category 9 – Stressful events/situations resulting from the child’s own disorder disability and includes 9.0 institutional upbringing; 9.1 removal from home carrying significant contextual threat and 9.2 – events resulting in loss of self-esteem as a result of the child’s behavior

114

tic categories, with the addition of a statistically significant difference for psychosocial category 7 (acute social stressors). This category consists of two subcategories: 7.0 – persecution or adverse discrimination; high score on this category means the child experiences discrimination based on his ethnic, religious, skin color or affiliation to a group. Exclusion was any discrimination based on the child’s personality. To qualify for high score on this category those experiences must terminate in physical injury or exclusion from activities that are important for the child; 7.1– migration or social transplantation; high score the child is transferred to another area with/without family with loss of personal confidence or loss of welfare or social status. Subjects with affective disorders had the highest scores for category 7; lower scores were noted for patients with conduct disorder and schizophrenia.

Discussion In a previous study we concluded that it is possible to make reliable and relevant psychosocial diagnoses in severely ill adolescents (10). The low agreement between clinicians and research-

Silvana Fennig et al.

ers emphasized the need for systematic probing so all the relevant information for diagnostic assessment becomes available. The findings of the present study support the hypothesis of an association between ICD-10 Axis I diagnoses and Axis V diagnoses obtained by semi-structured interview. We found only one study in the literature that examined the relationship between Associated Abnormal Psychosocial Situations Axis V and psychiatric disorders in children and adolescents (23). The investigators in this study compared inpatient adolescents with Emotional Disorders (mainly anxiety disorders and depression) with inpatient adolescents with a diagnosis of Disruptive Behavior Disorders, Specific Developmental Disorders and Non Specific Developmental Disorders and found that psychosocial categories were more frequently found in children and adolescents with Emotional Disorders or Disruptive Behavior Disorders than in those with Developmental Disorders but there was no diagnostic specificity in the distribution of the psychosocial categories. Their sample was large and included 1,050 patients.

The differences in findings between our study and Doyen et al.’s (23) might be in the difference methodology (in their study they did not use a structured interview while we used systematically a structured interview with the mothers), the difference in the diagnostic groups (theirs not including schizophrenia and eating disorders and ours not including developmental disorders), and the difference in the methodology of arriving at a diagnosis.

The differences might also emanate from the differences in the settings: in our setting we hospitalize only patients with severe forms of pathology while the French sample is based on the composition of diagnosis, less severe forms of disorder are used.

Studies in the 1980s demonstrated the cumulative effects of stressful life events in childhood and adolescence on the development of mental disorder (24-26). Stressful life events were associated with the majority of severe mental disorders (1, 26). In the present study, patients with an Axis II diagnosis of conduct disorder had a higher mean score for the psychosocial category of “abnormal upbringing,” which reflects parental overprotectiveness, a deficit in social experiencing, and parental control and pressure inappropriate to the child’s gender, age or capabilities.

These findings are supported by previous studies showing a correlation of conduct disorder and criminal behavior in children and adolescents raised in homes with a lack of parental discipline and guidance, parental rigidity and severe punishment, inconsistency in teaching habits of discipline, or vague or absent discipline habits (1, 27, 28). Our

findings are also supported by in-home observations of inconsistent behavior of parents of children with conduct disorder. Specifically, the parents tended to be rigid, tough and controlling, while rewarding unacceptable behavior and disregarding positive behavior.

The association of abnormal bringing with anorexia in our study is in line with the known conflict of anorexic girls between control and dependence on the one hand and fear of their own sexual development and independence on the other hand (29, 30). Although recent studies, when including adolescents with a short evolution of the disease fail to find a relationship between altered family relationships in general and anorexia nervosa (31), the presence in our sample of chronic patients with a severe form of the disease might explain the differences.

Accordingly, the relative lack of association between schizophrenia and abnormal qualities of upbringing emphasized in this sample the smaller role of upbringing in the evolution of the disease.

Studies have shown that affective patients, more than patients from other diagnostic categories, experience more negative life events in the period preceding the onset of the episode. In the present study, the stressful life events probed in section 7 deal with social discrimination that cause physical and emotional humiliation, public stigmatization, status of social isolation, and mockery by the peer group. Adolescence is a period when social acceptance and social ties are the major developmental tasks, and failure in these domains can lead to the development of an affective disorder. The findings of an association between social stigmatization and discrimination and affective disorder are particularly important in Israel, where religious and ethnic pluralism and acceptance of others are assumed to play an important role in the mental health of adolescents from immigrant families. Like adolescence, the immigration process is accompanied by emotional instability and vulnerability and an absence of the family as a source of social support. Their combination increases the importance of the peer group and, consequently, the risk of psychopathology in cases of rejection and humiliation.

The third domain which was specifically associated with a clinical diagnosis was the need to remove the child from the home because of his (or her) symptomatology (26). This was the only situation in which the interviewers were instructed to rate the subjects on the basis of their current condition. Schizophrenia and conduct disorder were associated with this psychosocial category. Both these disorders are expressed by symptoms that are difficult to handle and contain at home. The psychotic 115

ICD-10 psychosocial diagnosis

symptoms of schizophrenia and the antisocial impulsive behavior associated with conduct disorder threatened the integrity of the family.

Limitations of the Study

1. The sample included only hospitalized adolescents with the severe form of the disorders.

2. The sample was small, especially regarding anorexia and OCD. Further research on a larger sample should be done to replicate our findings.

3. The design of the study could lead only to correlations and the findings can be explained in both directions: as the causes as well as the results of the disorders investigated.

Conclusions 1. In an inpatient sample with severe psychopathology specific association between ICD-10 Axis I diagnoses and Axis V categories obtained by semi-structured interview was found.

2. The study indicates the usefulness of systematically categorizing and quantifying psychosocial diagnostic information in addition to a psychiatric diagnosis in adolescents. The validity of diagnoses based on contemporary nosological systems might be strengthened by data moving toward an etiological rather than a descriptive system. Such data would probably include socio-cultural as well as genetic and congenital factors phasing in at various points in development.

References 1. Hetherington EM, Martin BM. Family factors and psychology in children. In: Quay HC, Werry JW, editors. Psychopathological disorders of childhood, 3rd edition. New York: Wiley, 1986: pp. 332-390.

2. Jacob T. Family interaction and psychopathology: Theories, methods and findings. New York: Plenum, 1987.

3. Reich W, Earls F. Rules for making psychiatric diagnoses in children on the basis of multiple sources of information: Preliminary strategies. J Abnorm Child Psychol 1987;15:601-616.

4. Herjanic B, Reich W. Development of a structured psychiatric interview for children: Agreement between child and parent on individual symptoms. J Abnorm Child Psychol 1982;10:307-324.

5. Fennig S, Carlson G, Bromet E. Who provides the best retrospective information while assessing adultâ&#x20AC;&#x2122;s premorbid functioning? A methodological study in a first-admission sample with psychosis. Isr J Psychiatry Relat Sci 1999;36:79-87.

6. Van Goor-Lamboo G, Orley J, Poutska F, Rutter M. Classification of abnormal psychosocial situations: Preliminary report of a WHO scheme. J Child Psychol Psychiatry 1990;31:229-241.

7. World Health Organization. The International Classification of Disease 10th edition. Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva, Switzerland: World Health Organization, 1992.

8. World Health Organization. Psychosocial Axis of the Multi-Axial Classification of Child and Adolescent Psychiatric Disorders. Parent

116

Interview Schedule. Draft for comments and field testing. WHO Document MNH/MND/90.13. Geneva, Switzerland: World Health Organization, 1990.

9. World Health Organization. Multiaxial Classification of Child and Adolescent Psychiatric Disorders. U.K.: Cambridge University, 1996.

10. Zalsman G, Horesh N, Arzids R, Edelist D, Har Even D, Tyano S, Poustka F, Apter A. Psychosocial diagnosis in psychiatrically hospitalized adolescents. Compr Psychiatry 2001;42:223-227.

11. Sarason IG, Johnson JH, Siegel JM. Assessing the impact of life changes: Development of the life experience survey. J Consult Clin Psychol 1978;46:932-946.

12. Harris TO, Brown G, Bifulco A. Loss of parent in childhood and adult psychiatric disorder: The role of lack of adequate parenting. Psychol Med 1986;16:641-659.

13. Brown GR, Anderson B. Psychiatric morbidity in adult inpatients with childhood histories of sexual and physical abuse. Am J Psychiatry 1991;148: 55-61.

14. Bruch H. Eating disorders: Obesity, anorexia nervosa and the person within. Basic Books: New York, 1973.

15. Halmi KA. Eating disorders. In Kaplan H, Sadock BJ, editors.

Comprehensive Textbook of Psychiatry, Volume II, 7th Edition.

Philadelphia: Lippincott Williams & Wilkins, 200, pp. 1663-1676.

16. Webster JJ, Palmer RL. The childhood and family background of women with clinical eating disorders: A comparison with women with major depression and women without psychiatric disorder. Psychol Med 2000;30:53-60.

17. Castro J, Toro J, Cruz M. Quality of rearing practices as predictor of short-term outcome in adolescent anorexia nervosa. Psychol Med 2000;30:61-67.

18. Norman RM, Mall AK. Stressful life events and schizophrenia. Br J Psychiatry 1993;162:161-168.

19. Holmes SE, Slaughter JR, Kashani J. Risk factors in childhood that lead to the development of conduct disorders and antisocial personality disorder. Child Psychiat Human Dev 2001;31:183-193.

20. Guzder J, Paris J, Zlkowitz P, Feldman R. Psychological risk factors for borderline pathology in school-age children. J Am Acad Child Adolesc Psychiatry 1999;38:206-210.

21. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (ed. 4) Washington, DC: American Psychiatric Association, 1994.

22. Apter A, Orvschel H, Laseg M, Moses T, Tyano S. Psychometric properties of the K-SADS-P in an Israeli adolescent psychiatric population. J Am Acad Child Adolesc Psychiatry 1989;28:61-65.

23. Doyen C, Mallet L, Fallisard B, Bouvard MP, Dugas M, Mouren-Simeoni MC. Abnormal psychosocial situations among inpatients from a child and adolescent psychiatric department. Eur Child Adolesc Psychiatry 1999;8:207-213.

24. Dohrenwend BS, Dohrenwend BP. Stressful life events and their context.

New York: Prodist, 1981.

25. Goodyer IM. Life experience, development and childhood psychopathology. West Sussex, England: John Wiley, 1990.

26. Goodyer IM. Recent stressful life events: Their long term effects. Eur Child Adolesc Psychiatry 1993;2:1-9.

27. Kadzin AE. Conduct disorder in childhood and adolescence. California: Sage, 1987.

28. Kirikadis SP. Perceived parental care and supervision: Relations with cognitive representations of future offending in a sample of young offenders. Int J Offender Ther Comp Criminol 2006;50: 187-203.

29. Smolak L, Levine MP. Separation-individuation difficulties and the distinction between bulimia nervosa and anorexia nervosa in college women. Int J Eat Disord 1993; 14:33-41.

30. Horesh N, Apter A, Lepkifker E, Ratzoni G. Life events and severe anorexia nervosa in adolescence. Acta Psychiatr Scand 1995;91: 5-9.

31. Rastam M, Gillberg C. The family background in anorexia nervosa: A population based study. J Am Acad Child Adolesc Psychiatry 1991;30:283-289.

Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Antonio Félix Raya et al.

Family variables related to behavioral problems in childhood Antonio Félix Raya, PhD, María José Pino, PhD, and Javier Herruzo, PhD Department of Psychology, University of Cordoba, Spain

ABSTRACT The aim of this study is to ascertain whether there are any differences in the parenting practices received by two groups of children who obtain low-risk and high-risk scores, respectively, in relation to conduct problems and determine which parenting variables are linked with the presence or absence of this kind of problematic behavior. We selected a sample of 30 children between 6 and 14 years old with risk scores in behavioral problems according to the Behavior Assessment System for Children (BASC), and another similar group with low scores in this variable. After applying the Parent-Child Relationship Inventory (PCRI) to both parents, we carried out a binomial logistic regression analysis which resulted in a prediction model for the 80% of the sample, composed of the Parenting variables: communication and role orientation from the mothers, and parental support, autonomy and limit setting (the most significant factor) from the fathers.

Finally, the utility of results to raise intervention strategies within the family is discussed.

Introduction In the DSM-IV-TR, the category of Attention Deficit Hyperactivity Disorders and Disruptive Behavior makes the most direct reference to disruptive behavior, involving the diagnosis of Conduct Disorder, characterized by a variety of persistent antisocial behaviors including acts of aggression, destruction of property, deceitfulness, theft and violation of rules (1). These anti-social behavioral patterns provoke a significant deterioration in everyday functioning at home and school (2). Another useful defi-

nition is offered by Benjumea and Mojarro (3), referring to persistently inappropriate patterns of behavior for the child’s age, characterized by the violation of others’ rights and the transgression of social norms of coexistence.

These patterns of behavior usually include aggression and other behavioral problems such as dishonesty, theft, skipping school, lying, running away from home, drinking alcohol or taking drugs (4).

Conduct Disorder is more frequently diagnosed among boys, with a prevalence ranging from 6% to 16%, whereas in girls prevalence varies between 2% and 9% (1), and several studies have reported that externalizing behavior diminishes during childhood and increases during adolescence (5). For specific behavioral problems relating to tantrums, disobedience, demands and complaints, which generate a high number of problems affecting coexistence both at school and at home, estimated prevalence is much higher, around 60%, although this does not entail a diagnosis of Conduct Disorder (6).

Behavioral problems usually deteriorate as children get older, exacerbated by factors such as academic failure, peer rejection or ineffective parental style as parents lack the skills to run a family effectively, establishing coercive interactions with their children, who end up incorporating this model into their own repertoire and applying it within the family context as well as other settings with children and adults (7-10). Recent studies have referred to this parenting model as negative or dysfunctional discipline, which acts as a mediator between the personality of parents and children and behavioral problems (11, 12).

As regards the influence of parental styles on behavioral problems, undoubtedly the best-known model was put forward by Baumrind (13-15), and redrafted

by Maccoby and Martin (16). This model points to the existence of four parental styles – authoritative, authoritarian, negligent and indulgent – which foster to a greater or lesser extent the appearance of behav-

Address for Correspondence: Antonio Felix Raya, PhD, Facultad de Ciencias de la Educación. C/San Alberto Magno s/n 14071, Cordoba, Spain m02ratra@uco.es, jherruzo@uco.es, mjpino@uco.es

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ioral problems in children. Based on this model, recent studies, for example by Steinberg, Blatt-Eisengart and Cauffman (17) or Villar, Luengo, Gómez and Romero (18), have drawn the conclusion that the authoritative style offers the best prevention of behavioral problems in children, whereas negligent and indulgent styles present the most direct links with these problems. Although parental styles have proved to be extremely important in the explanation of behavioral problems in children, the distinction drawn by Darling and Steinberg (19) between parental styles and parenting practices has influenced the study of family dynamics in recent years.

These authors suggest that parental style is a constellation of attitudes that lead to a series of parenting practices and socialization goals, which have a more direct influence on the problematic behavior of children.

Based on the study of parenting practices and attitudes, in recent years a wide variety of variables have been examined, referring to a series of parental behaviors in their everyday interaction with their children. Some of the most widely studied aspects are discipline, consistency or behavioral control. Most recent studies concur that reasoned and consistent disciplinary guidelines are related with a lower instance of problematic behavior in children (20-25). One of the main requirements to establish consistent and reasoned disciplinary guidelines is the existence of adequate communication between parents and children. Along these lines, numerous data offered by different researchers have linked a lack of communication with behavioral problems (18, 26-28). Other studies associate aspects inherent in communication such as mutual respect or honesty with behavioral problems (29).

Another frequently studied aspect, owing to its relationship with behavioral problems, is what most authors refer to as autonomy. although numerous authors indicate that a certain degree of autonomy in decisionmaking fosters responsibility and is linked with a lower instance of problematic behavior in children and teenagers (25, 30, 31), a high degree of autonomy could be identified with a negligent attitude on the part of the parents, which could give rise to a situation of risk as regards the possible appearance of behavioral problems in children (32-34).

Finally, other types of variables inherent in parenting which bear a close relationship with behavioral problems in children refer to the level of social support perceived by parents and the collaboration of both parents in parenting tasks. As regards perceived support, some studies have linked behavioral problems in chil118

dren with different factors such as chronic poverty (35), ethnic background (23, 35), unemployment (22) and the quality of social networks (36). As for the second of these variables, Webster-Stratton and Hammond (37) highlighted various aspects such as negative communication and affection within the couple and a lack of collaboration in parenting as aspects that are strongly linked with behavioral problems in children.

Previous studies carried out on Spanish sample populations have shown that variables such as autonomy and discipline (limit setting), pertaining to the parenting practices of mothers and fathers, bear a close relationship with certain behavioral problems in their children, such as hyperactivity and impulsiveness (38) or aggressive behavior (39-41). Furthermore, the equal distribution of household chores towards which we are heading confers a new status on the parenting practices of fathers, which until now has been studied to a much lesser degree than that of mothers (42). Until now, little has been known about the way in which the interaction between the parenting practices of the father and mother affect the functioning of the family. However, as Lindsey and Mize (43) affirm, based on a systemic perspective of the family, the relationship between the parenting practices of the father and mother could be expected to make a more significant contribution to the development of the child than the effect of the mother’s or the father’s practices individually.

