201002_psychiatry

israel journal of

psychiatry

A NEW treatment option for Major Depressive Episodes.

Vol. 47 - Number 2 2010

ISSN: 0333-7308

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Editorial: Developmental Psychopathology Doron Gothelf, Tamar Steinberg, Ofer Golan, Alan Apter

95 Volume 47, Number 2, 2010 Israel Journal of Psychiatry and Related Sciences

The Historical Origins and Developmental Pathways of the Discipline of Developmental Psychopathology Sheree L. Toth, Dante Cicchetti

Today she took a giant leap.

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Tourette's Syndrome: a Review from a Developmental Perspective Tamar Steinberg, Robert King, Alan Apter

110

The Neurodevelopmental Theory of Schizophrenia: Evidence From Studies of Early Onset Cases Jess Kinros, Abraham Reichenberg, Sophia Frangou

118

Social-Sexual Education in Adolescents with Behavioral Neurogenetic Syndromes Maya Plaks, Ronit Argaman, Mike Stawski, Tova Qwiat, Dan Polak, Doron Gothelf

125

Auditory and Visual Processing in Williams Syndrome Omer Zarchi, Joseph Attias, Doron Gothelf

132

Gender Identity Disorder: A Literature Review from a Developmental Perspective Tomer Shechner

139

Environmental risk factors for psychopathology Karin Schlossberg, Anda Massler, Gil Zalsman

Symptoms of low motivation and energy in patients with major depression have been associated with noradrenaline and dopamine dysfunction.1 Now there is an alternative: Wellbutrin XR, a dual acting antidepressant, providing both Noradrenaline and Dopamine Re-uptake Inhibition (NDRI).2, 3 References 1. Nutt DJ, Demyttenaere K, Janka Z, Aarre T, Bourin M, Canonico PL, et al. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J Psychopharmacol 2007; 21: 461-471.

2 . Stahl SM, Pradko JF, Haight BR et al (2004) A review of the neuropharmacology of bupropion a dual Norepinephrine and dopamine reuptake inhibitor. Prim Care Companion, J Clin Psychiatry, 6, 159-166.

3. Fava M, Rush AJ, Thase ME, Clayton A, Stahl SM, Pradko JF, et al. 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL. Prim Care Companion J Clin Psychiatry 2005; 7: 106-13.

Special section:

The ONLY Noradrenaline & Dopamine Re-uptake Inhibitor.

‫י‬Developmental ‫ י‬Psychopathology

144

Genetic and Environmental Links between Children’s Temperament and their Problems with Peers Maya Benish-Weisman, Tamar Steinberg, Ariel Knafo

israel journal of

psychiatry and related sciences EDitor

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Rael Strous Editorial Board

Alean Al-Krenawi Alan Apter Yoram Barak Elliot Gershon Talma Hendler Ehud Klein Ilana Kremer ltzhak Levav Yuval Melamed Shlomo Mendlovic David Roe Ronnen Segman Eliezer Witztum Zvi Zemishlany International Advisory Board

Yoram Bilu Aaron Bodenheimer Carl Eisdorfer Julian Leff Margarete Mitscherlich-Nielsen Peter Neubauer Phyllis Palgi Leo Rangell Melvin Sabshin Robert Wallerstein Myrna Weissman

‫י‬Developmental ‫ י‬Psychopathology 93 > Editorial: Developmental Psychopathology Doron Gothelf, Tamar Steinberg, Ofer Golan, Alan Apter

95 > The Historical Origins and Developmental Pathways of the Discipline of Developmental Psychopathology Sheree L. Toth, Dante Cicchetti

105 > Tourette's Syndrome:

a Review from a Developmental Perspective Tamar Steinberg, Robert King, Alan Apter

110 > The Neurodevelopmental Theory Of Schizophrenia: Evidence From Studies of Early Onset Cases Jess Kinros, Abraham Reichenberg, Sophia Frangou

118 > Social-Sexual Education in Adolescents with Behavioral Neurogenetic Syndromes Maya Plaks, Ronit Argaman, Mike Stawski, Tova Qwiat, Dan Polak, Doron Gothelf

The Official Publication of the Israel Psychiatric Association Vol. 47 - Number 2 2010

125 > Auditory and Visual Processing in Williams Syndrome Omer Zarchi, Joseph Attias, Doron Gothelf

132 > Gender Identity Disorder: A Literature Review from a Developmental Perspective Tomer Shechner

139 > Environmental risk factors for psychopathology Karin Schlossberg, Anda Massler, Gil Zalsman

144 > Genetic and Environmental Links between Children’s Temperament and their Problems with Peers Maya Benish-Weisman, Tamar Steinberg, Ariel Knafo

152 > Correspondence, Obituary, Book Reviews Narayana Manjunatha & G Roopa, Leo Sher et al., Mehmet E Ceylan et al., Itzhak Levav, Assaf Shelef, Natan PF Kellermann, Alan Apter, Pesach Lichtenberg Hebrew Section

160 > News and Notes 162 > Abstracts

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Shula Ben-Daat Alperovitch, diagnosed as having bipolar disorder, past director of a consumer program, Benafshenu, and on the board of Lishma consumer organization. Concerning the picture: "The sensations of inner parts and feelings that gather shape were very strong during my therapy dealing with early traumas. The parts are women, children or feelings consolidating into shapes expressing turbulence, sorrow, confusion, distance and connection."

Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Editorial: Developmental Psychopathology With the intensifying focus on the proposed revision of the Diagnostic and Statistical Manual (DSM-5) in 2013, the role of development in the conceptualization of psychiatric diagnosis will hopefully gain more recognition.

Unfortunately, previous versions of the DSM included only brief considerations of developmental themes.

In the early parts of the last century developmental psychiatry was dominated by so-called “Grand Theories” of development which were derived mainly from philosophy and psychoanalysis. Although the insights from these theories continue to be a rich source for hypothesis building and prospective research, their early promise of explaining all of psychopathology proved disappointing. The “Grand Theories” were replaced, therefore, by painstaking evidence based research which has attacked much smaller issues. However, as this body of study increases in substance, it is becoming increasingly apparent that psychiatrists need to base their clinical work on sound developmental theory. Perhaps the most important landmark for this approach was the publication by Donald Cohen and Dante Cicchetti of their seminal work Developmental psychopathology: Theory and method (1). In the introductory presentation of this special issue, Toth and Cicchetti describe the evolution and principles of Developmental Psychopathology and how such principles are fundamental for understanding child psychiatric disorders.

It is our suggestion that one of the major frameworks for the new DSM-5 revision needs to be developmental and thus the publication of the present issue of the Israel Journal of Psychiatry and Related Sciences is extremely timely. This is perhaps even more so as the late Donald Cohen had a major role in the development of this Journal.

It is now well established that most psychiatric disorders have strong genetic predispositions with abnormal brain development trajectories. Two papers this special issue are devoted to Tourette syndrome and autism, diseases with strong genetic diatheses and a developmental emergence of both psychiatric and neurological symptoms. Despite intensive research, the genetic variants associated with the genetic risk for these neuropsychiatric disorders are as yet uncertain.

With advancements in molecular biology and cytogenetics we are now able to screen the whole genome 93

for the presence of small microdeletions and microduplications collectively termed copy number variations (CNVs). CNVs currently account for the etiology of autism in 10%-20% (2), and there is evidence for the important role of CNVs in other psychiatric disorders, such as schizophrenia (3). Two papers in this special issue focus on microdeletion syndromes – velocardiofacial syndrome and Williams syndrome – associated with unique psychiatric, cognitive and behavioral phenotypes. Velocardiofacial is the most common known genetic risk factor for schizophrenia and Williams syndrome is associated with characteristic deficits in auditory processing and a distinct social phenotype.

Developmental psychopathology is thus an excellent framework for understanding a myriad of psychiatric disorders with distinctive abnormal neurodevelopmental trajectories, such as early onset schizophrenia (reviewed in the special issue by Kinros et al.). It is also a context for understanding extreme behaviors, such as gender identity disorder which according to the review

by Schechner is a form of gender behavior which should be understood as a continuum rather than as a dichotomy of normal versus abnormal categories.

Developmental psychopathology is also important for formulations of normal development. Research by Weismann et al. in the current special issue shows how early psychological traits – temperament of children – are strongly associated with development of peer relations and problems with peers.

It is now well recognized that there are sensitive periods in core psychological functions, such as language acquisition. Traumatic events – such as brain injury, or adverse psychosocial events – occurring early in life, may cause life disruptions in language acquisition with more-marked effects on adult functioning than if these same experiences occur later in life (4).

According to Pine (4), charting children’s ongoing development, as opposed to examining their functioning at any one specific point in time, is the best way to characterize such adverse effects. This reflects the fact that risk for poor outcome is higher among children who show consistent patterns of dysfunction over time than among children who show dysfunction at only one point in time. This suggests a view of psychopathology that highlights a child’s failure to undergo

Doron Gothelf et al.

typical, expected changes in behavior and cognition with maturation, or a child’s failure to overcome transient perturbations in function.

“Developmental Psychopathology” can be defined as the study of the development of psychological disorders.

Developmental psychopathology has the following (noncomprehensive) list of assumptions: 1. Atypical development and typical development are mutually informative. 2. Developmental psychopathology is not the study of pathological development, but the study of the basic mechanisms that cause developmental pathways to diverge toward pathological or typical outcomes. 3. Development leads to either adaptive or maladaptive outcomes and this depends to a great degree on the context in which the developmental process takes place. 4. Many variables influence development and research designs should incorporate multivariate designs to examine the mechanisms underlying development. 5. Development arises from a dynamic interplay of physiological, genetic, social, cognitive, emotional, and cultural influences across time (4).

Developmental Psychopathology thus attempts to understand atypical development in the context of a comparison with typical development. Pathology represents a failure of mature behaviors to appear or immature behaviors to disappear. For example, separation anxiety and stranger anxiety are well established developmental milestones but when they fail to disappear with development their persistence over time accounts for the majority of anxiety disorders seen in adulthood (4). Behavioral inhibition in infants may be a precursor for social anxiety disorders in adulthood and while most toddlers go through a period of intense fears their persistence during adolescence may be quite crippling. Many adolescents go through normal periods of social anxiety especially when meeting unfamiliar peers for the first time and this also has to be differentiated from social anxiety disorder.

Conduct and antisocial disorders is another area where the understanding of their appearance in the context of normal development is all important. Thus conduct disorders appearing de-novo in adolescence in most cases reflect social norms and most such individuals grow up to be useful members of society. Where this aberrant behavior begins in early childhood especially when associated with violence and in a non-group setting the prognosis is extremely poor.

Another area of developmental research which has become increasingly salient in recent years is the area of depression and suicide. It has become increasingly recognized that depression previously thought to be

an adult disease usually has its origin in childhood and adolescence. Interestingly depression becomes more common with the onset of puberty, especially in girls where it is preceded by the onset of a ruminative style of thinking. Suicide attempts and nonsuicidal self injury are highly concentrated in the adolescent period of life whereas suicide leading to death is far more common as adulthood ensues.

The importance of critical periods is now being increasingly recognized. There is accumulating evidence for the existence of a complex bidirectional gene environment interaction in causing psychiatric disorders, which is the topic of the review by Schlossberg et al. in this special issue. Epigenetics may lead to an understanding of how environment at a critical stage of development may impinge on gene structure and produce cross generational effects. These developmental influences sculpt the development of the brain circuitry devoted to processing danger and have been linked to developmental manifestations of clinically-significant anxiety (5).

While such advances are unlikely to impact current conceptualizations contained in DSM-5, their reverberating influences are likely to exert increasingly profound effects in future years. The list of examples of research based on the principles of developmental psychopathology is obviously infinite. In this issue we will try to highlight just some detailed illustrations of the importance of developmental psychopathology for our field in the hope that our issue will have some influence both on DSM-5 and perhaps even on DSM-6!

References 1. Cicchetti D, Cohen D (Eds.). Developmental psychopathology: Theory and method (Vol. 1, 2nd ed.). New York: Wiley, 2006.

2. Abrahams BS, Geschwind DH. Advances in autism genetics: On the threshold of a new neurobiology. Nat Rev Genet 2008;9:341-355.

3. International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008;455:237-241.

4. Pine DS. Editorial: Lessons learned on the quest to understand developmental psychopathology. J Child Psychol Psychiatry 2010;51:533-534.

5. Pine DS. Developing developmental psychopathology. J Child Psychol Psychiatry 2007;48:113-114.

Doron Gothelf, MD,1, 2 Tamar Steinberg, MD,2, 3 Ofer Golan, PhD,4 and Alan Apter, MD2,3 Guest Editors 1

The Child Psychiatry Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Centre, Tel

Hashomer, Israel.

gothelf@post.tau.ac.il 2

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

3

The Feinberg Child Study Center, Schneider Children's Medical Center of Israel, Petah Tikwa, Israel

4

Department of Psychology and Gonda Brain Science Center, Bar-Ilan University, Ramat Gan, Israel

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

The Historical Origins and Developmental Pathways of the Discipline of Developmental Psychopathology Sheree L. Toth, PhD,1 and Dante Cicchetti, PhD 1, 2 1

Mt. Hope Family Center,University of Rochester, Rochester, New York, U.S.A. Institute of Child Development, Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, U.S.A.

2

ABSTRACT The historical origins of the field of developmental psychopathology are discussed and the meaning of a developmental psychopathology perspective is described. The definitional principles and tenets of the discipline of developmental psychopathology are delineated and they are utilized to highlight diversity in process and outcome. The definitional principles that are discussed include: 1) the mutual interplay between the study of normality and psychopathology; 2) the importance of a multiple-levels of analysis and multidisciplinary approach; 3) the processes that contribute to resilient adaptation in the face of significant adversity; 4) translational research; and 5) implications for prevention and intervention. Examples derived from research and clinical contexts are provided to illustrate these principles. Advances in our knowledge base in developmental psychopathology not only have benefitted the scientific understanding of the relation between normal and abnormal development, but also have contributed to reducing the individual and societal burden of mental illness.

In this article, the historical origins and scientific advances in the field of developmental psychopathology are described and the principles that have guided its evolution are explicated. The definitional parameters of the discipline are then discussed. Examples of research derived from academic settings and from clinical research contexts are included to illustrate these principles. Finally, important directions for prevention and

intervention are proffered that possess implications for enhancing our understanding of normal and abnormal development and for reducing suffering in persons with mental disorders.

Historical Origins of Developmental Psychopathology The field of developmental psychopathology owes its emergence and coalescence to a number of historically based endeavors in a variety of disciplines, including embryology, genetics, the neurosciences, psychoanalysis, and clinical, developmental, and experimental psychology (1). Many of the great theorists in these influential disciplines have reasoned that we can learn more about the normal functioning of an organism by studying its pathology, and likewise, more about its pathology by investigating its normal condition (2). A number of these integrative thinkers conceived of psychopathology as a magnifying mirror in which normal biological and psychological processes could better be observed. Because these systematizers conceptualized psychopathology as a distortion or exaggeration of the normal condition, the study of pathological phenomena was thought to throw into sharper relief one’s understanding of normal processes.

A basic theme that appears in the writings of these earlier thinkers is that because all psychopathology can be conceived as a distortion, disturbance or degeneration of normal functioning, it thus follows that, if one wishes to understand pathology more fully, then one must understand the normal functioning against which psychopathology is compared (2). Not only is knowledge of normal biological, psychological and social pro-

Address for Correspondence: Sheree Toth, PhD, Director, Mt. Hope Family Center, Associate Professor, Clinical and Social Sciences in Psychology, University of Rochester, 187 Edinburgh Street, Rochester, NY 14608, U.S.A.   sheree_toth@urmc.rochester.edu.

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cesses extremely helpful for understanding, preventing and treating psychopathology, but also the deviations from normal development that are seen in pathological processes indicate in exciting ways how normal ontogenesis may be better investigated and understood.

Indeed, for many thinkers the very essence and uniqueness of a developmental psychopathology approach lies in its focus on both normal and abnormal, adaptive and maladaptive, ontogenetic processes (2-6).

The field of developmental psychopathology first came into ascendance during the 1970s, predominantly through being highlighted as an important perspective by researchers conducting prospective longitudinal studies of children at risk for developing schizophrenia (7). Also instrumental in the field’s emergence were epidemiological investigations of families exhibiting discord, disharmony, and disruption but where there was no parental mental disorder (8) and studies of the links between cumulative risk factors and developmental outcome (9). Likewise, research on the causes, correlates and consequences of secure and insecure attachment (10, 11), investigations of children with a variety of handicapping conditions (12-16), and studies in life span developmental psychology (17) were influential in furthering interest in developmental psychopathology. These investigations generated important knowledge about basic developmental processes in a variety of biological and psychological systems that provided a solid empirical basis against which developmental psychopathologists could discover new truths about the processes underlying adaptation and maladaptation, as well as the best means of preventing and treating psychopathology.

Over the course of the past four decades, developmental psychopathology has emerged as an integrative discipline that is the product of the confluence of various efforts that had been previously distinct and separate (1, 2, 18, 19). Rather than competing with existing theories and facts, the developmental psychopathology perspective represents a broad, integrative framework within which the contributions of separate disciplines can be realized in the larger context of understanding individual development and functioning. The principles of developmental psychopathology can provide the conceptual scaffolding for facilitating this multidisciplinary integration. Through the organizing principles of the concept of development and of systems theory, the discipline of developmental psychopathology has brought together fields of study and investigators that were once disparate in order to examine complex questions of the

etiology, course, and sequelae of psychopathology and resilience (19).

What is Developmental Psychopathology?

Although definitional divergence exists (19), developmental psychopathology is a scientific discipline whose predominant focus is elucidating the interplay among the biological, psychological and social-contextual aspects of normal and abnormal development across the lifespan (20). In recent years, developmental psychopathology has become increasingly contextual, multi-level, dynamic and multidisciplinary (21-23).

In one of the initial statements concerning the goals of developmental psychopathology, Cicchetti (1, p. 20) remarked, “Developmental psychopathology should bridge fields of study, span the life cycle, and aid in the discovery of important new truths about the processes underlying adaptation and maladaptation, as well as the best means of preventing or ameliorating psychopathology.” Cicchetti further commented, “This discipline should contribute greatly to reducing the dualisms that exist between the clinical study of and research into childhood and adult disorders, between the behavioral and biological sciences, between developmental psychology and psychopathology, and between basic and applied science” (p. 20).

Theorists and researchers in the field of developmental psychopathology strive to bring together, within a life span framework, the many contributions to the understanding of individuals at high risk for developing mental disorders as well as those who have already manifested such disorders. Developmental psychopathologists do not espouse or adhere to one particular theory that could account for all developmental phenomena (24, 25).

Rather, they seek to integrate knowledge across scientific disciplines at multiple levels of analysis and within and between developmental domains (21, 22, 26, 27).

Developmental psychopathologists also engage in a comprehensive evaluation of biological, psychological, social and cultural processes and strive to ascertain how the interaction among these multiple levels of analysis may influence individual differences, the continuity or discontinuity of adaptive or maladaptive behavioral patterns, and the pathways by which normal and pathological developmental outcomes may be achieved. In practice, this entails comprehension of and appreciation for the developmental transformations and 96

Historical Origins of Developmental Psychopathology

reorganizations that occur over time; an analysis of the risk and protective factors and mechanisms operating within and outside the individual and his or her environment over the course of lifespan development; the investigation of how emergent functions, competencies and developmental tasks modify the expression of a disorder or lead to new symptoms and difficulties; and the recognition that a particular stressor or set of stressful circumstances may eventuate in different biological and psychological difficulties, depending on when in the developmental period the stress occurs (28).

Moreover, various difficulties will constitute different meanings for an individual depending on cultural considerations (29), as well as an individual’s experiential history and current level of psychological and biological organization and functioning. Importantly, the increasing diversity among populations within and outside of the United States demands that developmental psychopathology must similarly evolve to adequately examine and intervene with racially and ethnically diverse groups (30). In an investigation of the role of cultural context in moderating associations between early risk and children’s adaptation in Israeli and Palestinian couples, culture-specific effects of risk and protective factors were found (31). Studies such as this highlight the importance of incorporating cultural considerations into diagnostic and treatment decisions. For example, because individuals in Puerto Rican and Hispanic cultures operate in the context of familism, which is defined as a strong identification to the family group, it may be more adaptive for adolescents in these cultures to remain dependent on parents for longer periods and to be less autonomy striving than adolescents from Eurocentric cultures (32).

Therefore, considerations of cultural context must be prominent when determining whether an individual has diverted onto a maladaptive pathway and when deciding whether, or how best, to intervene.

The dynamic interplay between risk and protective factors is conceived as influencing the developmental course through the impact it has on the quality of the organization of biological and psychological systems as the individual develops (28, 33). Developmental psychopathology research emphasizes probabilistic, rather than deterministic, models of dysfunction (25, 34).

However, various risk factors have been shown to be especially harmful to competent functioning, thereby promoting the development of psychopathology (24, 35). In addition, as risk factors become multiplicative, their influence on development becomes increasingly 97

pernicious (36). Thus, for example, being a teen parent in and of itself may not significantly increase the risk of developmental maladaptation in offspring; however, if the young mother resides within an impoverished community with frequent intra- and extra-familial violence present, then the likelihood of negative offspring adaptation increases exponentially. It is important to note that the establishment of a process or condition as a risk factor is not a simple matter and that, even when the predictive status of a risk factor has been confirmed, this represents the starting point of a developmental psychopathology analysis. For example, although negative attributional biases that are associated with depression have been established for both children and adults (e.g., 37, 38), a developmental psychopathology perspective requires an understanding of how these biases originate and develop (24).

Furthermore, attention to the protective factors that individuals possess and experience throughout development is critical, especially since these intra- and extra-organismic sources of protection may promote adaptation and resilience in their own right (39, 40).

In addition, some protective factors may be influential in preserving competent functioning in the context of specific risk factors (24). Research on biological, as well as psychological protective factors is vitally important for identifying processes that contribute to the development of either the recovery of function or resilient adaptation in the face of significant adversity (41). Moreover, understanding the dynamic transactions between risk and protective factors plays a central role in building developmentally informed models of prevention (42). If a given capacity, such as the failure to develop a secure attachment relationship with the primary caregiver, is identified as being a risk factor for maladaptation, and if it can be modified as a function of intervention, then the probability of successful adaptation is enhanced.

Through increasing the relative balance of protective processes over risk factors, the potential for righting the developmental course, attaining adaptive developmental pathways, and reducing the emergence of psychopathology may be achieved (43).

Developmental psychopathologists stress that disordered individuals may move between pathological and nonpathological forms of functioning. In addition, even in the midst of psychopathology, individuals may display adaptive and maladaptive processes so that it becomes possible to delimit the presence, nature, and boundaries of the underlying psychopathology.

Sheree L. Toth and dante cicchetti

Furthermore, developmental psychopathology is a perspective that is especially applicable to the investigation of transitional points in development across the life span (20, 44, 45). Development extends throughout the entire course of life, and adaptive and maladaptive processes emerge over the life span. It is only by examining a range of conditions and populations from infancy through adulthood and into old age that developmental continuities and discontinuities can be elucidated fully.

Studies on the emergence of conduct disorders serve to illustrate this point. For example, Moffitt (46, 47) has distinguished between childhood-onset (“life-coursepersistent”) and adolescent-onset (“adolescence-limited”) conduct disorders and has found that individuals with adolescent-onset behavior problems are less likely to engage in adult criminality than are those with life-course-persistent conduct disorders. In a similar developmental analysis of the continuity/discontinuity of early externalizing behavior problems, Campbell and her colleagues (48) have found that a number of intra- and extra-organismic factors affect continuity of behavior problems. For example, multiple risk factors, including high levels of early hyperactivity and aggression, in combination with high levels of negative parenting and family stress, have been associated with problems at school entry for boys.

The above examples highlight the fact that all periods of life usher in new biological and psychological challenges, strengths and vulnerabilities. From infancy through senescence, each period of life has its own developmental agenda and contributes in a unique manner to the past, present, and future organization of individual development. Rutter has conjectured that key life turning points may be times when the presence of protective mechanisms could help individuals redirect themselves from a risk trajectory onto a more adaptive developmental pathway (49, 50). Likewise, Toth and Cicchetti (51) have suggested that these periods of developmental transition may also afford opportunities when individuals are most amenable to profiting from therapeutic interventions.

Whereas change in functioning remains possible at each transitional turning point in development, prior adaptation does place constraints on subsequent adaptation. In particular, the longer an individual continues along a maladaptive ontogenic pathway, the more difficult it is to reclaim a normal developmental trajectory (5). Furthermore, recovery of function to an adaptive level of developmental organization is more likely to

occur following a period of pathology if the level of organization prior to the breakdown was a competent and adaptive one (52, 53).

With respect to the emergence of psychopathology, all stages of life are consequential in that the developmental process may undergo a pernicious turn toward mental disorder at any phase (46, 53-57). Many mental disorders have several distinct phases (25). The factors that are associated with the onset of a disorder may be very different from those that are associated with the cessation of a disorder or with its repeated occurrence (58, 59). For example, although genetic factors frequently are associated with the onset of a major depressive disorder, relapse has been linked with aspects of the family climate, such as negative expressed emotion (60). In contrast to the dichotomous world of mental disorder/ nondisorder held by many mental health providers, a developmental psychopathology perspective recognizes that normality often fades into abnormality, that adaptive and maladaptive may take on differing definitions depending on whether one’s time referent is immediate circumstances or long-term development, and that processes within the individual can be characterized as having shades or degrees of psychopathology (57).

Definitional Parameters of Developmental Psychopathology The Mutual Interplay Between Normal and Psychopathological Functioning

Although the field of developmental psychopathology focuses predominantly on the investigation of highrisk and disordered populations, a commitment to the importance of applying knowledge of normal development to the study of atypical populations also is inherent in this approach. Thus, even before the emergence of a psychopathological disorder, certain pathways signify adaptational failures in normal development that probabilistically forebode subsequent pathology (5). Similarly, a developmental psychopathology perspective recognizes the value in examining abnormality in order to enhance our understanding of normal processes. Accordingly, individuals who are at risk for the development of pathology but who do not manifest it and individuals who develop an actual mental disorder are of equal interest (61, 62). As such, developmental psychopathologists also are committed to understanding pathways to resilience – i.e., the attainment of competent adaptation despite exposure to conditions of adversity (40, 63).

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Historical Origins of Developmental Psychopathology

Despite the fact that the mutual interplay between normal and atypical development are emphasized within this discipline, most contemporary theory and research have focused on the contributions that normal development can make to advancing our knowledge of psychopathological processes. There has been significantly less recognition that the investigation of high-risk conditions and mental disorders can augment our comprehension of normal developmental processes; however, this is beginning to change (see, e.g., 64-66).

The examination of individuals with high-risk conditions and mental disorders can provide a natural entrée into the study of system organization, disorganization and reorganization that is otherwise not possible due to the constraints associated with research involving human participants. Through investigating a variety of high-risk and mentally disordered conditions, it is possible to gain significant insight into processes of development not generally achieved through sole reliance on investigations of relatively homogeneous nondisordered populations. Research conducted with atypical populations also can elucidate the behavioral and biological consequences of alternative pathways of development, provide important information about the range and variability of individual response to challenge and adversity, and help to specify the limits of behavioral and biological plasticity (67-70). Finally, findings revealed by experiments of nature also hold considerable promise for informing prevention and intervention strategies (71-73). For example, although it is ethically impossible to experimentally manipulate the quality of caregiving that is provided, investigations of children in maltreating families or of children reared by a depressed parent provide insights into the effects of non-optimal care on children’s development.

Developmental psychopathologists have articulated the expectation that there are multiple contributors to adaptive and maladaptive outcomes in any individual, that these factors and their relative contributions vary among individuals, and that there are myriad pathways to any particular manifestation of adaptive and disordered behavior. Accordingly, the principles of equifinality and multifinality, derived from general systems theory, are germane. Within the discipline of developmental psychopathology, equifinality has been invoked to explain why a variety of developmental pathways may eventuate in a given outcome, rather than expecting a singular primary pathway to the adaptive or maladaptive outcome. In this regard, for example, childhood 99

depression may emanate from the experience of being maltreated, the death of a parent, and/or genetic factors.

Likewise, multifinality is used to explain why individuals may begin on the same major pathway and, as a function of their subsequent “choices,” exhibit very different patterns of adaptation or maladaptation (5, 52, 74-76). For example, although child maltreatment typically leads to maladaptation, subsequent psychopathology may involve outcomes such as depression, conduct disorder, substance abuse, and/or a combination of such problems.

Moreover, some children exhibit resilient functioning even in the context of severely impaired parenting.

Multiple Levels of Analysis and Multi-Disciplinary Efforts The discipline of developmental psychopathology provides a framework for integrating knowledge within and across disciplines, contexts and domains of inquiry. In this regard, developmental psychopathology as a field will be enriched by increased interactions with geneticists, neuroscientists, molecular biologists, anthropologists, sociologists and epidemiologists. Research conducted within a developmental psychopathology framework has challenged assumptions about what constitutes health or psychopathology and has begun to redefine the manner in which the mental health community operationalizes, assesses, classifies, communicates about, and treats the adjustment problems and functioning impairments of infants, children, adolescents and adults (18, 77). Through its principles and tenets, developmental psychopathology transcends disciplinary boundaries and provides fertile ground for moving beyond mere symptom description to a process level understanding of normal and atypical developmental trajectories. Moreover, multi-level analyses of psychopathology often require a range of expertise that necessitates synergistic interdisciplinary, collaborative research (78). Successful interdisciplinary scientific research has the potential to transform the field of developmental psychopathology given the increased likelihood that such investigations will uncover innovative scientific discoveries and generate findings that will influence multiple disciplines (78).

Nonetheless, most of what is known about the correlates, causes, pathways and sequelae of mental disorders has been gleaned from investigations that focused on relatively narrow domains of variables. It is apparent from the questions addressed by developmental

Sheree L. Toth and dante cicchetti

psychopathologists that progress toward a processlevel understanding of mental disorders will require research designs and strategies that call for the simultaneous assessment of multiple domains of variables both within and outside of the developing person (26).

In some instances, reference to variables measured in other domains is essential to clarify the role(s) of variables of interest for other questions; it is necessary to consider variables from other domains as competing explanations for postulated causal paths. To understand psychopathology fully, all levels of analysis must be examined and integrated. Each level both informs and constrains all other levels of analysis. Moreover, the influence of levels on one another is almost always bidirectional (53, 75).

An interesting approach to a multiple levels of analysis perspective on psychopathology has emanated from investigations of gene-environment (G x E) interactions.

The majority of G x E studies have focused on depression and antisocial behavior, although a smaller number of investigations have examined schizophrenia and attention deficit hyperactivity disorder. In a seminal longitudinal investigation, Caspi and his colleagues (79) sought to explain why stress resulted in depression for some, but not all, adults. These investigators found that the 5-HTTLPR polymorphism moderated the effect of stressful life events on adult depression. Specifically, Caspi et al. (79) discovered that adult depression was predicted by the interaction between individuals carrying the s/s or the s/l genotype in the 5-HTTLPR gene-linked promoter region and child maltreatment that occurred during the first decade of life. Results such as these have converged to demonstrate that early adverse environments interact with genetic make-up to exert a greater negative impact on genetically at risk children (80).

Resilience As the developmental perspective has assumed a more prominent role in psychopathology research, there has been a growing interest in the study of resilience (81).

Specifically, research has been directed toward identifying the biological and psychological factors that stem the trajectory from risk to psychopathology, thereby resulting in adaptive outcomes even in the presence of adversity. A developmental psychopathology perspective on resilience highlights the importance of examining multiple biological and psychological systems concurrently (21, 67, 82). Along these lines, the

investigation of multiple aspects of the developmental process concurrently can shed light on the nature of the interrelation among various ontogenetic domains. For example, how do cognition, affect and neurobiological growth relate with one another at various developmental periods? When an advance or a lag occurs in one system, what are the consequences for other systems?

Pursuing answers to questions such as these will enable researchers to formulate more precise definitions of resilience.

As is true for all developmental phenomena, resilience is a dynamic process, not a static phenomenon (83). We believe that the concept of resilience as “invulnerability� must be avoided. Resilient individuals, although giving the impression of being somewhat herculean in their resistance to stress, must also undergo struggles associated with this process (cf. 84). Thus, these resilient individuals also may need support to deal with the emotional difficulties that often accompany the experience of adversity.

Another vital aspect of the scientific study of resilience is that it affords an additional avenue for examining biological and social constraints that may operate on aspects of the developmental process throughout the life course (61, 85). Moreover, through investigating the determinants of resilient adaptation, we are in a position to discover the range and variability in individuals’ attempts to respond adaptively to challenge and ill fortune (86). For example, in an investigation of the multilevel determinants of resilient functioning, Cicchetti and Rogosch (87) found that the personality variables of ego-resiliency and ego-control and the regulation of the adrenal steroid hormones dehydroepiandrosterone (DHEA) and cortisol each made independent contributions in predicting resilience among maltreated children. In addition, Curtis and Cicchetti (88) discovered that emotional regulation predicted resilient functioning in both maltreated and nonmaltreated comparison children; however, Curtis and Cicchetti (88) found that electroencephalogram (EEG) asymmetry in central cortical regions independently predicted resilience only in maltreated children.

Finally, the ability to function resiliently in the presence of biological and/or environmental disadvantage may be achieved through the use of developmental pathways that are less typical than those negotiated in the course of usual circumstances. For example, Cicchetti and Rogosch (89) found that whereas relationship factors were related to resilience in low-income nonmaltreated 100

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children, self-strivings were associated with resilience in children with histories of maltreatment. Thus, an important question for researchers to pursue is whether the use of alternative pathways to attaining competence renders individuals more vulnerable to manifesting subsequent delays or deviations in development. Only longitudinal investigations can fully address this issue, but it will be critical to ascertain whether these individuals are more prone to developing psychopathology later in life. Research on resilience is an excellent example of translational research as it also lends itself to informing prevention and intervention initiatives.

Translational Research Translational research has been defined as examining how basic behavioral and biological processes inform the diagnosis, prevention, treatment and delivery of services for mental disorder, and, conversely, how knowledge of mental illness enhances our comprehension of basic behavioral and biological processes (90). The new era of translational research is not only exerting impacts on developmental psychopathology, but also is affecting all fields of research in the medical, physical, social and clinical sciences (91). The impetus to conduct translational research in the behavioral sciences has emanated largely from the National Institute of Mental Health (92, 93) and was spurred by the recognition of the tremendous individual, social and economic burden associated with mental illness (90). Hence, the emphasis on translational research by funding agencies is quickly translating itself into increased priorities within the academic arena.

This formulation of translational research is in direct accord with two of the key tenets of a developmental psychopathology perspective, namely, the reciprocal interplay between basic and applied research and between normal and atypical development (94). Thus, the parameters of developmental psychopathology lend themselves to fostering translational research that has implications for society, policymakers and individuals with mental disorders and their families.

Prevention and Intervention: A Multi-level Perspective The preeminent objective of the field of prevention science is to intervene in the course of development in order to reduce or eliminate the emergence of maladaptation and mental disorder, as well as to promote resilient adaptation 101

in individuals at high-risk for psychopathology (71, 95).

To fulfill this laudable goal, it is important that prevention scientists possess a complex, multilevel understanding of the course of normality to formulate an in-depth portrayal of how deviations in normal developmental processes can eventuate in maladaptation and psychopathology (96).

Because of its focus on the interplay between normal and abnormal development, the discipline of developmental psychopathology is uniquely poised to provide the theoretical foundation for prevention and intervention initiatives (42, 72, 97).

From the integrative developmental psychopathology framework, randomized controlled trials may be conceptualized as veridical experiments in modifying the course of development. Therefore, these randomized preventive trials may be conceived as tests of theory and causal mechanisms, thereby proffering insights into the etiology and pathogenesis of maladaptation and disordered outcomes (98, 99). The incorporation of biological measures into the design and evaluation of these RCT preventive interventions will enable prevention scientists to grasp the development of maladaptation, psychopathology, and resilience in their full complexity (100, 101). For example, in the evaluation of an attachment-based intervention on cortisol production of infants and toddlers in foster care, Dozier and her colleagues (102) found that their relational intervention was effective in helping children to regulate their biology. Methodologically sound prevention science that incorporates a theoretically informed and guided multiple levels of analysis perspective will provide a unique lens through which the processes responsible for the development, maintenance and modification of both typical and atypical functional outcomes can be discerned (72, 100, 101, 103).

Collaborative interdisciplinary preventive interventions between researchers and clinicians that take into account multiple levels of influence also will help to reduce the schisms that have long existed between science and practice (104). The incorporation of an interdisciplinary, multiple level perspective will enable prevention scientists to derive a more precise and comprehensive understanding of the mediators and moderators underlying successful and unsuccessful intervention outcomes. For example, although efficacious treatments are increasingly being identified, the field has been slower to uncover the processes and mechanisms that contribute to positive outcomes. As Kazdin (105) states â€œâ€Śwe really do not understand very much about therapy, why

Sheree L. Toth and dante cicchetti

and how it achieves change and for who it is and is not effective and why‌� (p. 533). This becomes even more problematic when efforts to translate research-derived efficacious treatments into the broader clinical world occur. In fact, therapies that are evaluated scientifically in randomized control trials continue to far outperform those involving the usual clinical care provided in real world clinical settings (106). The field of developmental psychopathology holds great promise for increasing the theoretical bases of interventions, for elucidating the contributors to positive outcome, and for fostering increased availability of these treatments.

Clearly, the results of randomized prevention trials will be informative to practitioners. Equally essential, however, is the need for prevention scientists to conceptualize, design and evaluate prevention trials in such a way that also enables their results to enhance our understanding of development and the pathways contributing to intervention efficacy at multiple levels of influence. Determining the multiple levels at which change is engendered through the conduct of randomized prevention trials will provide more insights into the mechanisms of change, the extent to which neural plasticity may be promoted, and the interrelations between biological and psychological processes in maladaptation, psychopathology and resilience (67, 100, 101, 107). Furthermore, preventive interventions with the most in-depth empirical support, based on integrative multilevel theories of psychopathology and resilience, can be implemented in effectiveness trials in community or real-world settings to reach the broadest number of people and to prevent, or alleviate, suffering from mental disorders (104, 108).

Conclusion These are exciting times for the discipline of developmental psychopathology and the field has grown considerably as it has traversed its own developmental pathway. Advances in genomics, gene x environment interactions and epigenetics, growth in our understanding of neurobiology and neural plasticity, and progress in the development of methodological and technological tools, including brain imaging, hormone assays, and statistical analysis of change set the stage for integrating disciplines and multiple levels of analysis that will greatly enhance the knowledge base of the development and course of mental disorders (77). Moreover, prevention and intervention trials are being increasingly

based on theoretical models and efforts to elucidate the mechanisms and processes contributing to change are being initiated. The information that is emanating from the field of developmental psychopathology can be integrated into the armamentariums of professionals from diverse disciplies, even when they do not consider themselves to be developmental psychopathologists.

These knowledge gains will not only benefit the scientific study of psychopathology and resilence, but also permit translation to informing developmentally-based preventive interventions that will contribute to reducing the individual and societal burden of mental illess.

Acknowledgements: Work on this paper was supported by a grant received from the Spunk Fund, Inc.

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Tourette's Syndrome: A Review from a Developmental Perspective Tamar Steinberg, MD, 1 Robert King, MD, 2 and Alan Apter, MD 1 1

The Harry Freund Neuro-Psychiatric Clinic, Schneider Children's Medical Center, Petah Tikva, Israel Yale Child Study Center, New Haven, Connecticut, U.S.A.

2

ABSTRACT The object of this review is to summarize some of the recent developments in the understanding of Tourette’s Syndrome which can be regarded as the prototype of a developmental psychopathological entity. The review covers the following topics: tics and their developmental course; sensory phenomena related to tics including measurement of these phenomena; pathophysiology of tics and compensatory phenomena and the parallel development of the various psychiatric comorbidities as they emerge over the life span. Finally there is an attempt to summarize the major points and future directions.

Background Tourette’s Syndrome (TS) is a prototypical developmental neuropsychiatric disorder that usually begins in childhood, around the age of five or six, involving a variety of motor and sensory phenomena that wax and wane throughout development (1). It encompasses emotional and cognitive aspects of behavior and both influences and is influenced by the environment and life events as the life cycle proceeds. Thus the syndrome comprises physical, psychical as well as social phenomena that evolve in an interactive stepwise fashion, illustrating how motor and emotional development interact.

For this reason the study of TS is of immense interest in the study of developmental psychopathology.

Tics TS is characterized by tics which are sudden, involuntary, repetitive, non-rhythmic movements or vocalAddress for Correspondence: tamarst@clalit.org.il

izations. Simple motor tics are sudden, fleeting or fragmentary movements such as blinking, grimacing, head jerking, or shoulder shrugs. Complex motor tics consist of several simple motor tics occurring in an orchestrated sequence or semi-purposeful movements, such as touching or tapping; these may also have a more sustained, twisting, and dystonic character (2).

Simple phonic tics consist of simple, unarticulated sounds such as throat clearing, sniffing, grunting, squeaking, or coughing. Complex phonic tics consist of out-of-context syllables, words, phrases or paroxysmal changes of prosody.

Complex tics may involve socially inappropriate or obscene gestures (copropraxia) or utterances (coprolalia), as well as echo phenomena, such as echolalia or echopraxia (repeating others’ words or gestures), which exemplify the suggestibility of tics. Infrequently, complex tics may include self-injurious behavior (cheek chewing, eye-poking and self-hitting). Tic complexity, also, generally evolves with age (2).

Developmental Course of Tics The severity of tics in TS waxes and wanes throughout the course of the disorder and is characterized by changing symptoms as it follows the child’s development.

The tics of TS and other tic disorders are highly variable from minute to minute, hour to hour, day to day, week to week, month to month and even year to year.

Tic episodes occur in bouts, which in turn also tend to cluster (2). Tic symptoms, however, can be exacerbated by stress, fatigue, extremes of temperature and external stimuli (as with echolalic or echopraxic tics). Intentional movements attenuate tic occurrence over the affected area and intense involvement and concentration in activities tend to dissipate tic symptoms (3).

Tamar Steinberg, MD, Schneider Children's Medical Center of Israel, 14 Kaplan St., Petah Tikva, Israel 49202

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Tourette's Syndrome: A Review from a Developmental Perspective

Initial sniffing or blinking tics may be mistaken for allergies or eye problems, and it is mainly their waxing and waning and the subsequent appearance of other tics that help make the diagnosis. There is also often an anatomical progression, with head and facial tics being the first to appear and more caudal and more complex tics appearing later. Longitudinal studies of TS have found that the tics of TS typically have an onset around the age of 5-6 years and usually reach their worst ever severity between the ages of 10-12 years (4-6). Approximately one-half to two-thirds of children with TS will experience a substantial decrease or remission of tics during adolescence (2). A small proportion of those who continue to have tics into adulthood suffer from tics that are severe, complex or that cause social embarrassment or self injury (4). A small minority of TS patients experience catastrophic outcomes in adulthood, although these are the exception. Most individuals do not experience either a sustained worsening or improvement of their symptoms after the third decade of life.

Identifying clinical measures that can predict whose tic symptoms will persist into adulthood is an area of great concern for patients and their families, as well as for researchers seeking clues as to the underlying pathophysiology of tics. Among a battery of neuropsychological measures administered to a group of children with TS, age 8-14 years, the Purdue Pegboard, a test of fine motor skills, best predicted tic severity and global psychosocial functioning at follow-up clinical assessment 7.5 years later (7). Poor performance on the Purdue Pegboard and Beery Visual-Motor Integration test (VMI) also predicted worse adult global psychosocial functioning. It has been hypothesized that performance on these tests might serve as an endophenotype as a measure of basal ganglia dysfunction in young TS patients. However, it is probably too optimistic to envisage that simple tests such as these will provide an answer to the very complicated problem of predicting outcome in individual cases.

Tic Associated Sensory Phenomena Tics are not purely motor phenomena but also have in many cases an associated sensory and/or cognitive component. These include uncomfortable bodily sensations that “force” the individual to perform the tics, and unexplained internal urges or energies situated from within the body. The discomfort associated with these feelings can cause more distress than the tics themselves. These 106

mental components also have a developmental trajectory and most children recall first noticing the sensory phenomena beginning around the age of 10 (8), three years after the onset of tics on average.

Premonitory Urge and its Assessment Most systematic studies suggest that premonitory urge prevalence rates are 77% in patients with TS who are older than 13 years and 93% in a tic disorder sample ranging in age from 8 to 71 years (9).

A scale for urge severity the Premonitory Urge for Tics Scale (PUTS) was developed by Woods et al. (10, 11), comprising nine items designed to measure premonitory urges in children with tics. This questionnaire asks TS patients and their parents the question: “Do you feel a kind of pre-sensation immediately before the tic?” and “Are you able to suppress tics for a while?” Studies with the PUTS have shown that premonitory sensation awareness is a maturational process independent of tic duration and of age of tic onset. This maturational step occurs between 8-10 years and 10-14 years, emphasizing that tic awareness and the ability to suppress tics are correlated and age related (10).

The questionnaire deals with both sensory and mental phenomena. PUTS severity scores are correlated with tic severity as measured by the Yale Global Tic Severity Score (YGTSS), and specifically with complexity, interference and number of tics. Other interesting correlations were found between premonitory urge and Obsessive-Compulsive symptoms (OCS), as measured by the children’s version of the Yale Brown Obsessive Compulsive Scale (CYBOCS ) total score in older but not younger children. The internal consistency and other psychometric properties of this questionnaire were excellent for older children (>10 years ) but poor for those under the age of 10 years, underlining the fact that these urges have a developmental track perhaps relating to cognitive maturation and increasing internal awareness in older children. The ability to quantify these sensory phenomena has facilitated exploration of the links between these sensory phenomena, tic complexity and OCD symptomatology (10).

The maturational awareness of the premonitory urges and the accompanying ability to suppress tics plays an important role in the development of modern psychological treatments for tics. One such treatment, called Habit Reversal Therapy (HRT), is based on teaching the child to become aware of the premonitory urge preced-

Tamar Steinberg et al.

ing a tic, recognizing it, and developing a competing response incompatible with performing the tic (12).

Pathophysiology Accumulating knowledge on the developmental trajectories of sensory phenomena and suppressibility of tics in TS patients has also shed light on the pathophysiology of TS. It is postulated that the urge to perform motor actions involves sensory motor networks of the brain, specifically the supplementary motor area, as well as activity in the basal ganglia, thalamus, and frontal cortex (13). This hypothesis is derived from functional MRI studies of tic suppression and may be a basis for a better understanding of the neuronal networks involved in TS. Imaging Studies An increased overall volume in dorsolateral prefrontal regions in children, but not adults, with TS has been reported. This increase in volume was inversely related to tic severity such that patients with greater prefrontal volumes exhibited decreased tic severity.

Volumes of the corpus callosum (CC) are decreased in children with TS, correlate inversely with prefrontal volumes, and are positively related to tic severity. It is likely that these findings of increased prefrontal volumes and decreased CC size represent a compensatory mechanism developed in children with TS in order to facilitate suppression of tics. Larger prefrontal volumes found in children with TS may represent the occurrence of synaptic plasticity associated with the constant need to suppress tics in social contexts. Adults with TS may represent a subsection of the overall TS population who do not generate a plastic, compensatory response in the prefrontal cortex, leading to increased severity of the disorder and its persistence into adulthood. The development of TS is likely to be two-fold, involving an abnormality in basal ganglia output systems in conjunction with an impairment in frontal inhibition of this output. Considerable evidence indicates that the frontal lobes are not fully developed until young adulthood, suggesting that while impaired inhibition of striatal output is responsible for the commonly occurring tics and compulsions found in childhood, development of the frontal cortex in response to overactive striatal output in TS may be a determining feature of the longterm course of the disorder (14).

Neuro-psychology Although deficient motor inhibition is often considered to be the basic underlying pathology, cognitive and affective development are also liable to be impaired.

Thus cognitive inhibitory deficits have been found in a variety of neuropsychological and experimental paradigms, especially in those children with comorbid ADHD and OCD or in those children whose frontal lobes are not fully developed.

Impaired development of affective regulation is also frequently found, with explosive rage attacks and/or self injurious behaviors (SIB) occurring in at least onefourth of children with TS in some clinical samples.

It is likely that developmental dysfunction in orbitofrontal-basal ganglia circuitry contributes in part to the problems of impulsivity and rage attacks, although this hypothesis remains to be proven. The subtle but complex homeostatic influences of development in TS are best summed up in the statement by Stern et al.

(14): “Although inhibitory motor deficits in TS might be expected to lead to more general problems with cognitive and social self-regulation, a developmental approach suggests otherwise. In particular, the developmental approach suggests that compensatory processes occurring over time and in response to motor inhibition deficits could work either to offset or to exacerbate cognitive and social self-regulation deficits in persons with TS……. One hypothesis concerning the differentiation of persons for whom symptoms attenuate from those who retain symptoms into adulthood concerns the development of frontal cortical top-down control of motor deficits. Specifically, given the relatively protracted course of the development of the prefrontal cortex and processes of use dependent synaptic plasticity, it is likely that attenuation of the disorder is due to compensatory developmental neurobiological processes.

From a developmental standpoint, it makes sense to also ask whether or not variation in cognitive inhibitory control or impulse inhibition in TS is associated with the unique experiences of the patient during the course of the disorder. Here, it is important to consider the developmental process as it occurs in response to the psychosocial environment in which the individual is situated in addition to constraints imposed by the neurobiological motor deficit. Such an approach can increase understanding of longer-term outcomes and also suggest some potentially efficacious therapies to improve quality of life for patients with TS” (pp. 14-15).

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Comorbidities As development progresses several other neuropsychiatric syndromes develop either prior to, concomitant with or following tic onset. These include attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and other anxiety disorders, learning disability, oppositional defiant disorder including rage attacks, self injurious behavior (SIB) and depression (15). Many late adolescent and adult TS patients regard their behavioral problems (including ADHD and OCD) and learning difficulties as having had an impact on their life function equal or greater to that of the tics themselves. In the natural course of comorbid psychiatric illness in TS, ADHD symptoms are usually present from early childhood and often precede the onset of tic symptoms by several years, whereas OC symptoms more commonly present in later childhood after tics have reached their peak severity, though they may be apparent earlier on (3).

ADHD, as well as irritable or oppositional behavior, is found in at least one-half of clinically referred children and adolescents with TS. It is also not uncommon to see children with ADHD who have developed transient or persistent tics following being started on stimulant medication, posing a sometimes difficult therapeutic dilemma (16). A recent meta-analysis has supported the use of stimulant medications in children with tics (17).

The nature of the association between TS and ADHD is still a matter of debate, but it is clear that youngsters with TS plus comorbid ADHD usually have more adaptive difficulties than those with tics alone (18, 19). In a large international database of 6,805 cases of TS, the prevalence of ADHD in TS was 55%. If a proband was diagnosed with ADHD, a family history of ADHD was much more likely. Comorbid ADHD was associated with earlier diagnosis of TS, great peak tic severity, and an increased male-to-female predominance of 7.3:1 (20).

Moreover, the group with comorbid ADHD has much higher rates of anger control problems, sleep problems, specific learning disability, OCD, oppositional-defiant disorder (ODD), mood disorder, social skill deficits, inappropriate sexual behavior and self-injurious behavior. The greatest behavioral difficulties in subjects with ADHD are associated with the Combined or Hyperactive-Impulsive Subtypes of ADHD. These findings confirm other clinical research indicating the important contribution of ADHD to the behavioral problems often associated with TS. The high rates of comorbidity with ADHD found in clinical samples may be an artifact of referral bias since children 108

with tics only may not require treatment at all (20).

However, one epidemiological study suggests an association between tics and ADHD even in a non-referred community child sample (17).

About 50% of patients with TS also have symptoms of obsessive compulsive disorder (OCD) and genetic studies raise the possibility of a shared genetic vulnerability common to both disorders (21). OCD usually appears a few years later than the tics. Although patients with TS may manifest the usual harm-avoidant obsessions and compulsions found in other OCD patients without tics, concerns about symmetry, ordering and exactness, as well as intrusive aggressive, sexual or religious images, appear to be more common in tic-related OCD. TS-related compulsions are often driven by the need to get some appearance or physical sensation “just right.” In this subgroup of patients with OCD and tics, compulsions are sometimes performed in response to intrusive experiences or feelings such as urges, tactile sensations or a sense of incompleteness rather than obsessions or harm-avoidance (22). Compared to nontic-related OCD, tic related OCD is characterized by earlier age of onset, predominantly affects males, and has a distinct pattern of treatment response (23, 24).

Patients with TS plus OCD also present with higher rates of ADHD, social phobia, trichotillomania, and body dysmorphic disorder, suggesting that a subtype of OCD that is etiologically linked to TS has an earlier onset than OCD without tics (25).

A variety of studies suggest that, compared to later onset OCD, early onset OCD (before the age of 10) is a distinctive subtype of OCD associated with a greater likelihood of tics, a preponderance of compulsions (rather than obsessions) (as indicated by higher scores on the compulsion subscale of the CY-BOCS [23]), an increased family loading for OCD, male preponderance, and a poorer response to SSRIs (26). A new rating scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale (CY–BOCS), measures the presence and severity of OCD symptoms within six thematically related dimensions and has helped elucidate the distinctive features of tic-related OCD. In addition, tic-related OCD is significantly less responsive to pharmacological therapy with SRIs than non-tic-related OCD and appears to be more responsive to augmentation with antipsychotic agents. Tic-related OCD also responds less well to psychological therapies than does non-tic-related OCD (3).

Youngsters with TS may be prone to comorbid depression or anxiety as they grow older for a variety

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of reasons. The constant barrage of tics and premonitory urges, as well as the frequently comorbid ADHD, OCD and learning difficulties, can induce feelings of hopelessness and learned helplessness in children. Like children with ADHD uncomplicated by tics, children with comorbid TS and ADHD experience greater academic and social difficulties with deleterious effects on their self-esteem (27). The behavioral and learning difficulties that many of these children experience tend to induce stressful life events such as school failure or social rejection that increase the likelihood of developing depression. Furthermore, the various medications used in treating TS, OCD, and/or ADHD can all cause sedation, dysphoria or increased anxiety as unintended side effects. On a constitutional level, TS appears to be associated with increased autonomic lability and sensitivity to stress (26), and there is evidence that some other basal ganglia disorders (such as Parkinson’s disease) may confer a vulnerability to depression even prior to the onset of movement symptoms.

CONCLUSIONS AND FUTURE DIRECTIONS TS remains a prototypical model for studying developmental neuro-psychopathology and as such has an interest far beyond the clinical implications for the specific symptoms. Prospective longitudinal research beginning in early childhood in TS patients will surely contribute to the understanding of the relationships between brain structure, brain function, behavior, and environment - the very essence of developmental psychopathology. Thus the timing of the tic onset, the fractal nature of the tic episodes and the attenuation of symptoms in some but not all patients remain unsolved dilemmas. Are there basic oscillatory rhythmic disturbances that have their origin in neuro-developmental processes, and do patients march to a “drumbeat” that sets them apart (28)? Not considered in this review but of interest is the role of immunological processes. How do these fit in with brain development?

New exciting methodologies in brain research and genetics enable us to be optimistic about finding the answers to some of these intriguing questions in the near future.

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2. Leckman JF. Phenomenology of tics and natural history of tic disorders. Brain Dev 2003;25 Suppl 1:S24-8.

3. Leckman JF, Bloch MH, Scahill L, King RA. Tourette syndrome: The self under siege. J Child Neurol 2006;21:642-649.

4. Erenberg G, Fahn S. Tourette syndrome. Arch Neurol 1996;53:588.

5. Leckman JF, Zhang H, Vitale A, Lahnin F, Lynch K, Bondi C, Kim YS, Peterson BS. Course of tic severity in Tourette syndrome: The first two decades. Pediatrics 1998;102:14-19.

6. Pappert EJ, Goetz CG, Louis ED, Blasucci L, Leurgans S. Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome. Neurology 2003;61:936-940.

7. Bloch MH, Sukhodolsky DG, Leckman JF, Schultz RT. Fine-motor skill deficits in childhood predict adulthood tic severity and global psychosocial functioning in Tourette's syndrome. J Child Psychol Psychiatry 2006;47:551-559.

8. Leckman JF, Walker DE, Cohen DJ. Premonitory urges in Tourette's syndrome.

Am J Psychiatry 1993;150:98-102.

9. Kurlan R, Lichter D, Hewitt D. Sensory tics in Tourette's syndrome. Neurology 1989;39:731-734.

10. Woods DW, Piacentini J, Himle MB, Chang S. Premonitory Urge for Tics Scale (PUTS): Initial psychometric results and examination of the premonitory urge phenomenon in youths with tic disorders. J Dev Behav Pediatr 2005;26:397-403.

11. Woods DW, Twohig MP, Flessner CA, Roloff TJ. Treatment of vocal tics in children with Tourette syndrome: Investigating the efficacy of habit reversal. J Appl Behav Anal 2003;36:109-112.

12. Piacentini J, Chang S. Behavioral treatments for Tourette syndrome and tic disorders: State of the art. Adv Neurol 2001;85:319-331.

13. Peterson BS. Neuroimaging studies of Tourette syndrome: A decade of progress.

Adv Neurol 2001;85:179-196.

14. Stern ER, Blair C, Peterson BS. Inhibitory deficits in Tourette's syndrome. Dev Psychobiol 2008;50:9-18.

15. King RA, Scahill L. Emotional and behavioral difficulties associated with Tourette syndrome. Adv Neurol 2001;85:79-88.

16. Roessner V, Becker A, Banaschewski T, Freeman RD, Rothenberger A. Developmental psychopathology of children and adolescents with Tourette syndrome - impact of ADHD. Eur Child Adolesc Psychiatry 2007;16 Suppl 1:24-35.

17. Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF. Meta-analysis: Treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry 2009;48: 884-893.

18. Sukhodolsky DG, Scahill L, Zhang H, Peterson BS, King RA, Lombroso PJ, Katsovich L, Findley D, Leckman JF, et al. Disruptive behavior in children with Tourette's syndrome: Association with ADHD comorbidity, tic severity, and functional impairment. J Am Acad Child Adolesc Psychiatry 2003;42:98-105.

19. Hoekstra PJ, Steenhuis MP, Troost PW, Korf J, Kallenberg CG, RB M. Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems in tic disorders. J Dev Behav Pediatr 2004;25:272-279.

20. Freeman RD. Tic disorders and ADHD: Answers from a world-wide clinical dataset on Tourette syndrome. Eur Child Adolesc Psychiatry 2007;16 Suppl 1:15-23.

21. Pauls DL. An update on the genetics of Gilles de la Tourette syndrome. J Psychosom Res 2003;55:7-12.

22. Miguel EC, do Rosario-Campos MC, Prado HS, do Valle R, Rauch SL, Coffey BJ, Baer L, Savage CR, O'Sullivan RL, Jenike MA, Leckman JF. Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder. J Clin Psychiatry 2000;61:150-156.

23. Miguel EC, Coffey BJ, Baer L, Savage CR, Rauch SL, Jenike MA. Phenomenology of intentional repetitive behaviors in obsessive-compulsive disorder and Tourette's disorder. J Clin Psychiatry 1995;56:246-255.

24. Leckman JF, Grice DE, Barr LC, de Vries AL, Martin C, Cohen DJ, McDougle CJ, Goodman WK, Rasmussen SA. Tic-related vs. non-tic-related obsessive compulsive disorder. Anxiety 1994;1:208-215.

25. Coffey BJ, Miguel EC, Biederman J, Baer L, Rauch SL, O'Sullivan RL, Savage CR, Phillips K, Borgman A, Green-Leibovitz MI, Moore E, Park KS, Jenike MA. Tourette's disorder with and without obsessive-compulsive disorder in adults: Are they different? J Nerv Ment Dis 1998;186:201-206.

26. March JS, Franklin ME, Leonard H, Garcia A, Moore P, Freeman J, Foa E. Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder. Biol Psychiatry 2007;61:344-347.

27. Stokes A, Bawden HN, Camfield PR, Backman JE, Dooley JM. Peer problems in Tourette's disorder. Pediatrics 1991;87:936-942.

28. Leckman JF, Vaccarino FM, Kalanithi PS, Rothenberger A. Annotation: Tourette syndrome: A relentless drumbeat - driven by misguided brain oscillations. J Child Psychol Psychiatry 2006;47:537-550.

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

The Neurodevelopmental Theory of Schizophrenia: Evidence from Studies of Early Onset Cases Jess Kinros, PhD, Abraham Reichenberg, PhD, and Sophia Frangou, MD, PhD, FRCPsych Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, King’s College, London, U.K.

ABSTRACT The neurodevelopmental theory of schizophrenia has been of great importance focusing most etiologic research over the past two decades. We review research on the neurodevelopmental aspects of Early Onset Schizophrenia, a rare and severe form of schizophrenia in which onset occurs during childhood or adolescence. Developmental, cognitive, genetic and brain imaging findings are outlined and discussed in relation to the neurodevelopmental theory. The main limitations of the theory are presented, and future conceptualizations are formulated.

Introduction Schizophrenia is a clinical syndrome with peak onset in late adolescence or early adulthood, whose symptoms are manifest in multiple domains of behavior. Although delusions and hallucinations are the hallmark of psychosis patients also present with impairments in social communication, as well as motor, volitional and emotional abnormalities. While some patients only experience one acute psychotic episode, for a majority the condition is considered lifelong, with episodes of illness followed by periods of remission (1).

A neurodevelopmental etiologic theory of schizophrenia has been influential during the past decades.