Ultimately, this study aims to determine the relationship between the different factors that comprise the parenting practices and attitudes of mothers and fathers according to the Parent Child Relationship Inventory (PCRI; 44) and the behavioral problems of their children as reported by parents using the Behavior Assessment System for Children (BASC; 4). In other words, the intention is to ascertain whether there are differences in the parenting practices and attitudes received by two groups of children who obtain low-risk and high-risk scores respectively on the instrument used to measure the variable conduct problems and determine which parenting variables are linked with the presence or absence of this kind of problematic behavior.

Method Participants

To select a broad sample of participants from an average socioeconomic background, pupils from three Nursery, Primary and Secondary Schools were analyzed, located in the provinces of Cordoba and Jaen in Spain. Having

Antonio Félix Raya et al.

administered a total of 500 questionnaires, information was obtained from 432 participants, from which 60 subjects were selected and divided into two groups of 30: the first group encompassed all participants situated in the high-risk group in terms of the variable conduct problems as reported by their parents (risk group), having obtained a T score over 60, as discussed in greater detail in the description of the instrument provided below. In the second group, with a low score in conduct problems, all participants registered a T score for this variable below the normative mean indicated by the instrument (T<50).

Both groups were made up of 21 boys and 9 girls aged from 6 to 14 years old, with an average age of 9.37 (SD= 2.189) in the high-risk group and 9.37 (SD=2.327) in the low-scoring group for conduct problems. Breaking the sample down by school year, both groups comprised 15 children enrolled in grades 1 to 4 in Primary Education, and another 15 children between grade 5 of Primary Education and grade 2 of Compulsory Secondary Education.

Instruments

In order to compile information, the following instruments were used: An adaptation into Spanish of the BASC (4).

The purpose of this system is to evaluate a wide range of pathological and adaptive dimensions using different sources of information (parents, teachers and children) and different methods (questionnaires, developmental history and observation). In this case, the questionnaire for parents was used.

The questionnaires used in this study, which are divided into two levels according to age (6/12, 12/18), present an internal consistency index of .70 for parents. Test-retest correlation (three months interval) was .88 and .70 for the two levels of questionnaire completed by parents.

Of all the different scales included in this instrument, the conduct problems scale was used for this study, defined by the instrument as “a tendency to show antisocial behavior, which breaks the rules, including destruction of property.” This scale presents internal consistency indexes between .68 and .75, depending on the age of the subjects.

The scores obtained for any of the scales are transformed into T scores, which indicate the distance of a particular score in relation to the control group mean, thereby enabling comparisons to be made between subjects of different ages. These T scores can vary between 0 and 100 and present a mean of 50 and SD of 10. On the basis of these T scores, different levels are estab-

lished: scores below 30 are considered very low, under 40 low, between 40 and 60 intermediate, over 60 at risk, and over 70 clinically significant.

The other instrument utilized was a Spanish version of the PCRI (45), which measures paternal and maternal practices and attitudes towards parenting using a direct score. It comprises 78 items with four response options (totally disagree, disagree, agree and strongly agree), which are grouped into seven scales. High scores on the different scales indicate greater agreement with the situation defined in each scale. The seven scales are: • Support, social and emotional, received by a mother or father.

• Satisfaction with parenting: satisfaction obtained by a parent through parenthood.

• Involvement: level of interaction and parental knowledge about their child.

• Communication: perception regarding the effectiveness of communication with their child.

• Limit setting: level of exigency in obedience of rules.

• Autonomy: ability to give the child independence.

• Role orientation: attitudes about the role played by each gender in parenting.

A small social desirability scale is also included.

The internal consistency of the instrument for this sample, obtained using Cronbach’s alpha coefficient, is .87. For each scale, this coefficient ranges from .68 for the Support scale to .78 for the Satisfaction scale.

Furthermore, in the case of this sample, the questionnaire presents good construct validity, given the correlations between the different scales on the questionnaire, especially in the most important parenting scales such as Involvement-Satisfaction with parenting (.51), Involvement-Communication (.64), Limit setting-Support (.42), Limit setting-Autonomy (.44) and Satisfaction with parenting-Limit setting (.37).

Procedure

Once the schools were selected, as indicated in the Participants section, contact was made with the head teachers of the schools once their school board had provided their consent to participate in the study. To inform the families in writing of this study and provide them with the instrument, the form teachers collaborated in the distribution and collection of questionnaires. Families that agreed to collaborate voluntarily completed the P format (parents) of the BASC in its different versions depending on the age of the children, and the PCRI, completed by both the father and mother.

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Table 1. Variables included in the model 95% C.I. Exp (B) VARIABLES

B

S.E.

Wald

d.f.

Sig.

Exp (B)

Lower

Higher

Father’s support

-.159

.132

1.455

1

.228

.853

.659

1.104

Father’s limit setting

-.322

.117

7.557

1

.006

.724

.576

.912

Father’s autonomy

.267

.139

3.720

1

.054

1.307

.996

1.715

Mother’s communication

-.174

.094

3.406

1

.065

.840

.698

1.011

Mother’s role orientation

.162

.083

3.802

1

.051

1.176

.999

1.383

Constant

8.008

3.869

4.285

1

.038

3006.017

Data analysis

To evaluate the possible effect of parenting variables on conduct problems, an ex-post-facto design was applied with a quasi-control group. Hence, a dichotomic variable was used as the dependent variable, derived from the T score obtained in conduct problems. The two options for this variable were 0 for subjects with a low conduct problems score, and 1 for subjects in the risk area. For this purpose, subjects were selected if their T score in conduct problems, as reported by their parents, situated them above the level of risk, and another group was chosen with low conduct problems scores, equivalent to the first group in terms of gender and school level.

Subsequently, binary logistic regression analysis was performed. Based on the coefficients estimated by logistic regression for each of the variables, in accordance with its probability of belonging to either level of the dependent variable, this process classed each subject into one of the two categories proposed.

Logistical regression enabled various models to be established, the most efficient one being the model that predicts the highest percentage of correctly classified subjects with the lowest number of possible variables, since the main purpose of this analysis is to establish a model that predicts the dependent variable using the independent variables. The model comprises an equation made up of estimated coefficients and the scores of the different variables, giving a resulting score between 0 and 1, with a cut-off point of .5: scores between .5 and 1 indicate the probability of obtaining a high score in conduct problems; scores between 0 and .5 indicate the contrary.

To perform these analyses, the following predictive variables were taken into account, from the perspective of both the father and the mother: Support, Satisfaction with parenting, Involvement, Communication, Limit setting, Autonomy and Role Orientation.

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Results On the conduct problems scale, for possible T scores between 0 and 100, the risk group obtained a mean T score of 66.10 (SD= 8.023), ranging from 60 to 87, whereas the low conduct problems group obtained a mean score of 39.93 (SD= 3.269), with a minimum of 37 and a maximum of 45.

By applying binary logistical regression analysis to these two groups, between the different possible models, a prediction model was established comprising five factors described in Table 1. This five-factor model was selected since it predicts whether a subject will belong to one or the other group for a large percentage of the sample with a fairly small number of variables. The goodness-of-fit for the model was good, with a Chi-Square of 25.744 and five degrees of freedom, statistically different from zero. Furthermore, the Cox & Snell R-square and the Nagelkerke R-square presented acceptable values: .349 and .465, respectively. The Hosmer-Lemeshow test to evaluate correspondence between real and predicted values of the dependent variable did not provide significant results, since X2= 11.446 (p=.178).

As for the classification of subjects, a mean percentage of 80% was obtained for correctly classified subjects, obtaining small differences between both groups: 83.3% for the risk group and 76.7% for the low score group.

One of the main applications of logistical regression analysis is the possibility of creating an equation that can be used to classify a subject in one of the conditions of the dependent variable and knowing the probability of manifesting a high level of conduct problems depending on the score obtained for one or more of the independent variables.

The equation is: b1= 1/1+e-z where: Z= B0 + B1(X1) + B2(X2) + B3(X3) + Bn(Xn)

Antonio Félix Raya et al.

and: Z= linear combination of variables.

B0= estimated coefficient of the constant regression.

B1= estimated coefficient for variable 1.

X1= subject’s score for variable 1. b1= probability of belonging to the risk group. e= base of natural logarithms (2.718).

By transferring the data from the study to the equation described above, we get: Z= 8.008 + (-.159)(X1) + (-.322)(X2) + (.267)(X3) + (-.174)(X4) + (.162)(X5) where: X1= father’s score for support.

X2= father’s score for limit setting.

X3= father’s score for autonomy.

X4= mother’s score for communication.

X5= mother’s score for role orientation.

Finally, the result obtained for Z is transferred to the first equation to obtain the probability of b1 or probability of obtaining a risk score in conduct problems.

When two subjects were chosen at random, one from the low score group (subject number 22) and another from the risk group (subject number 51), the probability of b1 obtained for the first was .039 < 0.5, hence this subject was correctly classified by the model in the low score group; and the score obtained by the second was .975 > 0.5, and therefore this subject was also correctly classified by the model in the risk group.

Furthermore, of particular note was the strong joint influence of the variables “father’s discipline” and “father’s autonomy” on the possibility of belonging to the risk or low-score group, since when logistical regression analysis was applied, only inserting this factors as the independent variables, 76.7% of subjects were correctly classified, although the father’s autonomy was not significant.

Discussion and conclusions The purpose of this study was to analyze which factors in the parenting practices and attitudes of fathers and mothers were linked with a higher or lower probability of obtaining a score in the risk area of the BASC in relation to conduct problems.

Based on the model of parenting practices suggested

by Darling and Steinberg (19), certain family models or general patterns of parental behavior could be established that would be directly related with behavioral problems in their children. Accepting some methodological limitations like small group size, a wide age range, cross-sectional, or

using questionnaires and behavior reports taken from a single source of information, the results obtained reflect major differences between the two groups; for four out of every five subjects included in the sample, a combination of high scores in autonomy granted by the father and role orientation on the part of the mother together with low scores in perceived support and limit setting for the father and communication for the mother have a significant influence on the increased probability of scoring in the high-risk area of the BASC for conduct problems.

The model created is made up of variables that, although not significant in some cases, make an important contribution to the model’s predictive ability, increasing the number of correctly classified subjects. In this respect, discipline (limit setting), understood as the establishment of clear limits, acts as an excellent predictor of higher levels of adaptation in children, coinciding with the affirmations made by Aunola and Nurmi (20), Elgar et al. (21), Knutson et al. (22), McCoy et al. (23), Pfiffner et al. (24), and Tur et al. (25). Autonomy or the level of Independence granted to the child has revealed in this case its most negative side, since the data found in this study concur with statements made by Adalbjarnardotir and Hafsteinsson (32), Beyers et al. (33), and Vazsonyi (34), who suggest that excessive autonomy is a kind of negligence, a predictor of high scores in behavioral problems.

We cannot ignore that these kinds of problems must be analyzed in terms of interaction, since although the family situation described might be a precursor to conduct problems, these problems in children can also destabilize the family dynamic, generating inappropriate patterns of interaction with the parents. However, although the method used doesn’t allow us to establish causal relationships, the information obtained has broad applications for interventions with families with problematic children, since the parents’ responses to the instruments utilized reveal patterns of behavior that can be modified in both parents and children. In this respect, clear rules could be established, ensuring they are enforced, coming up with daily monitoring strategies in different tasks, being communicative with their children and involving all members of the family unit in the different parenting tasks to favor the work/life balance for both parents.

Finally, in terms of the future, further research could be conducted to provide information about certain aspects yet to be clarified such as possible differences between the most important variables in the prediction of conduct problems in young children and adolescents.

Moreover, this study opens up a broad new avenue of 121

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research, through which other problems – both externalizing and internalizing in nature – could be tackled.

References 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000.

2. Kazdin AE. Child, parent, and family dysfunction as predictors of outcome in cognitive-behavioral treatment of antisocial children. Behav Res Ther 1995;33:271-281.

3. Benjumea P, Mojarro MD. Trastornos de conducta. Los comportamientos disociales. Clínica. Diagnóstico. Tratamiento. In: Rodríguez-Sacristán J, director. Psicopatología Infantil Básica. Madrid: Pirámide, 2002: pp.

253-267.

4. Reynolds, CR, Kamphaus, RW. Behavior Assessment System for Children (BASC). Circle Pines, Minnesota (USA): American Guidance Service, Inc., 1992.

5. Bongers IL, Koot HM, Van der Ende J, Verhulst FC. Developmental trajectories of externalizing behaviors in childhood and adolescence.

Child Dev 2004;75:1523-1537.

6. Schroeder CS, Gordon BN. Assessment and treatment of childhood problems: A clinician’s guide. New York: Guilford, 1991.

7. Patterson GR. Coercive family process. Eugene, Oregon: Castalia, 1982.

8. Patterson GR. The early developmental of coercive family process. In: Reid JB, Patterson GR, Snyder J, editors. Antisocial behavior in children and adolescents: Developmental theories and models for intervention.

Washington, DC: American Psychological Association, 2002: pp. 25-44.

9. Patterson GR, Debaryshe BD, Ramsey E. A Developmental perspective on antisocial behavior. Am Psychol 1989;44:329-335.

10. Patterson GR, Reid JB, Dishion TJ. Antisocial boys. Eugene, Oregon: Castalia, 1992.

11. Prinzie P, Onghena P, Hellinckx W. A cohort-sequential multivariate latent growth curve analysis of normative CBCL aggressive and delinquent problem behavior: Associations with harsh discipline and gender. Int J Behav Dev 2006;30:444-459.

12. Prinzie P, Onghena P, Hellinckx W, Grietens H, Ghesquière P, Colpin H. Parents and child personality characteristics as predictors of negative discipline and externalizing problem behavior in children. Eur J Pers 2004;18:73-102.

13. Baumrind D. Child care practices anteceding three patterns of preschool behaviour. Genet Psychol Monogr 1967;75:43-88.

14. Baumrind D. Current patterns of parental authority. Developmental Psychology Monograph 1971;4 (1, Pt.2).

15. Baumrind D. Parenting styles and adolescent development. In: Lerner RM, Petersen AC, Brooks-Gunn J, editors. Encyclopedia of adolescence (Vol. 2). New York: Garland, 1991: pp. 746-758 16. Maccoby EE, Martin JA. Socialization in the context of the family: Parent-child interaction. In: Mussen PH, editor. Handbook of child psychology (Vol. 4). New York: John Wiley & Sons, 1983: pp. 1-101.

17. Steinberg L, Blatt-Eisengart I, Cauffman E. Patterns of competence and adjustment among adolescents from authoritative, authoritarian, indulgent and neglectful homes: A replication in a sample of serious juvenile offenders. J Res Adolesc 2006;16:47-58.

18. Vilar P, Luengo MA, Gomez JA, Romero. An assessment proposal of family variables for prevention of problem behavior in adolescence.

Psicothema 2003;15:581-588 (in Spanish).

19. Darling N, Steinberg L. Parenting style as context: An integrative model.

Psychol Bull 1993;113:487-496.

20. Aunola K, Nurmi JE. The role of parenting styles in children’s problem behavior. Child Dev 2005;76:1144-1159.

21. Elgar FJ, Waschbusch DA, Dadds MR, Sigvaldasson N. Development and validation of a short form of the Alabama parenting questionnaire.

J Child Fam Stud 2007;16:243-259.

22. Knutson JF, DeGarmo DS, Reid JB. Social disadvantage and neglectful parenting as precursors to the development of antisocial and aggressive child

122

behavior: Testing a theoretical model. Aggress Behav 2004;30:187-205.

23. McCoy MG, Frick PJ, Loney BR, Ellis ML. The potential mediating role of parenting practices in the development of conduct problems in a clinic-referred sample. J Child Fam Stud 1999;8:477-494.

24. Pfiffner LJ, McBurnett K, Rathouz PJ, Judice S. Family correlates of oppositional and conduct disorders in children with attention deficit/ hyperactivity disorder. J Abnorm Child Psychol 2005;33:551-563.

25. Tur A, Mestre V, Del Barrio MV. Los problemas de conducta exteriorizados e interiorizados en la adolescencia: relaciones con los hábitos de crianza y con el temperamento. Acción Psicol 2004;36:207-221.

26. Denton RE, Kampfe CM. The relationship between family variables and adolescent substance abuse: A literature review. Adolescence 1994;29:475-495.

27. Krinsley KE, Bry BH. Sequential analyses of adolescent, mother and father behaviors in distressed and non distressed families. Child Fam Behav Ther 1992;13:45-62.

28. Pons J, Berjano E. Analysis of socialization parenting styles related to adolescent alcohol abuse. Psicothema 1997;9:609-617 (in Spanish).

29. Tasić D, Budjanovac A, Nejovšek M. Parent-child communication in behaviourally disordered and “normal” adolescents. Psicothema 1997;9:547-554.

30. Bynum MS, Kotchick BA. Mother-adolescent relationship quality and autonomy as predictors of psychosocial adjustment among African American adolescents. J Child Fam Stud 2006;15:529-542.

31. Reitz E, Dekovic M, Meijer AM. Relations between parenting and externalizing and internalizing problem behaviour in early adolescence: Child behaviour as moderator and predictor. J Adolesc 2006;29:419-436.

32. Adalbjarnardottir S, Hafsteinsson LG. Adolescent’s perceived parenting styles and their substance use: Current and longitudinal analyses. J Res Adolesc 2001;11:401-423.

33. Beyers JM, Bates JE, Pettit GS, Dodge KA. Neighbourhood structure, parenting processes, and the development of youths’ externalizing behaviors: A multilevel analysis. Am J Community Psychol 2003;31:35-53.