According to this theory there is deviance in early brain development whose full adverse consequences emerge only in adolescence or early adulthood (2-4).

Considerable research has focused on the brain changes and behavioral abnormalities that precede onset of illness as indicators of abnormal development in an effort

to identify possible risk markers and biological mechanisms underlying psychosis.

Early Onset Schizophrenia Early Onset Schizophrenia (EOS) is a rare and severe form of schizophrenia in which onset occurs during childhood (COS) or adolescence (AdOS) up to the age of 17 years.

Only around 4% of schizophrenia patients will experience an early onset (5). Longitudinal studies have shown diagnostic stability to be high in EOS at around 80-90% (6, 7).

Studies investigating prognosis in this group used a range of variables to assess outcome; typical indicators include presence of symptoms, length of remission, number and duration of hospitalizations, educational and occupational impairment and social disability. Evidence from studies that followed up EOS patients over 40 years confirm that outcome on such measures is consistently worse for EOS compared to adult-onset schizophrenia (AOS) (7-9), with some evidence that COS, with an onset before age 12, is associated with the worst clinical and psychosocial outcomes (10). EOS is clinically and neurobiologically continuous with AOS, but is associated with greater neurodevelopmental deviance early in life (11, 12). EOS could therefore provide an opportunity to learn more about the neurodevelopmental aspects of schizophrenia.

This paper presents a selective overview of research on the neurodevelopmental aspects of EOS: namely, premorbid development, cognitive function, genetics and neurobiology. Particular attention is given to research on developmental delay and impairment in the areas of motor, social and language function.

Methodological Considerations Table 1 presents a summary of studies of early development in EOS. Because EOS is rare, true prospective data

Address for Correspondence: Abraham Reichenberg, PhD, Institute of Psychiatry, King’s College London, Main Bldg. 7th Fl. Box 068, De Crespigny Park, London, SE5 8AF United Kingdom avi.reichenberg@iop.kcl.ac.uk

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collection is practically impossible. Therefore, as can be seen in the table, assessments of premorbid functioning are generally made retrospectively using self- and/ or parental recall, or school and medical records review.

Popular instruments for assessing premorbid function are the Premorbid Adjustment Scale (PAS) (13), and Child Behavior Checklist (CBCL) (14). Although these instruments have been shown to be reliable and valid in measuring premorbid functioning (15), studies should be viewed and interpreted in light of this limitation.

Cognitive Development in EOS Motor Impairments: Delayed motor milestones, poor coordination and repetitive movements are widely reported in EOS and appear to be more frequent the earlier the age of onset. Watkins et al. (16) reported that 64% of their COS sample had motor delays and difficulties, including delayed milestones and poor coordination. Alaghband-Rad et al. (17) found that 35% of their COS sample were delayed in walking.

This figure is comparable to the finding of Hollis (18), who used subjects from the Maudsley Case Register in his study, and reported that 33% of the COS group also showed this delay, with 31% of the whole EOS sample exhibiting stereotyped movements and coordination problems premorbidly. Nicolson et al. (19) reported that 57% of cohort of COS recruited by the National Institute of Mental Health (NIMH), showed delayed motor milestones as well as abnormal repetitive movements. Schothorst et al. (20) found that 35% of a group consisting of AdOS cases and adolescent onset affective psychosis cases showed delayed motor development and poor coordination. Vourdas et al. (11) tested EOS subjects recruited for the Maudlsey Early Onset Schizophrenia Study and reported much lower rates of motor delay, specifically delayed walking, in an EOS group, at only 3%. However, they suggest that this discrepancy may have occurred because their sample consisted mainly of AdOS cases and only included a single measure of motor development.

Speech and Language Impairment: Delayed speech production and childhood problems with receptive and expressive language appear to be common in schizophrenia and have been found in major cohort studies of AOS (21-23). Watkins et al. (16) found that 55% of COS cases had deficits in speech development or no speech prior to 30 months. Similarly, Alaghband-Rad et al. (17) reported that 43% of their COS sample showed delayed

sentence production. Hollis (18) found that his COS group was more likely to have premorbid speech and language impairment than an AdOS group, and this difference was accounted for by impairments in language production and perception, which were apparent only in the COS group. Nicolson et al. (19) found that 55% of their COS sample had premorbid speech and language impairment, including problems with receptive and expressive language as well as delayed speech milestones. In addition, COS patients with speech and language problems had greater familial loading for Schizophrenia Spectrum Disorders (SSD). Vourdas et al. (11) found that 19.4% of their EOS group showed language impairments consisting of delayed speech and difficulties with reading and spelling.

Social Functioning: Abnormal social behavior including isolation and social withdrawal are often reported in pre-schizophrenic children and adolescents. Kolvin et al. (24) reported that 87% of parents of EOS children reported “odd or unusual� behavior in their children prior to illness, mainly shyness or introversion. Watkins et al. (16) found that 82% of their COS sample were socially impaired in early childhood. Hollis (18) found that 30% of his Maudsley Case Register AdOS sample and 50% of his COS sample showed social impairments premorbidly compared to non-psychotic psychiatric controls. Two studies that did not use the PAS but assessed similar items related to social adaptation found comparable results. Nicolson et al. (19) reported that 55% of their COS sample had deviant social development including abnormal peer relationships, isolation and social disinhibition. Finally, the degree of impairment in social interaction is moderated by gender and age of onset. Vourdas et al. (11) found that their EOS and AOS groups were similar premorbidly in terms of social adjustment measured by the PAS; however, EOS males showed more deviant social behavior in adolescence than AOS males. In addition, early developmental abnormalities including motor, speech and language deficits were associated with more problems in premorbid social functioning during adolescence.

Premorbid social deficits may be greater for patients with EOS compared to early onset cases of other mental disorders. Asarnow and Ben-Meir (25) found that a COS sample had worse PAS scores than a group with childhood onset depression, particularly for items relating to social behavior and adaptation. Similarly, Werry et al. (26) found that 54% of EOS cases in their study had 111

The Neurodevelopmental Theory of Schizophrenia

Table 1. Studies on Early Development in Early-Onset Schizophrenia Author

Sample

Method

Results

Comment

AlaghbandRad et al.

(1995)

COS cases with onset up to 12 years (N=12).

Psychological, school and medical records of premorbid history.

43% showed delayed sentence production, not related to IQ. 35% had delayed motor milestones.

36% of sample showed evidence of PDD and all were part of a trial for nonresponders to neuroleptics, so this group represented more severe cases.

Asarnow & Ben-Meir (1988)

Children aged 7 to 13 years with COS or childhood onset depression (N= 66).

School, hospital and family records of premorbid history and Premorbid Adjustment Scale (PAS).

COS group had worse PAS scores, particularly for items related to social behavior and adaptation.

Hollis (1995)

COS group (N=18, onset 7 to 13 years); AdOS group (N=43, onset 14 to 17 years); non-psychotic psychiatric controls (N=61).

Checklist of premorbid function administered at time of admission.

COS group more likely to have premorbid speech and language impairment than AdOS group. 33% of AdOS group and 28% of COS group showed impaired motor development, and 30% of the AdOS group and 50% of COS group showed social impairments compared to controls.

Difference between AdOS and COS in language was accounted for by language production and perception disorders, which were not apparent in the AdOS group.

Kolvin et al.

(1971)

Patients with infantile psychosis (< 3 years at diagnosis; N=41) and later onset psychosis (aged 5 to 15 years at onset; N=33).

Parental report

87% of parents of later onset cases reported odd or unusual behavior in their children before illness. This was mainly shyness and introversion. 46% of this group had not produced three word phrases by age 3 years. 17% of this group exhibited motor abnormalities.

An early study that aimed to differentiate infantile psychosis from late onset childhood psychosis.

Motor abnormalities consisted of repetitive movements of the whole body, particularly hands and fingers.

McClellan et al.

(2003)

EOS group (N=27); BD group (N=22); psychosis NOS group (N=20).

Compared premorbid histories using PAS based on information obtained at admission into study combined with medical records and parental interviews.

Only 13% of EOS and NOS group considered â&#x20AC;&#x153;normalâ&#x20AC;? before onset of illness. EOS cases more globally impaired and socially withdrawn than those with BD. Sociability scale of the PAS was only significant predictor between BD and EOS, with greater introversion predictive of schizophrenia.

Muratori et al.

(2005)

EOS group, healthy control group and psychiatric control group (anorexics) N=23 for each group.

Maternal report using the Child Behavior Checklist.

Focus on social and behavioral problems up to 11 years of age.

At age 2-3 years, significant difference on all scales compared to healthy controls but not anorexic controls. At age 4-11 years higher mean scores on all scales compared to healthy controls and higher scores than anorexic group on social, thought and attentions problems and school competencies.

Social problems relate to shyness, underactivity and hypersensitivity.

Chose anorexics as a control group because this disease is considered developmental in origin.

Nicolson et al.

(2000)

COS patients N=49

Examined case histories and used parental recall for missing information.

55% had speech and language impairment premorbidly, including problems with receptive and expressive language and delayed milestones. 57% had motor impairment premorbidly consisting of delayed milestones, abnormal repetitive movement, poor coordination. 55% had deviant social development including abnormal peer relationships, isolation and social disinhibition.

More boys than girls had premorbid motor problems.

Patients with speech and language problems had greater familial loading for SSD.

Schothorst et al.

(2006)

EOS group (onset aged 12-18, N=36); Affective psychosis group (N=40) including BD, depression with psychotic symptoms and schizoaffective disorder.

Reviewed medical records.

No difference between subgroups in premorbid function. 35% of all patients showed problems in motor development, particularly coordination, 67% showed social problems, particularly isolation and withdrawal

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Table 1. Studies on Early Development in Early-Onset Schizophrenia Author

Sample

Method

Results

Comment

Vourdas et al. (2003)

EOS group (onset before 18th birthday, N=40); AOS group (N=54); Healthy control group (N=40).

Maternal interviews and PAS

EOS and AOS groups the same for premorbid social adjustment. EOS males showed more deviant social behavior in adolescence than AOS males.

EOS cases had delayed milestones compared to control groups, in speech development, with more reading and spelling difficulties. 19.4% of EOS group showed language impairments. 3% of sample was delayed in walking. In 20% of EOS cases, delay in some area was sufficiently pronounced to warrant professional help (10 times higher than healthy controls).

Low rate of motor impairment compared to other studies could be due to older onset and/or not including wider range of motor behaviors.

Walker et al. (1994)

Pre-schizophrenic children and healthy siblings, preaffective disorder children and their healthy siblings, healthy control children.

Researchers watched home movies of all subjects.

Higher rate of neuromotor abnormalities in pre-schizophrenic children compared to all other groups during first two years of life. Abnormalities were mainly on left side, including choreoathetoid movements and posturing of the upper limbs.

AOS cases

Watkins et al. (1988)

Children with COS (onset before 10th year; N=18). One third of this sample had autistic symptoms early in childhood.

Child Behavior Checklist Symptoms rated at four time points from 0 to 12 years for each case, based on school and medical records.

For the COS cases without history of autism: 55% had deficits in language development or no language prior to 30 months. 64% had motor problems before the 6th year consisting of delayed milestones and poor coordination. 82% were socially impaired in early childhood.

Werry et al.

(1991)

EOS group (N=30) with mix of COS and AdOS cases.

Group of patients diagnosed with psychosis during childhood or adolescence but later confirmed to have BD (N=23).

Medical records, parental and patient interviews.

54% of schizophrenics had moderate to severely abnormal personalities, compared to 26% of mood disorder cases. The personality type ascribed to schizophrenic patients tended to be “odd” (30%) whereas most bipolar cases were described as “normal” (52%).

moderate to severely abnormal personalities premorbidly, compared to 26% of a group who were diagnosed with psychosis but later had this diagnosis changed to bipolar disorder. The personality traits ascribed to EOS patients tended to be “odd,” whereas most bipolar disorder cases were described as “normal” premorbidly.

Mcclellan et al. (27) reported that only 13% of EOS and psychosis not otherwise specified (psychosis NOS) cases were considered “normal” before onset of illness.

They also found that the sociability scale of the PAS was the only significant variable that distinguished between later bipolar disorder and EOS, with greater introversion predictive of later schizophrenia. Muratori et al.

(28) used the CBCL to examine social and behavioral problems in an EOS group compared to both healthy controls and a psychiatric control group with anorexia.

They found evidence of behavioral problems in both psychiatric groups at age 2 to 3 years, but by age 4 to 11 years, the EOS group had worse scores on all CBCL

Main motivation for study was to examine stability of diagnosis over time rather than detailed exploration of premorbid history.

scales compared to control groups, encompassing social, thought and attention problems as well as school competencies. The social problems were related to shyness, underactivity and hypersensitivity. However, there is at least one contradictory report by Schothorst et al. (20) who found that 67% of their AdOS and affective psychosis patients showed social problems premorbidly, particularly isolation and withdrawal.

Intellectual ability: Several studies examined childhood and adolescence intellectual functioning (IQ) in individuals who later were diagnosed with schizophrenia (predominantly Adult-Onset). Jones et al. (21) examined educational assessments conducted at ages 8, 11 and 15 in the 1946 British birth cohort, and found that low scores were a risk factor for adult schizophrenia. Cannon et al. (23) used standard age-appropriate intelligence scales to assess cognitive development in the Dunedin birth cohort at ages 3, 5, 7, 9 and 11. Individuals who later developed schizophreniform disorder performed 113

The Neurodevelopmental Theory of Schizophrenia

more poorly than both healthy controls and psychiatric controls at all five assessments, suggesting that persistently low scores in premorbid cognitive testing have some specificity for schizophrenia. Studies of conscripts (29-31) have also demonstrated that, as a group, future schizophrenia patients have lower IQ scores than controls. Gochman et al. (32) in a 13-year follow-up study of COS cases, reported that COS cases had lower IQ scores before diagnosis, as well as a decline in general intellectual function that was not associated with a particular developmental period but occurred, on average, in the two years preceding and following the onset of psychosis and remained stable thereafter.

Structural Neuroimaging Findings in EOS Findings from structural MRI studies in AOS show increased volume of the lateral ventricles (33), and slightly decreased overall brain, gray and white matter volumes (34, 35). A recent meta-analysis suggests that the left medial temporal lobe and left superior temporal gyrus (STG) are key regions of reduced volume (35). Volume decreases are found in numerous other regions, including the hippocampus and amygdala (36), frontal lobes (37) and a relatively modest reduction in thalamic size (38).

Studies of COS have also found gray matter reduction and ventricular enlargement (39, 40) as well as reduced overall cerebral volume (41). However, in contrast to AOS, findings with regard to temporal lobe structures and hippocampal volume are mixed, suggesting that volume reduction in these regions may be moderated by age of onset and illness durarion. Hippocampal volumes in EOS cases may be comparable to healthy individuals in childhood and early adolescence (42, 43) with progressive volume decreases occurring as patients approach adulthood (39). With regards to other temporal lobe structures, one study found evidence of reduced volume of the right STG in EOS (43); others reported no difference between COS patients and controls in temporal lobe structures (41, 42), and another study reported increased volume of the right posterior STG (44). An intriguing finding of EOS studies to date is the apparent importance of parietal lobe integrity and connectivity for schizophrenia. Thompson et al. (45) reported that the earliest deficits in NIMH COS were seen in parietal gray matter. In a new cohort of EOS patients, recruited at the Maudsley Hospital, diffusion tensor imaging (DTI) revealed abnormalities in parietal white matter compared to healthy controls (46), supporting the 114

above finding that parietal abnormalities may play an early role in the pathophysiology of schizophrenia.

Thompson et al. (45) followed 12 COS patients and matched controls over a five-year period during adolescence in order to investigate deficits related to disease progression during this stage of development. They report a dynamic wave of gray matter loss in the COS group beginning in the parietal association cortex that progressed anteriorally into the dorsolateral prefrontal cortex and temporal lobes, including STG. However, the pattern of change over time was diverse for different brain regions. A more recent study of the NIMH COS sample initially tested by Thompson et al. found dorsal to ventral frontal reductions in gray matter, which the authors interpret as an exaggeration of normal adolescent gray matter loss (47). Greenstein et al. (48) found that as COS patients approached adulthood, cortical gray matter development in the parietal cortex appeared to normalize, and volume deficits were mainly found in frontal and temporal regions, consistent with findings in AOS and providing further evidence for continuity between COS and AOS. Genetics and EOS Schizophrenia is known to be highly heritable (49). The concordance rate for monozygotic twins is higher than for same-sex dizygotic twins (50), suggesting that both genetic and environmental factors shape the developmental path leading to illness. While there are numerous susceptibility genes for schizophrenia, it is still unclear which of these genes are clinically relevant, and many genes may be of general importance for neurodevelopment and thus implicated in a wide range of neurodevelopmental disorders (51). In addition, genes may have different developmental effects at different points in time; only by studying the effect of the various candidate genes at different time points during the lifespan will more precise neurodevelopmental genetic models for schizophrenia emerge. Several of the genes conferring risk for schizophrenia have been examined in COS in terms of their association with various phenotypic measures (51). These genes are briefly discussed below.

Genes Related to Neurodevelopment and EOS Two important general findings have emerged from the NIMH COS studies. First, that familial risk for

Jess Kinros et al.

Schizophrenia Spectrum Disorders is higher for COS than AOS groups (52), suggesting that risk genes in this group may exert a greater effect on neurodevelopmental processes. Second, that risk genes for autism were not contributing to risk for schizohrenia in the COS group, despite high rates of Pervasive Developmental Disorders in this sample, suggesting that these genes cannot be seen as general risk factors for the neurodevelopmental problems in COS (53).

The 2q31.1 gene GAD1 is implicated in cortical, thalamic, cerebellar and hippocampal development. In the NIMH COS sample it was associated with greater frontal gray matter loss in adolescence and more severe deficits in smooth pursuit eye tracking (54). Specifically, six single nucleotide polymorphisms (SNPs) were associated with an increased rate of frontal gray matter loss over time and a different SNP was associated with eyetracking dysfunction and worse scores on a measure of premorbid function which included social, speech and motor delays.

Addington et al. (55) investigated the two overlapping genes G72/G30 on 13q33.2. SNPs at the G72/G30 locus were associated with both bipolar illness and schizophrenia, suggesting that G72/G30 is a susceptibility locus for both illnesses. In addition, G72/G30 was specifically associated with later age of onset and better premorbid development, shown by better scores on the Autism Screening Questionnaire. They suggest that G72/G30 may act later than other risk factors in their sample, given its association with longer normal development prior to illness.

The 8p12 gene NRG-1 regulates aspects of neural development and synaptic plasticity and is associated with abnormal brain development in schizophrenia (56). In the COS group, the risk allele at 420M9-139 was associated with poorer premorbid social functioning (early childhood social withdrawal and poor peer relationships, measured by the PAS) and a different pattern of brain volume changes than healthy controls (56).

The key finding was that risk allele carriers in the COS group had greater gray matter volumes during childhood but a steeper rate of decline of these volumes during adolescence.

The 6p22.3 gene DTNBP1 is involved in multiple neuronal functions, suggesting that it may play an important role in the pathophysiology of schizophrenia (51). In the COS group, it was associated with poor premorbid functioning; specifically, four adjacent SNPs of this gene were associated with worse PAS scores (12).

Summary of Findings in EOS Although methodologies and sample sizes vary considerably between studies, collectively the evidence confirms that significant premorbid delay and impairment occur (and often co-occur) in EOS in the areas of motor, language and social development. Studies of EOS thus clearly support a neurodevelopmental theory for schizophrenia.

These often subtle developmental deficits show some specificity for schizophrenia and are considered to reflect early neurodevelopmental processes that may already be acting to predispose the child to later psychotic illness (51). In particular, speech and language delays and deficits are observed in many EOS cases and may be an early sign of a neurodevelopmental pathway to schizophrenia (52). Genetic factors, broadly associated with schizophrenia, are also associated with EOS, suggesting common genetic contribution across psychosis phenotypes. Risk genes potentially express their effects on both brain development, and cognitive/ behavioral developmental characteristics.

Conclusions and Further Directions For more than two decades, the neurodevelopmental theory has been the prevailing explanatory theory for the etiology of schizophrenia. In its simplest form this theory posits that schizophrenia is the behavioral outcome of an aberration in neurodevelopmental processes that begins long before the onset of clinical symptoms and is caused by a combination of environmental and genetic factors (51).

Attempts to provide a more specific conceptualization of the neurodevelopmental hypothesis contrasted those favoring an early (pre- or perinatal), â&#x20AC;&#x153;staticâ&#x20AC;? brain lesion theory (4), and those advocating a late adolescent disturbance in brain maturation (2). However, subsequent research, including brain imaging studies that reveal a pattern of progressive changes both for early onset as well as chronic adult patients, indicated that the pathophysiological processes involved in schizophrenia need not be restricted to the pre- or perinatal period (51).

It is becoming increasingly evident that risk genes for schizophrenia have multiple actions and variable expression at different developmental stages and different brain regions (51). This suggests that genetic factors model the brain across the lifespan, and therefore distinctions between early and late theories and between 115

The Neurodevelopmental Theory of Schizophrenia

neurodevelopmental and neurodegenerative hypotheses may be outdated (51). Furthermore, despite the wealth of evidence on premorbid function and brain changes, no unitary neurodevelopmental account of these early subtle impairments currently exists, and more research is needed to try and link the behavioral and neurobiological aspects of aberrant neurodevelopment to the characteristic symptomatology in schizophrenia.

The variable expression and actions of genes may allow associating specific genetic factors with specific aspects of neurodevelopment. As discussed previously in this article, the gene dysbindin (DTNBP1), a schizophrenia susceptibility gene, has been also associated with poor premorbid functioning in COS (12), supporting the hypothesis that this (and possibly other schizophrenia susceptibility genes) also contribute to early neurodevelopmental impairment. This is only one example how susceptibility genes for psychosis also affect neurodevelopment and behavior. There are also clear hypotheses of how and when various etiological genetic factors might interact with early and later onset environmental risk measures (57, 58). Thus, two main lines of evidence will likely contribute to the development of more specific etiological models for schizophrenia: The study of single gene effects on brain and behavior, and the study of gene environment interactions.

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Social-Sexual Education in Adolescents with Behavioral Neurogenetic Syndromes Maya Plaks, MD, 1 Ronit Argaman, MSW, 2 Mike Stawski, MB, BS, MRCPsych, 1 Tova Qwiat, MA, 3 Dan Polak, MA, 4 and Doron Gothelf, MD1 1

The Behavioral Neurogenetics Center, Feinberg Department of Child Psychiatry, Schneider Children’s Medical Center of Israel, Petah Tikwa, Israel, and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel 2 Ram Institute for Sexual, Social and Psychological Treatment, Fontovich Psychological Service Ltd., Tel Aviv, Israel 3 Clinic for the Art Therapy, Savion, Israel 4 Shalom School for Special Education, Department for Special Education, Ministry of Education, Culture and Sport, Petah Tikwa, Israel

ABSTRACT Background: Adolescents with developmental disabilities have unmet needs in their sexual and social knowledge and skills. We conducted a sexual social group intervention in adolescents with neurogenetic syndromes, mainly with Williams and velocardiofacial syndromes and their parents.

Method: Ten adolescents with neurogenetic syndromes and 14 parents participated in a Social Sexual Group Education Program. The program was delivered in 10 biweekly sessions to the adolescents and their parents separately.

Results: The focus of psychoeducation in both groups was the adolescents’ self-identification, acceptance of the developmental disability, independence, establishment of friendship and intimate relationship, sexual knowledge and sexual development, and safety skills. Change in independent activities of adolescents and in their concept of "Friend" was measured.

Conclusions: Social and sexual education programs are of the utmost importance for adolescents with neurogenetic developmental disabilities. These programs should start already before adolescence and follow the children into young adulthood.

INTRODUCTION Issues of sexuality are as important to adolescents with developmental disabilities as they are to other adoles-

cents without disabilities. Adolescents with disabilities have the same needs, drives, desires and interests as other youth and go through the same changes – physical, emotional, social (1). However, sexuality is a more complicated issue in people with learning disabilities, where the sexual component of growth is often denied by parents and caretakers. The presence of sexuality in this population has frequently been seen as presenting problems rather than a positive human attribute (2, 3).

Parents of adolescents with developmental disabilities often avoid the issue of sexuality as a result of fear: fear that talking about these issues would promote sexual interest, fear of embarrassing situations, fear of sexual abuse, pregnancy or sexually transmitted diseases (4).

Parents are also influenced by social stigmas and myths about sexuality in disabled children which may include ideas that adolescents with developmental disabilities do not possess a sexual drive at all or they will inevitably transmit the disability to their offspring (5, 6). Although there is a growing recognition of the need for parents’ consultation, only few receive guidance or education regarding sexuality of their disabled child. This lack of information about sexuality leads to a feeling of helplessness and to choosing dysfunctional ways of coping (7).

The recommended approach to help disabled children to develop their sexuality lies in educating both the adolescents with learning disabilities and their parents, providing them the necessary information on sexuality (8).

While there is some increasing awareness of the need for psychosexual education in individuals with developmental disabilities, there is lack of awareness for this need in individuals with neurogenetic syndromes.

Address for Correspondence: Doron Gothelf, MD, Feinberg Child Study Center, Schneider Children’s Medical Center of Israel, 14 Kaplan St., P.O. Box 559, Petah Tikwa 49202, Israel. gothelf@post.tau.ac.il

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In the Behavioral Neurogenetics Center at Schneider Children’s Medical Center of Israel we treat individuals with neurogenetic syndromes associated with learning disabilities including Williams syndrome (WS) and velocardiofacial syndrome (VCFS).

Williams syndrome is caused by a microdeletion in the long arm of chromosome 7 (9). Most cases are sporadic and not inherited, which means that most of the patients are single cases in their families. Because of their impaired functioning, most people with Williams syndrome do not get married and do not give birth to children. In addition to some medical comorbidities (e.g., supravalvular aortic stenosis), individuals with WS have a mean IQ in the mild to moderate range of mental retardation (10). Individuals with WS are very friendly towards strangers, and tend to approach them without making appropriate social judgments, asking them personal questions and sometimes initiating physical contact in an undifferentiated way (11). Because of their strong social appetite individuals with WS often reveal submissive and pleasing behavior. Therefore during adolescence and adulthood they are at high risk for sexual abuse. In spite of being outgoing, people with WS, like most of the people with learning disabilities, suffer from social isolation, impaired social skills, loneliness and difficulties in making friends. Parents of adolescents with WS often fear that their children may become sexually abused or remain in social isolation.

Velocardiofacial syndrome (VCFS) also known as DiGeorge syndrome is caused by a microdeletion in the long arm of chromosome 22, and is the most common microdeletion syndrome in humans, occurring in about 1 to 2,000 live births (12). While the physical comorbidities associated with VCFS are often relatively mild and the major ones like the palate and cardiac anomalies can be corrected by surgery, the cognitive deficits and psychiatric disorders have a more profound impact on affected individuals (13). Consequently, following the first years of life, the cognitive deficits and behavioral/neuropsychiatric symptoms become the most debilitating aspect of individuals with VCFS. Individuals with VCFS tend to be shy, withdrawn, stubborn, emotionally labile, and afflicted with social and communication impairments (13). The average IQ in VCFS is within the borderline range and about 25% of individuals with VCFS develop schizophrenia-like psychotic disorder by early adulthood (12, 14). Autistic spectrum disorder symptoms are also common in children and adolescents with VCFS (15).

Because of the cognitive deficits and psychiatric comor-

bidities adolescents with VCFS are impaired in their social skills and are also frequently lonely.

As we felt that social and sexual issues of adolescents with WS and VCFS are crucial for the development and well-being we decided to conduct a Social-Sexual Group Education Program and to measure its effectiveness.

METHODS Subjects

In 2002, 10 adolescents with developmental disabilities and their parents participated in a Social-Sexual Group Education Program. They were recruited from the Behavioral Neurogenetics Center at Schneider Children’s Medical Center of Israel. Of the 10 participants five had WS, three had VCFS, one neurofibromatosis, and one idiopathic learning disability. The age range of adolescents was 15 to 24 years, mean= 19.5 years, SD=2.6 years, and they consisted of five males and five females. Eight of 10 subjects completed the 10 group sessions. Two subjects and their parents discontinued after the first session.

The group for parents included 14 participants: in six cases one parent and in four cases both parents participated in the group sessions. The study was approved by the Institutional Review Board of Rabin Medical Center of Israel.

The Social-Sexual Group Education Program

The treatment was delivered in 10 bi-weekly group sessions. Each meeting was devoted to a special topic and was held in the form of psychoeducation promoting attitudes, skills and knowledge. The focus of psychoeducation in both groups was the adolescents’ self-identification, acceptance of the developmental disability, independence in social life, establishment of friendship and intimate relationship, sexual knowledge and sexual development, and safety skills.

The specific aims of the adolescents’ group were: (1) to help the participants to discuss their attitudes and feelings regarding human sexuality, their own development and future perspectives; (2) to inform the adolescents regarding sexual development, physical, emotional and social changes; (3) to instruct how to develop healthy social and sexual relationships, appropriate sexual behavior and their right over their bodies.

The specific aims of the parents’ group were: (1) to support parents in working through their attitudes, feelings and uncertainties regarding their children’s devel119

Social-Sexual Education in Adolescents with Behavioral Neurogenetic Syndromes

opment and sexuality; (2) to provide parents knowledge on sexual development of adolescents with intellectual disability; (3) to emphasize to the parents the importance of sexual education, and to advise them how to help their children manage their sexuality in a healthy and protected way; (4) to encourage parents to foster more skills of independence in their children according to each adolescent’s developmental level.

Measures The following questionnaires were administered before and after the group treatment.

1. The Skills and Independent Activities Questionnaire is comprised of a list of 19 questions about independent activities at home and social basic skills (16). It contains two subscales: “Social Entertainment” (9 questions) and “Independent Activities” (10 questions).

The questionnaire was completed by the parents.

2. The Assessment of Sexual Knowledge, Experience and Needs Scale for People with Intellectual Disability (17).

The questionnaire contains eight sections comprised of 170 questions that assess sexual knowledge and behavior (18, 19). In the present study we chose to use three sections. The first section assesses sexual behavior and is composed of seven questions; the second section assesses sexual assertiveness and contains five questions regarding one’s reactions in situations of risk for sexual abuse; and the third section evaluates the adolescent’s sexual knowledge and contains four questions regarding sexual organs (using pictures) and eight questions about sexual interactions and its consequences.

3. The Assessment of the understanding of the concept of a friend (16).

RESULTS Summary of social-sexual group education meetings with the parents

Acceptance of the adolescents’ disability and limitations Most parents noted that their children aspire to be a part of a normal, healthy society. However, at the same time it was painful regarding their children’s experiences of being teased for intellectual disabilities, for their dysmorphic facial features and for their inappropriate social behavior. Some parents admitted that in order to protect their children they pretend as if these insults did not occur. One of the parents frankly disclosed to the 120

group, “I pretend as if nothing had happened but inside I feel a lot of pain.”