34. Vazsonyi AT. Parent-adolescent relations and problem behaviors: Hungary, the Netherlands, Switzerland, and the United States. Marriage Fam Rev 2004;35:161-187.

35. Pachter LM, Auinger P, Palmer R, Weitzman M. Do parenting and the home environment, maternal depression, neighbourhood, and chronic poverty affect child behavioral problems differently in different racialethnic groups? Pediatrics 2006;117:1329-1338.

36. Vandewater EA, Lansford JE. A family process model of problem behaviors in adolescents. J Marriage Fam 2005;67:100-109.

37. Webster-Stratton C, Hammond M. Marital conflict management skills, parenting styles, and early-onset conduct problems: Processes and pathways. J Child Psychol Psychiatry 1999;40:917-927.

38. Raya AF, Herruzo J, Pino MJ. Parenting styles and their relationship with hyperactivity. Psicothema 2008;20:691-696 (in Spanish).

39. Mestre V, Samper P, Nácher MJ, Cortés M, Tur A. Estilos de crianza y agresividad en la infancia. Paper presented at the II Congreso HispanoPortugués de Psicología. Lisbon, Portugal, 2004.

40. Samper P, Aparici G, Mestre V. La agresividad auto y heteroevaluada: Variables implicadas. Acción Psicol 2006;2:155-168.

41. Raya AF, Pino MJ, Herruzo J. Aggression in childhood: Parenting style as related factor. Eur J Educ Psychol 2009;2:211-222 (in Spanish).

42. Winsler A, Madigan AL, Aquilino SA. Correspondence between maternal and paternal parenting styles in early childhood. Early Child Res Q 2005;20:1-12.

43. Lindsey EW, Mize J. Interparental agreement, parent-child responsiveness, and children’s peer competence. Family Relations: J Appl Fam Child Stud 2001;50:348-354.

44. Gerard A. Parent-child relationship inventory: Manual. Los Angeles: Western Psychological Services, 1994.

45. Roa L, Del Barrio V. Adaptación del cuestionario de crianza parental (PCRI-M) a población española. Rev Latinoam Psicol 2001;33:329-341.

Medine Yazıcı GÜLEÇ and Çiçek HOCAOĞLU Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Relationship between Personality and Disability in Patients with Major Depressive Disorder Medine Yazıcı GÜleÇ, MD,1 and Çiçek Hocaoğlu, MD2 1

Erenköy Mental Research and Training Hospital, Istanbul, Turkey Department of Psychiatry, School of Medicine, Karadeniz Technical University, Trabzon, Turkey

2

ABSTRACT Objective: The co-morbidity of major depressive disorder (MDD) with personality disorders (PDs) in patients with long-standing work disability at a psychiatry clinic was investigated. The purpose of our study was to evaluate personality for contributing to disability in patients with MDD and to investigate the relationship with these two psychometric characters in patients with MDD. Method: Seventy-two patients with a MDD and 72 healthy controls were assessed by means of both clinician and self-rating scales for depression, anxiety, disability, and the SCID-II personality inventory.

Results: There was no difference between the personality parameters of the groups regarding schizotypal and antisocial PDs. Avoidant personality was found to be less common in the patient group (p=0.030). Dependent (p<0.001), obsessive (p=0.003), passive-aggressive (p=0.025), self-defeating (p<0.001), paranoid (p<0.001), schizoid (p=0.012), histrionic (p=0.001), narcissistic (p<0.001), and borderline (p<0.001) PDs in patients were more common than in controls. On the disability sub-scales, physical role limitation, vitality, social functioning, emotional role limitation, and mental health were significantly lower in patient group than normal control group. While Cluster A was not related to any disability subscale, Cluster B had a positive correlation with vitality and mental health, whereas Cluster C and Cluster NOS had a negative correlation with emotional role limitation.

Only the emotional role limitation predicts the presence of depression, whereas only self-defeating, obsessive,

paranoid, and passive aggressive personality predict the emotional role limitation.

Conclusion: Patients with MDD have personality and disability problems. PDs in depression contribute to disability. Our results demonstrated that the emotional role limitation is the unique sub-scale that predicts the MDD group.

Introduction Major depressive disorder (MDD) is the fourth leading disease causing functional impairment, disability, and workforce loss worldwide (1). Considering that the life-long prevalence of depression is between 16% and 20% (2), MDD is expected to be the most frequent cause of work absenteeism (3) among psychiatric diseases. Moreover, predicting the further increase in this ratio, the World Health Organization has reported that in 2020 MDD will be the second after ischemic heart diseases among diseases that lead to disability (4).

Several cross-sectional studies have reported that MDD with co-morbid mental disorders is mainly associated with impairment rather than pure MDD (5, 6).

Rytsala et al. (7) found that not only current severity and recurrence of depression, but also older age, comorbid anxiety, and personality or substance use disorders are associated with the patient’s current level of functioning. Furthermore, in another study of Rytsala et al. (8), it was also indicated that the presence of co-morbid psychiatric disorders, personality trait neuroticism,

Address for Correspondence: Medine Yazıcı Güleç, MD, Erenköy Training and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, 34736 Turkey yazicimedine@yahoo.com

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Personality and Disability in depression

and perceived social support significantly influenced the level of functioning and social adjustment.

Although the overall impact of personality pathology is less well-characterized, it is also common in populations with a prevalence of approximately 13.4% (9), increasing to almost one-half of the patients in secondary care (10). Therefore, it is not surprising to find that co-morbidity of two disorders is common. Individuals with MDD are characterized by higher rates of personality disorders (PDs), as compared with non-depressed samples. Methodologic differences between studies, however, including method of assessment and sample characteristics, have resulted in widely varying estimates of this co-morbidity, ranging from 15% to 95% (11).

Clearly, the interrelation of the personality and disability is both common and important to clinical care.

Personality pathology can also influence the severity and course of depression and vice versa. Thus, experiencing a MDD leads to a change in personality traits.

This phenomenon has two hypotheses. The scar hypothesis states that following a MDD, measurements of personality traits do not return to their premorbid level and alterations in personality traits will persist (12, 13).

This has also been called a trait effect. The complication hypothesis suggests that measurements of personality traits deteriorate during a MDD, and after remission, return to their baseline level. This is also called the state effect of depression (14).

The relationship between personality and disability is important; however, its nature is still unknown.

Personality may be a factor of illness, disability, or may modify the natural progress of illness and response to treatment. On the other hand, it may be a subclinical expression of the underlying vulnerability.

The importance of the disability in depression, and due to the high prevalence of co-morbidity of depression and personality pathologies, the association between personality traits and disability is still an important research issue. In order to discuss the findings more easily, it was planned that MDD patients who had had their first episode would be involved in the present study, considering the contribution of personality traits to the disease and the contribution of disease to the development of personality traits. The aim of this study was to evaluate the disability and personality traits in patients with MDD and to determine the relationship between these two psychometric characteristics. Our hypotheses were as follows: the mean of disability scores in patients with MDD would be higher than the normal healthy group, the rate of PDs 124

in patients would be higher than controls, and personality traits would contribute to disability in MDD. Materials and Methods Subjects and Procedure

One hundred and forty-four subjects, of whom 72 were graduate students (38 females and 34 males; mean age, 23.1Âą4.8 years), who attended the Medico-Social Psychiatry Policlinic of Karadeniz Technical University between February 2006 and August 2006 and were diagnosed with MDD for the first time according to DSM-IV criteria, and 72 healthy subjects (38 females and 34 males; mean age, 22.5Âą3.3 years) comprised of volunteer university students as a control group with similar age and education status were included in the present study. During the first examination a total of 86 patients with MDD, who were consecutively admitted to Medico-Social Psychiatry Policlinic, were rated according to the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Sociodemographic Data Collection Form, Short Form-36 (SF-36) and Structured Clinical Interview for DSM-IV (SCID-II) personality inventory was given to the included patients in a suitable room.

During the psychiatric examinations, in order to make a diagnosis for PD, SCID-I and SCID-II were applied to the patients and controls. Patients with a chronic medical condition or a history of psychiatric disorder or who use psychotropic drugs were excluded. Of the 86 patients with MDD, 79 were diagnosed as first episode of MDD and of the remaining seven patients, six were diagnosed as recurrent depressive disorder and one was diagnosed as bipolar disorder due to having one hypomanic episode. Of the 79 patients, three patients were excluded due to their refusal to participate in the study and four patients were excluded due to having comorbid psychiatric disease (three had anxiety disorders and one had a dissociative disorder). No other exclusion criterion was encountered among patients. Interestingly, a low level of co-morbid anxiety disorder was observed in the MDD group. This might be depending on cultural structure, characteristic of students or phase of disorder. This study was approved by the Institutional Review Board and under the principles of the Helsinki Declaration. All subjects were informed in detail by one of the researchers before the study and gave their informed consents. Subjects were free to withdraw from the study at any time for any reason.

Medine Yazıcı GÜLEÇ and Çiçek HOCAOĞLU

Materials

Sociodemographic Data Collection Form: Patients are asked to fill out a form, including questions on their age, gender, education status, marital status, history of psychiatric disorders, and presence of other medical disorders.

Hamilton Depression Rating Scale (HDRS): The scale, developed by Hamilton (15), measures the level of depression in patients. It consists of 17 questions. The maximum score that can be obtained is 53. Scores ≥ 14 indicate depression. The validation and reliability of the Turkish form has been conducted by Akdemir et al. (16).

Hamilton Anxiety Rating Scale (HARS): The scale, developed by Hamilton (17), measures the level of anxiety, the distribution of symptoms in the subjects and the alteration in the level of severity. It consists of 14 items questioning both emotional and physical symptoms.

In this scale, the presence of items and their severity is evaluated by the interviewer. The Turkish validation and reliability has been conducted by Yazici et al. (18).

Short Form-36 (SF-36): SF-36 is a scale used to measure the quality of life. It assesses eight dimensions of health-related quality of life, such as physical functioning, physical roles limitations, emotional roles limitations, social functioning, mental health, vitality, bodily pain, and general health perception via 36 items.

Patients are asked to mark the item that represents their status best. The scale was developed by Ware and Sherbourne (19), and the Turkish validation and reliability has been conducted by Kocyigit et al. (20).

Structured Clinical Interview for DSM-III-R (SCID) Axis I and Axis II Disorders: SCID-I is a semi-structured clinical interview developed for the major diagnosis of DSM-IV Axis I disorders (21). Structured interviews have been developed to enhance the reliability of the diagnosis by the standardization of the evaluation process, to enhance the validity of the diagnosis by facilitating the application of diagnostic criteria of DSM-IV, and to systematically investigate certain symptoms which may not be noticed. One of the purposes for developing the SCID is to create an effective and easily applicable scale. Thus, the advantages of structured interviews can be applied to a clinical evaluation. SCID-II is a form consisting of 120 questions, prepared according to the diagnostic criteria of personality disorder in the DSMIII-R classification system. The answers to the questions are in a “yes” or “no” format. The answer “yes” is important regarding personality disorders. The definite diagnosis is not made according to responses to the questions, rather it is made by the evaluation of the cli-

nician after the interview. The validation and reliability of the Turkish version of SCID has been conducted by Sorias et al. (22).

Statistical analysis

SPSS for Windows 9.0 was used for the evaluation of the data obtained in this study. The Kolmogorov–Smirnov test was used to test the normal distribution of the data. As data were normally distributed, the differences in the age, education status, HDRS, HARS, and SF-36 scores between the MDD patients and the control (healthy normal) group were compared using Student’s t-test. A chi-square test was used to compare gender, marital status, and SCID-II scores. Pearson’s analysis was used for the correlation between disability and SCID-II, and specific personality dimensions; 0.30 is assumed as the significance level for correlation (r). A stepwise linear regression model was developed in which the entire sample was accepted as the dependent variable and after the process of stepwise selection method all SF-36 subscales scores were involved into the equation. Quantitative data are represented as the mean±standard deviation, and the level of significance was accepted as p<0.01 to avoid the Type II error.

Results The sociodemographic characteristics of both the depression and control groups are represented in Table 1. No significant difference was found between the groups in terms of mean age, education duration (years), gender, and marital status.

The mean HDRS and HARS scores of the patient group were 25.82±4.06 and 25.24±7.73 (high scores indicate worse), respectively, and each of these variables were statistically higher than the mean scores of the control group (p<0.001; Table 2).

When the sub-scales of SF-36 (oppositely low scores indicate worse) were evaluated in the patient group, the Table 1. Sociodemographic variables of major depressive disorder (MDD) and normal healthy control (NHC) group MDD (mean±S.D.)

NHC (mean±S.D.)

Age

23.06±4.78

22.49±3.25

Gender F/M (F%)

38/34 52.8%

38/34 52.8%

Education duration (years)

13.53±2.81

13.19±1.90

Marital status S/Ma (S%)

63/9 87.5%

63/9 87.5%

S.D.: Standard Deviation, F: Female, M: Male, S: Single, Ma: Married

125

Personality and Disability in depression

Table 2. Comparison of clinical parameters between major depressive disorder (MDD) and normal healthy control (NHC) group MDD

NHC

Hamilton Depression Rating Scale

(mean±S.D.)

(mean±S.D.)

t

p

25.82±4.06

6.82±3.71

-29.289

<0.001

Hamilton Anxiety Rating Scale

25.24±7.73

6.94±3.96

-17.859

<0.001

SF-36 subscales 77.99±12.52

MDD

NHC

p

Avoidant

16/56 22.2%

28/44 38.9%

0.030

Dependent

26/46 36.1%

5/67 6.9%

<0.001

Obsessive

33/39 45.8%

16/56 22.2%

0.003

Passive-aggressive

33/39 45.8%

20/52 27.8%

0.025

Self-defeating

35/37 48.6%

7/65 9.7%

<0.001

Paranoid

47/25 65.3%

14/58 19.4%

<0.001

Schizotypal

7/65 9.7%

4/68 5.6%

N.S.

Schizoid

6/66 8.3%

0/72 0%

0.012

Histrionic

54/18 75%

35/37 48.6%

0.001

Narcissistic

33/39 45.8%

9/63 12.5%

<0.001

78.06±18.15

Physical role limitations

36.11±33.27

Bodily pain

54.10±19.36

60.68±10.34

2.545

0.012

General health perception

49.64±23.36

55.03±13.70

1.688

N.S.

Vitality

28.69±17.01

60.56±12.15

12.932

<0.001

Borderline

52/20 72.2%

8/64 11.1%

<0.001

Antisocial

12/60 16.7%

14/58 19.4%

N.S.

6.891

N.S.

Present/absent (Present%)

Physical functioning

77.43±38.49

-0.027

Table 3. Comparison of personality parameters between major depressive disorder (MDD) and normal healthy control (NHC) group*

<0.001

Social functioning 36.18±22.80

88.37±12.82

16.929

<0.001

Emotional role limitations

4.58±13.91

94.42±20.97

30.292

<0.001

* χ² test, N.S.: Non-significant.

Mental health

38.06±14.80

65.44±11.71

12.314

<0.001

were negatively correlated with emotional role limitation (r=-0.30, p=0.009; r=-0.33, p=0.004, respectively).

As a result of stepwise linear regression analysis, depression was predicted only by emotional role limitation (constant: 0.976, B: -9.66E-03, F: 892.910, df: 1, p: 0.000), whereas emotional role limitation was predicted by self-defeating, obsessive, paranoid, and passive-aggressive personality traits (F: 10.019, df: 4, p: 0.000; Table 5).

t: Student’s t test, S.D.: Standard Deviation, N.S.: Non-significant, SF-36: Short Form-36 item

physical role limitation was 36.11±33.27, bodily pain was 54.10±19.36, vitality was 28.69±17.01, social functioning was 36.18±22.80, emotional role limitation was 4.58±13.91, and mental health was 38.06±14.80 (Table 2).

The ratio of PDs in patients with MDD was 56.9% whereas this ratio was 10.1% in controls. Odds Ratio (OR) corresponded to 5.63. Among personality parameters, there was no difference between the groups with respect to schizotypal and antisocial PDs. Avoidant personality traits was found to be less common in the patient group (p=0.030). Dependent (p<0.001), obsessive (p=0.003), passive-aggressive (p=0.025), self-defeating (p<0.001), paranoid (p<0.001), schizoid (p=0.012), histrionic (p=0.001), narcissistic (p<0.001), and borderline (p<0.001) personality disorders were more common in the patient group (Table 3).

The relationship between disability and personality is represented in Table 4. While in the Cluster A (paranoid, schizoid, and schizotypal) no correlation between the personality traits and any of the disability subscales was observed, Cluster B (antisocial, histrionic, borderline, and narcissistic) had a positive correlation with vitality and mental health (r=-0.43, p<0.001; r=-0.33, p=0.005, respectively). Cluster C (avoidant, dependent, and obsessive) and Cluster NOS (self-defeating and passive-aggressive) 126

Discussion In the present study, carried out with 72 patients with MDD and 72 healthy controls, the effect of personality traits on disability in depression was investigated.

Although there was no difference between the patients and healthy controls with respect to schizotypal and antisocial personality traits, in patients it was found that avoidant personality was less common while other specific sub-personalities were more common compared to controls. In the disability sub-scales, physical role limitation, vitality, social functioning, emotional role limitation, and mental health in patients were lower than controls. While in Cluster A no correlation between the personality traits and any of the disability subscales was observed, Cluster B had a positive correlation with vitality and mental health.