The parents differed from each other by the degree of their acceptance of their child’s disability. Some of them felt ashamed of their child’s limitations and tried to give their children a feeling that they can do everything that regular adolescents do and this way they assume that they provide their child with a feeling of being normal. Other parents were proud of their children being special, and were proud of their investments in their development.

Most of the parents did not inform their children that they carry a genetic syndrome. They thought that their adolescents were not able to understand the meaning of the syndrome and were confident that discussing this issue would be distressful to their child. They also spoke about their guilt over transmitting “a defective gene” to their child. Some of the mothers reported that since their child was born they had left their jobs and devoted themselves to take care of the child and his disability.

At the group sessions we reflected to the parents their difficulties in accepting the child’s limitations and disabilities and the guilt feelings the genetic syndrome of their child and its consequent disabilities invoke in them. We stressed their ability to assist their child to develop adequate self-concept. We also emphasized the importance of conducting a dialogue with the child and its role in reducing the feeling of shame for having the syndrome and for reducing the denial of its consequences in his life. We further suggested that adolescents who deny their limitations are prone to be involved in abusing and frustrating relationships. An adequate self-concept is a basis for finding an appropriate social reference which leads to equal and mutual social relationships.

Parenting style We noticed two poles of parenting styles in the group, one being the overprotective type and the other denying the child’s limitation. Overprotective parents would not allow their children to go out of the house unaccompanied, would not leave them alone at home even for a short period of time and would help them in all their activities, including dressing and washing – even when the adolescent was capable of doing it all by himself. The overprotective parents expressed their worries about the naivety of their children in everyday life, their lack of trust in strangers and the fear that their children were prone to sexual abuse. The parents denying their children’s limitations encouraged their children to func-

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tion beyond their limitations and tended to ignore the disability. They would encourage their children to work hard and get married at an early age.

Parents complained that the adolescents do not share with them the experiences they undergo in their treatment group. We used this issue that they raised to discuss the process of maturation of adolescents with learning disabilities. We explained that similarly to typically developing adolescents, adolescents with developmental disabilities sometimes choose to distance themselves from their parents and that it serves the developmental purpose of creating their self-identity. Some parents raised concerns that without constant supervision their child will be exposed to dangerous situations.

Encouragement of independence The importance of encouraging the adolescents to acquire independent skills was greatly emphasized during the meeting sessions. Parents were encouraged to enable their children to wash themselves on their own, to choose their own clothing or hair style, etc. Parents were instructed to teach their children how to talk on the phone, to enrich their children’s conversation topics, for example by discussing with them the news or favorite tv program, and to encourage the children to develop hobbies. Where appropriate, parents were encouraged to allow their children to go out of the house unaccompanied, after they had learned basic safety skills. Parents exchanged information about possible entertainments for their children.

Parents raised concern regarding who would take care of their disabled child in the future, after they would die. Only one adolescent of the 10 participating in the group was already in a residential facility. The parents of that adolescent shared with the other parents their positive experience with this transition. As a result, other parents started considering out of home placement for their child. Some parents raised guilt feelings as if they were throwing their child out of their home. They also expressed their emotional symbiotic dependency feelings towards their child, as one of the mothers said: “My daughter is like my baby-doll, that provides meaning to my life and when she leaves the house I will feel emptiness.” All parents stressed they felt relieved to be able to share these feelings with other parents who face the same dilemmas.

Sexuality and relationship To warm the parents up to speak on this difficult issue, we asked the parents to recall what their parents had

told them about sexuality when they were at their child’s age. All the parents admitted that their parents did not speak at all with them on this matter, and that they felt embarrassed to speak about sexuality with their children. Parents claimed that the issue of sexuality relates to one of the most painful issues of the child’s life.

We shared with the parents the ignorance of their children in issues related to sex, such as knowledge of the anatomy and physiology of genitalia and basic social skills.

We also educated the parents about the relation of the genetic syndromes with certain types of social behaviors.

Adolescents with WS express their feelings in a dramatic and disinhibited way, whereas adolescents with VCFS tend to be shy and not to disclose their feelings.

Parents were instructed how to teach their children cautious measures in intimate relations such as explaining to their child that “it is possible to touch me only if I agree.” At the same time parents were encouraged to convey to their children the message that sexuality is a positive and potentially satisfying part of life.

Parents discussed the degree that they should be involved in their child’s process of finding an intimate partner. Some parents thought they should choose a partner for their child. We thought that preparing the adolescents to be able to choose a partner is an important developmental challenge to be accomplished by adolescents.

The parents came to the conclusion that a need for an intimate relationship is a universal need for all people. However, they also recognized that the intimate relationship their children could have would be more passive and would rely on much external support. We stressed the importance of a developmental model, where adolescents first need to define their adequate self-concept, and consequently are able to relate to a peer group that is equal to their abilities and limitations.

In such a peer group they can have satisfactory social relationships and find romantic relationships.

Summary of social-sexual group education meetings with adolescents

The meeting sessions of the adolescents were held in an entertaining, playful, warm and open atmosphere. The sessions relied less on formal conversations and more on expressive modes including dancing, drawing and role play. While each meeting was devoted to a certain topic the meetings had a routine structure. The sessions started with a summary of the previous session, introduction of the present session content and goals, and summary and conclusions at the end of the session.

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Self-concept The adolescents were requested to compose their own identity card in which they describe themselves. An adolescent with WS gave the following description: “I've got a special face and a good sense of music.” Another adolescent with VCFS who suffered from hypernasal speech said: “I've got a strange voice and that's why people look at me in a bus.”

Participants shared their bitter experience of social rejection and insults regarding their disability. They were comforted to share this feeling with the group and to learn that other group members are coping with similar experiences. As one of the adolescents in the group stated: “Here in our group I feel confident, I can share all my feelings without being scared of people mocking me.”

Social relationships Participants in the group revealed their wish for developing social and romantic relations and even spoke of their desire to marry and give birth to children. They also expressed feeling lonely and finding it difficult to make friends. Loneliness was pervasive for those participants who graduate the special education schools and found themselves out of any rehabilitation program.

Most adolescents did not attend any social group.

We encountered vast social deficits among the adolescents. For example most participants had difficulties approaching somebody and inviting him for a dance.

They refrained from making eye contact because of fear of rejection. Only one adolescent had a positive experience of romantic relationships while the others had negative experiences. The sessions were devoted to providing knowledge of the concept of social relationship. For that purpose, in one of the exercises we asked the adolescents to write an advertisement: “looking for a friend.” A male with WS wrote: “I am looking for a friend who will love music and discs, who will be my age and will find me a girlfriend.” A female with VCFS wrote: “she needs to be a good listener, understanding, and she should not be hurting, cursing or gossiping.” The group therapists summarized the desired traits of a friend as they arose from the adolescents’ scripts. These traits included trust, mutuality, sincerity and mutual entertainment.

Sexual knowledge and behavior We encountered ignorance related to knowledge of sexual organs and their function. For example, a female from the group thought that babies are delivered from the gastrointestinal system. The adolescents also seemed 122

to view sexuality as something forbidden or dangerous.

Some of the males were frequent consumers of pornography sites on the internet and some of the males had had sexual relations with prostitutes. The group therapists educated the group using pictures regarding anatomic parts of the sexual system, differences between males and females sexual organs, sexual development, and changes occurring in the body during adolescence.

They also educated the group regarding appropriate sexual behavior, for example that masturbation is something one does in private.

Sexual assertiveness and prevention of sexual abuse Two adolescents shared their experience of being in sexually abusive situations. Both cases happened in their schools for special education by other students with disabilities. During the dance exercises aimed to establishing limits in body touching, they revealed inappropriate touching behaviors, and lack of assertiveness in saying “no” when they do not feel comfortable that another person is touching them. During the meeting we strengthened the assertiveness skills of the adolescents. We repeated the following guidelines: “Touching is allowed only when your friend agrees to be touched and forbidden if he or she does not agree to be touched” and “You are responsible for your body and its sole owner.” Participants also developed their skills to identify potentially abusive situations, to resist abusive situations, leaving a place where abuse might happen and immediate report of abuse to their parents or other authorities.

Evaluation of outcome

On the Skills and Independent Activities Questionnaire parents reported an improvement in adolescents Entertainment scores (from mean ± SD of 2.0 ± 1.7 to 3.7 ± 2.9, t = -2.7, p < 0.05). No other significant improvement was noted on the other subscales of the questionnaire.

On the Assessment of Sexual Knowledge, Experience and Needs Scale there were no statistically significant differences in total scores before versus after the group treatment intervention.

On the Assessment of Relationship and Social Support of the Family, Friends and Feeling of Loneliness, there was significant improvement in the Friend Concept Subscale (from 1.3 ± 1.2 before intervention to 2.3 ± 1.4 after intervention, t = -2.7, p <0.05). This was marked improvement in the approach for choosing

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a partner in five of eight adolescents so that following the intervention they mentioned traits like loyalty and equal relations for choosing a friend.

A careful descriptive analysis also suggested several changes occurring following the intervention. Six out of eight adolescents enriched their vocabulary of definitions of sexual activities. For example instead of describing sexual relations as “being with a woman in a bed,” they used the expression “to make love with a woman.”

They began to use more words of pleasure in association with sexual relations. They also had a more positive approach to sexual relations. For example, following the group intervention they used expressions like nice, pleasant, enjoying, one is in love with another, to describe sexual relations.

DISCUSSION To our knowledge this is the first report on Social-Sexual Education Group Treatment for adolescents with genetic syndromes. Adolescents with genetic syndromes exhibited feelings of social rejection, low self-esteem, and high level of dependence on the environment and internalized negative attitudes towards sexuality. All these factors are considered to be risk factors for sexual abuse and feelings of frustration (16). These negative feelings and overdependence are also common in adolescents with nonsyndromic developmental disability but may be even more intense in adolescents with genetic syndromes because of dysmorphic facial features, medical complications and exceptionally extroverted (in WS) or introverted (in VCFS) behavior (11, 13).

The current treatment program was designed as two groups running in parallel, one of the adolescents and the other of parents. While sexual education interventions with adolescents are conducted in special education schools in Israel, there is rarely any educational or therapeutic work held with their parents. In our work with the parents we learned that they have grave difficulties in accepting developmental changes occurring in their disabled adolescents. The parents expressed anxiety that their children would not be able to cope properly with their social and emerging sexual drive.

The parental anxiety tends in some cases to strengthen mutual dependence, limiting the abilities of adolescents with developmental disabilities to develop their social and sexual aspects and skills towards being partially independent adults (20, 21). We identified two patterns of parenting style of parents in the group, one char-

acterized by anxious overprotection of the adolescent and the other characterized by denial of the adolescent’s limitation and unrealistic expectations that the adolescent will grow up to live a normal and fully independent adult life (22, 23). Parents exhibited shame regarding the sexuality of their children. They expressed fears of their children being victims of sexually abusive interactions, unwanted pregnancy, and giving birth to a disabled baby. To help the parents to cope with these issues there is an urgent need for receiving support and knowledge from clinicians knowledgeable in working with individuals with developmental disabilities (4, 24, 25). To induce a significant change in sexual and social maturation of adolescents with developmental disabilities requires long-term work with the adolescent and even more so with his parents. In our view one of the main achievements of the group therapy for the long run was to provide some tools and legitimacy to the parents to help their adolescents implement their right to have satisfactory social and sexual lives.

The overarching principles we were following in both the parent and the adolescent groups is shown in Figure 1. To develop safe and satisfactory social and sexual lives, adolescents with genetic syndromes and developmental disabilities first need to acquire an adequate self-concept, that is, knowing their abilities and accepting their disabilities. Adequate self-concept leads to choosing a proper social relatedness group of adolescents with similar developmental level. Only in such social relatedness groups can the adolescent feel equal and have true friendships that are based on reciprocal relations. In cases where adolescents with develFig. 1: general principles in the social-sexual treatment program Appropriate Self-Concept

Finding social relatedness group of adolescents with similar developmental level Prevention of abusive relations

Relations are based on equality and reciprocity Satisfactory intimate-romantic relations

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opmental disability fail to develop adequate self-concept and choose as a group of reference typically developing adolescents, they are predisposed to abuse and humiliation (7, 16). The ability to establish intimate-romantic relations is the top stage in this hierarchical pyramid relying on the accomplishment of proper self-concept and proper social group relatedness (7, 16).

As can be expected from such a short-term intervention we did not encounter a dramatic change in the social and sexual maturity of the adolescents following the 10 group sessions. The significant quantitative changes following the group meetings were in social development marked by increase of entertainment activities of the adolescents outside the home and the development of a more mature concept of friendship.

There were no significant quantitative differences in the measures of sexual knowledge or behavior suggesting that changes in these domains are more difficult to achieve than changes in the social domain. This also goes in line with the hierarchical model presented in Figure 1 in which intimate-romantic relations are at the top level of the pyramid and follow social developmental changes.

It is unknown what the intensity and extensiveness of social sexual education intervention in adolescents with developmental disabilities should be. However, in our view these interventions should be started at a younger age, even before adolescence, and work with the child and his parents is needed on a long-term basis into adulthood.

Of note, this study has several limitations. The sample is relatively small and heterogeneous and there was no control group that received another intervention or no intervention. We hope this preliminary study will lead to further research on social-sexual interventions in other syndromes and other countries. Although most of the paper focuses on describing the rationale of the program and the content of the therapeutic sessions some qualitative and quantitative statistical analyses were conducted. Obviously, since the sample size is small these results are merely preliminary and cannot be viewed as indicating efficacy of the intervention. While there are differences in the social and sexual behaviors of individuals with Williams syndrome and VCFS, there are also many psychosexual issues common to the two syndromes including ignorance related to sexual issues and deficits in social skills.

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References 1. Committee on children with disabilities (COCWD). Sexuality education of children and adolescents with developmental disabilities. Pediatrics 1996; 97:275-278.

2. Heshusius L. Sexuality, intimacy, and persons we label mentally retarded: What they think â&#x20AC;&#x201C; what we think. Ment Retard 1982; 20:164-168.

3. Kreutner A K. Sexuality, fertility, and the problems of menstruation in mentally retarded adolescents. Pediatr Clin North Am 1998; 28:475-480.

4. Ballan M. Parents as sexuality educators for their children with developmental disabilities. Siecus Report 2001; 29:14-19.

5. Malkin R, Gaylin W. Mental retardation and sterility: A problem of competency and parentalism. New York, Plenum, 1981.

6. Hall JE. Sexual behavior in mental retardation and developmental disabilities.

New York: Bruno Mazel Inc., 1975.

7. Argaman R, Lahover Y. Manual for people working in special education system - approaching sexual education from the social point of view. Tel Aviv: Maalot Publishing House, 2007.

8. Aloni R, Ramot A, Riberman A, Dovdovani A, Hovav M. Sexual treatment of people with Learning Disabilities. Parenting and developmental disabilities in Israel. Jerusalem: Magnes, 1998: pp. 151-165.

9. Bayes M, Magano LF, et al. Mutational mechanisms of Williams-Beuren syndrome deletions. Am J Hum Genet 2003;73:131-151.

10. Bellugi U, Lichtenberger L, Mills D, et al. Bridging cognition, the brain and molecular genetics: Evidence from Williams syndrome. Trends Neurosci 1999; 22:197-207.

11. Doyle TF, Bellugi U, Korenberg JR, et al. ''Everybody in the world is my friend": Hypersociability in young children with Williams syndrome. Am J Med Genet 2004; 124:263-273.

12. Shprintzen R J. Velo-cardio-facial syndrome: 30 years of study. Dev Disabil Res Rev 2008; 14:3-10.

13. Gothelf D. Velocardiofacial syndrome. Child Adolesc Psychiatr Clin N Am 2007; 16:677-693.

14. Murphy KC, Jones LA, Owen MJ, et al. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 1999; 56:940-945.

15. Antshel KM, Aneja A, Strunge L, et al. Autistic Spectrum Disorders in Velo-cardio Facial Syndrome (22q11.2 Deletion). J Autism Dev Disord 2006; 35:461-470.

16. Argaman R. Predicting factors of sexual abuse in people with Learning Disabilities living in institutions. Tel Aviv, Israel: Tel Aviv University, 2003.

17. McCabe M P. Sexuality Knowledge, Experience and Needs Scale for people with intellectual disability (SEX KEN-ID) Melbourne, Australia: Deakin University, School of Psychology, 1992.

18. Ousley OY, Mesibov GB. Sexual attitudes and knowledge of high-functioning adolescents and adults with autism. J Autism Dev Disord 1991; 21:471-481.

19. Konstantareas MM, Lunsky YJ. Sociosexual knowledge, experience, attitudes, and interests of individuals with autistic disorder and developmental delay. J Autism Dev Disord 1997; 27:397-413.

20. Hauser-Cram P, Warfield M, Shonkoff JP, Wyngaarden Krauss M, Overton WF. Children with disabilities: A longitudinal study of child development and parent well-being. Hoboken, N.J.: Wiley-Blackwell, 2001.

21. Wikler L. Chronic stresses of families of mentally retarded children. Fam Relations 1981; 30:281-288.

22. Crnic K A, Friedrich WN, Greenberg M T. Adaptation of families with mentally retarded children: A model of stress, coping, and family ecology. Am J Ment Defic 1983; 88:125-138.

23. Heiman T. Parents of children with disabilities: Resilience, coping, and future expectations. J Dev Phys Disabil 2002; 14:159-171.

24. Floyd FJ, Gallagher EM. Parental stress, care demands, and use of support services for school-age children with disabilities and behavior problems. Fam Relations 1997; 46:359-371.

25. Champagne MP, Walker-Hirsh LW. Circles: A self-organization system for teaching appropriate social/sexual behavior to mentally retarded/ developmentally disabled persons. Sex Disabil 1982; 5:172-174.

Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Auditory and Visual Processing in Williams Syndrome Omer Zarchi, BA,1,2 Joseph Attias, PhD,2, 3 and Doron Gothelf, MD1 1

Behavioral Neurogenetics Center, Feinberg Department of Child Psychiatry, Schneider Children’s Medical Center of Israel, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 2 Institute of Audiology and Clinical Neurophysiology, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel 3 Department of Communication Disorders, Haifa University, Haifa, Israel

ABSTRACT Williams syndrome is a neurodevelopmental disorder caused by a deletion on chromosome 7.

It is characterized by a range of medical problems in addition to severe impairments in visuospatial processing and oversensitivity to sounds, including hypersensitivity to sounds (hyperacusis) and extreme fear from sounds (phonophobia). In spite of impairments in visuospatial processing, object and face processing abilities are relatively preserved in WS. The present review discusses the growing research in the field linking the unique sensory phenotype in WS with underlying structural and functional brain abnormalities. In addition, possible associations between the genetic defect and the abnormal sensory processing are presented. Because Williams syndrome is etiologically homogeneous, it may serve as a model to promote understanding of visuospatial and auditory processing in humans. The findings may also have important implications for other developmental psychopathologies, such as autism, schizophrenia and attention deficit hyperactivity disorder.

“When I hear the sound of an electric drill, I feel as if it is drilling into my body.”

Tamar is a 16-year-old girl with Williams syndrome who has had phonophobia and hyperacusis since an early age.

INTRODUCTION Williams syndrome (WS) is a neurodevelopmental disorder caused by a hemizygous microdeletion of approximately 1.6 Mb containing ~28 genes on the long arm of chromosome 7 (7q11.23). Its estimated prevalence ranges from 1:7500 to 1:20000 live births (1). Affected subjects have a wide range of medical diseases and a unique behavioral and cognitive profile. The main physical characteristics are typical faces, supravalvular aortic stenosis, failure to thrive, short stature, transient neonatal hypercalcemia, and delayed language and motor development (2, 3). Behaviorally, WS subjects have a strong social appetite and a low level of social fear (4).

The mean cognitive level is within the range of mild to moderate retardation, with some peaks and valleys in mental domains, particularly severe visuospatial construction deficits accompanied by a relative strength in expressive language (5) and relatively spared face and object recognition. In addition, subjects have a strong attraction to music and a strong auditory fascination alongside extreme hyperacusis and phonophobia.

Because WS is etiologically homogeneous, it serves as an excellent model for the study of the biological developmental processes underlying sensory processing in humans. The findings may also have important implications for other developmental psychiatric disorders associated with pathological sensory processing and sensitivity, such as autism, schizophrenia, post-traumatic stress disorder, and attention deficit hyperactivity disorder. The aim of this work was to review the current research linking the auditory and visual abnormalities in WS with underlying impairments, as seen in neuroimaging and electrophysiological findings. Possible associa-

Address for Correspondence: Omer Zarchi, Feinberg Department of Child Psychiatry, Schneider Children’s Medical Center of Israel, 14 Kaplan St., POB 559, Petah Tikva 49202, Israel omerz@post.tau.ac.il

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tions between the WS chromosomal deletion and the abnormal sensory processing are presented as well.

AUDITORY PROCESSING Peripheral Findings

Middle-ear morbidity in WS is common; the reported incidence of otitis media ranges from 19% to 61% (6, 7). In the inner ear, auditory and electroacoustic findings in subjects with WS have indicated a mild cochlear hearing loss in the high frequencies, which tends to worsen with age (8-10), while prolonged cochlear nerve conduction time is indicated in brainstem auditory evoked response (BAER) (11). Findings reveal an association of cochlear hearing loss with acoustic reflex dysfunction in WS (11). Moreover, preliminary studies have suggested a deficit in the efferent auditory system which modifies cochlear function (7, 12).

Acoustic reflex as well as the efferent auditory system protect against loud sound, and their dysfunction in WS may contribute to cochlear vulnerability especially to repeated exposures to high level sounds. Interestingly, the configuration of the cochlear hearing loss in WS involves the high tones, resembling a noise induced hearing loss.

Central Auditory Processing and Auditory Short-Term Memory

The hypersensitivity to sounds in WS does not seem to be associated with peripheral mechanisms only. The diverse sensitivity to sounds as well as high interest in music (discussed broadly later) is assumed to be related to features of central auditory processing.

Central auditory processing (CAP) involves the extraction of auditory significant features by intricate processes such as analysis of the spectrum and selective amplification of important representational elements.

Those processes are thought to take place in auditory centers of the thalamus and cortex. Additionally, it seems to rely on a specific short-term auditory memory module. Of the many abilities associated with CAP, only pitch perception has been investigated in WS. Pitch perception had been in the center of interest due to the perfect pitch ability reported to be very common in individuals with WS (13). Yet, on tests of pitch perception, children with WS performed worse than agematched controls (14). In contrast, auditory short-term memory in WS, as indicated in rhythmic sequences test, was found to be a relative strength in WS (15).

Neurophysiologically, evoked response potential (ERP) studies suggested that auditory processing in 126

individuals with WS is characterized by neural hyperexcitability and is carried out by neural systems different from those activated in typically developing subjects (16-19). Neville et al. (17, 18) reported that the auditory responses of subjects with WS were less refractory and more excitable than those of control subjects, a neural pattern which did not extend to visual modalities.

Similarly, Bellugi et al. (16) reported marked increases in the amplitude of the N100 and P200 responses to auditory stimuli with fast repetition rates. Together, the findings point to cortical-level hyperactivity.

On fMRI scans, subjects with WS exhibited different patterns of neural organization from age-matched controls (20). The superior temporal and other regions that normally support music and noise processing were not consistently activated, whereas the limbic structures, particularly the right amygdala, showed above-normal activation. Furthermore, during music processing, a widely distributed network of cortical and subcortical structures, including the brain stem, was activated.

To increase our understanding of central auditory processing in WS, further investigations are needed using standardized behavioral tests â&#x20AC;&#x201C; albeit difficult to administer in this population â&#x20AC;&#x201C; as well as their most significant brain correlate, the Mismatch Negativity ERP. Sensitivity to Sounds

The hypersensitivity to sounds in WS is composed of three interacting components: hyperacusis, phonophobia and auditory fascination. Hyperacusis is the perception of common everyday sounds as unbearable, strong or painful (21, 22); it is sometimes referred to as lower uncomfortable loudness levels. Phonophobia is an aversion to or morbid fear of normal sounds (23).

Whereas hyperacusis refers to loudness, a psychoacoustic aspect, phonophobia refers to the emotional perception of a sound, which is not necessarily related to its physical features (e.g., fear evoked by the sound of rain).

Physiologically, hyperacusis is assumed to derive from an abnormality in the auditory pathways. By contrast, phonophobia is assumed to derive from an abnormality in the limbic and autonomic systems (24). Auditory fascination, the third prominent auditory phenomenon in WS, is defined as an above-normal attraction to or fascination with certain sounds (23).

Several surveys have been conducted to determine the prevalence of sensitivities to sound in WS. However, different questionnaires were used in the various assessments, and most of the studies did not clearly differen-

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tiate hyperacusis from phonophobia (11, 25, 26). The reported prevalence of hyperacusis in WS ranged from 84% to 100%, compared to 0-12% in typically developing controls (11, 25, 26). Levitin et al. (23) used a parental questionnaire to compare the auditory hypersensitivities in subjects with WS to two other neurodevelopmentally impaired groups, patients with autism and with Down syndrome, in addition to healthy controls. Hyperacusis (which they termed odynacusis) was identified in about 80% of the WS group, 33% of the autism group, 33% of the Down syndrome group, and 4% of the normal control group. The corresponding rates for phonophobia (auditory allodynia) were 91%, 27%, 7% and 2%. Although hyperacusis and phonophobia occurred most frequently in WS, they were also common in subjects with the other neurodevelopmental disorders. The rate of auditory fascination in the WS group was about 9% compared to less than 1% in the other groups. Interestingly, in every case in which auditory fascination was identified, the same sound had previously evoked high anxiety in that subject. That is, every fascination began as an aversion (23).

The aversion of sounds in WS is present already at infancy. It peaks at around age 6 years and moderately decreases thereafter (11, 23). In typically developing children the peak age of sensitivity to sounds is between 5 to 8 years (27). When exposed to disturbing sounds, children with WS respond with avoidance and anxiety behaviors (e.g., crying, escaping from sound source) (11). The common sounds that trigger hypersensitivity are fireworks, car engines, thunder, and electric machines â&#x20AC;&#x201C; all characterized by broad-band frequencies and high intensities (6, 11, 23).

To our knowledge there are no treatment studies of the sensitivity to sounds in WS. Based on our clinical experience we suggest utilizing the fascination and attraction of individuals with WS to sounds and music for behavioral treatments based on gradual exposure and extinction of the phonophobia. At the same time, because the auditory system of individuals with WS is vulnerable to the effects of loud sounds, it is important that subjects with WS will use earplugs when exposed to noisy environment. Also because of the hearing loss identified in WS all subjects with WS should be followed by audiologists.

Musicality

Although it is well-established that subjects with WS are more interested in music than typically developing individuals and subjects with other neurodevelopmen-

tal disorders (14, 26, 28, 29), their musical talent is controversial. According to parental reports, subjects with WS have good musical memory and music recognition ability, and a selective pick of music (30). They also score higher on musical accomplishments and engagement than subjects with autism and Down syndrome, and equivalent on most measures to typically developing controls (28). However, on behavioral assessments, subjects with WS exhibit performances at mental age level and well below chronological age level in tasks involving pitch and rhythmic processing (14, 15, 26). At the same time, Levitin and Bellugi (15) noted a distinctive pattern of musical errors among subjects with WS. They reported that the errors made by subjects with WS were far more likely to be musically compatible with the target rhythm than the errors made by typically developing controls. However, the subjects with WS in this study were recruited from music camp, which may have created a bias.

The reason for the discrepancy between the parental reports and the behavioral measures may be attributed to the earlier development of the interest in and emotional response to music in children with WS compared to children with autism and normal controls, as well as to the tendency of the emotional effects (positive or negative) from music to last longer (28). Brain fMRI findings of enhanced activation of the amygdala coupled with inconsistent activation of regions in temporal lobe in response to music, support the presence of a unique neural music-processing in WS population which may alter their experience of music.

Overall, the cumulative data suggest that whereas subjects with WS lack analytical skills in the formal aspects of music, they possess unique strengths in engaging music as a means of expression, play and, perhaps, improvisation.

VISUAL PROCESSING Peripheral Findings

Peripheral dysfunctions in the visual system are common in WS. Reported rates of strabismus, mainly esotropia, range from 29% to 79% (31-34), and the rate of visual acuity deficit and amblyopia is about 50% (35).

Unique abnormalities in the anatomy of the eye have also been reported, including white satellites or incomplete anterior irises and bright irises (usually blue) (31).

No association has been found between the ocular abnormalities and the visuospatial deficits (35).

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Primary Visual Processing

There is little evidence of primary visual abnormalities in WS. Neurophysiological studies reported atypical neural functioning during perceptual contour square completion (36). Additionally, findings of cytoarchitectonic abnormalities of the primary visual cortex, including abnormal tissue density and neural organization (37), were later supported by structural MRI studies (38, 39). Whereas some visual fMRI studies reported hypoactivation in the primary and secondary visual cortices (40), others failed to detect primary visual abnormalities (1). The structural and functional visual cortex abnormalities may contribute to the higher incidence of visual-perceptual problems in WS, including reduced stereopsis and visual acuity.

Visuospatial Processing

A major feature of the cognitive profile in WS is the marked impairment of visuospatial abilities as demonstrated on drawing or copying tasks (41, 42) and on motor tasks requiring visuospatial guidance, such as walking over uneven surfaces or down steps (43).

By contrast, face processing and object recognition are relatively spared (19, 44). Form-, color- and faceprocessing functions are associated with the ventral (“what”) visual stream, with predominant input from the parvocellular pathway; spatial-integrative and motion-processing functions are associated with the dorsal (“where”) extrastriatal stream linked to the magnocellular pathway. Thus, the split in WS between the extremely poor visuospatial abilities and the relatively preserved face and object processing skills suggests a neural processing abnormality limited to the dorsal stream (35, 45). This assumption was supported by the study of Meyer-Lindenberg et al. (45) wherein highfunctioning subjects with WS performed similarly well to controls in matching shapes, but significantly worse in assembling the shapes into squares. On fMRI, the ventral stream was equally activated in both groups.

However, subjects with WS showed hypoactivation in the dorsal stream areas adjacent to the intraparietal sulcus, which takes part in perceptual-motor coordination and visual attention control. Accordingly, on tasks of attention to objects vs. location (45), brain structure analyses revealed reduced gray matter volume in the intraparietal sulcus. It is suggested from path analysis that the structural anomaly in the intraparietal sulcus may be responsible for the deficits in dorsal stream of the visual system (45).

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Subjects with WS are also characterized by a deficiency in perception of global spatial arrangements, with relatively preserved perception of local spatial arrangements. This pattern can explain their poor drawing abilities (46) as well as their poor performance on block design task, in which the subject is required to organize blocks into a global pattern (47). For instance, when children with WS are asked to draw a house, they tend to place the windows and doors as separate entities from the house itself. By contrast, in a typical drawing of a child with Down syndrome, the house elements will be simplified, but there will be a better gestalt relationship among them (47).

In summary, the main cognitive phenotype of WS consists of impairment in most visuospatial abilities with a local bias and deficiency in the perception of global spatial arrangements; face processing and object recognition are relatively spared. The phenotype is attributed in part to a deficiency in the dorsal visual stream alongside a relatively intact ventral visual stream.

Visuospatial Short-Term Memory

Subjects with WS have visuospatial short-term memory deficits compared to typically developing controls and to subjects with Down syndrome (19, 48, 49).

Physiologically, there is a reduction in the volume of the parahippocampal gyrus, an essential component of the neural system underlying visuospatial memory (39). The short-term memory deficit might be partly explained by the impaired visuospatial perception typical of these children, but it apparently extends beyond it (50). Whether the deficit is related to coding, storage or retrieval processes is not yet known.

Face Processing

As mentioned before, face processing, being part of the ventral visual stream, is relatively preserved in WS. On various standardized tests of facial perception, discrimination, recognition and memory, subjects with WS performed significantly better than subjects with Down syndrome and nearly equal to typically developing controls (51, 52). However, more recent studies indicated an abnormal pattern of face processing in WS (53). These authors noted that the overall performance of individuals with WS on face recognition tasks was below that of controls matched for chronological age but similar to that of controls matched for mental age. Yet, they did not show the bias toward a global mode of facial and geometric-

Omer Zarchi et al.

shape processing that was characteristic of the typically developing controls (54). These findings suggest that the face-processing domain in subjects with WS undergoes an abnormal developmental trajectory, so that they rely mainly on components or features of objects and faces for processing and less on configural or holistic elements.

This assumption has been supported by neurophysiological and neuroimaging studies. Mills et al. (55) measured ERPs (N320) in adults with WS during a face-matching task and found that the subjects employed a similar neural network for recognizing upright vs. inverted faces, much like typically developing young children. Additionally, there was an abnormal early ERP pattern in the matchmismatch face condition (decreased N100 and robust N200 amplitudes), apparently owing to the subjectsâ&#x20AC;&#x2122; increased attention to faces. This might explain the spared facial perception function in WS. Since the unique ERP pattern was found in all subjects with WS and in none of the typically developing controls or subjects with other impairments, the authors suggested that it might serve as an electrophysiological marker of WS (55).

Structurally, high-resolution MRI studies revealed that subjects with WS have a disproportionately large volume and increased density of gray matter in areas known to be important for face processing (39). The larger the gray matter volume in the fusiform gyrus area, the better their face recognition on the Benetton test (56).

Functional MRI neural activation studies during tasks of face and eye-gaze direction processing demonstrated preserved neural functioning in the frontal and temporal regions, including the fusiform gyrus, coupled with impairments in visual regions (40). It is possible that the preserved functioning of the fusiform and frontal regions, including the anterior cingulate cortex, which has strong connections to the limbic system, may mediate the increased social interest and attention to faces characteristic of subjects with WS. This assumption is in line with the robust ERP N200 amplitudes found in scalp regions adjacent to the anterior cingulate cortex during face-processing tasks (55). The impairments in the visual cortical regions may account for the disrupted globalcoherence and visuospatial aspects of face and gaze processing in WS, as manifested by diminished accuracy and longer response time on behavioral measures (40).

In summary, although face processing is relatively spared in WS and may indicate an intact ventral stream, it is apparently executed via atypical neural processing mechanisms that rely on component strategies instead of holistic ones. The face processing in subjects with WS

benefited from the high attention resources which may be associated with the increased social appetite typical of the syndrome.

Genotype-Phenotype Link

The pervasiveness of hyperacusis and exaggerated startle response in WS suggests that one or more of the 28 genes from the deleted 7q11 region are pivotal in auditory processing. So far, only the elastin gene (ELN) has been definitely associated with the WS phenotype of supravalvular aortic stenosis (57). Studies have suggested that a haploinsufficiency of the ELN gene may also be involved in the peripheral impairments mediating hyperacusis. Since the elastase enzyme disintegrates the stereocilia tip links (58), an elastin deficiency could lead to a desynchronized movement of the stereocilia, resulting in hearing loss and delayed cochlear nerve activation. This would, in turn, adversely affect the acoustic reflex and lead to hyperacusis (11).

Another candidate gene that may be responsible for the auditory phenotype in WS is LIMK1, which encodes for a serine/threonine kinase that is specifically expressed in neuronal tissue and regulates actin reorganization (59). LIMK1 knockout mice subjected to a fear-conditioning test showed significantly longer and more constant freezing than wild-type mice when exposed to certain sounds (60). It remained unclear, however, if the aggravated response was specific to auditory stimuli.

The possible contribution of CYLN2 haploinsufficiency to the visuospatial deficits in WS comes from reports of individuals with atypical deletion who had clinical features of WS, but without the specific spatial and constructive impairment (57). Studies conducted in CYLN2 knockout mice revealed features resembling WS, such as particular deficits in motor coordination coupled with hippocampal dysfunction, but no specific spatial deficit (61).

Other genes from the critical region, such as GTF2IRD1 and GTF2I, which encode for transcription factors, may also contribute to the mental and cognitive aspects of the WS phenotype (57). Additional in-depth studies are needed to clarify these issues.

CONCLUSIONS AND REMARKS WS is a homogeneous genetically based syndrome and as such may serve as an excellent model to promote our understanding of visual and auditory process129

Auditory and Visual Processing in Williams Syndrome

ing, as well as their underlying brain mechanisms in humans. Particularly, findings from research on WS greatly enhanced our knowledge on the function of the ventral and dorsal visual streams in human. Moreover, the research conducted to date has shed light on the dissociation of local and global perception and the partial distinction of face processing from other visuospatial and object processing. Furthermore, the findings in WS have important implications for the development of treatments to alleviate the adverse impact of the auditory hypersensitivity symptoms on the subjects’ quality of life. They might also be extendable to other genetic syndromes with a similar neurocognitive profile, such as velocardiofacial syndrome, fragile X syndrome, and Turner syndrome (62). At present, less is known about the atypical auditory processing mechanism than the visual processing mechanism in WS, and future research needs to focus on this area.

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Gender Identity Disorder: A Literature Review from a Developmental Perspective Tomer Shechner, PhD Department of Psychology, Tel Aviv University, Ramat Aviv, Israel, and Feinberg Child Study Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel

ABSTRACT The present paper reviews the theoretical and empirical literature on children and adolescents with gender variant behaviors. The organizational framework underlying this review is one that presents gender behavior in children and adolescents as a continuum rather than as a dichotomy of normal versus abnormal categories. Seven domains are reviewed in relation to gender variant behavior in general, and to Gender Identity Disorder (GID) in particular: theories of normative gender development, phenomenology, prevalence, assessment, developmental trajectories, comorbidity and treatment.

Introduction Gender identity disorder (GID) is one of the most controversial diagnoses of the DSM-IV (1) and almost incomparable in the complexity of its social, ethical and political considerations to any other diagnosis. Because not many children meet complete diagnostic criteria for GID, the clinical experience of mental health professionals working with GID children and adolescents is limited. What is far more common, however, are parents seeking counseling about their children’s gender variant behaviors, and therefore it is important to distinguish between these two conditions. The aim of the present paper is to review the available research data and clinical literature on gender variant behaviors in general, and on GID in particular, in children and adolescents.

Terminology In this section, a brief review of key terms in the field of gender development is presented.

Address for Correspondence: shechner@post.tau.ac.il

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• Sex – The genetic, hormonal and anatomical characteristics that determine if one is a biological male or a biological female.

• Gender – The psychological and cultural characteristics associated with biological sex.

• Gender role – Attitudes, behaviors and personality traits that a society, in a given cultural and historical context, associates with the male or female social role. Masculinity and femininity, the main concepts in gender role, pertain to the presence of qualities and behaviors in an individual that are consistent with those expected from males and females.

• Gender identity – Perception of one’s self as male or female. In children, gender identity is related to the ability to reliably answer the question: “Are you a boy or a girl?” The individual’s comfort with the sex and gender categories assigned at birth is a major element of gender identity.

• Sexual orientation – The sex of the person or persons to whom the individual’s sexual fantasies, sexual arousal and sexual activities are predominantly directed. Sexual orientation ranges along a continuum from exclusive heterosexuality to exclusive homosexuality and includes various forms of bisexuality. A less common sexual orientation is asexuality, or the absence of sexual attraction to either sex.

Theories of Gender Development Gender is one of the most salient social categories, and it plays a major role in the way people define themselves and experience their social world. Extensive theoretical and empirical work has been invested in understanding the mechanisms underlying the trajectories of gender development. In this section, a brief description of theories of normative gender development is presented as

Tomer Shechner, PhD, Department of Psychology, Tel Aviv University, POB 39040, Ramat Aviv 69978, Israel.

Tomer Shechner

the basis for the discussion of gender nonconformity which follows. (For a comprehensive review of gender development theories, see 2, 3.)

Theories of gender development may be divided into four types: psychoanalytic theories, gender essentialism, environmental theories and cognitive theories.

Psychoanalytic theories of sex differentiation are rooted in Freud’s early work. Freud (4) claimed that a child’s gender role is determined during the phallic stage. Fear of castration motivates the child to identify with the same-sex parent, thereby incorporating that parent’s gender roles and attitudes. These concepts were later expanded by Horney (5), Chodorow (6) and others. Psychoanalytic theories are not amenable to empirical study and have therefore not received much empirical support (3).

Gender essentialism attributes gender differentiation largely to biological differences and focuses on genetics, hormones and neurological factors. One example is the evolutionary perspective which explains human sex differences by the survival value of certain traits and characteristics adopted by men and women in primeval times (for example, see 7). Another is based on developmental neurophysiological studies of the causal effects of different biological factors on sex-typing attitudes and behaviors (for example, see 8).

Environmental theories explain gender development according to learning theory. Three elements are required for learning: the stimulus, the response to the stimulus and the resulting behavior. Reinforcement increases the probability that the behavior will recur, whereas punishment decreases the probability. Learning theory considers the organism to be passive and emphasizes experience and the role of the environment in shaping behavior. Accordingly, children learn expectations about social gender by the reactions to their behavior of various social agents, such as parents and teachers (9).

Cognitive theories claim that gender development is shaped by children’s cognitive abilities, interests, knowledge and other personal characteristics. Liben (10) divided cognitive theories into two approaches: cognitive-environmental and developmental-constructivist.

The cognitive-environmental approach emphasizes the interaction of the environment with the individual’s personal characteristics. For example, Bussey and Bandura (11) proposed that besides direct learning, gender development involves learning through such advanced processes as modeling and imitation, and these require that the individual acquire certain skills and abilities.

Factors that contribute to the evolution and preservation of gender-typed behaviors include cognitive ability, emotional state, motivation, past experience and anticipated outcomes. Similarly, social-cognitive theories claim that gender-typed behaviors result from the triadic interaction among environmental events, personal factors and behavioral patterns.

The developmental-constructivist approach to gender development considers individuals to be active participants who seek, organize and use information they are exposed to in social contexts. It includes three major schools of thought: cognitive-developmental stage theory, gender schema theory and intergroup theory. For the purpose of this paper, only the first two are discussed.

The cognitive-developmental stage theory (12) derives from Piaget’s studies of cognitive development which showed that cognition is the result of self-driven processes and not merely previous environmental experience. The same cognitive abilities that make it possible for children to understand constancies in the physical world such as the conservation of liquid quantity (i.e., that the quantity of liquid remains unchanged even if the liquid is poured into a container of a different shape) also make it possible for them to understand the consistency of gender. Kohlberg (12) described three cognitive stages of gender development: 1. Gender identity, achieved at age 2-3 years, is the individual’s ability to label him/herself as a boy or girl, and serves as the core motivation for future gender-related behaviors. That is, a child recognizing the fact that he is a boy leads him to seek and perform activities his society defines as boylike. 2. Gender stability, reached at age 4-5 years, is the ability of the individual to understand the lasting nature of gender. 3. The final cognitive stage of gender development, gender consistency, reached at age 6-7 years, refers to the individual’s ability to understand that gender is a fixed category that does not change even in the face of external or physical changes. The acquisition of cognitive abilities of gender stability and consistency motivates the individual to actively perceive, process and apply information about gender derived from the environment.

Gender schema theory focuses on the way in which the individual’s attitudes and knowledge about gender, termed collectively the gender cognitive schema, are used as a cognitive prism through which information from the environment is perceived and then manifested as behavior. As formulated by Martin and Halverson (13), the theory claims that young children understand to which gender group they belong and formulate cog133

Gender Identity Disorder: A Literature Review from Developmental Perspective

nitive categories that classify stimuli (objects or activities) as appropriate for males or females (13). Thereafter, stimuli encountered in the world activate this schema and are evaluated accordingly. Stimuli that are congruent with individuals’ gender schema increase their interest and prompt them to actively seek to acquire gender-appropriate skills. In an extension of this theory, Liben and Bigler (2) proposed the dual-pathway gender schema theory which emphasizes individual differences explicitly. The theory suggests two pathways of development. One is an attitudinal pathway similar to the gender schema of Martin and Halverson (13) in which the individual’s gender attitudes lead him or her to engage in one activity or the other, with a directional link from the attitude to the specific behavior(s).The second is a personal pathway with an opposite directional link in which the individual’s activity affects his or her gender attitudes. In the personal pathway, the individual’s personal interests are more dominant than the gender attitude, and they determine if he or she engage in a specific activity. This, in turn, can affect the gender schema. For example, a boy who finds himself in a situation where he plays with dolls may come to believe that playing with dolls is for boys as well as for girls. The dual pathway model is particularly relevant to individual differences in gender behaviors in general, and gender variant behaviors in particular (14).

GID Phenomenology GID was first recognized as a psychiatric entity in the DSM-III (15), where it was included as two separate diagnoses by age: GID of childhood, and transsexualism (adolescents and adults). In the fourth edition of the DSM (16), the two diagnoses were collapsed into one, GID, with different criteria for children and for adolescents and adults.

The DSM-IV-TR (1) lists four criteria (A-D) for the diagnosis of GID (p. 576), as follows: A − Strong and persistent cross-gender identification.

The individual meets this criterion if he or she is characterized by at least four of the following five features: 1. Repeated stated desire to be, or insistence that he or she is, of the other sex.

2. Preference for cross-dressing and wearing stereotypical clothes of the opposite sex.

3. Strong preference for cross-sex roles in fantasy and make-believe play.

4. Intense desire to participate in stereotypical games of 134

the opposite sex.

5. Strong preference for playmates of the other sex.

In adolescents and adults, cross-sex identification is manifested by a constant statement of the person’s desire to be, live as, and be treated as the other sex.

B − Persistent discomfort with one’s assigned sex or a sense of inappropriateness in the gender role of that sex. The individual meets this criterion if he/she has any of the following features: in boys, a feeling of disgust for their penis or testes, a wish not to have male sexual organs, aversion toward rough-and-tumble play, and rejection of stereotypical male activities and games; in girls, a wish not to have female sexual organs, an assertion that she has or will grow a penis, and a marked aversion towards normative feminine clothing. Affected adolescents and adults are preoccupied with getting rid of primary and secondary sex characteristics and/or express beliefs that they were born the wrong sex.

C − (exclusion criterion) – The presence of a physical intersex condition excludes the diagnosis of GID. D − Clinically significant distress or severe functioning impairment due to the disturbance.

Prevalence of GID There are no reported epidemiological studies of the prevalence of GID in children or adolescents (17).

Most of the published data are derived from samples of adults attending gender clinics for hormonal or surgical treatments, who represent only a specific segment of the population with cross-gender identification and behaviors. In addition, there is considerable empirical evidence indicating that GID in childhood does not necessarily persist into adulthood. Therefore, it is reasonable to assume that the prevalence varies by age (17).

One potential approach to determining the prevalence of GID in normative samples is to use screening instruments that include items on cross-gender or cross-sex identification (17), such as the Child Behavior Checklist (CBCL) (18). Of the 118 items in the English version of the CBCL, two measure cross-gender identification: “behaves like opposite sex” and “wishes to be opposite sex.” Like the other items, they are scored on a 3-point scale of 0 – not true, 1 - somewhat true, and 2 - very true. One study of non-referred children aged 4-11 years reported that among the boys, 3.8% assigned a score of 1 (somewhat true) to the item “behaves like the opposite sex” and 1.0% assigned it a score of 2 (very true). The corresponding rates for the non-referred girls were 8.3%

Tomer Shechner

and 2.3%. The item â&#x20AC;&#x153;wishes to be the opposite sex" was assigned a score of 1 by 1.0% of the boys and 2.5% of the girls, and a score of 2 by none of the boys and 1.0% of the girls (19). The findings suggest that there is a sex difference in mild, but not extreme, cross-gender behaviors and that the tendency of children to behave like the opposite sex is greater than their tendency to actually wish to be the opposite sex. Very similar results were reported in a recent study of Dutch twins (20). In the Hebrew version of the CBCL there are only 113 items none of which measure cross-gender identification.

Numerous studies reported consistent findings indicating significantly higher referral rates for boys from age 3 to 12, than for girls. However, this difference decreases dramatically with age to almost no sex differences in referral rates for adolescents (21). The earlier difference might be explained by the relative tolerance of society for gender nonconformity in girls during childhood but not in adolescence, when gender roles intensify.

Assessment of GID As is true for other DSM diagnoses, a systematic clinical interview is the most comprehensive tool for the assessment of GID. The evaluation should include both the child and the parents and, in some instances, also teachers or other relevant social agents involved in the childâ&#x20AC;&#x2122;s life. The clinical interview is difficult, because it may deal with unpleasant experiences that can become intensified, accompanied by feelings of shame or embarrassment. Sometimes a prolonged intake process is needed before the parents or child feels secure enough to talk openly about sex and gender identification issues.

Personal clinical experience suggests that many parents do not even inform their young children of the reason for attending counseling.

In addition to the clinical interview, the clinician has several instruments with which to assess sex-typing behavior. The Occupational, Activity and Trait Personal Interest and Attitude Measure Scales for Children (COAT-PM/AM) and Preschoolers (POAT-PM/AM) have been applied in normative samples in the United States (21, 22) and Israel (23). The Activities and Traits domains of the personal interest questionnaires are recommended for the assessment of sex-typing behaviors and preferences. Although they are not clinical measures, they offer the possibility of evaluating the child in a pleasant and nonthreatening manner. Although further empirical research examining the utility of these measures in a clini-

cal context is necessary, there is some evidence that sextyping measures assessing play preferences, in particular toy choice, can be useful in assessing children referred for concerns about their gender development (24).

Several reviews and empirical studies have emerged examining the common measures available for assessment of gender identification and gender roles for both research and clinical purposes (for a review, see 25).

Developmental Trajectories in GID Retrospective studies provide strong empirical evidence that adults with a homosexual sexual orientation, with or without a specific diagnosis of GID, have a high level of recall of cross-gender behaviors in childhood. A meta-analysis of these studies revealed that homosexual men and women had significantly greater recollections of such behaviors than heterosexual men and women (26). This finding was later confirmed by others (for a review, see 27).

To avoid the limitations of retrospective designs, several groups conducted prospective studies of developmental trajectories for the identification of children with GID. Probably the most important to date is the work of Green (28) who compared 66 feminine boys and 56 normative boys aged 4-12 years with a follow-up measure for the available 44 feminine boys and 30 normative boys at ages 14 to 24 years. Homosexual fantasies were reported by 75% of the study group compared to none of the controls, and homosexual or bisexual behaviors were reported by 80% and 4%, respectively.

Of the 44 boys who completed follow-up, only one had gender dysphoric feelings to the extent of considering sex reassignment surgery. Later prospective studies documented higher rates of 20% (29) and 16.1% (30) for gender dysphoric mood among boys diagnosed with GID or subclinical GID in childhood.

There is only one prospective study to date of the developmental trajectories of masculine girls (31). At enrollment, 60% of the girls met the criteria for GID and 40% had subthreshold GID. At follow-up, 12% had GID or gender dysphoria, 32% were classified as bisexual or lesbian in fantasy, and 24% were classified as bisexual or lesbian in behavior.

This body of prospective research suggests that GID often remits from childhood to adolescence and adulthood. Furthermore, cross-gender fantasies and behaviors in childhood appear to be largely predictive of a homosexual sexual orientation in adulthood (32). Liben 135

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and Bigler (14) suggest a comprehensive explanation to the developmental trajectories of GID. Using the dual pathway model, they propose that both environmentalexogenous factors as well as internal-endogenous factors may account for the longitudinal drop in GID. Cognitive development from childhood to adulthood may lead to complex thinking abilities, resulting in modification of gender attitudes and behaviors. For example, a boy who thinks that there are only two kinds of people, masculine boys and feminine girls, might perhaps reconcile his own feminine interests by desiring to be female. It is reasonable to predict declines in GID over time as children realize that there can be both more and less feminine and masculine males and females. Changing cognitive attitudes about “right” and “wrong” gender behavior is likely to alleviate gender dysphoria.

Comorbidity in GID Most of the systematic data on psychopathologies associated with a childhood diagnosis of GID are derived from parental reports in screening measures such as the CBCL (21). Zucker and Bradley (29) showed that clinically referred children with GID have, on average, significantly more behavioral problems than their siblings or non-referred children. Similar results were reported from cross-nation and cross-clinic studies, wherein children with GID had mean CBCL total score in the clinical range, with a predominance of internalizing symptomatology relative to externalizing problems (33). In a recent study, boys with GID had a significantly higher total CBCL score than normative boys and normative girls, and significantly higher scores for externalizing symptoms than normative boys but not normative girls. In addition, there were no differences in scores for internalizing symptoms between the study and control groups (34). These findings are not totally in line with the theoretical model of GID proposed by Zucker and Bradley (29) and Coates and Person (35), which emphasized the major role of anxiety and assumed a higherthan-normal level of anxiety in individuals with GID. Two more recent studies of GID comorbidity have used different psychopathological measures. One study used a structured psychiatric interview with parents of children diagnosed with GID (36). The results showed that 52% of the children had one or more additional psychiatric diagnoses, with more internalizing (37%) than externalizing (23%) symptoms in both boys and girls. However, only 31% had anxiety disorder.

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In another study, anxiety was measured via physiological correlates of cortisol level, heart rate and skin conductance in stressful situations. Although the authors concluded that their data provided some evidence that children with GID are more prone to anxiety, the results indicated that children with GID showed higher levels only in skin conductance but not in other measures such as cortisol or heart rate levels (37).

Treatment The complex ethical and social aspects of GID or subthreshold GID become all the more apparent when considering treatment. The most acute ethical issue concerns the relationship between gender nonconformity in childhood and later homosexuality. Although parents often express concern about the future sexual orientation of their child, homosexuality is not considered a mental disorder, and there is no justification for applying psychological interventions that aim to prevent it. In addition, empirical evidence from efficacy studies of sexual conversion therapies of any kind are, at best, extremely limited (38).

The DSM-IV diagnostic criterion B for GID makes no clear differentiation between dissatisfaction with one’s biological sex and dissatisfaction with gender roles. This distinction is important because a child who feels disgusted or alienated from his or her body organs would probably exhibit symptoms similar to those of body dysmorphic disorder (BDD), which is characterized by a preoccupation with either an imaginary or slight physical anomaly that causes significant distress or impairment of functioning. Furthermore, if the dominant clinical symptom is a persistent discomfort with one’s own sex, treatment should focus on ways to aid the child to accept and come to terms with his or her body, assuming that drastic surgical or hormonal interventions are not tenable at that point in development.

For those situations in which hormonal treatments are indeed appropriate, however, Cohen-Kettenis developed a protocol for treatment of GID in adolescents desiring sex-reassignment (21). The protocol guidelines distinguish between three types of physical interventions: wholly reversible, partly reversible and irreversible ones. Wallien and Cohen-Kettenis suggest that in order to decide upon the appropriate physical intervention (32), it is clinically important to discriminate between children with persistent GID and children who will eventually cease experiencing GID.

Tomer Shechner

If the dominant symptom is cross-gender identification or discomfort with assigned gender roles, treatment is far more multifarious and complex. Because discomfort with one’s biological sex is not an obligatory condition for criterion B, it is disconcerting that a diagnosis of GID is sometimes based exclusively on cross-gender behaviors.

Therefore, it is highly recommended to conduct an extensive intake to comprehensively assess both the child’s and the parents’ difficulties and to formulate the treatment goals accordingly. The fundamental principle guiding treatment is the child’s well-being, which does not necessarily imply changing his or her gender behaviors.

It should be borne in mind that a diagnosis of GID can subject the child to the social stigma associated with being labeled mentally ill (39). At the same time, some scholars argue that psychiatric labeling confers meaning to an otherwise inconceivable behavioral pattern, thereby reducing stigma, conflict and atrocities (40). Clinicians are advised to take these advantages and disadvantages of psychiatric labeling into account when making a diagnosis of GID or any other DSM-related disorders.

Clinical Aspects of Treatment

There are 13 single-case reports of behavioral interventions for GID, all based on an environmental approach to gender development with a focus mainly on sextyped play behaviors (21). Entirely apart from ethical considerations, behavioral interventions have been found to be clinically ineffective. Some of the treated children reverted to cross-sex play in the absence of the reinforcing adult. Moreover, there was little generalization to untreated cross-sex behaviors (21).

Various individual and group psychosocial interventions for children and adolescents have been reported.

These focused primarily on acceptance, support and self-esteem enhancement in addition to psychoeducation for both the children and their parents (for example, see 41). Treatment goals included reducing preoccupation with thoughts of gender identity issues, social ostracism, body dysphoria and possible psychiatric comorbidities and dealing with negative thoughts and emotions related to a possible future homosexual orientation. Targeting the objective to the individual child and family according to the intake information is highly recommended.

The question of how to identify “right” and “wrong” gender behaviors is very much an educational issue.

Thus, even if the therapist does not advocate changing sex-typing behaviors as a treatment goal, it is his

or her duty to provide the parents with the clinical and research literature, so they can decide for themselves the best way to cope with the situation. The therapist must also accept the parental choice, provided it is not harmful to the welfare of the child.

The involvement of the parents in therapy is also crucial to preventing or alleviating problems in the parent-child relationship that derive from the child’s cross-gender behaviors. In addition, the parents themselves often report feelings of shame, blame and helplessness. Seeing a therapist on a regular basis may help them understand and handle such feelings, eventually leading them to accept their child more fully.

Zucker (17) suggested that parents be trained in setting limits to the child’s cross-gender behaviors by encouraging gender-neutral or sex-typed activities.

Parents can be shown how to encourage their child to find alternative activities they consider more genderappropriate, such as same-sex peer interaction. Parents must be cautioned, however, to be aware of the difference between empathic encouragement and harsh imposition. Others suggested that when parents bring a child exhibiting gender variant behaviors to treatment in the fear that the child will develop a homosexual orientation, the appropriate change-orientated intervention should target the parents rather than the child (39).

For those who oppose conceptualizing cross-gender behavior as pathological the treatment goal is not to change the child’s non-conforming behavior. Rather, the central objective of treatment should be to change the environment, in particular the parents, to accept and support the child’s success in coping with negative social response to cross-gender behaviors (42). In addition to seeking to increase parental acceptance and support of their child’s cross-gender behavior, some researchers and organizations have called for programs aimed at teaching other children to accept and support cross-gender behaviors in their peers (43).

Acknowledgements The author wishes to thank Lynn S. Liben, for her helpful comments, and Gloria Ginzach of the Editorial Board, Rabin Medical Center.

References 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed., text revision. Washington, D.C.: American Psychiatric Association, 2000.

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4. Freud S. Three essays on the theory of sexuality. 1905: standard Edition. London: Hogarth, 1953.

24. Fridell SR, Owen-Anderson A, Johnson LL, Bradley SJ, Zucker KJ. The playmate and play style preferences structured interview: A comparison of children with gender identity disorder and controls. Arch Sex Behav 2006;35:729-737.

5. Horney K. The dread of women. Int J Psychoanalysis 1922;13,348-360.

6. Chodorow N. Mothering, object-relations, and the female oedipal configuration.

Feminist Studies 1978;4:137-158.

25. Zucker KJ. Measurement of psychosexual differentiation. Arch Sex Behav 2005;34:375-388.

7. Cosmides L, Tooby J. Origins of domain specificity: The evolution of functional organization. In: Hirschfeld LA, Gelman SA, editors. Mapping the mind: Domain specificity in cognition and culture. New York: Cambridge University, 1994: pp. 85-116.

26. Bailey JM, Zucker KJ. Childhood sex-typed behavior and sexual orientation: A conceptual analysis and quantitative review. Dev Psychol 1995;31:43-55.

27. Zucker KJ. Gender identity disorder. In: Weiner IB, editor. Adult psychopatology case studies. New York: Wiley, 2004: pp. 207-228.

8. Liben LS, Susman EJ, Finkelstein JW, Chinchilli VM, Kunselman S, Schwab J, Dubas JS, Demers LM, Lookingbill G, D’Arcangelo MR, Krough HR, Kulin HE. The effects of sex steroids on spatial performance: A review and an experimental clinical investigation. Dev Psychol 2002;38:236-253.

28. Green R. The "sissy boy syndrome" and the development of homosexuality. New Haven: Yale University Press, 1987.

9. Mischel W. Sex typing and socialization. In: Mussen PH, editor. Carmichael’s handbook of child psychology, Vol. 2. New York: Wiley, 1970: pp. 3-72.

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10. Liben LS. Cognitive approaches to gender development. In: Blakemore JEO, Berenbaum SA, Liben LS, editors. Gender development. New York: Taylor & Francis, 2008: pp. 197-226.

11. Bussey K, Bandura A. Social cognitive theory of gender development and differentiation. Psychol Rev 1999;106:676-713.

12. Kohlberg LA. A cognitive-developmental analysis of children’s sex role concepts and attitudes. In: Maccoby EE, editor. The development of sex differences.

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13. Martin CL, Halverson CF. A schematic processing model of sex typing and stereotyping in children. Child Dev 1981;52:1119-1134.

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39. Langer SJ, Martin JI. How dresses can make you mentally ill: Examining gender identity disorder in children. Child Adolesc Soc Work J 2004;21:5-23.

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Environmental Risk Factors for Psychopathology Karin Schlossberg, MD, Anda Massler, MD, and Gil Zalsman, MD Child and Adolescent Psychiatry Division, Geha Mental Health Center, and Sackler Faculty of Medicine, Tel Aviv University, Israel

ABSTRACT In the past all psychopathologies were viewed as caused by the environment. Later on case-control and familybased studies of major psychiatric disorders found genetic associations, but in many cases these findings did not survive replications. A gene-environment approach gave new hope for possible associations.

Gene environment correlations emphasized that the relationship are bidirectional. However, recent meta-analyses raised doubts about the consistency of these findings as well. The review summarizes the current view on the environmental factors in the major psychopathologies.