Cluster C and Cluster NOS were negatively correlated with emotional role limitation. The presence of depression was only predicted by emotional role limitation, whereas emotional role limitation was only predicted by self defeating,

Medine Yazıcı GÜLEÇ and Çiçek HOCAOĞLU

Table 4. Relationship with disability and personality in major depressive disorder Cluster A r

Cluster B

p

r

p

Cluster C r

p

Cluster NOS r

p

Physical functioning

0.22

N.S.

0.01

N.S.

0.24

0.041

0.04

N.S.

Physical role limitations

-0.02

N.S.

-0.01

N.S.

-0.21

N.S.

-0.11

N.S.

Bodily pain

0.10

N.S

0.22

N.S.

0.24

0.043

0.10

N.S.

General health perception

0.23

N.S.

-0.25

0.035

0.25

0.032

-0.12

N.S.

Vitality

0.20

N.S.

0.43

<0.001

-0.02

N.S.

-0.22

N.S.

Social functioning

-0.05

N.S.

0.19

N.S.

-0.06

N.S.

-0.16

N.S.

Emotional role limitations

0.02

N.S.

17

N.S.

-0.30

0.009

-0.33

0.004

Mental health

0.08

N.S.

0.33

0.005

-0.08

N.S.

-0.01

N.S.

NOS: Not Otherwise Specified, N.S.: Non-significant

Table 5. Stepwise linear regression of the SCID-II subscales of presence of emotional role limitation in the major depressive disorder subjects Standardized coefficient Model

B

Standard error

(Constant)

12.093

2.779

Selfdefeating

-10.229

2.824

β -0.370

t

p

4.351

0.000

-3.622

0.001

Obsessive

-14.199

3.024

-0.512

-4.696

0.000

Paranoid

12.287

3.177

0.424

3.868

0.000

Passive aggressive

-8.837

2.917

-0.319

-3.030

0.003

obsessive, paranoid, and passive aggressive personality.

In a recent investigation, it has been suggested that while all PDs are elevated among depressed samples, paranoid and obsessive-compulsive PDs have the highest prevalence (23). Corruble et al. (24) reported that antisocial, borderline, histrionic, and schizotypal PDs were particularly common in depressed samples. In contrast, Skodol et al. (25) proposed that the most rigorous studies reported elevated levels of borderline, avoidant, and dependent PDs in depressed individuals. In the present study, when the personality traits were compared in ageand gender-matched groups, avoidant was found to be low while all other PDs, except for schizotypal and antisocial personality, were found to be high. The difference in the findings of the present study might be due to the patient group consisting of young, highly educated university students. The reasons for the lower rate of patients with avoidant PD may be lower rates of treatment needs and fewer attending the policlinic.

In the previous studies, low scores of the SF-36 disability in MDD were also reported (26, 27). In the present study, the scores of all disability subscales, except for physical functioning and general health, were significantly low. There being no difference in physical functioning and general health scores may be related to the low rates of somatization of the group due to their high level of education. The slight elevation in bodily pain scores (chi-square, 2.542; p, 0.012) could support this consideration.

In the present study, when the relationship between present personality traits and present disability level was examined, the specific sub-personalities in Cluster A were not correlated with any of the disability subscales in depression. Considering that the majority of this group suffers from paranoia, it is suggested that the presence of disability in depression and this personality trait do not affect each other.

The specific sub-personalities in Cluster B positively correlated with vitality and mental health. The subjects of this erratic cluster might have created a different profile by using a denial mechanism during their depression.

The result is surprising, so that it should be supported by larger and different groups in further studies.

In specific sub-personalities of Cluster C and Cluster NOS, a negative correlation was demonstrated with emotional role limitation. It was an expected result for group C, which was the anxious group, and could be explained by the functional impairment resulting from anxiety. Since this finding was not observed in Cluster A, Cluster B, or the control group (r=0.02, r=0.17, and r=-0.08, respectively, p>0.05), it was considered not to have originated from MDD. The emotional characteristics of the Cluster NOS personality group may be domi127

Personality and Disability in depression

nantly depressive, as evidenced by the low emotional role limitation ability.

Based on stepwise linear regression analysis, it was determined that only the emotional role limitation predicts the depression, whereas the emotional role limitation is predicted by self-defeating, obsessive, paranoid, and passive-aggressive personality traits.

Our study had some limitations. The cross-sectional design of the study might be inadequate to explain the interaction between the two dimensions. In order to overcome this limitation, prospective cohort studies to explore the changes in psychological factors and personality of the MDD subjects for long intervals are being conducted. The second limitation was involving only students, as the results could not be generalized for all patient groups.

In conclusion, MDD patients have both personality and disability problems. The results of the present study identified the importance of the emotional role limitation, which is one of the disability sub-scales.

The emotional role limitation was significantly different compared to normal controls. The emotional role limitation was correlated particularly with Clusters C and NOS, and was the unique sub-scale that predicted the MDD group. The specific personality traits that predict this variable are self-defeating, obsessive, paranoid, and passive-aggressive personality traits. Further studies are necessary to determine the relationship between the patterns of the personality and disability dimensions along with the longitudinal course of MDD. References 1. Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 17:1436-1442.

2. Rihmer Z, Angst J. Mood disorders: Epidemiology: In mood disorders.

In Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. Sadock BJ, Sadock BA, editors. Pennsylvania: Lipincott Williams and Wilkins, 2005: Eighth edition, pp. 1575-1582.

3. Wells KB, Stewart A, Hays RD, Burnam MA, Rogers W, Daniels M, Berry S, Greenfield S, Ware J. The functioning and well-being of depressed patients. Results from the Medical Outcomes Study. JAMA 1989;18:914-919.

4. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997; 24:1498-1504.

5. Isometsä ET, Katila H, Aro T. Disability pension for major depression in Finland. Am J Psychiatry 2000; 157:1869-1872.

6. McDermut W, Mattia J, Zimmerman M. Comorbidity burden and its impact on psychosocial morbidity in depressed outpatients. J Affect Disord 2001; 65:289-295.

7. Rytsälä HJ, Melartin TK, Leskelä US, Sokero TP, Lestelä-Mielonen PS, Isometsä ET. Functional and work disability in major depressive disorder. J Nerv Ment Dis 2005; 193:189-195.

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8. Rytsälä HJ, Melartin TK, Leskelä US, Lestelä-Mielonen PS, Sokero TP, Isometsä ET. Determinants of functional disability and social adjustment in major depressive disorder: A prospective study. J Nerv Ment Dis 2006; 194:570-576.

9. Torgersen S, Kringlen E, Cramer V. The prevalence of personality disorders in a community sample. Arch Gen Psychiatry 2001; 58:590-596.

10. Keown P, Holloway F, Kuipers E. The prevalence of personality disorders, psychotic disorders and affective disorders amongst the patients seen by a community mental health team in London. Soc Psychiatry Psychiatr Epidemiol 2002; 37:225-229.

11. Bagby RM, Quilty LC, Ryder AC. Personality and depression. Can J Psychiatry 2008; 53:14-25.

12. Cloninger CR, Bayon C, Svrakic DM. Measurement of temperament and character in mood disorders: A model of fundamental states as personality types. J Affect Disord 1998; 51:21-32.

13. Kendler KS, Neale MC, Kessler RC, Heath AC, Eaves LJ. A longitudinal twin study of personality and major depression in women. Arch Gen Psychiatry 1993; 50:853-862.

14. Reich J, Noyes R Jr, Hirschfeld R, Coryell W, O'Gorman T. State and personality in depressed and panic patients. Am J Psychiatry 1987; 144:181-187.

15. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56-62.

16. Akdemir A, Örsel S, Dağ İ, Türkçapar H, İşcan N, Özbay H. Hamilton Depression Rating Scale: Reliability, validity and clinical utility. Psikiyatri Psikoloji Psikofarmakoloji Dergisi 1996;4:251-259 (in Turkish).

17. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32: 50-55.

18. Yazıcı MK, Demir B, Tanrıverdi N, Karaağaoğlu E, Yolaç P. Hamilton Anxiety Rating Scale: Interrater reliability and validity study. Türk Psikiyatri Dergisi 1998;9:114-120 (in Turkish).

19. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30:473-483.

20. Koçyiğit H, Aydemir Ö, Ölmez N, Memiş A. Reliability and Validity Study of Turkish version of Short Form 36 (SF-36). İlaç ve Tedavi Dergisi 1999;12:102-106 (in Turkish).

21. Spitzer RL, Williams JBW, Gibbon M. Structured Clinical Interview for DSM-III-R. Washington, D.C.: American Psychiatric Press, 1987.

22. Sorias S, Saygılı R, H Elbi. DSM-III-R yapılandırılmış klinik görüşmesi Türkçe versiyonu (SCID). Bornova: Ege Üniversitesi Basımevi, 1990 (in Turkish).

23. Grant BF, Hasin DS, Stinson FS, Dawson DA, Patricia Chou S, June Ruan W, Huang B. Co-occurrence of 12-month mood and anxiety disorders and personality disorders in the US: Results from the national epidemiologic survey on alcohol and related conditions. J Psychiatr Res 2005; 39:1-9.

24. Corruble E, Ginestet D, Guelfi JD. Comorbidity of personality disorders and unipolar major depression: a review. J Affect Disord 1996; 37:157-170.

25. Skodol AE, Stout RL, McGlashan TH, Grilo CM, Gunderson JG, Shea MT, Morey LC, Zanarini MC, Dyck IR, Oldham JM. Co-occurrence of mood and personality disorders: A report from the Collaborative Longitudinal Personality Disorders Study (CLPS). Depress Anxiety 1999; 10:175-182.

26. Buist-Bouwman MA, Ormel J, de Graaf R, Vollebergh WA. Functioning after a major depressive episode: Complete or incomplete recovery? J Affect Disord 2004; 82:363-371.

27. Kruijshaar ME, Hoeymans N, Bijl RV, Spijker J, Essink-Bot ML. Levels of disability in major depression: Findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). J Affect Disord 2003; 77:53-64.

Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Gregory Katz

Tachyphylaxis/ Tolerance to Antidepressive Medications: A Review Gregory Katz, MD The Jerusalem Mental Health Center, Kfar Shaul Hospital, Jerusalem, Israel

ABSTRACT Tachyphylaxis is the appearance of progressive decrease in response to a given dose after repetitive administration of a pharmacologically or physiologically active substance; the symptoms could appear also during treatment with antidepressants. Although the real frequency of the phenomenon is unclear, it may be as high as 33% during the pharmacological treatment of depression. The review deals with the possible causes and the treatment of the tachyphylaxis following antidepressant treatment.

Definition and Diagnosis Patients who complain about the loss of effectivity of antidepressants despite allegedly taking a full therapeutic dose are common in clinical practice. Is it to be explained by patients’ lack of adherence or lost placebo effect or could some other bio-pharmacological explanations be involved? Surprisingly (or not, taking into account the possible role of “big pharmas” in medical research) these important questions are far from having clear answers.

The pharmacological term tachyphylaxis is defined as a rapid appearance of progressive decrease in response to a given dose after repetitive administration of a pharmacologically or physiologically active substance (1).

Phylaxis in Greek means guarding, protection. The term “antidepressant tachyphylaxis” was coined by Leib and Balter in 1984 (2), although some case studies had been published previously (3, 4). In most studies tachyphylaxis (or “poop-out”) is defined as a relapse or recurrence of an episode of major depression after full recovery from

a major depressive episode despite continued treatment with a previously effective antidepressant (5).

While some authors characterize the phenomenon as a return of depressed mood, others characterize it by symptoms of apathy or decreased motivation (described by patients as “the blahs”), fatigue, dullness in cognitive function, sleep disturbance, weight gain, and sexual dysfunction (6). Patients frequently state that they feel worse than they felt after initially achieving remission on the antidepressant, but not as bad as they felt before treatment when they were in an episode of major depression (7). Some have suggested that a more appropriate term for this phenomenon should be antidepressant bradyphylaxis (8, 9) or antidepressant tolerance (10). While the term antidepressant tachyphylaxis stresses mostly the possibility of habituation/ sensitization mechanisms, the term tolerance is much more comprehensive and includes the mechanisms of pharmacodynamic tolerance, pharmacokinetic tolerance, increase in disease severity, change in disease pathogenesis, depleted effector substance, prominent increase of drug serum level and existence of detrimental metabolite (10). Therefore, the term tolerance could be more correct from the pharmacological point of view, but in most clinical studies the term tachyphylaxis is used. This confusion in terminology underlines the deficit of knowledge and lack of consensus on this issue. In the present review the terms have been used interchangeably.

Terms that should be distinguished from antidepressant tolerance/ tachyphylaxis are depressive relapse and recurrence. Relapse is defined as an episode of major depressive disorder that occurs within 6 months after either response or remission while recurrence is defined as another depressive episode that occurs after 6 months have elapsed (11). While in the definition of tachyphylaxis/ tolerance the existence of continuous treatment is compulsory, no such factor is vital for the definition of relapse or recurrence.

Address for Correspondence: Gregory Katz, MD, The Jerusalem Mental Health Center, Kfar Shaul Hospital, Givat Shaul Beith, Jerusalem 90805, Israel ngkatz@012.net.il

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Tachyphylaxis/ Tolerance to Antidepressive Medications: A Review

Rothschild (7) proposed the special rating scale: The Rothschild Scale for Antidepressant Tachyphylaxis (RSAT). The RSAT consists of 5 self-report items assessed over a 2-week period (energy level, motivation and interest, cognitive functioning, sleep, and sexual functioning) and one self-report item assessed over a 4-week period (weight). A seventh item, affect, is assessed by the interviewer. Each item is measured within a 5-point ordinal scale with anchor points developed to illustrate each rating.

The scale was designed primarily to assess the disturbances in patients on antidepressants who do not currently fulfill the criteria for an episode of major depression and had a previous good response to antidepressant therapy.

Rothschild evaluated by RSAT and the Hamilton Depression Rating Scale (HDRS) 50 patients successfully treated for major depression in the past 4 to 12 months who were currently complaining to their psychiatrist that “the antidepressant had stopped working” or had “pooped-out” but who did not meet the criteria for a relapse or recurrence of major depression and whose Hamilton Depression Rating Scale Score was <12. Based on preliminary experience with the RSAT, as well as predications based on the design of the scale, Rothschild hypothesized that an RSAT score of ≥7 would reflect antidepressant tachyphylaxis.

The study demonstrated RSAT’s excellent internal consistency, scale reliability and strong test-retest reliability. The lack of any statistically significant correlations between total RSAT score and individual RSAT items with the total score on the HDRS or HDRS item 1 (depressed mood) supports the discriminative validity of the RSAT as measuring something different from full-blown relapse or recurrence of major depression.

Frequency The frequency of antidepressant tachyphylaxis is still unknown. The return of depressive symptoms during maintenance antidepressant treatment (in full dosage) occurs in 9% to 33% of patients in published trials (10).

In double-blind, crossover study (12) depressed patients were studied over a 12-week period. One hundred sixtyfour patients were randomly assigned to placebo, 174 to imipramine, and 169 to phenelzine. Results indicated that 31% of the patients who responded to placebo showed symptoms of possible tachyphylaxis in the 7- to 12-week phase while only 12% of imipramine-respond130

ers, and approximately 9% who were taking phenelzine were suspected of developing tolerance.

Quite different findings were observed in the NIMH Collaborative Depression Study (5) with 20 years of prospective follow up; all main classes of antidepressants were used during the study. For 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder.

The median duration of maintenance treatment was 20 weeks. The primary objective of the study was to describe the rate of antidepressant tachyphylaxis as a recurrence of major depression despite maintenance pharmacotherapy of the treatment responders. Tachyphylaxis occurred in 43 treatments (about 25%) with two-fold risk elevation in cases of melancholic (endogenous) depression. No discriminative analysis of different groups of antidepressants was made in this study.

The issue of possible difference of antidepressants’ classes in maintenance efficacy and tachyphylaxis frequency also remains unsettled. Despite results from randomized, controlled trials demonstrating the efficacy of SSRIs in preventing relapse or recurrence of depression (13, 14) some have questioned their efficacy in maintaining long-term response (10). MacGrath et al. (15) examined 570 persons with major depressive disorder treated with fluoxetine for 12 weeks to determine their pattern of response. Those who responded (N=292) underwent random assignment, under double-blind conditions, to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse. The results showed that although fluoxetine was significantly more effective than placebo (35.2% of exacerbations for the fluoxetine group and 61.8% for the placebo group) this chronically ill group had a high rate of return of the depressive symptoms.

The pattern of acute response was not predictive for the depressive exacerbations after 1 year – there were 45.9% of exacerbations for the fluoxetine group and 72.0% for the placebo group. Though, according to the results, it can be postulated that tolerance to SSRI played an important role in the appearance of the depressive exacerbations the authors did not indicated it clearly.

Posternak and Zimmerman (16) compared rates of tachyphylaxis of venlafaxine and tricyclic antidepressants (TCAs), which act as dual reuptake inhibitors (though, usually, in high dosages) versus SSRIs. Two hundred thirty-seven patients who presented for outpatient treatment suffering from major depressive disorder were interviewed with the semi-structured

Gregory Katz

Treatment Response to Antidepressant Questionnaire.

The trial was retrospective and with no randomization.