Introduction The views about the role of environmental and genetic risk factors for psychopathology have changed over the years from “extreme environmentalism” through denial to the appearance of critiques of environmental risk mediation, and the concept of a single genetic cause, to the acceptance of the multi-factorial origin of psychopathology, which is the currently prevailing view (1). By agreeing with the multi-factorial origin, the importance of environmental influences was reaccepted without dismissing the genetic influences. The interest in gene-environment interaction was renewed.

Genes interact with environment at a few levels, and some authors emphasized the bilateral influence which was described as gene-environment correlations (1). Gene-environment correlations (rGE) refer to the genetic control of exposure to the environment (2). rGE are divided into “passive,” “active” and “evocative” (3).

Gene-environment interactions (GXE) refer to genetic

differences in susceptibility to specific environmental risks. In other words, environmental pathogens cause disorder and genes influence susceptibility to pathogens (4). Therefore the relationship between genes and environment is bidirectional: organisms both impact on and are impacted by the environment (5-7). The study of endo-phenotypes instead of the external phenotypic "DSM disorder" may shed light on the difficulties in finding genetic associations in some cases (4).

Psychiatric illnesses are affected by both genetic and environmental factors. The aim of this review is to focus on the environmental effects on psychopathology.

While testing causal hypotheses for psychopathology by twin and adoption studies, a number of counter arguments to the theory of environmentally mediated risks have been raised. Among them were: Measurement issues concerning the possibility of bias resulting from retrospective recall and Bell’s (5) reexamination of socialization effects, where he argued that some of the effects reflected reverse causation, namely the effects of children on their environments rather than the effects on the children of experiences stemming from their upbringing (5).

Two challenges came from behavioral genetics: 1. Plomin and Daniels’ (8) study showing that siblings growing up in the same family tend to differ despite their common environment. Thus, a shared environment may affect children in different ways.

2. Three studies by Plomin, Bergeman and Rowe (9-11) showed that at least some, if not most, of the effects of risk environments were genetically mediated, rather than environmentally mediated (12).

Still, some studies have shown that rearing environments have important effects on psychopathology (13, 14). Also, the critique of Plomin (9), although presenting a serious challenge, did not minimize the importance of environmental mediation, but showed that there is a genetic mediation between environmental risk factors and psychopathology.

Address for Correspondence: Gil Zalsman, MD, Director, Child and Adolescent Psychiatry Division Geha Mental Health center, POB 102, Petach Tikva, Israel 49100 zalsman@post.tau.ac.il

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As studies continuously demonstrated genetic influences on most types of psychopathology, it became apparent that genetic influences are ubiquitous, with heritability for psychopathology ranging between 20-60%. However, it never reaches 100%. Therefore it points to the existence of non-genetic effects (15, 16).

Additional evidence for the existence of environmental effects can be found in the psychopathology in populations. Over the last half century, there has been a significant increase in the rates of crime and drug use among young people (17). This cannot be explained by changes in the gene pool since such changes require much longer periods of time. Therefore it must be due to environmental influences (15).

Thus the empirical evidence points to the fact that environmentally mediated risk effects are both real and important (18).

Major Depression (MDD) Twin studies have demonstrated a role for genetic and environmental factors (19). There is considerable evidence for the familial aggregation of depression in adults (20). A meta-analysis of five recent studies found that first-degree relatives of individuals with MDD have a nearly threefold increase in risk of developing MDD compared with control subjects. The heritability of depressive disorders is around 40% to 50% (21).

Genetically sensitive designs have shown various environmentally mediated effects from specific risk environments for anxiety and depression (7). Kendler, Karkowski, and Prescott (22) referred to negative life events and Pike et al. (23) to family discord and negativity.

Stressful life events such as abuse, poverty or death of a parent are connected with the development of major depression. These events are modulated at least in part via an interaction with genetic predisposition (24-28). This was demonstrated in a study devised

by Kendel et al. (29) in which data about stressful life events and the development of major depressive episodes was collected from female-female twin pairs. A monozygotic twin with depressive disorder, as well as her co-twin, constituted those with the highest genetic risks, because they shared all their genes. The fact that both are affected was likely to have been influenced by genetic predisposition.

A monozygotic twin with depressive disorder with a healthy co-twin constituted those with the lowest genetic risks. That is, despite genetic similarity, the co140

twin did not develop depression, therefore the genetic liability was likely to be low.

The results demonstrated that 1. Stressful life events predicted the onset of major depression. 2. The highest probability for a co-twin to develop a depressive disorder after a stressful life event was for those who had high genetic liability (1).

In a prospective longitudinal study by Caspi and colleagues (30), of a birth cohort, the 5HTTLPR polymorphism was found to moderate the impact of stressful life events on depression. The short allele variant was connected with severe depression in relation to stressors.

This was replicated in children (26), adolescents (31), and young adults (32). Zalsman et al. (32), in addition to using tri-allelic genotyping of the 5HTTLPR polymorphism, used also a unique rating scale of stressful life events, the St. Paul Ramsey Scale, that takes into account both objective and subjective impact of life events on the individual and not just number of life events in the past.

Two recent meta-analyses one by Risch et al. (33) and one by Munafo et al. (34) with conflicting results on the 5HTTLPR polymorphism interaction with life events raised the question of these studies. Both meta-analyses did not include the tri allelic methodology (32) in their analyses since it was not used by all studies.

Anxiety Disorders and Post Traumatic Stress Disorder (PTSD) The existence of genetic risk factors has been documented for all major anxiety disorders (35). However, stressful life events also have an etiological effect on the development of anxiety disorders and are likely to have nonspecific effects across disorders (35). For example, sexual abuse in childhood increases the risk for developing generalized anxiety (GAD), panic disorder and other psychopathologies (36, 37). A study by Hettema and others (35-38) found that there are genetic and environmental causes for the comorbidity exhibited in anxiety disorders. Genes predispose to two groups of disorders.

One includes GAD, panic disorder, agoraphobia and social phobia while the other includes specific phobias.

The remaining associations between the disorders are due to environmental factors (unique and common).

Genetic and environmental risk factors for anxiety disorders are similar between men and women (38).

Both quantitative and molecular genetic studies have shown that the relationship between environmental

Karin Schlossberg et al.

risks for anxious behaviors is dependent on genetic characteristics (39). Genes increase the likelihood of developing an anxious personality trait by â&#x20AC;&#x153;anxiety sensitivityâ&#x20AC;? (40). When interaction with stressful life events occurs, a threshold for the development of one or more disorders is lower (38).

Relations between stressful life events and later post traumatic stress disorder (PTSD) was well studied by Copeland et al. (41), who conducted a prospective study of 1,420 children. Subjects aged 9, 11 and 13 years at intake were followed up annually through 16 years of age. More than two-thirds of children reported at least one traumatic event by 16 years of age, with 13.4% of those children developing some PTSD symptoms. Few PTSD symptoms or psychiatric disorders were observed for individuals experiencing their first event, and any effects were short-lived. Less than 0.5% of children met the criteria for full-blown DSM-IV PTSD. Violent or sexual trauma was associated with the highest rates of symptoms. The PTSD symptoms were predicted by previous exposure to multiple traumas, anxiety disorders and family adversity. Lifetime co-occurrence of other psychiatric disorders with traumatic events and PTS symptoms was high, with the highest rates for anxiety and depressive disorders. Researchers concluded that in the general population of children, potentially traumatic events are fairly common and do not often result in PTSD symptoms, except after multiple traumas or a history of anxiety. The prognosis after the first lifetime trauma exposure was generally favorable.

It seems that apart from PTSD, traumatic events are related to many forms of psychopathology, with the strongest links being with anxiety and depressive disorders.

Psychosis and Schizophrenia Genetic factors are clearly important in the etiology of schizophrenia, but the environment in which an individualâ&#x20AC;&#x2122;s genes find expression is also crucial to the development of the illness. As the etiology of schizophrenia is unraveled, the picture becomes more complex, but also more obviously relevant to the plight of the individual patient (42). Rates of schizophrenia differ significantly between groups that differ at the social level, e.g., urban/rural comparisons, different neighborhoods, and ethnic minority status (43). More than 10 studies have consistently shown that around one-third of all schizophrenia incidences may be related to environmental factors operating in the urban environment,

and impacting developing children and adolescents to increase the later expression of overt psychotic disorders (44). The effect associated with urban living has grown among more recent birth cohorts, while studies focusing on within-city contrasts have found significant variation in the incidence of schizophrenia associated with neighborhood social characteristics (44).

There is also renewed interest in the relationship between early childhood trauma and risk of psychosis in adulthood. There are a large number of studies of psychiatric inpatients and outpatients in which a majority has psychotic disorders that suggest that the prevalence of childhood trauma in these populations is high.

However, these are generally small studies of diagnostically heterogeneous and chronic samples and, as such, can tell us very little about whether childhood trauma is of etiological importance in psychosis (45). Compelling evidence from several countries points to a higher risk of developing schizophrenia and other psychotic disorders among migrant groups (46). Finally, Cougnard et al. (47) suggested that environmental risks for psychosis act cumulatively, and that the level of environmental risk combines synergistically with non-clinical developmental expressions of psychosis to cause pathology and, eventually, need for care.

It is well known that cannabis use is associated with poor outcome in existing schizophrenia and may precipitate psychosis in individuals with preexisting liability. To investigate the overall effect size and consistency of the association between cannabis and psychosis, Henquest et al. (48) performed a meta-analysis from prospective studies and found a pooled odds ratio of 2.1 that could not be explained by confounding or reverse causality. Cannabis is a clear environmental risk factor for psychosis, although evidence suggests that mechanisms of gene-environment interaction are most likely to explain this association (48).

Suicide Suicide is a destructive act of aggression directed towards the self, and is often associated with violent and impulsive traits (49). Adoption studies suggest that there may be a genetic susceptibility to suicide, which is mostly independent of the presence of a psychiatric disorder (50-52). Zalsman et al. published two family based studies of the genetics of suicidality. The first examined the TPH gene polymorphism in 88 adolescents who had recently attempted suicide (53) and 141

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the second examined the association of 5-HTTLPR with suicidal behavior and related traits in 48 Israeli suicidal adolescent inpatients using the HRR method (54). Review of the current literature on the genetics of suicidal behavior shows that no single cause has yet been identified as being significantly associated with suicidality, even when family-based methods are used.

However, association to some suicide-related traits (e.g., violence, depression) was reported when multiple measures were applied (55).

The equifinality approach conceptualizes behavior as an outcome of many etiologies, which include, beside genetics, negative life events, non-adaptive cognitions and cognitive style, abnormal affect regulation, low self esteem, neuroendocrine dysregulation and defects in brain structure (56). Environmental factors such as negative life events may act as a significant contributor to suicidal behavior. However, in many cases the exposure to the same environmental stress does not result in increased suicidality (57). A recent crosssectional sample of Canadian youth between the ages of 12 and 15 revealed statistically significant correlations between suicide ideation and some lesser examined socially based measures. In particular, ability to communicate feelings, negative attachment to parents/ guardians, taunting/bullying or abuse, and presence of deviant peers were significant predictors of suicidal ideation illustrating the importance of environmental factors (54). Future studies aim to identify and resolve complex patterns and mechanisms of neurobiological gene-environment interactions, which may contribute to suicide (57).

In summary, environmental risk factors have an important role in psychiatric disorders. Both genetic and environmental risks participate in the development of psychopathology by bi-directional interplay. Large meta-analyses raised the question whether the simple GxE interaction can explain genetic vulnerability to specific psychiatric disorders (58). It seems that there are more factors to add to the equation, for example the time window in which the environmental risk was introduced during development, gender and other factors (59). The field of environmental influences, especially childhood maltreatment and trauma, on psychopathology will be the center of research in the next decade.

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Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010)

Genetic and Environmental Links between Children’s Temperament and their Problems with Peers Maya Benish-Weisman, PhD,1 Tamar Steinberg, MD,2 and Ariel Knafo,PhD1 1

Psychology Department, The Hebrew University of Jerusalem, Jerusalem, Israel Schneider Children's Medical Center and The Sackler Faculty of Medicine at Tel Aviv University, Ramat Aviv, Israel

2

ABSTRACT Peer relationships become central to children ’ s development as they develop social skills and theory of mind in their early development. We investigated the role of temperament in children’s peer problems.

Mothers of three-year-old twins (N=759 pairs) rated their children’s temperament using the EAS scale (1) and children’s peer problems using the Strengths and Difficulties Questionnaire (2). Children’s peer problems were positively associated with their negative emotionality, and related negatively to their sociability and activity level. Genetics contributed to individual differences in temperament and peer problems, with peer problems substantially heritable (44%). The remaining variance is attributed to environmental factors. Genetic factors largely mediated the correlations between peer problems and temperament.

The findings point to the importance of children ’ s temperamentally-based characteristics in their social development.

Peer relationships become important as children develop social skills and theory of mind in early development (3). Substantial individual differences in children’s social skills are observed by the third year of life, and peer problems observed in the first years of life are related to social and emotional problems in later ages (4). Peer problems are characterized by children’s reduced ability to relate to other children in a positive and satisfactory way. These problems may be manifest in a child’s avoidance of the company of other children, or in a negative attitude or rejection by other children.

Peer Problems and Temperament Research has identified numerous predictors of children’s peer problems. For example, experience with attachment figures (5), and some child personal characteristics, such as aggression and prosocial behavior, predict peer problems (6). We studied the role of temperament, early emerging (and arguably biologically based) individual differences in emotional and physiological reactivity and regulation (1), in children’s peer problems. These differences, observable as early as during the fetal period (7), are expressed in traits such as negative and positive emotionality, activity level, sociability and shyness (1, 8).

Research found a relationship between temperament and social behavior. For example, difficult temperament in infancy is related to children’s externalizing behavior (9) and negative or little affect in toddlers relates to less empathy (10). Empathy and externalizing problems are factors that can influence the quality of children’s social relationships. Research reported relationships between temperament and peer problems, suggesting that early temperament (e.g., shyness) can predict peer problems at a later age (11, 12). For example, reticent children with higher scores in mother-reported social fears at 14 and 24 months tended to have low levels of social behavior with unfamiliar peers at 4 years (12). Our study adds a genetic and environmental perspective to the peer problems-temperament relationship. Specifically, we investigate the relationships, at the phenotypic level, between children’s peer problems, on the one hand, and three temperamental dimensions, on the other hand: Negative emotionality, sociability and activity level. We then investigate the genetic and environmental contributions to these phenotypic relationships.

Negative emotionality indicates an individual ten-

Address for Correspondence: Ariel Knafo, PhD, Psychology Department, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel msarielk@mscc.huji.ac.il.

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dency to experience distress, ranging from lack of reaction to extreme, uncontrolled emotional responses to negative events (13). Children who become upset quickly will find it hard to play or maintain relationships with other children. Therefore, we expected a positive relationship between children’s negative emotionality and their peer problems.

Sociability refers to children’s enjoyment of interpersonal contexts (13). Children who enjoy the presence of other children are expected to look for the company of others and therefore are more likely to initiate and maintain close relationships, in comparison to children who prefer to be alone. Therefore, children’s sociability was hypothesized to relate negatively to their peer problems.

Activity level is composed of vigor and tempo, ranging from lethargy to an extreme push of energetic response (13). Active and energetic children create more opportunities for contacts as opposed to children who are more passive and less dynamic. Although there is no direct evidence for the role of activity level in peer problems, there is some evidence that inhibitory control relates positively to social competence (14). Thus, extremely active children may have problems relating to their peers; for example, children with an attention-deficit hyperactivity disorder (ADHD) are more likely than other children to suffer from peer problems as adolescents (15). On the other hand, the play patterns of young children require at least a moderate degree of activity in order to engage with other children. Therefore, we are not proffering a specific hypothesis for the direction of the relationship between activity levels and peer problems.

Genetic and Environmental Effects on Peer Problems and Temperament

We approach the issue of genetic and environmental contributions to individual differences using the twin design, comparing monozygotic (MZ) twins, who share all of their genes, with dizygotic (DZ) twins, sharing 50% of their genes. Assuming that twins of both types similarly share their environments, higher similarity in MZ versus DZ twins indicates genetic influence.

Similarity beyond this genetic effect is attributed to the environment shared by twins, and further differences between twins are ascribed to non-shared environment or to measurement error (16).

Research has found both genetic and environmental contributions to individual differences in temperament (17, 18). For example, genetic factors were found for

activity level in different contexts (19). Similarity in temperament is substantially higher for MZ twins than for DZ twins, indicating heritable effects (e.g., 20, 21).

Genetic factors were found to be significant in peer problems as well (11, 22), affecting both peer rejection (3) and popularity (23). In a study using the Strengths and Difficulties Questionnaire (SDQ) (2), heritability for seven-year-old British twins was estimated as accounting for 56-57% of individual differences in parent-reported peer problems, and at 37-76% for teacherreported problems (24).

The Current Study In this study we ask three main questions: (a) What are the relationships between temperament and peer problems? (b) What are the relative contributions of genetics and the environment to individual differences in temperament and peer problems? (c) What are the genetic and environmental contributions to the relationship between temperament and peer problems? We answer these questions with mother report data from a sizeable sample of MZ and DZ three-year-old twins. Although parental reports may be biased due to parental perceptions and beliefs, they provide an efficient way to obtain estimates of genetic and environmental influences from a large community sample. Other data collection methods, such as behavioral observations, may be less biased.

However, they are based on relatively brief time frames and lack the “long time frames within a context of what is likely to be meaningful in the child’s life” (25, p. 1450).

Method Participants

Families in this study were participants in the Longitudinal Israeli Study of Twins (LIST) (26, 27). All Jewish families identified as having twins by the Israeli Ministry of the Interior were contacted by mail close to the twins’ third birthday. Mother report data from 754 twin pairs born in 2004 and in early 2005 were available for this report. In addition, father reports were available from a small sample of 44 twin pairs (32 of which overlapping with the twins rated by their mothers) who participated in lab assessments of empathy at the age of 3.5 years (28). Twin zygosity was assessed through a parent questionnaire of physical similarity, which has been shown to be over 95% accurate when compared to DNA testing (29). The sample included 162 monozy145

Genetic and Environmental Links between Children’s Temperament and peer problems

Table 1. Means (and Standard Deviations) of Scores on Peer Problems and Temperament.

MZM (N=86) DZM (N=139) DZO-boys (N=151) MZF (N=79) DZF (N=157) DZO-girls (N=148)

Peer problems

Negative emotionality

Sociability

Activity

3.68

15.40

15.92

20.44

(1.60)

(4.51)

(2.51)

(2.91)

3.70

15.52

15.68

20.09

(1.27)

(4.29)

(2.57)

(3.12)

3.99

15.89

15.47

20.11

(1.66)

(4.50)

(2.68)

(3.54)

3.62

16.29

15.89

19.83

(1.28)

(6.42)

(2.67)

(3.23)

3.66

15.59

15.46

19.36

(1.41)

(4.21)

(2.79)

(3.13)

3.58

15.12

15.72

19.84

(1.36)

(4.12)

(3.02)

(3.29)

Note. MZM=monozygotic males; DZM=dizygotic males; MZF=monozygotic females; DZF=dizygotic females; DZO=dizygotic opposite sex twins. Sample sizes refer the number of individuals for which means were computed (one twin per pair selected randomly).

gotic, 294 dizygotic same-sex, and 298 opposite-sex twin pairs (Table 1).

Measures

Peer problems were assessed with the Peer Problems subscale of the 25-item SDQ (2), which measures peer problems, emotional symptoms, conduct problems, hyperactivity/inattention and prosocial behavior, with five items for each subscale. This measure is widely used for screening, longitudinal monitoring of therapeutic effects, and scientific research (e.g., 30). In this report, only the peer problem scale was used. One item, “Rather solitary, tends to play alone,” was judged to be too similar in content to the sociability items described below, and was therefore dropped for current purposes. In a factor analysis all items loaded (.44 or more in absolute value) on a first factor, accounting for 33% of the variance. The scores on the four items were summed to a single peer problems score.

Temperament was rated by parents using the EAS Temperament Survey (1) which assesses children’s negative emotionality, activity level, sociability and shyness.

For current purposes, we did not use the shyness scale because of the strong conceptual overlap between shyness and peer problems. A Multidimensional Scaling analysis of the three EAS scales showed clear distinctions between the items of each subscale. Nevertheless, one sociability item was dropped because it appeared 146

close to the negative emotionality items, which can be attributed to its focus on negative feelings (“When alone, child feels isolated”).

Analyses

Descriptive analyses included mean comparison of peer problems and temperament scores across zygosity and sex, and correlations between peer problems and temperament. In addition, we regressed peer problems on the temperament measures to test their relationships simultaneously. Twin correlations for all five zygosity groups (male and female MZ and DZ, and opposite-sex DZ pairs) were calculated for each variable.

Model-fitting analyses. We analyzed a bivariate genetic model, including peer problems and each temperament measure using Mx (31), using variance-covariance matrices from both twins within a pair, the models estimate the variance components and correlations across individuals (capitalizing on genetic differences between different types of pairs).

For each variable separately, variance components were estimated for additive genetic influence (A, correlating 1.0 and .5 for MZ and DZ twins, respectively), shared or common environment (C correlating 1.0 for both MZ and DZ pairs), and non-shared environment and error (E), which include any environmental effect not shared by twins, such as differential parental treatment, unique to each member of a twin pair and therefore correlating 0 for all twins. Model fitting can also be used to assess sex differences in ACE parameters (sex-limitation models; 32, 33). Basically, we looked for (a) qualitative sex differences as assessed by rgo (overlap of genetic influences on male and female behavior) smaller than .50, (b) quantitative sex differences in ACE parameters (e.g., differences in heritability), and (c) phenotypic variance differences between the sexes.

In addition to estimating variance components for each variable separately, this correlated factors model (32) specifies correlated genetic, shared environmental and non-shared environmental effects that influence both peer problems and temperament. The extent that the MZ cross-trait (peer problems and temperament) cross-twin correlation exceeds the DZ cross-trait twin correlation indicates the degree of genetic overlap between the two traits weighted by the square roots of heritabilities of the two traits. This genetic contribution to the phenotypic correlation between the traits includes the genetic correlation, indicating the extent to which the genetic influences on peer problems over-

Maya Benish-Weisman et al.

lap with the genetic influences on temperament regardless of the heritabilities of the two traits. Similarly, the correlation between shared environmental influences on peer problems and temperament and the nonshared environment correlation (the extent to which the non-shared environmental influences on the two traits overlap) are estimated. Bivariate heritability, i.e., the proportion of the phenotypic covariance between two variables attributed to genetic covariance between them, is the product of the genetic path coefficient influencing each variable and the genetic correlation between them, divided by the total phenotypic correlation between the variables. Bivariate shared and non-shared environmental contributions to variance and covariance between the two variables are similarly estimated. Together, bivariate heritability, shared and non-shared environmental effects sum to the total phenotypic correlation.

Results Average Differences

Table 1 presents the means and standard deviations of all study variables, separately for each zygosity group.

Because twin scores are not independent, of each other, for mean comparisons only the scores of one twin per pair were used. A set of analyses of variance tested for sex and zygosity differences, separately for each variable, using a 2 (male vs. female) X 3 (monozygotic, dizygotic, same-sex, and dizygotic, opposite-sex) design. No effects for sex, zygosity or their interaction were found.

Peer problems and temperament: Phenotypic relationships

Table 2 presents the correlations among twinsâ&#x20AC;&#x2122; scores on peer problems and temperament. separately for each zygosity group. Cross-twin same-trait correlations are printed in boldface type on the diagonals of each zygosity group. Same-twin cross-trait correlations appear below the diagonals, and cross-twin cross-trait correlations above them.

Using data from a single twin randomly selected from each pair, across gender and zygosity, peer problems correlated positively with negative emotionality, as hypothesized, r =.12, p < .001. Also as hypothesized, sociability related negatively to peer problems, r = -.25, p < .001. Finally, activity level related negatively to peer problems, r = -.22, p < .001. As Table 2 shows, most of the correlations were in the same direction in the differ-

Table 2. Twin Correlations for Peer Problems and Temperament Peer problems

Negative emotionality Sociability

Activity

.22*

-.11

-.22*

Monozygotic male twins Peer problems

.92**

Negative emotionality .18

.59**

.01

.01

Sociability

-.06

.06

.62**

.23*

Activity

-.22*

-.02

.38**

.68**

.08

-.16

-.20*

.21*

.13

.05

Dizygotic male twins Peer problems

.66**

Negative emotionality -.03 Sociability

-.32**

-.02

.21*

-.01

Activity

-.09

-.10

.48**

-.03

.08

-.24*

-.21

Negative emotionality .07

.43**

.05

.09

Sociability

-.22

.03

.76**

.26*

Activity

-.28*

.03

.37**

.66**

.15

-.04

.18*

.34**

-.08

.00

Monozygotic female twins Peer problems

.88**

Dizygotic female twins Peer problems

.68**

Negative emotionality .22** Sociability

-.34**

-.13

.28**

-.06

Activity

-.26**

-.05

.42**

-.06

.15**

-.11

-.13*

Dizygotic Opposite-sex twins Peer problems

.68**

Negative emotionality .14*

.38**

.02

-.04

Sociability

-.25**

-.02

.21**

.04

Activity

-.25**

.03

.41**

.05

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

Note. Cross-twin same-trait correlations are printed in boldface type and appear on the diagonals. Within-twin correlations appear below the diagonals, and cross-twin correlations above it.

ent zygosity groups, although six of the 15 correlations were not significant (this was true mainly for the smaller monozygotic subsamples). As an exception, the positive correlation between negative emotionality and peer problems was not found among dizygotic male twins.

Because two of the temperament dimensions interrelated (sociability and activity level, r = .42, p < .001), we ran a multiple regression analysis to examine the joint predictive contributions of the different temperament dimensions to peer problems. All three temperament variables had independent contributions, as indicated by their significant relationships with peer problems when entered together in the regression analysis: nega147

Genetic and Environmental Links between Children’s Temperament and peer problems

tive emotionality, β = .11, t = 3.10, p < .005; sociability, β = -.20, t = 5.14, p < .001; activity level, β = -.14, t = 3.57, p < .001; Adjusted R2 = .09.

The father subsample enabled a small-scale replication of the main phenotypic findings. First, positive correlations were found between mothers’ and fathers’ reports on all study variables: peer problems, r =.56, p < .001; negative emotionality, r =.52, p < .005; sociability, r =.39, p < .05; activity, r = .52, p < .005. Second, using father reports alone, the relationships between peer problems and temperament were replicated for negative emotionality although with the small sample size this effect was not significant, r =.21, ns. Moreover, as with the mother reports, peer problems correlated negatively with sociability, r = -.60, p < .001, and activity level, r = -.37, p < .05.

To see whether the same results could be obtained with different informants, we correlated mother-rated peer problems with father-rated temperament. The results were replicated for sociability, r = -.36, p < .05, and activity, r = -.39, p < .05, though insignificantly so for negative emotionality r =.08, ns. Similar findings, though weaker and not significant with this sample size, were found when we correlated father-rated peer problems with mother-rated sociability, r = -.13, ns, and activity, r = -.20, ns < .05, but not negative emotionality, r = -.01, ns.

were lower than half the MZ correlations, indicating no shared environmental influences on these variables.

Table 3 presents the estimates of the relative contributions of genetics and the environment to individual differences. The models fit the data moderately well, as indicated by root mean square error of approximation (RMSEA) coefficients between .02 and .08.

Regarding peer problems, constraining rgO to equal .50 for DZ opposite-sex (DZO) twins as for DZ samesex twins did not affect model fit (χ2(df=1) = 0, ns).

Equating ACE parameters for males and females did not worsen model fit (χ2(df=3) = 0.17 ns. We therefore estimated ACE parameters jointly for boys and girls.

Heritability accounted for 44% of individual differences in peer problems, and the remaining 56% were accounted for by both the shared (46%) and the nonshared environment and error (10%).

A different picture emerged for negative emotionality. Constraining rgO to.50 for DZO twins again did not affect model fit (χ2(df=1) = 0, ns). Dropping the genetic effect that was estimated at 0.06 for girls did not worsen model fit either and a model with no heritability for girls and setting rgO at .00 was preferred, (χ2(df=2) = 1.75 ns). Because of the sex differences in heritability, we estimated different ACE components for boys and girls, as noted in Table 3.

Constraining rgO in sociability and activity to.50 for DZO twins did worsen model fit (sociability, χ2(df=1) = 3.98, p < .05; activity, χ2(df=1) = 7.82, p < .01); rgO was thus unconstrained and estimated at .28 for sociability and .14 for activity. Equating ACE parameters for males and females, and dropping the shared environment effect (estimated at 0.00) did not worsen model fit (sociability, χ2(df=3) = 1.28 ns; activity, χ2(df=3) = 2.07 ns . We therefore estimated ACE parameters jointly for boys and girls. Heritability accounted for 70% of individual differences in sociability and 53% in activity, with the remaining variance accounted for by the non-shared environment and error.

Genetic and Environmental Effects on Peer Problems and Temperament

To examine genetic and environmental influences on peer problems and temperament, we began by comparing MZ and DZ twin correlations (shown in boldface type in Table 2). For all study variables, MZ correlations were larger than DZ correlations, indicating genetic influence. MZ correlations were less than 1.0, indicating influence of non-shared environment and measurement error. For peer problems, and for girls’ negative emotionality, DZ correlations were greater than half the MZ correlations, indicating shared environmental influence. For sociability and activity, DZ correlations

Table 3. Estimates of Variance Components (and 95% Confidence Intervals) Accounting for Individual Differences in Peer Problems and Temperament Variable

Heritability

Shared environment

Non-shared environment and error

Peer problems

.44

(.33

-

.57)

.46

(.34

-

.56)

.10

(.08

-

.12)

Negative emotionality (boys)

.55

(.41

-

.66)

.00

(.00

-

.00)

.45

(.34

-

.59)

Negative emotionality (girls)

.00

(.00

-

.00)

.28

(.17

-

.39)

.72

(.62

-

.83)

Sociability

.70

(.62

-

.76)

.00

(.00

-

.00)

.30

(.24

-

.38)

Activity

.53

(.39

-

.65)

.00

(.00

-

.00)

.47

(.36

-

.61)

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Maya Benish-Weisman et al.

Cross-twin/cross-trait correlations indicate whether there is genetic or environmental influence on the relationship between temperament and peer problems. As shown in Table 2 (above the diagonals), the cross-twin/ cross-trait correlations between peer problems and temperament tended to be stronger for MZ twins than for DZ twins, indicating a genetic influence common to peer problems and to temperament. One exception concerns the relationship between girls’ negative emotionality and their peer problems, which was similar for MZ and DZ twins, indicating a shared environment effect accounting for the relationship. Model-fitting analyses decomposed these phenotypic correlations into their genetic and environmental components by analyzing the variance-covariance matrices for peer problems and temperament.

Table 4 presents estimates for the genetic and environmental correlations between peer problems and the temperament measures. Estimates for negative emotionality are presented separately for girls and boys because of the results of the sex limitation analyses described above. Figure 1 presents the correlations between peer problems and temperament. Each correlation is depicted according to the relative contributions of bivariate heritability, bivariate shared environment effects, and bivariate non-shared environment to the correlations between temperament and peer problems.