Tachyphylaxis was diagnosed in cases of cessation of good or excellent response to antidepressants that had lasted for a minimum of 16 weeks. Cases in which treatment was stopped because the medication was not believed to be working were included in the trial. The cohort reported having undergone 326 prior SSRI trials, 47 prior venlafaxine trials, and 35 prior trials with a TCA. Rates of tachyphylaxis were significantly lower with the dual reuptake inhibitors venlafaxine and TCAs (3.7%) compared to rates of tachyphylaxis with SSRIs (14.1%). These results provided preliminary evidence that dual reuptake inhibitors may incur lower rates of tachyphylaxis than SSRIs. However, this retrospective study had obvious limitations and shortcomings.

Case reports and case series of different antidepressants (MAO inhibitors, cyclic antidepressants, some SSRI) have been reported (2, 3, 17, 18). Summarizing these reports Byrne and Rothschild (10) noted that most of the patients with reported tachyphylaxis were female; the mean age was 42 + 14 years old, the averaged length of successful treatment before relapse was 24 weeks; the average length of remission was 12 weeks.

Wijkstra with colleagues (19) described results of a 4-month open follow-up study of 59 patients with DSM-IV-TR major depressive disorder with psychotic features, aged 18 to 65 years, who had completed as responders a double-blind 7-week trial with imipramine, venlafaxine or venlafaxine plus quetiapine.

Main outcome measures were Hamilton Rating Scale for Depression and Clinical Global Impression Scale.

The results showed only 3.8% of tachyphylaxis after a previous good response. Interestingly, no SSRI medications were given in this trial.

Possible Causes for Antidepressants’ Tachyphylaxis/ Tolerance Nonadherence and the placebo-effect loss

In well-documented basic studies the cause of tachyphylaxis is not well understood. Some doubt the existence of true tachyphylaxis and attribute the loss of antidepressant response during most cases of maintenance phase therapy to either nonadherence and/or loss of placebo effect (20). Serma and colleagues (21) reported that out of 7,525 depressed outpatients 56% abandoned medication during the first four months. The special algorithms that had been developed by Quitkin and colleagues (12)

– 2X2 factorial design – drug versus placebo continuation phase therapy X “true drug response” versus “placebo response” – were applied (22, 23) for new generation of antidepressants in meta-analysis of the controlled studies according to follow criteria: continuation studies of new-generation antidepressants (SSRI, SNRI) began as placebo-controlled acute-phase studies. Following the data synthesis the exacerbation level of placebo responders was 24.1%, whereas for antidepressant responders it was only 7.4%. These results as many others indicated that nonadherence and loss of placebo effect could be responsible partially for the manifestation of the antidepressants’ tolerance. In the review, sponsored by a pharmaceutical company, they (24) postulated that, “…in the absence of data supporting the existence of true tachyphylaxis at the neuronal level, it is more appropriate to view loss of antidepressant response during maintenance phase therapy as the result of nonadherence and/or the loss of the placebo-expectancy component of therapeutic response.” This view could be congruent to the industries’ attitude, but it hardly could explain all possible mechanisms of the phenomenon discussed below, including the still open question of the existence of mechanism of receptors desensitization.

Genetic polymorphism in response to antidepressants

Several other factors have been thought to influence the outcome of antidepressant therapy. Among the factors influencing the interindividual variability in response to treatment with SSRI, differences in genetic features may play a significant role. Several genetic polymorphisms have been associated with therapeutic SSRI response, including genetic variants of the 5-HT transporter, 5-HT-2A-receptor, tryptophan hydroxylase, brainderived neurotrophic factor, G-protein beta3 subunit, interleukin-1beta, interleukin-6 and angiotensin-converting enzyme, although with conflicting results; also cytochrome P450 drug-metabolising enzymes may bear a particular importance, although further corroboration of the findings is necessary, and further key participating genes remain to be identified (25-27).

Receptors desensitization

Serotonin receptor desensitization has been hypothesized to be the primary actor responsible for the observation of an increased risk for the return of depressive symptoms during long-term treatment with selective serotonin reuptake inhibitors (28). This mechanism could be part of pharmacodynamic tolerance with adaptations at cellular 131

Tachyphylaxis/ Tolerance to Antidepressive Medications: A Review

or subcellular level that comprise the changes in sensitivity and/or number of cellular receptors, second-messenger systems or other systems (10). In the view of Cornelisse et al. (29) SSRIs do not appear to desensitize 5-HT(1A) receptors but rather one of the downstream components shared with GABA(B) receptors. According to some publications the repeated SSRI treatment alternates the effect of medication on extracellular 5-HT levels (30) and the postsynaptic 5-HT(1A) and 5-HT(2A) receptor binding levels (31).The data of higher frequency of “poop out” effect in SSRI medications compared to the dual reuptake inhibitors could be seen as an indirect support to this hypothesis (19). The clinical aspects of the theory of tachyphylaxis as “stepwise” receptor desensitization during unipolar major depression were studied by Amsterdam and colleagues (32). Two hundred seventy-six patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. After detailed analysis of the results conclusions were that the number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy. The odds ratio indicated a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. This observation supported the hypothesis that tachyphylaxis may develop after repeated antidepressant drug.

Pharmacokinetic tolerance

Tachyphylaxis can also occur also as a reaction to pharmacokinetic tolerance with alternations in plasma level of the medication due to different absorption, biotransformation and secretion changes due to previous exposure to the medication (33). The phenomenon of “therapeutic window” is described for different antidepressants including SSRIs (34). Individual genetic predisposition to pharmacokinetic alternations during the treatment of antidepressants (mainly SSRIs) may be connected to the phenomenon of tachyphylaxis (35).

The issues of possible antidepressants withdrawal and dependence may be connected to the effect of tolerance and, especially, in the prospect of the existence of a “real tachyphylaxis” phenomenon. The clinical data indicates that discontinuation (withdrawal) symptoms can fol132

low the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (36-39) and serotonin noradrenaline reuptake inhibitors (4045). The possible effect of dependence to antidepressants (MAO inhibitors and TCA) was reported only in case reports (46-50) with no well-documented and controlled studies published.

Undiagnosed bipolarity

Tachyphylaxis may occur more frequently in patients with bipolar type II major depressive episode (51). It could be connected to antidepressant-induced switching and cycle acceleration in bipolar disorder. As it was mentioned above the tachyphylaxis may also occur as a result of a physiological adaptation after repeated antidepressant exposure during unipolar and bipolar depression (52). Amsterdam and Shultz (53) examined the phenomenon of tachyphylaxis in patients with bipolar II major depression treated with either venlafaxine or lithium.

The authors hypothesized that a greater number of prior antidepressant exposures would result in a tolerance to venlafaxine, but not lithium, therapy. The results showed that the mean number of prior antidepressant and mood stabilizer exposures was significantly higher in patients with tolerance to venlafaxine than in the patients with stable effect of the drug. There was no significant association between response to lithium and the number of prior antidepressant and mood stabilizer exposures. The results showed that repeated use of antidepressants, but not lithium predisposes to tachyphylaxis in bipolar depression.

Other reasons

Among the other possible reasons for the appearance of tolerance to antidepressants are: prophylactic inefficacy of the medications, change in disease due to drug therapy, change in disease independent of drug therapy (10) and alleged paradoxical effect of antidepressants (27). Although substance abuse is known for alternating the reaction to antidepressants (54) no controlled data of existence of tachyphylaxis in dual-diagnosed patients has been published yet.

Treatment Strategies Evaluation

Following the differential assessment of tolerance versus resistance, ruling out nonadherence, and establishing the adequacy of treatment, clinicians should then conduct a diagnostic reassessment in order to confirm whether,

Gregory Katz

indeed, the correct diagnosis is nonpsychotic MDD by ruling out alternative diagnostic possibilities that would require a different treatment approach (for example a major depressive episode in the setting of bipolar disorder or MDD accompanied by psychotic symptoms).

Clinicians should also reassess for psychiatric comorbidities, including substance use disorders, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and eating disorders (54).

(in the absence of apparent side effects). All 4 patients improved during washout and went on to respond to a lower dose. The conclusion of this and above mentioned case reports was an apparent difficulty distinguishing fluoxetine’s adverse effects/toxicity (or a “therapeutic window” effect) from underlying depressive symptoms exists; it may suggest the option of lowering the dose in some cases of nonresponse or tolerance.

Dose changes

The attitudes to the treatment of antidepressants’ tachyphylaxis may also involve non-medication strategies. Leykin with colleagues (60) assessed the response to antidepressants’ therapy and cognitive therapy of patients with a history of prior antidepressant exposures.

A sample of 240 patients with moderate-to-severe major depressive disorder entered a randomized controlled trial comparing pharmacotherapy with paroxetine to cognitive therapy; treatment was administered for 16 weeks.

The results showed that a higher number of prior antidepressants’ exposures were significantly associated with a lower response to paroxetine with possible development of tachyphylaxis. The cognitive therapy results were not significantly related to the number of prior antidepressants’ exposures. This observation suggests that cognitive therapy may exert its therapeutic action via a different mechanism than that of antidepressant drug therapy, and may be less affected by the physiological adaptation resulting from prior drug exposure (53).

In 1997 Byrne and Rothschild (55) published results of a survey of 300 members of Massachusetts Psychiatric Society with specialization in psychopharmacology of affective disorders. A total of 145 psychiatrists responded to a survey about intervention in hypothetical cases of breakthrough depression if the patient was taking either 20 mg of fluoxetine, 100 mg of sertraline, 100 mg of nortriptyline, or 40 mg of fluoxetine. For all drugs and dosages, the most popular choice was increasing the dosage, followed by augmenting with lithium or another antidepressant or changing to a different drug. Though this empirical attitude seems to be based on “common sense,” the controlled data regarding the treatment of tachyphylaxis is very limited. Fava with co-authors (56) examined whether depressed patients who had recovered and then relapsed on fluoxetine 20 mg/day would benefit from an increase in fluoxetine dose. Eighteen patients who suffered from possible tachyphylaxis on fluoxetine 20 mg/day during long-term treatment with fluoxetine as part of a placebo-controlled study had their fluoxetine dose raised to 40 mg/day and were followed for at least 1 month. The authors reported the following results: 12 (67%) were full responders, 3 (17%) partial responders, and 3 (17%) dropped out because of side effects (e.g., insomnia and agitation). Overall, 11 (61%) of 18 patients maintained their response during their follow-up while taking the higher dose of fluoxetine: the study was not controlled. The conclusions of this observation were that an increase in dose of fluoxetine to 40 mg/day appears to be an effective strategy in the treatment of the tachyphylaxis of fluoxetine in dosage of 20 mg/day.

Based on the assumption of the possibility of “therapeutic window” for fluoxetine some authors studied the use of the strategy of lowering dosage (57, 58). Cain (59) reported that in an open label study 23 consecutive outpatients were treated with fluoxetine 20 mg/day for major depression. Four of them failed to sustain initial improvements during 4-8 weeks of treatment

CBT in the treatment of tachyphylaxis

Antidepressant tolerance and treatment of resistant depression

Tachyphylaxis may contribute to the development of treatment-resistant depression (TRD) and there are possible mutual mechanisms in their development (61).

Consequently, most of the therapeutic approaches to the treatment of TRD could be appropriate for the treatment of tachyphylaxis. As for pharmacological interventions: beside the dosage change, switching, augmentation and combination strategies in TRD are widely used (62 -65).

Generally, taking into consideration the above mentioned data of the possible serotonin receptors desensitization as a factor for developing of tachyphylaxis, the switching from SSRIs to different groups of antidepressants seems to be a preferable way of treating this condition.

In conclusion: tachyphylaxis may affect some groups of patients getting the antidepressive treatment, especially SSRIs. long-term, controlled and independent studies are of crucial importance for revealing the 133

Tachyphylaxis/ Tolerance to Antidepressive Medications: A Review

real frequency of the phenomena, its causes and treatment.

References 1. Stedman’s Medical Dictionary (27th ed.). Philadelphia: Lippincott, Williams, and Wilkins, 2000.

2. Leib J, Balter A. Antidepressant tachyphylaxis. Med Hypothesis 1984; 15:279-291.

3. Mann J. Loss of antidepressant effect with long-term monoamine oxidase inhibitor treatment without loss of monoamine oxidase inhibition. J Clin Psychopharmacol 1983;3:363-366.

4. Zetin M, Aden G, Moldawsky R. Tolerance to amoxapine antidepressant effects. Clin Ther 1983; 5:638-643.

5. Solomon DA, Leon AC, Mueller TI, Coryell W, Teres JJ, Posternak MA, Judd LL, Endicott J, Keller MB. Tachyphylaxis in unipolar major depressive disorder. J Clin Psychiatry 2005; 66:283-290.

6. Rothschild A. The Rothschild Scale for Antidepressant Tachyphylaxis Poster presented at 159th Annual Meeting of the American Psychiatric Association, May 20-25, 2006, Toronto, Canada.

7. Rothschild A. The Rothschild Scale for Antidepressant Tachyphylaxis: Reliability and validity. Compr Psychiatry 2008; 49: 508-513.

8. Ferrier N. Treatment-resistant mood disorders. Br J Psychiatry 2002; 181: 264.

9. Jefferson J. It looks like “bradyphylaxis” to me. J Clin Psychiatry 2005; 66: 1076.

10. Byrne S, Rothschild A. Loss of antidepressant efficacy during maintenance therapy: Possible mechanisms and treatments. J Clin Psychiatry 1998; 59: 279-288.

11. Nierenberg AA, Petersen TJ, Alpert JE. Prevention of relapse and recurrence in depression: The role of long-term pharmacotherapy and psychotherapy. J Clin Psychiatry 2003; 64 Suppl 15:13-17.

12. Quitkin FM, Stewart JW, McGrath PJ, Nunes E, Ocepek-Welikson K, Tricamo E, Rabkin JG, Klein DF. Further evidence that a placebo response to antidepressants can be identified. Am J Psychiatry 1993; 150; 562-565.

13. Keller MB, Kocsis JH, Thase ME, et al. Maintenance phase efficacy of sertraline for chronic depression: A randomized controlled trial. JAMA 1998; 280: 1665-1672.

14. Rapaport MH, Bose A, Zheng H. Escitalopram continuation treatment prevents relapse of depressive episodes. J Clin Psychiatry 2004; 65:44-49.

15. McGrath PJ, Stewart JW, Quitkin FM, Chen Y, Alpert JE, Nierenberg AA, Fava M, Cheng J, Petkova E. Predictors of relapse in a prospective study of fluoxetine treatment of major depression. Am J Psychiatry 2006; 163:1542-1548.

16. Posternak MA, Zimmerman M. Dual reuptake inhibitors incur lower rates of tachyphylaxis than selective serotonin reuptake inhibitors: A retrospective study. J Clin Psychiatry 2005; 66:705-707.

17. Cohen BM, Baldessarini RJ. Tolerance to therapeutic effects of antidepressants. Am J Psychiatry 1985; 142:489-490.

18. Rapport DJ, Calabrese JR. Tolerance to fluoxetine. J Clin Psychopharmacol 1993; 13:361.

19. Wijkstra J, Burger H, van den Broek WW, Birkenh‫ה‬ger TK, Janzing JG, Boks MP, Bruijn JA, van der Loos ML, Breteler LM, Verkes RJ, Nolen WA. Long-term response to successful acute pharmacological treatment of psychotic depression. J Affect Disord J Affect Disord 2010;123:238-242.

20. Kornstein SG. Beyond remission, rationale, and design of the prevention of recurrent episodes of depression with venlafaxine for two years (PREVENT) Study. CNS Spectr 2006; 11:12(Suppl 15):28-34.

21. Serna MC, Cruz I, Real J, Gasco E, Galvan L. Duration and adherence of antidepressant treatment (2003 to 2007) based on prescription database.

Eur Psychiatry Eur Psychiatry 2010;25:206-213.

22. Zimmerman M, Thongy T. How often do SSRIs and other new-

134

generation antidepressants lose their effect during continuation treatment? Evidence suggesting the rate of true tachyphylaxis during continuation treatment is low. J Clin Psychiatry 2007; 68:1271-1276.

23. Thase MA. Preventing relapse and recurrence of depression: A brief review of therapeutic options. CNS Spectr 2006; 11:12-21.

24. Serretti A, Artioli P. The pharmacogenomics of selective serotonin reuptake inhibitors. Pharmacogenomics J 2004; 4:233-244.

25. Neumeister A, Hu XZ, Luckenbaugh DA, Schwarz M, Nugent AC, Bonne O, Herscovitch P, Goldman D, Drevets WC, Charney DS. Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls.

Arch Gen Psychiatry 2006; 63: 978-986.

26. Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Ueda N, Nakamura J. Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33:722-726.

27. Fava GA. Can long-term treatment with antidepressant drugs worsen the course of depression? J Clin Psychiatry 2003; 64:123-133.

28. Muraki I, Inoue T, Hashimoto S, Izumi T, Koyama T. Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex: In vivo microdialysis study. Psychiatry Clin Neurosci 2008; 62:568-574.

29. Cornelisse LN, Van der Harst JE, Lodder JC, Baarendse PJ, Timmerman AJ, Mansvelder HD, Spruijt BM, Brussaard AB. Reduced 5-HT1Aand GABAB receptor function in dorsal raph‫ י‬neurons upon chronic fluoxetine treatment of socially stressed rats. J Neurophysiol 2007; 98:196-204.

30. Günther L, Liebscher S, Jankel M, Oehler J. Effects of chronic citalopram treatment on 5-HT1A and 5-HT2A receptors in group- and isolationhoused mice. Eur J Pharmacol 2008; 593: 49-61.

31. Kalant H. Drug tolerance and sensitization: A pharmacological overview. In Goudie A, Oment-Oglesby M, eds. Psychoactive drugs: Tolerance and sensitization. Clifton, N.J.: Human Press, 1989.

32. Amsterdam J, Williams D, Michelson D, Adler LA, Dunner DL, Nierenberg AA, Reimherr FW, Schatzberg AF. Tachyphylaxis after repeated antidepressant drug exposure in patients with recurrent major depressive disorder. Neuropsychobiology 2009; 59:227-233.

33. Charlier C, Pinto E, Ansseau M, Plomteux G. Relationship between clinical effects, serum drug concentration, and concurrent drug interactions in depressed patients treated with citalopram, fluoxetine, clomipramine, paroxetine or venlafaxine. Hum Psychopharmacol 2000; 15: 453-459.

34. Mancama D, Kerwin RW. Role of pharmacogenomics in individualising treatment with SSRIs. CNS Drugs 2003; 17:143-151.

35. Schatzberg AF, Haddad P, Kaplan EM, Lejoyeux M, Rosenbaum JF, Young AH, Zajecka J. Serotonin reuptake inhibitor discontinuation syndrome: A hypothetical definition. Discontinuation consensus panel.

J Clin Psychiatry 1997; 58 Suppl 7:5-10.

36. Lader M. Pharmacotherapy of mood disorders and treatment discontinuation. Drugs 2007;67:1657-1663.

37. Tint A, Haddad PM, Anderson IM. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: A randomized study. J Psychopharmacol 2008; 22:330-332.

38. Price JS, Waller PC, Wood SM, MacKay AV. A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br J Clin Pharmacol 1996; 42:757-763.

39. Himei A, Okamura T. Discontinuation syndrome associated with paroxetine in depressed patients: A retrospective analysis of factors involved in the occurrence of the syndrome. CNS Drugs 2006; 20:665-672.

40. Perahia DG, Kajdasz DK, Desaiah D, Haddad PM. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005; 89: 207-212.

41. Baboolal NS. Venlafaxine withdrawal syndrome: Report of seven cases

Gregory Katz

in Trinidad. J Clin Psychopharmacol 2004; 24:229-231.

42. Stone TE, Swanson C, Feldman MD. Venlafaxine discontinuation syndrome and suicidal ideation: A case series. J Clin Psychopharmacol 2007; 27:94-95.

43. Campagne DM. Venlafaxine and serious withdrawal symptoms: Warning to drivers. MedGenMed 2005; 6: 22.

44. Sir A, D’Souza RF, Uguz S, George T, Vahip S, Hopwood M, Martin AJ, Lam W, Burt T. Randomized trial of sertraline versus venlafaxine XR in major depression: Efficacy and discontinuation symptoms. J Clin Psychiatry 2005; 66:1312-1320.

45. Price JS, Waller PC, Wood SM, MacKay AV. A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br J Clin Pharmacol 1996; 42:757-763.

46. Quaglio G, Schifano F, Lugoboni F. Venlafaxine dependence in a patient with a history of alcohol and amineptine misuse. Addiction 2008; 103:1572-1574.

47. Harvey BH, Retief R, Korff A, Wegener G. Increased hippocampal nitric oxide synthase activity and stress responsiveness after imipramine discontinuation: Role of 5HT 2A/C-receptors. Metab Brain Dis 2006; 21:211-220.

48. Constantinescu C. Two unusual cases of psychotropic drug dependence (imipramine and reserpine). Agressologie 1978; 19:179-180.

49. Toro P, Nores JM, Remy JM. Clomipramine dependence in a drug addict. 1st case. Presse Med 1989; 28:132.

50. Eyer F, Jetzinger E, Pfab R, Zilker T Withdrawal from high-dose tranylcypromine. Clin Toxicol (Phila) 2008; 46: 261-263.

51. Sharma V. Loss of response to antidepressants and subsequent refractoriness: Diagnostic issues in a retrospective case series. J Affect Disord 2001; 64:99-106.

52. Amsterdam J, Maislin G, Potter L. Fluoxetine efficacy in treatment resistant depression. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 243-261.

53. Amsterdam J, Shultz J. Does tachyphylaxis occur after repeated antidepressant exposure in patients with Bipolar II major depressive

episode? J Affect Disord 2009; 115: 234-240.

54. Nierenberg A, Katz J, Fava M. A critical overview of the pharmacologic management of treatment-resistant depression. Psychtr Clin North Am 2007; 30: 13-29.

55. Byrne S, Rothschild AJ. Psychiatrists’ responses to failure of maintenance therapy with antidepressants. Psychiatr Serv 1997; 48: 835-837.

56. Fava M, Rappe SM, Pava JA, Nierenberg AA, Alpert JE, Rosenbaum JF. Relapse in patients on long-term fluoxetine treatment: Response to increased fluoxetine dose. J Clin Psychiatry 1995; 56:52-55.

57. Fichtner CG, Jobe TH, Braun BG. Possible therapeutic window for serotonin reuptake inhibitors. J Clin Psychiatry 1994; 55:36-38.

58. Fichtner CG, Jobe TH, Braun BG. Does fluoxetine have a therapeutic window? Lancet 1991;24:520-521.

59. Cain JW. Poor response to fluoxetine: Underlying depression, serotonergic overstimulation, or a “therapeutic window.” J Clin Psychiatry 1992; 53: 272-277.

60. Leykin Y, Amsterdam JD, DeRubeis RJ, Gallop R, Shelton RC, Hollon SD. Progressive resistance to a selective serotonin reuptake inhibitor but not to cognitive therapy in the treatment of major depression. J Consult Clin Psychol 2007; 75:267-276.

61. Fekadu A, Wooderson SC, Markopoulo K, Donaldson C, Papadopoulos A, Cleare AJ. What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies. J Affect Disord 2009; 116:4-11.

62. Papakostas G. Partial response or nonresponse: Switching, augmentation, and combination strategies for major depressive disorder. J Clin Psychiatry 2009; 70[suppl 6]:16-25.

63. Nierenberg A, Katz J, Fava M. A critical overview of the pharmacologic management of treatment-resistant depression. Psychiatr Clin North Am 2007; 30: 13-29.

64. Fava M. Management of nonresponse and intolerance: Switching strategies. J Clin Psychiatry 2000; 61 (suppl 2): 10-12.

65. Papakostas G, Fava M, Thase M. Treatment of SSRI-resistant depression: A meta-analysis comparing within- versus across-class switches. Biol Psychiatry 2008; 63: 699-704.

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Isr J Psychiatry Relat Sci - Vol. 48 - No. 2 (2011)

Controversies in Psychiatry Proceedings of the first Psychiatric Residents Interactive Course Over a two-day intensive course, residents in psychiatry were challenged with common clinical dilemmas. The results of their extensive literature review and discussions, led by leading academic and clinical tutors, were summarized in a lecture. Lectures were presented and judged by a panel of psychiatrists. Transcripts of lectures were transformed into a series of brief reports herein published.

The use of antidepressants for bipolar depression D. Shefet, O. Gerstein, Y. Leubov, E. Malik, M. Marom, M. Shapiro Rotman, L. Shapir and T. Shmuel Dr. Shefet's e-mail: daphnash@clalit.org.il

Clinical Dilemma: “You have diagnosed a 33-year-old male with bipolar disorder and initiated lithium treatment and psycho-social therapy. Two months later his lithium level is within the therapeutic range but his symptoms and function level correlate with moderate depressive episode. Is there a place for adjunctive antidepressant medication?”

Literature Survey: Intuitively, why not add an antidepressant? Bipolar disorder is a chronic and debilitating disorder, depression being the leading cause of impairment, both in symptom duration and degree of distress.

However, the efficacy of antidepressants is unclear, as reflected by the lack of FDA-approved antidepressants for bipolar depression. Furthermore, the potential harm, especially a manic switch or cyclic acceleration, is deterring. A short survey among 49 residents regarding treatment options in this case proved the current heterogeneous clinical practice, votes nearly equally divided between supporting an adjunctive antidepressant drug [33%], adding [24%] or switching [30%] a mood stabilizer, and a few for adjunctive atypical antipsychotic drug [13%].

This controversy is embodied in the major guidelines: APA guidelines tend to underestimate the benefit and emphasize the potential harm of antidepressants for 136

bipolar disorder. Patients without a mood stabilizer are recommended treatment with such: lithium as the first choice and lamotrigine second. If the patient is already receiving a mood stabilizer, optimize the dosage or add a second stabilizer. Only in severe depressive episodes should one consider adjunctive antidepressants, specifically bupropion or paroxetine, followed by other SSRIs, SNRIs or MAO inhibitors. The British NICE guidelines are more permissive, although somewhat unclear. In a mild depressive episode, a two-week wait-and-see policy is taken, whereas in a moderate or severe episode, addition of an SSRI or of quetiapine is equally supported. For those initially treated with an antidepressant, an addition of a stabilizer is advised. However, given a recent hypo/manic episode or rapid-cycling, one is advised to avoid antidepressants.

Regarding effectiveness of antidepressants in bipolar disorder, systematic reviews suggest “some efficacy in some populations” in immediate and maintenance treatment, especially paroxetine, bupropion and fluoxetine (1). The risk of a manic switch is strongly reduced when a mood stabilizer is given concurrently, and when tricyclic drugs, MAO inhibitors and SNRIs are avoided.

The risk of a switch is higher in patients with Bipolar I [rather than II], prolonged treatment (2) or when agitation, distractibility and thought racing are reported.

The most significant study to date is the STEP-BD, an NIMH funded, multi-centered, double blind, randomized-controlled study (3). The study assigned 366 subjects with bipolar depression to a 26-week trial of a mood stabilizer plus adjunctive antidepressant vs an adjunctive placebo, testing durable recovery and treatment emergent affective switch. The efficacy (23.5% vs.

27.3%, respectively) and risk of affective switch (10.1%

D. Shefet et al. / A. Olmer et al.

vs. 10.7%, respectively) did not differ significantly between the two groups. Attempts to reconcile the gap between this study and data from systematic reviews suggested the effects of variation in population selection, follow-up and treatment durations; a possible selection-bias; and the general heterogeneity of bipolar disorder characteristics worldwide.

Conclusion: In light of the complex and somewhat contradictory evidence, it seems adjunction of antidepressant drugs should be done on case basis. One should consider the current and previous affective episodes, in terms of symptoms, severity, duration and response to treatment. The core treatment is a mood stabilizer in an adequate dose. An antidepressant drug should be considered facing a severe and/or a prolonged depressive episode, especially with a bipolar II diagnosis. In patients with a past life threatening manic episode, antidepressants are best avoided. Options such as adjunction of atypical anti-psychotics or electro-convulsion therapy exist, but are beyond the scope of this review. Individualization of treatment is the key to bipolar depression.

References: 1. Salvi V, Fagiolini A, Swartz SA, et al. The use of antidepressants in bipolar disorder. J Clin Psychiatry 2008: 69:1307-1318.

2. Harel EV, Levkovitz Y. Effectiveness and safety of adjunctive antidepressants in the treatment of bipolar depression: A review. Isr J Psychiatry Relat Sci 2008:45:121-128.

3. Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. New Engl J Med 2007:356:1711-1722.ֿ

Prevention of recurrent postpartum depression – a reasonable option?

A. Olmer, H. Biadsi, A. Chola, Y. Dagan, L. Elishar, D. Keidar and V. Mironov Dr. Olmer's e-mail: ahikamolmer@gmail.com

Clinical Dilemma: “A 27-year-old woman is in the 32nd

week of her second pregnancy. After her first childbirth she suffered from postpartum depression (PPD) and was successfully treated with an antidepressant. Since then she has been asymptomatic. Now she asks for consultation whether she should be treated preventively for depression after her upcoming childbirth.”

PPD is a common disorder with health consequences for the mother, child, and family and a prevalence of 10–15%. The risk for PPD rises to 25-30% with a prior history of PPD or depression not related to childbirth. Other suggested risk factors for PPD are “baby blues,” past hormone-related mood symptoms such as premenstrual dysphoric disorder and mood symptoms during oral contraceptive use, depressive symptoms during pregnancy and psychosocial factors such as lack of partner support and low self-esteem.

Since a high-risk population (especially woman with history of depression) and defined period of risk for illness onset (first 1-3 months after childbirth) are identifiable, considering preventive measures for PPD is reasonable.

In a review on the use of antidepressant in the postpartum period (1), Payne points out that only few small randomized trials have been conducted in order to study the efficacy of therapy for treatment and prevention of PPD. In two small placebo-controlled studies on the prevention of recurrent PPD nortriptyline (n=26) failed to decrease the rate of postpartum depression while sertraline (n=14) succeeded. In double blind trials for the treatment of PPD, no differences were found between sertraline and nortriptyline in remission rates (46%–48%) and fluoxetine was found superior to placebo and counseling.

A number of open-label studies have supported the use of antidepressants to treat postpartum depression, including sertraline, paroxetine, bupropion, venlafaxine, and fluvoxamine. Among these medications sertraline is noted for the relatively low levels of the medication identifiable in breast milk.

Diverse psychosocial and psychological interventions such as antenatal and postnatal classes, professional and lay home visits, continuity of care debriefing, interpersonal psychotherapy and CBT were investigated for prevention for PPD in a number of trials. A meta-analysis (2) conducted to asses the effect of these interventions on the risk of PPD concluded that only intensive postpartum support provided by a health professional for “at risk” women has a clear preventive effect.

Although the research data on the prevention of postpartum depression are relatively sparse, a number of clinical recommendations can be made.

The patient and/or significant other should be educated about the potential risks and benefits of treatment. Considerations in favor of preventive antidepressant treatment would be a severe depressive episode in the past, favorable past response to medications, poor Literature Survey:

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Controversies in Psychiatry - Proceedings of the first Psychiatric Residents Interactive Course

psychosocial support, multiple risk factors for PPD, absence of both hypomanic symptoms (past or present) and family history of bipolar-spectrum disorders and an inability to commit to psychotherapy. Issues concerning patient's preference and breastfeeding should, of course, also be taken in account.

It seems that postpartum professional short-term psychotherapy should be offered for every “at risk” woman due to possible effectiveness in prevention of PPD, lack of treatment risks and the fact that engaging in such a treatment would provide the necessary followup for the patient.

In cases that preventive treatment was not initiated for any reason follow-up by a mental health person is necessary and the patient as well as significant others should be educated to seek professional help when depressive symptoms emerge.

Finally, all health care personnel involved in postpartum medical treatment should be aware of the patient history and pay attention to changes in mental state.

References: 1. Payne JL. Antidepressant use in the postpartum period: Practical considerations. Am J Psychiatry 2007;164:1329-1332.

2. Dennis CL. Psychosocial and psychological interventions for prevention of postnatal depression: Systematic review. BMJ 2005;331:15-23.

Dynamic psychotherapy or dialectical behavioral therapy – which is better for borderline personality disorder?

O. Tene, A. Har-Even, E. Dahan, Y. Babokshin, I. Reuveni, B. Penrovski, V. Rosman and L. Gluzman Dr. Tene's e-mail: orentene@gmail.com

Clinical Dilemma: “A 20-year-old female patient, diag-

nosed as suffering from borderline personality disorder, is referred to your clinic. Her disorder is characterized by unstable personal relationships, impulsivity, suicidal behavior, emotional instability and pan-anxiety. After initiation of pharmacological treatment which you have chosen, you meet with her parents who ask you which is better for their daughter – dynamic-analytic psychotherapy or dialectical behavioral therapy?”

138

Literature Survey: The challenge set before us is one well known (and sometimes well feared) by psychiatrists and psychotherapists world-wide – the treatment of borderline personality disorder. This disorder is characterized by “stable instability” in affect and interpersonal relationships, and the symptoms include fear of abandonment, diffused identity, chronic feelings of emptiness, impulsivity, suicidality, anger and rage attacks and psychotic or dissociative exacerbations.

All these might contribute, at times, to the development of a “problematic” counter-transference towards the patient.

So what can we offer the borderline patient portrayed above, aside from pharmacotherapy? The patient’s parents have accurately named two psychotherapeutic interventions which are considered efficient in such cases – dynamic psychotherapy and dialectical behavioural therapy (DBT). The two techniques differ in many aspects, such as setting, therapeutic tools, therapist’s “activity” level, aims set before initiation of treatment, duration of treatment, and more. But which is better?

A search conducted in current literature, trying to answer this question, brought about a sad conclusion: the data comparing the two techniques are “seriously limited.” We thought it was important to address this fact and explain why evidence based data regarding these issues are so difficult to obtain. First, the population involved is complex, and the diagnosis of borderline personality disorder heterogenic. Second, the outcome in such trials is problematic. What should it be? Cure? Alleviation of symptoms? Of some of the symptoms? Third – it is impossible to compare psychotherapeutic techniques using double-blind placebo controlled trials. And last but not least – many of the trials available were conducted by leading figures of one of the techniques compared, raising questions as to possible bias (mainly due to a possible more “passionate” or enthusiastic approach towards the “home technique”).

Having said that, what is the little that we do know?

The American Psychiatric Association (APA) guidelines conclude that as of 2001, there are no “head to head” comparison trials between the two techniques found efficient – Dynamic psychotherapy and DBT (we will soon show otherwise) – and that there is no proven way to predict which patient will respond to which technique. The APA guidelines recommend certain therapeutic measures to all therapists, regardless of

O. Tene et al. / M. Linder et al.

technique: building a strong therapeutic alliance and monitoring self-destructive and suicidal behaviors, as well as validating the patient’s suffering and experience and helping the patient take responsibility for his or her actions.