The negative correlations between sociability and activity and peer problems were accounted for by bivariate heritability and to a lesser extent by bivariate nonshared environment and error. A more complex picture emerged for negative emotionality. The positive correlation with boys’ peer problems was fully accounted for by the genetic correlation between peer problems and negative emotionality. In contrast, girls’ negative emotionality was not estimated as being substantially influenced by heritability. Its moderate relationship

Figure 1. Decomposing the Relationships between Peer Problems and Temperament to their Genetic and Environmental Components 0.20 0.15 0.10 0.05 correlation

Genetic and Environmental Effects on the Peer Problems – Temperament Relationship

0.00 -0.05

Sociability Negative emotionality (boys)

Activity

Negative emotionality (girls)

-0.10 -0.15

Bivariate non-shared environment Bivariate shared environment Bivariate heritability

-0.20 -0.25 -0.30

with peer problems was accounted for mainly by the bivariate shared environment.

Discussion Children’s temperament has meaningful associations with their peer relationships problems. Children characterized by negative emotionality and low sociability and activity level tended to have greater peer problems.

Importantly, all the three temperament variables had independent contributions to peer problems. Further research should address how temperament dimensions interact with each other and with additional factors in accounting for children’s peer problems. For example, sociability refers to children’s enjoyment of interpersonal contexts, and thus relates to lower peer problems.

However, a child can be highly sociable but lack the social competence needed to fulfill this motivational goal. Perhaps, due to high levels of negative emotionality as our results show.

Table 4. Genetic and Environmental Correlations (and 95% Confidence Intervals) between Peer Problems and Temperament Variable correlating with peer problems Negative emotionality (boys)

Shared environment correlation

Genetic correlation .28

(.13

-

.45)

.00

(.00

-

.00)

Non-shared environment correlation .00

(.00

-

.00)

Negative emotionality (girls)

.00

(.00

-

.00)

.17

(-.06

-

.40)

.12

(-.04

-

.27)

Sociability

-.43

(-.54

-

-.32)

.00

(.00

-

.00)

-.09

(-.24

-

.07)

Activity

-.30

(-.44

-

-.17)

.00

(.00

-

.00)

-.23

(-.39

-

-.05)

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Genetic and Environmental Links between Children’s Temperament and peer problems

Genetic and Environmental Effects on Peer Problems and Temperament

Peer problems showed strong familial influences, consisting of both genetic (44%) and shared environmental (46%) effects. The shared environment effects may indicate the role of parental behavior. A meta-analysis has shown that the quality of the child-mother attachment was related positively to peer relations (34). Interventions involving the promotion of secure attachment considering also children’s temperament might prove helpful in the reduction of peer problems. Parents’ monitoring and guidance in their children’s relationship may also be important, and especially likely at the young age of three. By age seven, shared environmental influences on peer problems diminish in importance (24). Although a decline in the importance of the shared environment has been observed for other traits as well (e.g., prosocial behavior, 35), peer problems may be especially affected by the life transitions associated with moving from preschool to school, as the social environment of children becomes increasingly diverse with age, leaving less room for familial environmental influences.

Sociability, activity, and peer problems. Genetic effects account for most of the variance in activity level (53%) and sociability (70%), replicating past findings of temperament heritability (36). The higher MZ twin correlations indicate heritable effects. However, the DZ correlations are much lower than could be expected based on the 50% shared genetic heritage of DZ twins.

This could indicate that the MZ correlation is so much higher because parents of MZ twins inflate their similarity, because there is a non-additive genetic effect, or because there are contrast effects, reducing DZ twin similarity. Research by Saudino et al. (24) indicates that the third possibility is the correct one.

Negative emotionality and peer problems. Negative emotionality presents a complex set of findings, as it was substantially heritable in boys but not in girls. We are not aware of other studies showing no heritability for girls’ negative emotionality. One study that tested for sex limitation did not find sex differences in the genetic and environmental influences on negative emotionality with a French twin sample (37). The different gender patterns may be culture-specific, but we would like to await a replication before speculating on the reasons for this finding.

Bivariate genetic and environmental effects. At the phenotypic level, children who are active and very sociable have less peer problems. The bivariate genetic 150

analyses traced most of this association to overlapping genetic influences. Because peer problems involve both the child and other children (the peers), the genetic effects on peer problems may actually reflect a geneenvironment correlation in which the child’s genetically-influenced temperament elicits peer reactions associated with the child’s genotype (38).

The bivariate non-shared environment effects also accounted for a small proportion of the phenotypic correlation between peer problems and temperament.

These effects may reflect differences in the environments children encounter. For example, one of the twins, due to having exclusively experienced a certain life event, may have become less sociable and subsequently developed more peer problems. Another possibility is that parental differential treatment accounts for the subtle differences making twins different on both peer problems and temperament (39).

Strengths and Limitations

The use of a large community sample is a methodological strength of this study. It enabled detecting the modest phenotypic correlations between different dimensions of temperament and peer problems and assessing the genetic and environmental contributions to these modest phenotypic correlations.

The reliance solely on parental reports is a limitation.

Parent reports were moderately positively correlated with teacher reports on children’s peer problems (24). Modest phenotypic correlations in activity and sociability (but not negative emotionality) were also found between teacher and tester ratings (36), indicating that no two sources of information are in perfect agreement. In future research, multiple rater scores from different contexts should be obtained and compared for better understanding the processes involved in temperament and peer problems.

Conclusion We found meaningful relationships between temperament and children’s peer problems. Bivariate heritability largely accounted for these effects. Our findings point to the importance of temperament and genetics in the social development of children. The findings indicate that temperament dimensions should be taken into account while building peer problem interventions. In addition, beside genetic factors, non-shared environmental influence (e.g., the environment in different classes at school) should be taken also into consideration.

Maya Benish-Weisman et al.

Acknowledgements

The authors are indebted to the parents of the twins in the Longitudinal Israeli Study of Twins (LIST) for making the study possible. LIST is supported by grant No. 31/06 from the Israel Science Foundation to the third author.

References 1. Buss AH, Plomin R. Temperament: Early developing personality traits. Hillside, N.J.: Erlbaum, 1984.

2. Goodman R. The Strengths and Difficulties Questionnaire: A research note. J Child Psychol Psychiatry 1997;38:581-586.

3. Deater-Deckard K. Annotation: Recent research examining the role of peer relationships in the development of psychopathology. J Child Psychol Psychiatry 2001;42:565–579.

4. Hay DF, Payne A, Chadwick A. Peer relations in childhood. J Child Psychol Psychiatry 2004;45:84–108.

5. Howes C, Matheson CC, Hamilton CE. Maternal, teacher, and child-care history correlates of children’s relationships with peers. Child Dev 1994;65:264-273.

6. Clark KE, Ladd GW. Connectedness and autonomy support in parentchild relationships: Links to children’s socioemotional orientation and peer relationships. Dev Psychol 2000;36:485-498.

20. Saudino KJ, McGuire S, Reiss D, Hetherington EM, Plomin R. Parent ratings of EAS temperaments in twins, full siblings, half siblings, and step siblings. J Pers Soc Psychol 1995;68;723–733.

21. Saudino KJ. Do different measures tap the same genetic influences? A multimethod study of activity level in young twins. Dev Sci 2009; 12:626-633.

22. Robinson JL, Kagan J, Reznick JS, Corley R. The heritability of inhibited behavior: A twin study. Dev Psychol 1992;28:1030-1037.

23. Iervolino AC, Pike A, Manke B, Reiss D, Hetherington EM, Plomin R. Genetic and environmental influences in adolescent peer socialization: Evidence from two genetically sensitive designs. Child Dev 2002;73:162-174.

24. Saudino K, Ronald A, Plomin R. Rater effects in the etiology of behavior problems in 7-year-old twins: Parent ratings and ratings by same and different teachers. J Abnorm Child Psychol 2005;33:113-130.

25. Emde RN, Plomin R, Robinson J, Reznick JS, Campos J, Corley R, DeFries JC, Fulker DW, Kagan J, Zahn-Waxler C. Temperament, emotion, and cognition at 14 months: The MacArthur Longitudinal Twin Study. Child Dev 1992;63:1437-1455.

26. Knafo A. The Longitudinal Israeli Study of Twins (LIST): Children’s social development as influenced by genetics, abilities, and socialization. Twin Res Hum Genet 2006;9:791-798.

7. DiPietro JA, Hodgson DM, Costigan KA, Johnson TR. Fetal antecedents of infant temperament. Child Dev 1996;67:2568-2583.

27. Knafo A, Israel S. Genetic and environmental influences on prosocial behavior.

In: Mikulincer M, Shaver PR, editors. Prosocial motives, emotions, and behavior: The better angels of our nature. Washington, DC: APA Publications, 2009: pp. 149-167.

8. Rothbart MK, Bates J. Temperament. In: Damon W, Eisenberg N, editors.

Handbook of child psychology: Social, emotional and personality development.

5th ed. New York: Wiley, 1998: pp. 105–176.

28. Knafo A, Zahn-Waxler C, Davidov M, Van Hulle C, Robinson J, Rhee SH. Empathy in early childhood: Genetic, environmental and affective contributions.

Ann NY Acad Sci 2009; 1167:103-114.

9. Miner JL, Clarke-Stewart KA. Trajectories of externalizing behavior from age 2 to age 9: Relations with gender, temperament, ethnicity, parenting, and rater.

Dev Psychol 2008;44:771-786.

29. Price TS, Freeman B, Craig IW, Petrill SA, Ebersole L, Plomin R. Infant zygosity can be assigned by parental report questionnaire data. Twin Res 2000;3:129133.

10. Young SK, Fox NA, Zahn-Waxler C. The relations between temperament and empathy in 2-year-olds. Dev Psychol 1990;35:1189-1197.

30. Becker A, Woerner W, Hasselhorn M, Banaschewski T, Rothenberger A. Validation of the parent and teacher SDQ in a clinical sample. Eur Child Adolesc Psychiatry 2004;13 :II11-II16.

11. Fox NH, Nichols KE, Henderson HA, Rubin K, Schmidt DH, Ernst M, Pine DS. Evidence for gene-environment interaction in predicting behavioral inhibition in middle childhood. Psychol Sci 2005;16:921-926.

12. Henderson H, Marshall P, Fox NA, Rubin KH. Psychophysiological and behavioral evidence for varying forms of nonsocial behavior in preschoolers.

Child Dev 2004;75:251-263.

13. Goldsmith HH, Buss AH, Plomin R, Rothbart MK, Chess S, Thomas A, Hinde RA, McCall RB. Roundtable: What is temperament? Four approaches. Child Dev 1987;58:505-529.

14. Vaughan Van Hecke A, Mundy PC, Acra CF, Block JJ, Delgado CEF, Parlade MV, Meyer JA, Neal AR, Pomares YB. Infant joint attention, temperament, and social competence in preschool children. Child Dev 2007;78:53-69.

15. Bagwell CL, Molina BSG, Pelham WE, Hoza B. Attention-Deficit Hyperactivity Disorder and problems in peer relations: Predictions from childhood to adolescence. J Am Acad Child Adolesc Psychiatry 2001;40:1285-1292.

16. Plomin R, DeFries JC, McClearn GE, McGuffin P. Behavioral genetics, 4th edn.

New York: Worth Publishers, 2001.

17. Saudino KJ, Plomin R, DeFries JC. Tester-rated temperament at 14, 20, and 24 months: Environmental change and genetic continuity. Br J Dev Psychol 1996;14:129-144.

18. Zawadzki B, Strelau J, Oniszcenko W, Riemann R, Angleitner A. Genetic and environmental influences on temperament: The Polish-German twin study, based on self-report and peer-rating. Eur Psychiatry 2001;6:272-286.

19. Saudino KJ, Zapfe JA. Genetic influences on activity level in early childhood: Do situations matter? Child Dev 2008;79:930-943.

31. Neale MC, Boker SM, Xie G, Maes HH. Mx:statistical modeling, 5th edn.

Department of Psychiatry, Box 126 MCV, Richmond, VA 23298, 1999.

32. Neale MC, Maes HHM. Methodology for genetic studies of twins and families.

Dordrecht, Netherlands: Kluwer, 1999.

33. Plomin R, DeFries JC. Multivariate behavioral genetic analysis of twin data on scholastic abilities. Behav Genet 1979;9:505-517.

34. Schneider BH, Atkinson L, Tardif C. Child-parent attachment and children’s peer relations: A quantitative review. Dev Psychol 2001;37:86-100.

35. Knafo A, Plomin R. Prosocial behavior from early to middle childhood: Genetic and environmental influences on stability and change. Dev Psychol 2006;42:771-786.

36. Schmitz S, Saudino KJ, Plomin R, Fulker DW, DeFries JC. Genetic and environmental influences on temperament in middle childhood: Analyses of teacher and tester ratings. Child Dev 1996;67,:409-422.

37. Saudino KJ, Carter AS, Purper-Ouakil D, Gorwood P. The etiology of behavioral problems and competencies in very young twins. J Abnorm Psychol 2008;117:48-62.

38. Burt A. A mechanistic explanation of popularity: genes, rule breaking, and evocative gene-environment correlations. J Pers Soc Psychol 2009;96:783-794.

39. Caspi A, Moffitt TE, Morgan J, Rutter M, Taylor A, Arseneault L, Tully L, Jacobs C, Kim-Cohen J, Polo-Tomas M. Maternal expressed emotion predicts children’s antisocial behavior problems: Using monozygotic-twin differences to identify environmental effects on behavioral development. Dev Psychol 2004;40:149-161.

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Correspondence, Obituary, Book Reviews

Correspondence What is the relevance of the term “functional” in psychiatric disorders in the era of functional brain imaging?

Dear Editor, raditionally mental illnesses are classified as organic (biological) or functional (non-biological) mental illness depending on the presence or absence of biological changes in the brain respectively (1). Sims (2) wrote about “organic and functional” terminology as follows: “I have not contrasted organic with the conventional functional, because functional is a most misleading term. It causes conceptual fog rather than enlightenment. A logical person who is innocent of medical jargon would be baffled to know why disturbance of human function by psychological mishap should be called functional, while similar disturbance of function from organic disease is not.” However, this classification has lost it original meaning with the increase in neurobiological findings in psychiatry.

Traditionally, imaging techniques are divided into structural and functional neuroimaging, despite some modalities containing a mixture (3). “Structural neuroimaging” involves techniques that map the anatomy of the brain, whereas “functional” neuroimaging (in the broadest sense) denotes electrophysiological assessment of brain functions. Current research in imaging in psychiatry is a combination of both structural and functional imaging. In general, structural imaging research in psychiatry is focused on non-specific structural abnormalities (e.g., ventromegaly in schizophrenia, abnormal amygdala and hippocampus in PTSD) and indirectly focuses on the functions of those abnormal areas, whereas, functional imaging research focuses on functional abnormalities of a particular brain area, which is relatively specific to a finding (e.g., increased activation of amygdala in response to fearful face in functional imaging, whereas there will be no changes in structural imaging). In view of low yield and low predictive power of structural imaging research these many years to find reliable structural markers for psychiatric disorders (4), the authors presume that functional imaging in psychiatric research will have more chances to provide new insights into the etiology of psychiat-

T

152

ric disorders in the near future. Undoubtedly the rapid growth in functional brain imaging techniques will increasingly offer more detailed diagnostic information of psychiatric disorders.

In the current clinical practice of psychiatry, structural brain imaging is being routinely used to exclude organicity especially in atypical presentations before making a definite diagnosis of a particular psychiatric disorder. The authors feel that the time may come in the near future when functional imaging modalities are routinely used in the clinical practice of psychiatry to make a definite diagnosis of psychiatric disorders because of the presence of comparatively specific findings of functional neuroimaging. This was also predicted in the editorial of Acta Psychiatrica Scandinavica in 2006 (5): “Brain imaging in psychiatry: from a technique of exclusion to a technique for diagnosis” and American Journal of Psychiatry in February 2009 issue (6): “Connecting brain structure and function in schizophrenia.”

Traditionally the functioning of the body is studied in the branch of “physiology.” The branch of “neurophysiology” deals with the function of brain. Current functional imaging research in psychiatry is heavily focused on different aspects of functional components of the brain (biochemicals as diagnostic biomarkers, neuron functions in molecular imaging and neuroimaging genomics) in the belief that brain functioning is associated with psychiatric disorders. Hence, future psychiatric disorders may be termed functional psychiatric disorders, meaning, neurophysiological disorders.

The authors are in favor of the revival of the term “functional” in psychiatry with a new meaning for an old term, “functional” meaning functional changes of the brain associated with psychiatric disorders and in favor of abandoning the literal meaning of the term “functional” as non-biological. We would like to revive the term “functional” to its logical meaning rather than the medical meaning to avoid confusion. Hence, the authors feel that the term “functional” in psychiatry still has relevance now and in the future.

CONCLUSION

The future of classification of psychiatric disorders heavily depends on neurophysiologic factors, which in turn depend more on functional neuroimaging research. The contributions of functional neuroimaging to the biological basis of psychiatric disorders are enormous and still evolving. In the future functional neuroimaging research needs to establish more specific

Correspondence, Obituary, Book Reviews

biological findings of psychiatric disorders. Once the more specific biological basis of psychiatric disorders is known, future psychiatric disorders may be referred to as functional psychiatric disorders denoting neurophysiological disorders.

The time may come in the future when psychiatrists routinely use functional imaging to diagnose functional psychiatric disorders whenever patients comes with psychiatric symptoms and to guide the choice of appropriate treatments from the findings of the functional imaging of patients.

Narayana Manjunatha, MD, DPM Senior Resident Department of Psychiatry National Institute of Mental Health and Neuro Sciences (NIMHANS) Bangalore – 560029, India manjunatha.adc@gmail.com G. Roopa Research Scholar Department of Instrumentation Indian Institute of Sciences, Bangalore, India

References 1. Casey P, Kelly B. Classification of psychiatric disorders. In: Fish’s clinical psychopathology: Signs and symptoms in psychiatry. 3rd edition. Royal College of Psychiatrists: Gaskell, 2007: pp 1-13.

2. Sims A. Fundamental concepts of descriptive psychopathology. In: Symptoms in mind - An introduction to descriptive psychopathology. London: Bailliere & Tindall, 2003: pp. 1-24.

3. Malhi GS, Lagopoulos J. Making sense of neuroimaging in psychiatry. Acta Psychiatr Scand 2008; 117: 100–117.

4. Manjunatha N, Saddichha S. Letter to editor on Mueller et al. (2006). Brain imaging in psychiatry – a study of 436 psychiatric inpatients at a university clinic. Acta Psychiatr Scand 2007; 115: 492.

5. Osuch E, Williamson P. Editorial: Brain imaging in psychiatry: from a technique of exclusion to a technique for diagnosis. Acta Psychiatr Scand 2006;114:73–74.

6. Tregellas J. Editorial: Connecting brain structure and function in schizophrenia.

Am J Psychiatry 2009;166:134-136.

Is disturbed sleep a clinically useful marker to determine the suicide risk in patients with posttraumatic stress disorder?

Dear Editor, leep abnormalities are prevalent in the general population and among patients with psychiatric illnesses. A growing body of research has associated sleep disorders such as primary insomnia, nightmares, sleep terrors, parasomnias and breathing-related sleep disorder (sleep apnea) with other psychiatric conditions including

S

posttraumatic stress disorder (PTSD), major depression, substance use disorders, schizophrenia and suicide.

For example, it has been reported that nightmares were associated with suicidality after controlling for depressive symptoms (1). Similar results were obtained by another group: it was found that adolescents who experienced frequent nightmares had a higher risk for suicide attempts or suicidal ideation (2). They also reported that adolescents sleeping less than eight hours per night had a higher risk to make a suicide attempt than the adolescents who slept nine hours per night or more. Changes in rapid eye movement (REM) sleep have also been reported, including a shorter mean REM latency, a higher mean REM percentage and different within-night distribution of dream quality in a sample of depressed patients with suicidal tendencies when compared with non-suicidal depressed patients (3). Despite these findings, it remains unclear whether the appropriate treatment of insomnia reduces the risk of suicide. Current knowledge already points out insomnia as a putative warning sign of future suicidal behavior among depressed patients.

We want to draw particular attention to the association of suicidality with disturbed sleep among patients with posttraumatic sleep disorder (PTSD). To date, there is still no clear understanding of this relationship.

Are sleep disturbances a consequence of the disorder or they are a risk factor for the development of PTSD? Spoormarker and Montgomery (4) proposed three possible links between disturbed sleep and PTSD: a) disturbed sleep acts as a risk factor for PTSD; b) they are separate disorders that share a common origin in trauma; c) disturbed sleep acts as a mediating factor, based on a common vulnerability and its influence on the development of PTSD. Of note, Spoormarker and Montgomery (4) also suggested that insomnia may be underdiagnosed and undertreated.

Several lines of evidence suggest that PTSD is associated with suicidal behavior (5). Several links between PTSD, sleep abnormalities and suicidal behavior may exist. For example, 1) suicidal behavior in PTSD may be mostly related to sleep abnormalities not to the diagnosis of PTSD per se; 2) suicidal behavior in PTSD may be mostly related to the diagnosis of PTSD and sleep abnormalities may be a contributing factor; 3) suicidal behavior in PTSD may be mostly related to psychological trauma not to the diagnosis of PTSD and sleep abnormalities may be a contributing factor; 4) the same neurobiological mechanisms may underlie PTSD, sleep problems, and suicidal behavior; for example, seroton153

Correspondence, Obituary, Book Reviews

ergic disturbances may play a role in the pathophysiology of all three conditions.

Clinicians may give more importance to the primary disorder, while considering sleep complaints as secondary symptomatology. However, it is reasonable to suggest that disturbed sleep may be a clinically useful marker to determine the suicide risk in PTSD patients and further research on this issue is warranted.

Leo Sher, MD, Diana Zambrano-Enriquez, MD, Mikkel Arendt, PhD Department of Psychiatry, Columbia University 1051 Riverside Drive, Unit 42, New York, NY 10032, U.S.A. LS2003@columbia.edu

References 1. Bernert RA, Joiner TE Jr, Cukrowicz KC, Schmidt NB, Krakow B. Suicidality and sleep disturbances. Sleep 2005; 28:1135-1141.

2. Liu X. Sleep and adolescent suicidal behavior. Sleep 2004; 27:1351-1358.

3. Agargun MY, Cartwright R. REM sleep, dream variables and suicidality in depressed patients. Psychiatry Res 2003; 119:33-39.

4. Spoormaker VI, Montgomery P. Disturbed sleep in post-traumatic stress disorder: Secondary symptom or core feature? Sleep Med Rev 2008; 12:169184.

5. Sher L. Suicide in war veterans: The role of comorbidity of PTSD and depression.

Exp Rev Neurother 2009; 9:921-923.

Affective disorder and polycythaemia vera To the Editor e are reporting on three siblings diagnosed as affective disorder with polycythaemia vera during the episodes. Polycythaemia disappearing with the remission of affective disorder is the focus of attention of these cases.

A 28-year-old single woman presented at our outpatient clinic for treatment of a manic episode. Her psychiatric history revealed that she had had manic and subclinical depressive episodes for almost ten years. Three days after polycythaemia vera developed, a manic episode began with abnormally elevated, irritable mood, grandiosity, decreased need for sleep, more talkative than usual, increase in goal directed activity such as spending too much money to solve troubles, anxiety. On physical examination there was a remarkable redness on her face. She complained of sensations of shortness of breath, smothering and choking.

She feared closed spaces. She was treated with typical antipsychotics. The manic episode disappeared within two months. Physical examination was performed in an internal medicine clinic. One week after the remission

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154

of manic episode her polycythaemia disappeared. The patient was given phlebotomies of 500cc weekly during the manic episode.

Our patient told us that her two brothers also suffered from similar psychiatric and hematological problems. One brother was 26 years old, single, with psychotic depression developing rapidly after a stressful life event. At the same time polycythaemia was present. Phlebotomy was performed four times during one month. Polycythaemia and depression remitted at the same time.

Another brother was 24 years old, single, with polycythaemia and nonpsychotic depression developing after his brother’s depression. Phlebotomy was performed three times during three weeks of treatment.

Again polycythaemia and depression remitted at the same time.

The siblings had no internal disease. Only our patient was on lithium treatment, 600mg/day for chronic affective disorder but her first polycythemia attack was prior to lithium treatment.

DISCUSSION

Polycythaemia signifies an increase above the normal in the number of red corpuscles in the circulating blood.

Relative polycythaemia occurs when, through loss of blood plasma, the concentration of the red corpuscles becomes greater than normal in the circulating blood.

This may be the consequence of abnormally lowered fluid intake, of the marked loss of body fluids such as vomiting or sweating (1). The term stress erythrocytosis has been applied to polycythaemia that is seen occasionally in active, very hard-working persons in a state of anxiety (1). These conditions may be suitable for our patient due to motor excitation.

Erythrocytosis develops as a consequence of a variety of factors and represents a physiologic response to conditions of hypoxia (2). Erythrocytosis, hypercapnia and somnolence may present in very obese individuals.

Erythrocytosis is found in Cushing’s Syndrome and can be produced by the administration of large amounts of adrenocortical steroids. Our patient was neither obese nor suffered from Cushing’s Syndrome.

In our case polycythaemia is not related with lithium treatment (3).

We found only one report on the relationship between affective disorder and polycythaemia vera in which mania, delirium and polycythaemia rubra vera were documented (4).

Correspondence, Obituary, Book Reviews

There is a letter to the editor reporting polycythaemia vera presenting as sudden-onset cognitive impairment in a 67-year-old woman with clinical dementia.

Cognitive dysfunction was due to watershed infarction caused by polycythaemia vera (5).

This case history presents polycythaemia that developed just before the onset of each manic episode and disappeared after the remission of the episode.

Mehmet E. Ceylan, Fulya Maner and Ahmet Türkcan Bakırköy State Hospital for Mental Health and Neurological Disorders, Istanbul, Turkey fmaner@ttmail.com

References 1. Braunwald E, Kahler RL, Wintrobe MM. Cyanosis, hypoxia and polycytheamia.

In: Thorn GW, Adams RD, Braunwald E, Isselbacher KJ, Petersdorf RG, eds.

Harrison’s Principles of Internal Medicine, Eighth Edition. Tokyo: Kosaldo, 1997: pp. 174-176.

2. Freeman MP, Wiegand C, Gelenberg AJ.Lithium. In: Schatzberg AF, Nemenoff CB, eds. Textbook of Psychopharmacology. Third Edition. Washington DC: American Psychiatric Publishing, 2004, pp. 547-565.

3. Ania BJ, Suman VJ, Sobell JL, et al. Trends in the incidence of polycythaemia vera among Olmsted County, Minnesota residents, 1935-1989. Am J Hematol 1994; 47:89-93.

4. Chawla M, Lindesay J. Polycythaemia, delirium and mania. Br J Psychiatry 1993;162:833-835.

5. Alkemade GM, Willems JM. Polycytemia vera presenting as sudden-onset cognitive impairment. JAGS 2008; 56: 2362-2363.

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Correspondence, Obituary, Book Reviews

Obituary Leon Eisenberg A Towering Figure in World Psychiatry

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hat can one add to the detailed obituary that Harvard University published in Wikipedia? Leon was a proud Jewish professional who used his familiarity with Judaism to spruce up his brilliant and mind-expanding presentations with Jewish jokes and quotes. (And Jewish jokes he did know! To watch two scholars, Leon Eisenberg and Joseph Zubin, exchange Jewish jokes was an experience never to forget.) As for quotes, I recall a seminal article where he called for the application of what the field knew about primary prevention. The title he borrowed, If not now, when? (Am J Orthopsychiatry 1962; 32:781793), came from Hillel,s quote in the Mishna.

L e on E i s e nb e rg w a s b or n i n 1 9 2 2 i n Philadelphia to Russian-Jewish immigrants who came to America in the search of a safer and better world. This was largely accomplished, and yet Leon Eisenberg had to experience the latent antiSemitism of which not even America was free. In a farewell letter Leon sent to family and friends he could not but rejoice that his battle against discrimination was a resounding success: “I was not wanted in medical schools but I became a professor and chairmen, first in Johns Hopkins and later in Harvard, leading universities.” At the last WPA Congress held in Prague he received an award, the last of a long list he accrued over his career that ended only a few months before his death. His candidacy for an award to be granted during the previous WPA Congress in Cairo did not prosper.

His CV fully justified the award while the list of supporters of his candidacy included the “Who,s who” in world psychiatry. He accepted the award in Prague with no resentment, since for him the Cairo rejection was just one of the obstacles he

156

always succeeded in overcoming.

Perhaps belonging to a minority made him into the staunch liberal psychiatrist that many of his colleagues did not appreciate - but could not help respect (Rudolf Virchow: The physician as politician. Medicine and War 1986; 2:243-250). As an expression of his vision he wrote in his farewell letter of another success he had witnessed “My life is full, I was able to see that a Black American became president of the US.” Dr. Carola Eisenberg, his spouse for 42 years, accompanied him fully in their support of human rights in psychiatry.

Leon Eisenberg has too long a list of contributions to summarize here. Two of his more recent papers reflected his full understanding how the social environment makes a brain and how the brain makes the environment (The social construction of the human brain. Am J Psychiatry 1995;152: 1563-1575). He resisted with powerful arguments that there is neither a brainless mind nor a mindless brain (Mindlessness and brainlessness in psychiatry. Brit J Psychiatry 1986; 148:497508). For him the person is too complex a being to reduce it to cells, while the environment cannot express itself in the person without a biological structure.

Leon was a dear friend, a true “eitzegiver” (mentor), his e-mails full of warmth and fun, his letter of farewell left Miriam and myself with tears of sadness and happiness at having been among those who witnessed such a fulfilled life.

Aged 87, Leon Eisenberg has died – but many follow his path. This knowledge gave him solace when his life went into a quick sunset.

Itzhak Levav, Jerusalem

Correspondence, Obituary, Book Reviews

Book reviews Handbook of Clinical Rating Scales and Assessment in Psychiatry and Mental Health Edited by Lee Baer and Mark A. Blais Humana Press, 2009, pp. 332, price €106 ISBN: 978-1-58829-966-6

M

ost clinicians do not use rating scales routinely.

The common reasons are time pressure, not knowing which scales to use, believing that rating scales are useful only in research settings and worrying whether scales will truly capture the important aspects of improvement in their patient.

This book attempts to address all these issues, since rating scales, according to the authors, not only facilitate targeted diagnoses and treatment, but also encourage links to empirical literature and systemize the entire management process. The purpose of this useful handbook is to provide the busy psychiatric clinician (psychiatrist, psychologist, social workers, GPs and others) with a practical guide to use in focused assessments.

The book includes “gold standard” rating scales, as well as screening tests in 13 mental health areas. There are ready-to-copy versions of the scales (when copyrights permit) and practical information about the clinical use.