Further search in the Cochrane Collaboration did not contribute to the clarification of the clinical dilemma. According to a comprehensive review published in 2006, all therapies aimed to treat borderline personality disorder remain experimental as the studies are too few and small to inspire full confidence in their results. The authors conclude that the findings so far require replication in larger “real-world” studies (1).

Clarkin and colleagues came to our rescue, and in 2007, they report findings after examining three yearlong outpatient treatments for borderline personality disorder: dialectical behavior therapy, transferencefocused (dynamic) psychotherapy, and a dynamic supportive treatment. When focusing on the first two therapeutic options as our clinical dilemma demanded, the results showed that both were equally efficient in many aspects, and that patients treated by both interventions showed significant positive change in depression, anxiety, global functioning, social adjustment and suicidality across one year of treatment. But when referring to a specific subset of symptoms of borderline personality disorder, such as anger, impulsivity, irritability and verbal and direct assault – it was only dynamic psychotherapy that was associated with improvement (2).

Conclusion: Based

on the little information available, we attempted to create a “clinical algorithm” for the treatment of borderline personality disorder. When a patient with the disorder applies for therapy, first evaluate his or her symptoms: which are more prominent – the hostility, anger and impulsivity or the depression, anxiety and suicidality? After assessing the patient, evaluate the clinician’s skill – is he or she an expert of DBT or dynamic psychotherapy? When the patient’s prominent symptoms are from the “depressive-anxious” subset, and not the “impulsive-angry” group, the decision about mode of therapy should be based upon the clinician’s expertise, as we saw no proof of one intervention being superior to the other. But if the patient’s major symptoms are those of anger, hostility and impulsivity, then at least according to the small trial quoted above, dynamic psychotherapy is a better option.

References: 1. Binks C, Fenton M, McCarthy L, Lee T, Adams CE, Duggan C. Psychological therapies for people with borderline personality disorder.

Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD005652. DOI: 10.1002/14651858.CD005652 2. Clarkin JF, Levy KN, Lenzenweger MF, Kernberg OF. Evaluating three treatments for borderline personality disorder: A multiwave study. Am J Psychiatry 2007;164:922-928.

The use of antipsychotics for dementia M. Linder, H. Bahagon, H. Boukani, G. Goren, P. Roitman, O. Rosenberg, R. Sagi and L. Sharoni Dr. Linder's e-mail: muli.linder@gmail.com

Clinical dilemma: “In

the Emergency Room you are asked to examine a patient diagnosed with dementia.

You diagnose active psychosis, and contemplate whether to prescribe antipsychotic (AP) medication?”

Literature Survey: Treating the elderly population is a

complicated challenge, which involves numerous considerations such as background diseases, polypharmacy, side-effects and sometimes lack of support.

Clinical guidelines: The National Institute for Clinical Excellence (NICE) recommends not to use AP in dementia, and the Food and Drug Administration (FDA) issued a Black Box Warning, and recommends reporting all the potential risks to patients and their families (1-3). The Israeli Ministry of Health has not published guidelines for antipsychotic use among dementia patients.

Epidemiology: Twenty-five million people suffer from dementia worldwide, 70,000 of them in Israel. About 80% of dementia patients experience a psychotic state.

Antipsychotic agents are prescribed in about 25% of the senior citizens’ homes. The problem increases commensurate with the increase in life expectancy.

There are several etiologies for dementia, i.e., vascular, AIDS dementia and others, but this review will focus on the most common – Alzheimer’s dementia.

Some clinicians find it difficult to separate agitation and psychosis. The clinical manifestation is often similar, and the body of research in this report does not distinguish between the two, thus treatment choices are derived from undifferentiated conclusions.

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Controversies in Psychiatry - Proceedings of the first Psychiatric Residents Interactive Course

Why treat patients with Alzheimer’s dementia with antipsychotics? One cannot ignore the price the patient and family pay in these situations as they seek a treatment for immense suffering. Antipsychotic agents putatively diminish agitation, violence and psychosis, and may help improve the patients’ integration in their environment. On the other hand, evidence-based data stresses the risks, and reveals that AP administered with dementia elevate rates of death twofold, cerebrovascular attacks threefold, and is related to falls, extrapyramidal symptoms and decline in quality of life, while its efficacy remains debated.

Extensive research was conducted on AP use among dementia patients: CATIE-AD concludes that there is no advantage for AP versus placebo, and that Olanzapine seems to be the most effective, but also had the most side-effects (3). Another study revealed higher mortality rates in the AP group (N=64) than in the control group (N=64).

The Cochrane Review reports: “Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is severe distress or risk to those living or working with the patient” (1).

Alternative treatments, pharmacological (acetylcholine esterase inhibitors, mementine, benzodiazepines, antiepileptic drugs, SSRIs and beta blockers) and nonpharmacological (sports, music therapy, dance therapy, snoezelen) did not prove to be as effective as AP, and require further research.

After reviewing the body of evidence, we suggest a framework for guidelines for treatment of dementia patients with psychoses: 1. Routine use of AP in dementia should be avoided.

2. Limited use in cases of immediate danger or severe distress to the patient or his surroundings.

3. Time-limited treatment – up to 12 weeks.

4. Continued treatment subject to psychiatric evaluation.

References: 1. Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev 2006;1:CD003476.

2. Rabins PV, Blacker D, Rovner BW, et al. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry 2007;164:5-56.

3. Sultzer DL, Davis SM, Tariot PN, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: Phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry 2008;165:844-854.

140

Does the duration of untreated psychosis affect prognosis in schizophrenia?

G. Mayer, I. Dekel, A. Domrab, M. Drobot, Y. Guttnik, E. Kalman, M. Kozal and I. Yifat Dr. Mayer's e-mail: gaddyma@clalit.org.il

Clinical Dilemma: “An 18-year-old patient, who has been suffering from a prolonged psychotic state, is hospitalized for the first time in his life in our department. We diagnose his condition as schizophrenia, and start anti-psychotic medication and supportive psychotherapy. His parents join the psycho-educational group for families in our department. After one of the group sessions, his parents worriedly approach us with the question whether the fact that their son had been psychotic and had not received anti-psychotic medications for many months before his hospitalization predicts a bad prognosis for his disease course and outcome. Does the duration of untreated psychosis (DUP) affect prognosis in schizophrenia?”

Literature Survey: DUP is the common term for the time span between the appearance of psychotic symptoms and the initiation of anti-psychotic medication.

Reasons for the prolongation of the DUP may include the stigma attached to the disorder, a lack of insight to the psychosis and lack of a supportive environment.

It has been suggested that a prolonged DUP may be detrimental to the prognosis of patients with schizophrenia based on the following hypotheses: i. Schizophrenia is hypothesized as a neurodegenerative disorder, i.e., it involves continuous central nervous system deterioration, which can be slowed down or terminated by the use of pharmacotherapy. ii. Drawing on the neurodegenerative hypothesis, the critical time hypothesis presumes that there is a period of time at the beginning of the disorder when the neurodegenerative processes can be terminated or halted, and after which continuous damage is irreversible. iii. The neurotoxicity hypothesis suggests that psychosis is damaging to the brain, and the corresponding neuroprotectivity hypothesis suggests that antipsychotic medications may protect the brain from the toxic effects of psychosis. iv. From a psychosocial point of view, psychosis is

G. Mayer et al.

thought to damage the patientâ&#x20AC;&#x2122;s psychosocial fabric.

Many studies have tried to address this question. The most recent meta-analysis we found was by Perkins and colleagues (1). This meta-analysis reviewed a total of 43 studies, trying to assess the influence of the DUP on the outcome of the first episode of schizophrenia.

Its main results were: a) prolonged DUP is associated with lower levels of symptomatic and functional recovery from the first psychotic episode, b) DUP did not appear to be associated with neurocognitive function at first treatment contact and c) DUP was associated with severity of negative symptoms but not with severity of positive symptoms at the time of initial clinical evaluation. The studies reviewed did not find a relationship between DUP and abnormalities in brain morphology.

The literature reviewed on the association between DUP and risk of subsequent psychotic episodes was not of sufficient strength to draw conclusions.

In order to address this unanswered question, and the question of the influence of DUP on long-term prognosis, we examined a recent study by Crumlish and colleagues (2). In this prospective, naturalistic cohort study, 118 consecutively referred patients with first-episode psychosis were followed for 8 years. DUP was found to predict remission, positive symptoms and

social functioning at 8 years.

Conclusion: The studies reviewed support the view that a prolonged DUP predicts a worse prognosis both in the short term and in the long term course and outcome of schizophrenia. Because the DUP is probably influenced by other factors that are known to affect prognosis in schizophrenia, such as: poor insight, negative symptoms, lack of social support and an indolent onset, it could be hard to determine to what degree DUP is an independent prognostic factor. The question could be answered if randomized controlled trials of intervention vs. non-intervention were conducted, but this option seems ethically implausible.

References: 1. Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: A critical review and meta-analysis Am J Psychiatry 2005;162:1785-1804.

2. Crumlish N, Whitty P, Clarke M, Browne S, Kamali M, Gervin M, McTigue O, Kinsella A, Waddington JL, Larkin C, Oâ&#x20AC;&#x2122;Callaghan E. Beyond the critical period: Longitudinal study of 8-year outcome in first-episode non-affective psychosis. Br J Psychiatry 2009;194:18-24.

Acknowledgements The weekend was supported by the Israeli Biological Psychiatry Association and AstraZeneca.

Correction: In "The relationship between type of insurance, time period and length of stay in psychiatric hospitals: The Israeli case" by Bodner, Sarel, Gilat and Iancu published in issue 4, 2010, vol. 47, pages 284-290, the third author's name was misspelled and should be Omri Gillath.

141

‫סיכום ישיבת ועד האיגוד הפסיכיאטרי ‪ -‬מרץ ‪2011‬‬ ‫‪1 .1‬במסגרת המשא ומתן בין ההסתדרות הרפואית לאוצר‪ ,‬הוכרה‬ ‫הפסיכיאטריה של ילדים ונוער כמקצוע במצוקה‪.‬‬ ‫‪2 .2‬המרכזים לברה"נ במזרע ובב"ש הוכרו כמוסדות בפריפריה‪.‬‬ ‫‪3 .3‬הועברה בקשה לראש שירותי בריאות הנפש במשרד הבריאות‬ ‫למנות נציג לוועדת סל התרופות לשם הצגת הצרכים‬ ‫המקצועיים בתחום הפסיכיאטריה‪ ,‬זאת לאור התוצאות‬ ‫העגומות של החלטות הוועדה בשנה שעברה‪.‬‬ ‫‪4 .4‬טופס ההסכמה מדעת לטיפול בנזעי חשמל הועבר לאישור‬ ‫הלשכה המשפטית במשרד הבריאות‪ ,‬טרם הכנסתו לשימוש‪.‬‬ ‫‪5 .5‬התייחסות יו"ר ההסתדרות הרפואית לחוזר מנהל הרפואה‬ ‫לגבי אמות המידה לאבחון הפרעת קשב וריכוז‪ ,‬הופצה לחברי‬ ‫האיגוד‪.‬‬ ‫‪6 .6‬המועצה הלאומית לברה"נ תומכת בהפעלת יחידות משפטיות‬ ‫בכל המרכזים ותקנון מנהלים ליחידות‪.‬‬ ‫‪7 .7‬יקודמו יחסי הגומלין והשת"פ עם האיגודים הבאים‪:‬‬ ‫ •האיגוד הפסיכיאטרי הרוסי ‪ -‬האחראי לתיאום עמם הוא‬ ‫ד"ר טיטלבאום‪.‬‬ ‫ •האיגוד הפסיכיאטרי הצרפתי ‪ -‬האחראי לתיאום עמם‬ ‫הוא ד"ר קרון‪.‬‬ ‫ •האיגוד הפסיכיאטרי האוקראיני ‪ -‬האחראי לתיאום עמם‬ ‫הוא ד"ר יופה‪.‬‬

‫‪ 23‬במרץ ‪2011‬‬

‫‪8 .8‬הצעות למועמדים פוטנציאליים ל"אות מפעל חיים" יועברו‬ ‫למזכיר האיגוד‪ .‬הבחירה תיעשה לאור הקריטריונים הקיימים‬ ‫ותוך שקיפות מלאה‪.‬‬ ‫‪9 .9‬הסילבוס של תוכנית ההתמחות המתוקן והמותאם יועבר‬ ‫להסתדרות הרפואית‪.‬‬ ‫‪1010‬האיגוד מאשר שוב את תמיכתו בהעברת האחריות לברה"נ‬ ‫לקופות החולים‪ ,‬במתכונת ובהתניות הר"י‪ ,‬תוך תמיכה בלתי‬ ‫מסויגת בכך שאם לא תועבר האחריות עד ל־‪01/07/2011‬‬ ‫תורד ההצעה מסדר היום‪ .‬משרד הבריאות מתבקש לפנות‬ ‫למשרד האוצר בבקשה להעברת התקציב החסר (כ־‪ 400‬מש"ח)‬ ‫ולהפעיל את התוכנית החלופית‪ ,‬תוך הטלת האחריות להפעלת‬ ‫השירותים הדרושים על המדינה‪.‬‬ ‫‪1111‬הכנס התלת שנתי יתקיים ב–‪ 2012‬בת"א בין התאריכים ‪.15-17/5‬‬ ‫‪1212‬האיגוד שותף בפרויקט ויקי–רפואה עם האיגוד לרפואת המשפחה‪.‬‬ ‫‪1313‬האיגוד תומך בפסיכולוגים הקליניים‪ ,‬בהמשך לתיקון סעיף ‪ 9‬ב'‬ ‫לחוק הפסיכולוגים‪ ,‬לגבי העיסוק בפסיכותרפיה‪ .‬לפי החוק "חל‬ ‫איסור על פסיכולוג להציע או לבצע שירות הדורש מומחיות‪,‬‬ ‫מיומנות או הכשרה מיוחדת‪ ,‬אלא אם כן יש לו מומחיות‪,‬‬ ‫מיומנות או הכשרה‪ ,‬כאמור‪ ,‬למתן השירות‪ ,‬בהתאם לתוכנית‬ ‫הלימודים ותוכנית ההתמחות"‪.‬‬ ‫בברכה‪,‬‬ ‫פרופ' זאב קפלן‬ ‫יו"ר האיגוד הפסיכיאטרי‬

‫כן תיבדק האפשרות למושבים משותפים בכינוס ‪ 2012‬בת"א‪.‬‬

‫איגוד הפסיכיאטריה בישראל ‪ -‬ההסתדרות הרפואית ‪ -‬המועצה המדעית‬ ‫‪Israeli Psychiatric Association‬‬

‫יו"ר‪ :‬פרופ' זאב קפלן ‪President: Prof. Z. Kaplan /‬‬ ‫‪Zeev.kaplan@pbsh.health.gov.il‬‬ ‫מזכיר‪ :‬ד"ר נמרוד גריסרו ‪Secretary: Dr. N. Grisaru /‬‬ ‫‪grisarun@gmail.com‬‬ ‫גזבר‪ :‬ד"ר בוריס נמץ ‪Treasurer: Dr. B. Nemets /‬‬ ‫‪nemetz@bgu.ac.il‬‬

‫המרכז לבריאות הנפש באר שבע‬ ‫‪Beer-Sheva Mental Health Center‬‬

‫ טל'‪ ;08-6401606 :‬פקס‪08-6401621 :‬‬ ‫ רח' הצדיק מירושלים ‪ ,2‬באר שבע‪ ,‬ת"ד ‪ 4600‬‬ ‫ ‪Hazadik from Jerusalem St. P.O. Box 4600‬‬ ‫ ‪www.psychiatry.org.il‬‬

‫יו"ר נבחר‪ :‬פרופ' משה קוטלר ‪Elected President: Prof. M. Kotler /‬‬ ‫‪Moshe.kotler@beerness.health.gov.il‬‬

‫יו"ר יוצא ואחראי קשרי חו"ל‪ :‬פרופ' אבי בלייך ‪/‬‬ ‫‪President Emeritus and Foreign Affairs: Prof. A. Bleich‬‬ ‫‪lean@bgu.ac.il ,ableich@lev-hasharon.co.il‬‬

‫‪142‬‬

‫קוגניטיביים אצל בעלי חרדה חברתית נבחנו בהרחבה‪ ,‬אפיוני‬ ‫הקוגניציה החברתית שלהם לא נבחנו מעולם‪ .‬במחקר הנוכחי‬ ‫שוער כי בעלי חרדה חברתית גבוהה עשויים להציג יכולות גבוהות‬ ‫של אמפתיה ושל מנטליזציה (‪.)Theory of Mind‬‬ ‫שיטה‪ :‬הערכת יכולות האמפתיה נעשתה באמצעות סולמות לדיווח‬ ‫עצמי של בעלי חרדה חברתית גבוהה (‪ 21‬משתתפים) ושל בעלי‬ ‫חרדה חברתית נמוכה (‪ 22‬משתתפים)‪ ,‬בהתבסס על ציונם בסולם‬ ‫לייבוביץ' להערכת חרדה חברתית‪ .‬נעשה שימוש במטלה ממוחשבת‬ ‫כדי לבחון את היכולת להעריך ייחוסי מצב מנטלי אפקטיבי (רגשי)‬ ‫לעומת מצב מנטלי קוגניטיבי (שאינו רגשי)‪ ,‬מדרגה ראשונה ושנייה‪.‬‬ ‫תוצאות‪ :‬בעלי חרדה חברתית גבוהה הפגינו נטיות גבוהות‬ ‫לאמפתיה אפקטיבית‪ .‬אולם‪ ,‬כשמשתנה החרדה הכללית הוגדר‬ ‫כמשתנה הקבוע‪ ,‬נמצא כי חרדה חברתית נקשרה עם מדדי אמפתיה‬ ‫קוגניטיבית ולא עם מדדי אמפתיה אפקטיבית‪ .‬נוסף לכך‪ ,‬בעלי חרדה‬ ‫חברתית גבוהה השיגו רמות דיוק גבוהות בתנאי הייחוס המנטלי‬ ‫האפקטיבי בהשוואה לבעלי חרדה חברתית נמוכה‪ ,‬אך היו פחות‬ ‫מדויקים מהם בייחוס מצב מנטלי קוגניטיבי בתנאים מקבילים‪.‬‬ ‫מגבלות‪ :‬נחוץ מחקר המשך הכולל מדגם רחב יותר ואוכלוסיה‬ ‫המאובחנת באופן קליני כלוקה בהפרעת חרדה חברתית‪.‬‬ ‫מסקנות‪ :‬הממצאים תומכים בהשערה כי בעלי חרדה חברתית גבוהה‬ ‫עשויים להציג פרופיל ייחודי של יכולות קוגניציה חברתית‪ ,‬עם נטיות‬ ‫גבוהות לאמפתיה קוגניטיבית ודיוק בייחוסי מצב מנטלי אפקטיבי‪.‬‬ ‫אחריות המטפל על מעשי המטופל‬ ‫(כללי טרסוף)‪ :‬עמדת הפסיכיאטרים‬ ‫י‪ .‬מלמד‪ ,‬י‪ .‬אור‪ ,‬ד‪ .‬רודינסקי‪ ,‬ש‪ .‬כהן‪ ,‬מ‪ .‬גלגופף‪ ,‬א‪ .‬לרנר‬ ‫וא‪ .‬בלייך‪ ,‬נתניה‬

‫רקע ומטרות‪ :‬סודיות רפואית ואחריות המטפל כלפי החברה‬ ‫עשויים להוות אתגר בקשר התרפויטי בין הפסיכיאטר למטופל‪.‬‬ ‫בדקנו את עמדותיהם של פסיכיאטרים מומחים ישראלים באשר‬ ‫לחובתם להזהיר ולהגן לפי כללי טרסוף‪.‬‬ ‫שיטות‪ :‬שאלונים לבדיקת דעותיהם של פסיכיאטרים מומחים‬ ‫לגבי יישום כללי טרסוף בישראל נשלחו לפסיכיאטרים מומחים‬ ‫בכירים למילוי אנונימי‪.‬‬ ‫תוצאות‪ )64%( 108 :‬שאלונים הוחזרו‪ )57%( 61 .‬ענו שנתקלו‬ ‫במצבים דומים‪.‬‬ ‫מסקנות‪ :‬הבנה מעמיקה של כללי טרסוף‪ ,‬בירור הסיכון‬ ‫הפוטנציאלי של המטופל ודיון מוקדם בנושא יסייע למטפל‪ .‬בדיקת‬ ‫הקונצנזוס הרפואי בקרב רופאים בכירים‪ ,‬כפי שנעשה בסקר שלנו‪,‬‬ ‫היא נקודת התייחסות לגיבוש דעה בנושא‪.‬‬ ‫הקשר בין הקטגוריות הפסיכו־סוציאליות של ‪ICD-10‬‬

‫והאבחנה הפסיכיאטרית במתבגרים ישראלים‬

‫ס‪ .‬פניג‪ ,‬א‪ .‬אפטר‪ ,‬נ‪ .‬חורש‪ ,‬ר‪ .‬ארצי‪ ,‬ג‪ .‬זלצמן‪ ,‬א‪ .‬ויצמן‬ ‫וש‪ .‬פניג‪ ,‬תל אביב‬

‫רקע‪ :‬דחק נפשי נמצא כגורם סיכון משמעותי להפרעות‬ ‫פסיכיאטריות‪ .‬יש צורך בהערכה תקיפה ומהימנה של הדחק‬ ‫‪143‬‬

‫הפסיכו–סוציאלי שתתבסס על מקורות מידע שונים‪ .‬ועדה בארגון‬ ‫הפסיכיאטרי העולמי הגדירה קריטריונים ספציפיים לאבחון‪,‬‬ ‫המאפשרים הערכה פסיכו–סוציאלית מהימנה ורלבנטית באוכלוסיה‬ ‫של מתבגרים וילדים הסובלים מהפרעות נפשיות קשות‪.‬‬ ‫מטרה‪ :‬לבדוק את הקשר בין הקטגוריות הפסיכו–סוציאליות‬ ‫כפי שהתקבלו מריאיון מובנה למחצה (ציר ‪ V‬של ‪)ICD-10‬‬ ‫לבין אבחנות פסיכיאטריות קליניות באוכלוסיה של מתבגרים‬ ‫המאושפזים במחלקה פסיכיאטרית‪.‬‬ ‫שיטות‪ :‬אוכלוסיית המחקר מנתה ‪ 71‬חולים שאושפזו במחלקה‬ ‫הפסיכיאטרית ואמותיהם‪ .‬האמהות עברו ריאיון חצי‪-‬מובנה‬ ‫שנגזר מהקטגוריות הפסיכו–סוציאליות של ציר ‪ V‬של ‪ICD-10‬‬ ‫ואילו המתבגרים אובחנו על ידי פסיכיאטרים מומחים שהשתמשו‬ ‫בריאיון המובנה של ‪.K-SADS-P‬‬ ‫תוצאות‪ :‬אנורקסיה נרבוזה והפרעות התנהגות נמצאו קשורות‬ ‫לקטגוריה של "בעיות אבנורמליות בגידול" ואילו הפרעות‬ ‫התנהגות וסכיזופרניה נמצאו כקשורות לקטגוריה של "אירועים‬ ‫הקשורים‪/‬נוצרו על ידי התנהגותו של הילד"‪.‬‬ ‫מסקנות‪ :‬הערכה סיסטמטית של הקטגוריות הפסיכו–סוציאליות‬ ‫הוסיפה מידע ספציפי התומך בתקפות האבחנה על ציר ‪.I‬‬ ‫אפיונים משפחתיים הקשורים‬ ‫לבעיות התנהגותיות בילדות‬ ‫א‪.‬פ‪.‬ריעה‪ ,‬מ‪.‬ג'‪.‬פינו וח‪.‬הרוזו‪ ,‬קורדובה‪ ,‬ספרד‬

‫מטרת מחקר זה היא לבחון אם יש הבדלים בהרגלי ההורות בין‬ ‫שתי קבוצות של ילדים שהיו בעלי מדדים לסיכון נמוך ולסיכון‬ ‫גבוה ביחס לבעיות התנהגות‪ ,‬וכן לבחון אילו אפיוני הורות‬ ‫קשורים לקיום או להיעדר סוג זה של התנהגות בעייתית‪.‬‬ ‫במחקר השוו בין מדגם של ‪ 30‬ילדים בגילאי ‪ 14-6‬עם מדדי סיכון‬ ‫לבעיות התנהגות לפי שיטה להערכת התנהגות לילדים (‪)BASC‬‬ ‫לבין קבוצה דומה של ילדים עם מדדי סיכון נמוכים‪ .‬שני ההורים‬ ‫של כל ילד מילאו שאלון קשר הורה–ילד (‪ )PCRI‬ובוצע ניתוח‬ ‫‪ .binomial logistic regression analysis‬ניתוח זה סיפק מודל ניבוי‬ ‫ל–‪ 80%‬מהמדגם‪ ,‬המורכב מאפיוני ההורות הבאים‪ :‬תקשורת ו–‪role‬‬ ‫‪ orientation‬מן האמהות‪ ,‬תמיכה הורית‪ ,‬אוטונומיה והצבת גבולות‬ ‫על ידי אבות (נמצא כמאפיין המשמעותי ביותר)‪.‬‬ ‫לסיכום‪ ,‬נידונו השלכות הממצאים על התערבויות טיפוליות בתוך‬ ‫המשפחה‪.‬‬ ‫טאכיפילאקסיס‪/‬סבילות (‪)Tachyphylaxis/Tolerance‬‬ ‫לתרופות נוגדות דיכאון ‪ -‬סקירת ספרות‬ ‫ג‪ .‬כץ‪ ,‬ירושלים‬

‫טאכיפילאקסיס היא תופעה של ירידה משמעותית בעוצמת‬ ‫התגובה של הגוף לחומרים ביו–אקטיביים (כולל תרופות) לאחר‬ ‫שימוש חוזר בהם‪ .‬התופעה עלולה להופיע גם במהלך שימוש‬ ‫בתרופות נוגדות דיכאון ובמיוחד בתרופות מסוג ‪.SSRI‬‬ ‫המאמר סוקר את ממצאי הספרות לגבי היקף התופעה‪ ,‬הסיבות‬ ‫להופעתה והדרכים לטפל בה‪.‬‬

‫כתב עת ישראלי‬ ‫לפסיכיאטריה‬ ‫תקצירים‬ ‫שיעורי רגשות מפורשים (‪ )EE‬אצל קרובי‬ ‫משפחה של חולי סכיזופרניה בפקיסטן‬ ‫א‪ .‬איקרם‪ ,‬ק‪ .‬סוהייל‪ ,‬ס‪.‬ג‪ .‬ג'אפרי וס‪ .‬סינג‪ ,‬לאהור‪ ,‬פקיסטן‬

‫רקע‪ :‬מחקרים הראו הבדלים משמעותיים בשיעור הרגשות‬ ‫המפורשים (‪ )EE‬אצל קרובים של חולי סכיזופרניה בתרבויות‬ ‫שונות‪ .‬מחקר זה הוא ניסיון ראשון למדוד את המרכיבים של ‪EE‬‬ ‫אצל קרובי משפחה של חולי סכיזופרניה בפקיסטן‪ ,‬במארג חברתי‬ ‫־תרבותי שונה ממחקרים קודמים‪.‬‬ ‫שיטה‪ :‬שלושים ושניים קרובים של חולי סכיזופרניה רואיינו‬ ‫בשיטת הריאיון המשפחתי ע"ש קאמברוול (‪ )CFI‬וכן נבדק מדגם‬ ‫דיבור של חמש דקות (‪.)FMSS‬‬ ‫תוצאות‪ :‬אצל ‪ 75%‬מהקרובים נמצא ‪ EE‬גבוה‪ ,‬לרוב (‪)59%‬‬ ‫בהתייחסות למרכיב תוקפנות מילולית בלבד‪ .‬המדד של התוקפנות‬ ‫אצל קרובי המשפחה הושפע בעיקר מהתנהגות סימפטומתית של‬ ‫החולה‪ .‬קרובים מפקיסטן הראו רמות גבוהות יותר של מעורבות‬ ‫יתר רגשית ותוקפנות לעומת תרבויות רבות אחרות‪ .‬בהשוואה‬ ‫ל–‪ ,CFI‬המדד של ‪ FMSS‬היה פחות רגיש באיתור קרובי משפחה‬ ‫עם ‪ EE‬גבוה‪ ,‬ויתכן שמדד זה אינו מתאים לשימוש כמדד יחיד‬ ‫בפקיסטן מסיבות תרבותיות‪.‬‬ ‫מגבלות‪ :‬היעדר נתוני מעקב ומדגם קטן מגבילים את משמעות המחקר‪.‬‬ ‫מסקנות‪ :‬אף על פי שנראה כי ‪ EE‬אינה תסמונת תלוית תרבות‬ ‫אצל משפחות בפקיסטן עם פרופיל ‪ EE‬מוכר‪ ,‬נראה שאצל קרובי‬ ‫משפחה של חולים בפקיסטן נמדדת יותר עוינות‪ ,‬אך גם מעורבות‬ ‫יתר רגשית וחום כלפי קרוביהם החולים בהשוואה למשפחות‬ ‫מדווחות במחקרים רבים אחרים‪.‬‬ ‫טיפול תרופתי מניעתי בסכיזופרניה ‪-‬‬ ‫גישה חדשה ומתפתחת‬ ‫ר‪ .‬סבג‪ ,‬ר‪ .‬לוין‪ ,‬ש‪ .‬אדלמן וא‪ .‬הרסקו־לוי‪ ,‬ירושלים‬

‫הטיפול בסכיזופרניה היה ונותר אחד האתגרים הגדולים של‬ ‫הרפואה המודרנית‪ .‬פיתוח גישות פרמקולוגיות חדשות לטיפול‬ ‫בהפרעה זו יכול להקל על סבלם הנוראי של החולים ולהביא‬ ‫למהפכה בשירותי בריאות הנפש‪.‬‬ ‫לעומת נוהלי הטיפול הנוכחיים‪ ,‬המתייחסים לשלבים שאחרי‬ ‫התפרצות הפסיכוזה במחלה‪ ,‬יש כיום עניין רב בהתערבות‬ ‫טיפולית מניעתית עוד בשלב הפרודרום של הסכיזופרניה‪.‬‬ ‫התפתחות זו נובעת בעיקר מההבנה שתהליכי ניוון נוירו–‬

‫‪israel journal of‬‬

‫‪psychiatry‬‬ ‫כרך ‪ ,48‬מס' ‪2011 ,2‬‬

‫ביולוגיים הקשורים לחומרה של הסכיזופרניה ולכרוניות שלה‬ ‫כבר מתרחשים בזמן שהתסמינים הקליניים ניכרים‪ .‬הטיפולים‬ ‫המניעתיים המוצעים כוללים תרופות הנמצאות בשימוש כיום‬ ‫ותרכובות ניסיוניות‪ ,‬שייתכן שיש להן פוטנציאל להשפיע על‬ ‫התהליכים הפתופיזיולוגיים בתחילת דרכם‪ .‬עתידו של רעיון‬ ‫הזיהוי וההתערבות המוקדמים בסכיזופרניה תלוי במידה רבה‬ ‫בתוצאותיהם של מחקרים שיעריכו את היכולת לאבחן את שלב‬ ‫הפרודרום‪ ,‬את יעילותו של הטיפול התרופתי ואת הדרכים לצמצם‬ ‫את החסרונות הכרוכים בטיפול תרופתי מוקדם‪.‬‬ ‫השוואה בין טיפול באמצעות מציאות‬ ‫מדומה לטיפול קוגניטיבי לאנשים הסובלים‬ ‫מפחד הרצאה בפני קהל‪ :‬מחקר פיילוט‬ ‫ה‪ .‬וולך‪ ,‬מ‪.‬פ‪ .‬ספיר ומ‪ .‬בר־צבי‪ ,‬חיפה‬

‫מטרות‪ :‬מחקר זה נועד לבחון את היעילות של חשיפה באמצעות‬ ‫מציאות מדומה (חמ"מ) לעומת טיפול קוגניטיבי (ט"ק) וטיפול‬ ‫התנהגותי־קוגניטיבי (טה"ק)‪.‬‬ ‫שיטה‪ :‬עשרים נבקדים הסובלים מחרדת הרצאה בפני קהל‬ ‫(חהב"ק) חולקו באופן רנדומלי לשתי קבוצות טיפול‪ ,‬חמ"מ‬ ‫(‪ )10‬וט"ק (‪ ,)10‬והשתתפו ב־‪ 12‬פגישות טיפוליות שבהן נעשה‬ ‫שימוש בחוברות טיפול מובנות‪ .‬התוצאות (שאלונים ודירוג מטלה‬ ‫התנהגותית על ידי הנבדק ועל ידי משקיף) הושוו לתוצאות מחקר‬ ‫קודם שבו קבוצה אחת טופלה בטה"ק (‪ )28‬וקבוצה אחרת שימשה‬ ‫כקבוצת המתנה (‪.)30‬‬ ‫תוצאות‪ :‬ט"ק לא היה יעיל יותר מחמ"מ בבחינת המדדים‬ ‫הקוגניטיביים‪ ,‬והיה יעיל יותר מחמ"מ במדד התנהגותי יחיד‬ ‫(‪ .)LSAS fear‬חמ"מ היה יעיל יותר מט"ק במדד התנהגותי יחיד‬ ‫(חרדה במטלה התנהגותית)‪ .‬לא נמצאו הבדלים בין חמ"מ לט"ק‬ ‫וטה"ק וכולם היו יעילים יותר מקבוצת המתנה‪.‬‬ ‫מגבלות‪ :‬קבוצות הנבדקים היו קטנות והומוגניות‪ .‬רצוי לחזור על‬ ‫המחקר עם קבוצות גדולות יותר והטרוגניות יותר‪ .‬כמו כן רצוי‬ ‫לשקול להגדיל את מספר הפגישות הטיפוליות‪.‬‬ ‫מסקנות‪ :‬שני סוגי הטיפול‪ ,‬חמ"מ וט"ק‪ ,‬הוכיחו את יעילותם‬ ‫בטיפול בחרדת הרצאה לפני קהל‪ ,‬בהבדלים מינוריים ביניהם‪.‬‬ ‫לפיכך אפשר להשתמש ביעילות בכל אחד מהם‪.‬‬ ‫קוגניציה חברתית בחרדה חברתית‪:‬‬ ‫עדות ראשונה ליכולות אמפתיה גבוהות‬ ‫י‪ .‬טיבי־אלחנני וס‪ .‬שמאי־צורי‬

‫רקע‪ :‬נמצא כי אנשים הסובלים מחרדה חברתית מגלים רגישות‬ ‫מוגברת למצב רוחם של אנשים אחרים‪ .‬אף על פי שתהליכים‬ ‫‪144‬‬