Each author of the 15 chapters wrote about the latest information available concerning the characteristics of the scales (such as reliability, validity, and sensitivity to treatment induced change). There are short discussions about the relative strengths and weaknesses of the scales and other issues concerning the assessment such as how to minimize bias, and assessment across different age groups, cultures, education and comprehension levels.

The book’s first chapter, written by both editors, is about basic psychometric and statistical concepts. Like all the chapters, it is concise, intensive and highly practical.

Chapter 6 offers brief but sophisticated screening scales for personality disorder patients. I found this information very useful in clinical settings, where those patients are often underdetected.

Chapter 12 discusses the efficient use of useful rating scales in psychotherapy. According to the authors of this chapter brief scales can be integrated into the psychotherapy process. It seems that data from those scales can enhance the treatment effectiveness.

Chapter 13 deals with a relatively new unique issue

of assessing the ongoing psychological impact of terrorism. After the 9/11 attack clinicians have developed instruments to measure fears of future attacks.

As a clinician the book stimulated me to use some of the screening and assessment scales not only in research settings. The vivid information about the advantages and shortcomings of each of the scales will help me to choose one that fits my patients.

Assaf Shelef, Bat Yam

Möglichkeiten sich zu schűtzen Christian Pross, Verletzte Helfer Leben Lernen - Klett-Cotta, Stuttgart, 2009, pp. 288, ISBN: 978-3-608-89090-7

T

rauma therapists are listening to personal accounts of torture, cruelty and violence on a daily basis. In this process, we become personal witnesses to massacres, rape and persecution of enormous proportions. We cannot remain personally unaffected by these experiences and they leave indelible marks on all of us, including (or especially) professionals with years of experience. Apparently, we become “vicariously” wounded by the pain and suffering of our clients, and, for some of us, it makes us feel so outraged that we tend to displace our anger on people who have nothing to do with the initial crime.

This is the subject matter of a new fascinating book on the "Wounded Healer" published in the German language by Dr. Christian Pross. The well-known trauma therapist and researcher was the co-founder in 1992 and director, until last year, of The Berlin Center for the Treatment of Torture Victims (BZFO). Since 2009, he is the scientific director of a working group for psycho-traumatology studies at the center for survivors in Berlin.

His earlier controversial book on the struggle over reparations for survivors of the Nazi terror received wideclaimed praise and was published both in German and in English (Pross 1988/2001, Pross, 1998).

This new book is based on material that was collected from interviews with 72 professionals who worked in treatment centers for victims of crisis regions, war, sexual abuse and political persecution and in organizations for human rights, supervisors and psycho-trauma experts from eight countries. Earlier publications on this theme have clearly described the concepts of “burnout,” “compassion fatigue,” “vicarious traumatization,” and “secondary traumatic stress,” emphasizing the constant need for some kind of “care for caregivers.” However, in contrast to 157

Correspondence, Obituary, Book Reviews

these earlier studies on the side effects of treating trauma survivors, which mainly focus on the helper and the helped, the present book deals with the effects of trauma therapy on teams and organizations working in this field. Since Pross observed that people working in such institutions â&#x20AC;&#x153;move through a minefield of the abysses of human existenceâ&#x20AC;? (p. 28), over-involved therapists tend to re-enact the vicissitudes of trauma within their specific institutional structure, often creating chaos and destruction. Studying such a hot and almost taboo subject is not only courageous, but also very important, since it has been largely neglected in earlier literature.

The book is well researched and written in an easily readable style, with a number of illustrative situations. It is a text suitable not only for staff and leadership, but also for organizational psychologists who are called upon to provide supervision and to facilitate team building and organizational development in such institutions.

References 1. Pross, C. (1988/2001). Wiedergutmachung - Der Kleinkrieg gegen die Opfer.

2. Berlin: Philo (English translation (1998); Paying for the Past, The Struggle over Reparations for Surviving Victims of the Nazi Terror. Baltimore: The Johns Hopkins University Press.

Natan P.F. Kellermann, Amcha

The Oxford Textbook of Suicidology and Suicide Prevention: A Global Perspective Danuta Wasserman and Camilla Wasserman, Editors 2009; Hardback, pp. 872, ÂŁ 75.00 ISBN: 987-0-198-57005-9

W

orldwide, one person dies every 40 seconds as a result of suicide, and every 5-10 seconds, there occurs a suicide attempt. Suicide is one of the main leading causes of death among certain groups, and has gained global attention as a serious public health problem.

However, the nature of suicide is a complex matter, as it is the end result of many underlying biological, psychological, cultural and social factors that often coincide with one another. Understanding the complexities of suicide and suicidal behavior are essential initiatives in formulating effective treatments and preventive inteventions.

The present textbook, edited by Danuta Wasserman and Camilla Wasserman, examines the multifaceted factors of suicide and suicidal behavior and provides a comprehensive resource for understanding the intricate context of suicidality. The textbook is strategically 158

divided into 15 parts and comprises 134 chapters. this textbook has a big folioformat that illustrate an articulate framework of the suicide processes.

In the first five parts in the textbook, there are several fundamental themes in focus, which primarily concentrate on the cultural, epidemiological, theoretical, biological, political and social implications of suicide and suicidal behavior. Depicted in the cultural chapters are the intriguing and sometimes controversial attitudes in different religions towards suicide. The chapters provide an overview on how the role of religion affects the ideology of suicide in modern and historical times. Moreover, it provides a proficient comparison among the diverse cultures (around the world), and the impact it has on suicidality, e.g., feelings of guilt and condemnation in Christianity and acceptance in Shinto religion.

The section on epidemiology underscores the magnitude and implications of suicide and suicidal behavior on all the continents, thus, demonstrating the significance of this major public health problem worldwide. In addition, theoretical concepts are addressed, which provides insight into the social, psychoanalytical and psychological schemes of suicidality, and demonstrates empirical evidence to support those assertions. Moreover, included in part three, are chapters that describe the biological and genetic factors associated with suicide. These remarkable chapters provide evidence-based research that exemplifies that suicide is not only a result of environmental circumstance, but entails also the biological and genetic predisposition. The subsequent chapters in the first five parts concentrate on the political and social implications of suicide across all continents. These profound chapters bring forth the realization of the influential dominance political, economic and social circumstance has on suicidality, i.e., it can amplify or mitigate the problem. One has observed increase of suicide due to unemployment, social hardships and during the political transition periods in the former communist East European countries.

Subsequent parts five through ten focus on the treatment aspects of suicide, consisting of clinical measures, health care and public health strategies, such as increasing awareness in the population about prevention, closing the exits by restriction of availability of lethal means for suicide and responsible media policies about informing the public about suicide. Clinical approaches embrace the various types of treatment of suicidality that include not only pharmacological means, but also psychological treatments such as cognitive behavioral therapy, dialectal behavioral therapy, as well as family

Correspondence, Obituary, Book Reviews

psycho-education. The chapters on treatment are extensive and illustrate professional- and research-based evidence for effective treatments for the suicidal patient.

The final five parts of the textbook describe extensively suicide prevention and what measures are in place among a magnitude of countries across all the continents.

Suicide prevention is vital in addressing the major problem of suicidal behavior, and this is certainly evident in the chapters, as countries depicted with parliamentary and governmental ratified prevention programs are clearly beneficial in counteracting taboos surrounding suicide and legitimating the prevention activities. National suicide preventive programs coincide with decrease of suicide rates in Finland, Norway and Sweden.

This remarkable textbook is unique as it embarks on addressing the many complexities encompassing the framework of the suicidal process.

To date, there has not yet been a book published of this magnitude, which comprises 194 authors who are renowned specialists working in the field of Medicine, Psychiatry, Psychology, Sociology, Anthropology and Suicidology. This textbook is particularly comprehensive with ample concepts and examples from the all continents.

It can be utilized by researchers, public health professionals, clinicians, nurses, and other professionals working within the field of suicidology and suicide prevention. This book will indeed be the future foremost resource for those conducting any type of activity in the area of suicidality.

Alan Apter, Petah Tikva

AA is the author of the part on youth suicide.

This part is not reviewed here.

The Center Cannot Hold Elyn Saks Hyperion: New York, 2007, pp. 351, US $14.95 (paperback)

E

lyn Saks needs to be thanked for having the courage to write this book. All her life, as she went from promising high school student to college valedictorian to Marshal scholarship winner at Oxford to Yale Law school to an academic career at the University of Southern California School of Law, she dared tell only her very closest friends that she believed alien beings were controlling her brain, or that she was responsible for hundreds of thousands of deaths, or that during her occasional extended absences she was being medicated or tied to a bed in a closed psychiatric ward. Her beliefs, her disorganized speech replete with clang associations and incoherence, her occasional

hallucinations, leave little doubt that she was correctly diagnosed as suffering from paranoid schizophrenia. Only the security provided by tenure, professional standing, supportive friends, and a loving husband, finally allowed her to come out of the closet, in the hope of helping others similarly beset with shame and fearful of stigma.

Were Professor Saks’s book a novel, it would strain the professional reader’s credulity. But the fact is that her influential writings on the rights of mental patients and the limits of restraints and other forms of coercion, which have influenced the laws pertaining to these issues in some states, were honed by her experiences of confinement in psychiatric wards in England and the USA. (How, indeed, has England managed to treat psychiatric patients without restraints for the past 200 years?)

The questions she raises about how we treat psychosis may not be new, but they take on a special urgency in this occasionally harrowing memoir. “Were [the inpatient department psychiatrists] wanting to help me get better?

Or did they just want me to be socially appropriate?” (p.

161). She testifies that being tied to a bed was far more horrifying than her worst hallucinations and delusions.

Coming from a woman who by then had completed three years of Kleinian analysis, and who therefore knew something about treatment, these questions demand our attention, and attempts to improve the way we treat patients. “It was unimaginable to me…that the ancient meaning of the word ‘hospital’ is ‘shelter’” (p. 150).

Most psychiatrists today would look askance at the notion of subjecting a person with schizophrenia to psychoanalysis. But many years on the couch - or, occasionally, upright in the chair - were central to her learning to cope with her illness, and, after much bargaining and denial, to her willingness to stay on medication (most recently and beneficially: clozapine). Her summary of this combination: “While medication had kept me alive, it had been psychoanalysis that had helped me find a life worth living” (p. 298). Professor Saks is the first to acknowledge that her success, fragile as it remains, will not be the outcome of most individuals with serious mental illness. But are we, the people entrusted to help such people, listening carefully enough to our patients to find a way not merely to control symptoms but to actually make their life more gratifying and meaningful? And are the departments where we incarcerate these patients suited to the overwhelming therapeutic challenge?

I hope that this book will become widely known among our patients and colleagues.

Pesach Lichtenberg, Jerusalem

159

‫)‪Isr J Psychiatry Relat Sci - Vol. 47 - No 2 (2010‬‬

‫ישיבת ועד האיגוד‬ ‫הפסיכיאטרי ‪ -‬אפריל ‪2010‬‬ ‫‏‪ 28‬באפריל ‪2010‬‬

‫‪ .1‬כנס בנושא "הטיפול בתרופות אנטי־פסיכוטיות" יתקיים‬ ‫במלון דן קיסריה בתאריכים ‪ 3-1‬ביולי‪ .‬הזימון עפ"י רשימת‬ ‫תפוצה‪.‬‬ ‫‪ .2‬כנס "עשור לחוק השיקום של חולי נפש"‪ ,‬יתקיים בתאריכים‬ ‫‪ 11-10‬באוקטובר‪ .‬הכנס מאורגן על ידי שירותי בריאות‬ ‫הנפש במשרד הבריאות‪ ,‬המועצה הלאומית לשיקום והאיגוד‬ ‫הפסיכיאטרי‪.‬‬ ‫‪ .3‬כנס בנושא "אלימות"‪ ,‬בהשתתפות פסיכיאטרים מצרפת‬ ‫וישראל יאורגן במהלך ‪ .2011‬נציג האיגוד בוועדה המארגנת יהיה‬ ‫ד"ר קרון‪ ,‬מנהל בית החולים שלוותה‪.‬‬ ‫‪ .4‬ועדת ההתמחות בהסתדרות הרפואית הכירה ב"מחלקות‬ ‫לטיפול יום בקהילה" כמוכרות להתמחות בחלק האשפוז‪ .‬הבקשה‬ ‫הועברה לאישור נשיאות המועצה המדעית בהר"י‪.‬‬ ‫‪ .5‬סוכם כי אין מקום לפרסם הנחיות להופעת פסיכיאטרים‬ ‫בתקשורת על ידי האיגוד‪.‬‬ ‫‪ .6‬הצעת השינויים בחוק לטיפול בחולי נפש‪ ,‬לגבי מעמד חולי‬ ‫הצו לאחר עבירות קשות‪ ,‬שגובשה בוועדת החקיקה בראשות‬ ‫ד"ר יובל מלמד‪ ,‬תועבר להתייחסות הלשכה המשפטית במשרד‬ ‫הבריאות טרם הפצתה להתייחסות חברי האיגוד‪.‬‬ ‫‪ .7‬הפעלת משרד יחצ"נות לעיצוב תקשורתי ולובינג תידון לאחר‬ ‫הצגת היכולות על ידי היועץ בפני מליאת הוועד‪ ,‬במפגש הקרוב‬ ‫בקיסריה‪.‬‬ ‫‪ .8‬העמדה לגבי הדיון בנושא "קיום יחסי מין אצל מאושפזים‬ ‫ממושכים במוסדות פסיכיאטריים" תגובש לאחר המלצת ועדת‬ ‫האתיקה של האיגוד בראשות ד"ר מיכאל שניידמן‪.‬‬ ‫‪ .9‬נייר העמדה של האיגוד לגבי "כשירות הפסיכיאטרים לטיפולים‬ ‫פסיכותרפיים" תגובש בהמשך להמלצת הוועדה בנושא‪ ,‬בראשות‬ ‫ד"ר שלמה מנדלוביץ‪.‬‬ ‫‪ .10‬עמדת האיגוד לגבי השינויים באבחון ובקלסיפיקציה של‬ ‫"הפרעות אוטיסטיות" תגובש יחד עם נציגי האיגוד הפסיכיאטרי‬

‫לילדים ולנוער‪ .‬נציג האיגוד בוועדה יהיה מנהל מחלקת‬ ‫האוטיסטים מהמרכז באברבנאל‪.‬‬ ‫‪ .11‬אושרה הצעת התוכנית לקידום מעמד המקצוע ומשיכת‬ ‫מתמחים לתחום‪ ,‬לסטודנטים לרפואה בשנה ו' מכלל הפקולטות‬ ‫לרפואה‪.‬‬ ‫‪ .12‬הצעת נייר העמדה לגבי "הקשר בין ניצולי השואה ודמנציה"‬ ‫תופץ בין החברים‪.‬‬ ‫‪ .13‬פגישת הוועד הבאה תהיה בכנס קיסריה ב־‪ 3‬ביולי‪.‬‬ ‫ ‬ ‫פרופ' זאב קפלן‬ ‫ ‬ ‫יו"ר האיגוד‬

‫ד"ר נמרוד גריסרו‬ ‫מזכיר האיגוד‬

‫משולחן מליאת‬ ‫ועד האיגוד‬

‫‪ 3‬ביולי ‪2010‬‬

‫‪ .1‬ועד האיגוד רואה חשיבות לקבלת יעוץ למיתוג פעילות‬ ‫הפסיכיאטריה בישראל בהיבט התקשורתי‪.‬‬ ‫‪ .2‬לצורך קבלת פטור של הועדה לחוו"ד בהליכים נגד המדינה‪,‬‬ ‫ירכז הועד שנית את כל שמות רופאי המדינה בהתפלגות סניפית‪.‬‬ ‫‪ .3‬שילוב קבוצות באלינט והכשרה ברפואה פסיכוסומאטית‬ ‫במיסגרת ההתמחות הועברה לדיון לועדת ההתמחות של האיגוד‪.‬‬ ‫‪ .4‬הערכת המסוכנות לעברייני מין הינה חלק מובנה מכישורי‬ ‫הפסיכיאטר במהלך התמחותו‪ .‬האיגוד מתנגד לתקנות הקובעות‬ ‫את תנאי ההכשרה הנדרשים על מנת לקבל ההסמכה כמעריך‬ ‫מסוכנות שהוצאו ע"י משרד הבריאות ופועל לשינוי התקנות‬ ‫לאחר תיקון הסילבוס של ההתמחות בהתאם‪.‬‬ ‫‪ .5‬נציג המתמחים באיגוד הציג פעילותו בכנס המתמחים‬ ‫בקרואטיה‪.‬‬ ‫‪ .6‬ועד האיגוד יגבש הצעותיו לבקשות לשינויים בהסכמי העבודה‬ ‫החדשים של הרופאים ויעבירם לנציגנו באר"מ‪.‬‬ ‫‪ .7‬תמליל הרצאות הכנס על "השימוש בתרופות אנטי‬ ‫פסיכוטיות"‪ ,‬של האיגוד‪ ,‬יופץ לאחר ההשלמות המתאימות‪.‬‬

‫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 ‪President: Dr. N. Grisaru /‬‬ ‫‪grisarun@gmail.com‬‬ ‫גזבר‪ :‬ד"ר בוריס נמץ ‪Treasurer: Dr. B. Nemets /‬‬ ‫‪nemetz@bgu.ac.il‬‬ ‫יו"ר נבחר‪ :‬פרופ' משה קוטלר ‪Elected President: Prof. M. Kotler /‬‬ ‫‪Moshe.kotler@beerness.health.gov.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 יוצא ואחראי קשרי חו"ל‪ :‬פרופ' אבי בלייך ‪/‬‬

‫‪President Emeritus and Foreign Affairs: Prof. A. Bleich‬‬ ‫‪ableich@lev-hasharon.co.il lean@bgu.ac.il‬‬

‫‪160‬‬

‫שנעשה בתחום תוך יצירת קישורים בין ממצאים התנהגותיים‪,‬‬ ‫מבניים ותפקודיים‪ .‬במאמר מוצגים כיוונים ראשונים המנסים‬ ‫לבחון את השפעת הגנים מאזור החסר על העיבוד החושי‬ ‫בתסמונת ויליאמס‪ ,‬ונדונות השלכות טיפוליות‪.‬‬ ‫הפרעה בהתפתחות המגדרית‪ :‬סקירת‬ ‫ספרות מנקודת מבט התפתחותית‬ ‫ת‪ .‬שכנר‪ ,‬פתח תקווה‬

‫המאמר סוקר את הספרות התיאורטית והאמפירית בנושא‬ ‫התנהגויות מגדריות לא נורמטיביות בקרב ילדים ובני נוער‪.‬‬ ‫הנחת הכותב היא שהתנהגות מגדרית נעה על רצף‪ ,‬והיא‬ ‫איננה משתנה דיכוטומי הניתן לחלוקה להתנהגות מגדרית‬ ‫נורמלית לעומת פתולוגית‪ .‬במאמר ייסקרו שבעה תחומים‬ ‫הרלוונטיים להתנהגות מגדרית בכלל‪ ,‬ולהפרעה בהתפתחות‬ ‫המגדרית בפרט‪ :‬תיאוריות של התפתחות מגדרית נורמטיבית‪,‬‬ ‫פנומנולוגיה‪ ,‬שכיחות‪ ,‬אבחון‪ ,‬המהלך ההתפתחותי מהילדות‬ ‫לבגרות‪ ,‬תחלואה כפולה וטיפולים אפשריים‪.‬‬ ‫גורמי סיכון סביבתיים בתחלואה פסיכיאטרית‬ ‫ק‪ .‬שלוסברג‪ ,‬א‪ .‬מסלר‪ ,‬ג‪ .‬זלצמן‪ ,‬פתח תקווה‬

‫בעבר יוחסה כל התחלואה הפסיכיאטרית לגורמים סביבתיים‪.‬‬ ‫בהמשך מצאו מחקרים גנטיים של אסוציאציה ומחקרי משפחות‬ ‫קשר גנטי בהפרעות הפסיכיאטריות העיקריות‪ ,‬אך הממצאים‬ ‫לא שוחזרו ברובם‪ .‬גישת האינטראקציה של גנים וסביבה נתנה‬

‫‪161‬‬

‫תקווה חדשה לקשר אטיולוגי‪ .‬נמצאה גם השפעה דו–כיוונית‬ ‫של הסביבה על התורשה‪ .‬כמה מטא–אנליזות העמידו לאחרונה‬ ‫גם את הממצאים האלו בסימן שאלה‪.‬‬ ‫סקירה זו מסכמת את הידע הנוכחי בהשפעת הסביבה על‬ ‫פסיכופתולוגיה‪.‬‬ ‫טמפרמנט ובעיות חברתיות בילדות‪:‬‬ ‫קשרים גנטיים וסביבתיים‬ ‫מ‪ .‬בניש־וייסמן‪ ,‬ת‪ .‬שטיינברג‪ ,‬א‪ .‬כנפו‪ ,‬ירושלים‬

‫יחסים עם קבוצת השווים הופכים להיות מרכזיים אצל ילדים‬ ‫עם התפתחותן של יכולות חברתיות וקוגניטיביות במהלך‬ ‫הילדות‪ .‬במחקר הנוכחי חקרנו את תפקיד הטמפרמנט בהופעת‬ ‫בעיות חברתיות אצל ילדים‪ .‬אמהות דירגו את הטמפרמנט של‬ ‫ילדיהן התאומים (‪ 759‬זוגות)‪ ,‬תוך שימוש בסקלת ‪ ,EAS‬וכן‬ ‫את בעיותיהם החברתיות של ילדיהן תוך שימוש ב–‪Strengths‬‬ ‫‪ .and Difficulties Questionnaire‬נמצא קשר חיובי בין בעיות‬ ‫חברתיות ורגש שלילי‪ ,‬וכן קשר שלילי בין בעיות חברתיֹות‬ ‫למידת חברתיּות ולמידת פעלתנות אצל ילדים‪ .‬גנטיקה‬ ‫תורמת להבדלים בין–אישיים בטמפרמנט ובבעיות חברתיות‪,‬‬ ‫כאשר בעיות חברתיות הן תורשתיות במידה ניכרת (‪.)44%‬‬ ‫השונּות הנותרת משויכת לגורמים סביבתיים‪ .‬גורמים גנטיים‬ ‫מתווכים במידה רבה בקשר שבין בעיות חברתיות וטמפרמנט‪.‬‬ ‫הממצאים מצביעים על חשיבות מאפיינים מבוססי טמפרמנט‬ ‫בהתפתחותם החברתית של ילדים‪.‬‬

‫כתב עת ישראלי‬ ‫לפסיכיאטריה‬ ‫תקצירים‬ ‫המקורות ההיסטוריים ונתיבי ההתפתחות‬ ‫של פסיכופתולוגיה התפתחותית‬ ‫ש‪.‬ל‪ .‬טות‪ ,‬ד‪ .‬קיצטי‪ ,‬מינסוטה‪ ,‬ארצות הברית‬

‫המקורות ההיסטוריים של פסיכופתולוגיה התפתחותית נדונים‬ ‫בסקירה זו‪ ,‬לצד המשמעות של נקודת המבט של הפסיכופתולוגיה‬ ‫ההתפתחותית‪ .‬הגדרות היסוד של התחום מתוארות ומשמשות‬ ‫להאיר את הרב–גוניות של התהליך ושל התוצאה‪ .‬העקרונות‬ ‫שנדונים בסקירה הם‪ )1 :‬הקשר ההדדי בין חקר הנורמליות‬ ‫והפסיכופתולוגיה; ‪ )2‬החשיבות של ניתוח ברמות שונות וגישה רב–‬ ‫תחומית; ‪ )3‬התהליכים שתורמים לחוסן הסתגלותי בהתמודדות‬ ‫עם קשיים; ‪ )4‬מחקר יישומי; ‪ )5‬השלכות למניעה ולהתערבות‪.‬‬ ‫דוגמאות מהקשרים מחקריים וקליניים מתוארות בסקירה זו‬ ‫על מנת להדגים את העקרונות‪ .‬הצטברות הידע המתבסס על‬ ‫פסיכופתולוגיה התפתחותית קידמה לא רק את הבנתנו המדעית‬ ‫של הקשר בין התפתחות נורמלית ואבנורמלית‪ ,‬אלא גם תרמה‬ ‫להקטנת העומס הנגרם ממחלות נפש על הפרט והחברה‪.‬‬ ‫תסמונת טורט‪ :‬מודל מההיבט ההתפתחותי‬ ‫ת‪ .‬שטיינברג‪ ,‬ר‪ .‬קינג‪ ,‬א‪ .‬אפטר‪ ,‬פתח תקווה‬

‫תסמונת טורט הינה מודל מייצג של הפרעה פסיכופתולוגית‬ ‫התפתחותית‪ .‬התסמונת מלווה את התהליך ההתפתחותי תוך‬ ‫שהיא משפיעה עליו ומושפעת ממנו‪ .‬בסקירה זו אנו מתארים‬ ‫את מהלך ההשתנות האופיינית של "טיקים" לאורך החיים‪ ,‬וכן‬ ‫התופעות הפסיכיאטריות הנלוות המשתנות עם הזמן‪ ,‬בשלבים‬ ‫התפתחותיים אופייניים‪.‬‬ ‫במאמר נסקרים ההיבטים הפתופיזיולוגיים של התסמונת תוך‬ ‫התייחסות לתהליך ההתפתחותי‪ ,‬להשתנות הממצאים הקליניים‬ ‫וההדמייתיים לאורך מעגל החיים והקשר שלהם לחומרת התופעה‪,‬‬ ‫ולבסוף מועלות מחשבות לגבי כיווני מחקר עתידיים‪.‬‬ ‫התיאוריה הנוירו־התפתחותית של סכיזופרניה‪:‬‬ ‫הוכחות ממחקרים של מקרים עם התחלה מוקדמת‬ ‫ג‪ .‬קינרוס‪ ,‬א‪ .‬רייכנברג‪ ,‬ס‪ .‬פרנגו‪ ,‬לונדון‪ ,‬אנגליה‬

‫בשני העשורים האחרונים תפסה התיאוריה הנוירו–התפתחותית‬ ‫של סכיזופרניה מקום מרכזי במחקר שהתמקד באטיולוגיה‬ ‫של המחלה‪ .‬מאמר זה סוקר היבטים נוירו–התפתחותיים של‬ ‫סכיזופרניה עם התחלה מוקדמת‪ :‬צורה נדירה וחמורה של‬ ‫סכיזופרניה שמתחילה בגיל הילדות או ההתבגרות‪ .‬ממצאים‬

‫‪israel journal of‬‬

‫‪psychiatry‬‬ ‫כרך ‪ ,47‬מס' ‪2010 ,2‬‬

‫התפתחותיים‪ ,‬קוגניטיבים‪ ,‬גנטיים וממצאי הדמיה יפורטו ויידונו‬ ‫בהקשר של התיאוריה הנוירו–התפתחותית‪ .‬המאמר מציג את‬ ‫המגבלות העיקריות של התיאוריה‪ ,‬וכן מציע תפיסות עתידיות‪.‬‬ ‫חינוך חברתי־מיני למתבגרים‬ ‫עם תסמונות נוירוגנטיות‬ ‫מ‪ .‬פלקס‪ ,‬ר‪ .‬ארגמן‪ ,‬מ‪ .‬סטבסקי‪ ,‬ט‪ .‬קויאט‪ ,‬ד‪ .‬פולק‪ ,‬ד‪ .‬גוטהלף‪,‬‬ ‫פתח תקווה‬

‫רקע מדעי‪ :‬מתבגרים עם נכויות התפתחותיות סובלים מהיעדר‬ ‫בולט של ידע וכישורים מיניים וחברתיים‪ .‬ניהלנו התערבות‬ ‫קבוצתית בנושא התפתחות חברתית ומינית למתבגרים עם‬ ‫תסמונות נוירוגנטיות‪ ,‬בעיקר תסמונת ויליאמס ותסמונת חֵך–‬ ‫לב–פנים‪ ,‬ולהוריהם‪.‬‬ ‫שיטה‪ :‬עשרה מתבגרים עם תסמונות נוירוגנטיות וארבעה–‬ ‫עשר מהוריהם השתתפו בתוכנית לחינוך חברתי–מיני‪ .‬התוכנית‬ ‫כללה ‪ 10‬פגישות דו–שבועיות עבור המתבגרים והוריהם בנפרד‪.‬‬ ‫תוצאות‪ :‬החינוך החברתי–מיני התמקד בשתי הקבוצות‬ ‫בזהות עצמית‪ ,‬בהשלמה עם המגבלות ההתפתחותיות‪ ,‬בפיתוח‬ ‫עצמאות‪ ,‬ביצירת קשרים חברתיים ואינטימיים‪ ,‬בידע מיני‬ ‫והתפתחות מינית‪ ,‬וכן בכישורי בטיחות אישית‪ .‬מדדנו שינוים‬ ‫בפעילות העצמאית של המתבגרים ובאופן תפיסתם את‬ ‫המושג "חבר"‪.‬‬ ‫מסקנות‪ :‬תוכניות לחינוך חברתי מיני הן בעלות משמעות‬ ‫גדולה ביותר עבור מתבגרים עם מגבלות נוירוגנטיות‪ .‬יש‬ ‫להתחיל הפעלת תוכניות מסוג זה עוד בטרם תחילת גיל‬ ‫ההתבגרות‪ ,‬ועליהן ללוות את הילדים עד לשנים הראשונות‬ ‫של בגרותם‪.‬‬ ‫עיבוד שמיעתי וראייתי בתסמונת ויליאמס‬ ‫ע‪ .‬זרחי‪ ,‬י‪ .‬אטיאס‪ ,‬ד‪ .‬גוטהלף‪ ,‬פתח תקווה‬

‫ילדים ובוגרים רבים בעלי לקויות התפתחותיות סובלים‬ ‫מליקויים בעיבוד החושי‪ ,‬הבאים לידי ביטוי בקשיים תפיסתיים‬ ‫וברגישות יתר לגירויים שונים‪ .‬לבעלי תסמונת ויליאמס‪,‬‬ ‫תסמונת נוירו–התפתחותית הנובעת מחסר מקטע מיקרוסקופי‬ ‫מכרומוזום ‪ ,7‬קיימת רגישות יתר לקולות הכוללת תחושת חוזק‬ ‫צליל מופרזת‪ ,‬וכן פחד מוקצן מקולות (פונופוביה)‪ .‬באפנה‬ ‫הראייתית‪ ,‬התסמונת מתאפיינת בפגיעה חמורה בעיבודים‬ ‫ויזו–מרחביים לצד זיהוי אובייקטים ועיבוד תווי פנים שמורים‪.‬‬ ‫מחקר הולך וגדל מנסה לאפיין את העיבוד החושי המיוחד‬ ‫הקיים בתסמונת ויליאמס ולגלות את המנגנונים המוחיים‬ ‫והפריפריים שבבסיסו‪ .‬סקירה ביקורתית זו מסכמת את המחקר‬ ‫‪162‬‬