Head Trauma

TSD, a brain region related to memory and

sion, and various other psychiatric disorders.

g. anterior cingulate). These findings are

ary-adrenal (HPA) axis and glial function, leading to

this model, pilot studies have shown normalization of

d by Thomaes et al. 2014). A subsequent elegant twin

ze as a predisposing factor for PTSD, rather than a conse-

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinc studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysreg ic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supp pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thom subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor consequence. More recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to an posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional process 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirm The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combine bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibitio prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic act and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demon posed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger res scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept s demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray matter cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with p structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of d

Head Trauma

structures constitute both vulnerabilities to and outcomes of

mygdala, activation in response to emotional processing (see Phan et

. (2007) therefore undertook a meta-analysis and confirmed these

ated, supporting a PTSD model of reduced top-down control combined with

f PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the

ous workmo suggesting that enhanced resting metabolic activity in the dorsal ry and ed to me

state marker for PTSD. ers. In this study, Shin et al. demonstrated that combat-exposed psychiatric disord

anterior cingulate and a larger response time difference scores on the Multi-Source hese findings are

-concept study on by, Bryant leadingettoal. (2008) demonstrated the possible utility of imaging and glial functi of es predict poorno response toncognitive behavior therapy (CBT) and eye movement desensitizarmalizatio es have shown

By Brie Kramer

Brie Kramer

twin nse to serotonergic drugs, enhanced response to glutamatergic antidepressants, suggesting gantbut nt ele 014). A subseque a conse-to serotonergic drugs (Abdallah et al. 2014). Bremner et al al deficits PT and treatment resistance rather than actor for SD, s ofnot all, have replicated this finding in PTSD, depression, and tcomebut and fearlne extinction. studies, to and ou rabilitiesSeveral both vu e Phan et ssing (seto procerelated olume in PTSD, a ot brain memory and fear extinction. Several studies, but not all, have ionalregion n response to em ese th ed rm D have also been in other brain regions (e.g. anterior cingulate). These findings are alysis and confi andemonstrated dertook a metad with rol combine down contglutamate glial function, leading top-increased excitotoxicity, and subsequent gray matter reduction. uced to red of l de mo SD n by the inhibitio limbic eatment (Levy-Gigi et al., 2013; reviewed

by Thomaes et al. 2014). A subsequent elegant twin study by se in increa (2012) found an l ity in the dorsa c activwork tabolirecent ather than a consequence. has presented a more complex picture wherein altered brain resting meMore g that enhanced posed that combat-ex nstratedactivation refrontal cortex, increased amygdala, in response to emotional processing (see Phan et al., 2002), et al. demo Shin ,but SD. In this study -Source res on the Multi difference scoThe lysis and confirmed specificity of the prefrontal impairment to PTSD was also demone timeabnormalities. nsthese po res r ge lar a and imaging ssible utility of trated the po zation. In contrast, inmo thensdissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by de ) 08 (20 al. zaBryant et ment desensiti T) and eye move erapy (CB vior thactivity at enhanced resting metabolic in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a ha be ve iti gn sponse to co s, suggesting c antidepressant rgi ate tam glu ponse to co-twins had significantly greater activation in the dorsal anterior cingulate and a ns with PTSD and their unexposed ed res hanc et al c drugs, but en

An original letter by Kurt Vonnegut with research from the National Center for PTSD

Head Trauma

Edited and designed by Kramer Press.

This book was produced for Katherine Hughes’s Type III class at the Massachusetts College of Art and Design, Spring 2017.

No portion of this publication may be reproduced by any means (electronic, mechanical, recording, photocopying or otherwise) without the explicit written permission of the author.

Head Trauma AN ORIGINAL LETTER BY KURT VONNEGUT WITH RESEARCH FROM THE NATIONAL CENTER FOR PTSD

Bre (1995) provided the first evidence of decreased

pal volume in PTSD, a brain region related to memory and fear extinct

studies, but not all, have replicated this finding in PTSD, depression, and va

psychiatric disorders. Gray matter reductions in PTSD have also been dem

other brain regions (e.g. anterior cingulate). These findings are consistent with cal model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA)

function, leading to increased glutamate excitotoxicity, and subsequent gray mat

Supporting this model, pilot studies have shown normalization of hippocampal

function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014

elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hip

as a predisposing factor for PTSD, rather than a consequence. More recent work has pr

complex picture wherein altered brain structures constitute both vulnerabilities to a

posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygd

response to emotional processing (see Phan et al., 2002), has been repeatedly—but not consistentl

in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities

the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced

combined with increased bottom-up emotional sensitization. In contrast, in the dissociative subtype of

(2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vie

to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and m

(dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demon

Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cin

difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co

by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment response. Oth

abnormalities predict poor response to cognitive behavior therapy (CBT) and eye movement desensitization and

emner et al Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. S

hippocamstudies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD have a

tion. Several demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates

FROM: arious other ic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supporting PFO. K. VONNEGUT, JR.,

monstrated in U.S. ARMY. pilot studies have 12102964 shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes e

h a hypothetisubsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PT

axis and glial a consequence. More recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and ou

tter reduction. posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (se

l structure and 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed th

4). A subsequent ties. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined

ppocampus size bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by th

resented a more TO: prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity i

KURT VONNEGUT, and outcomes of anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. dem WILLIAMS CREEK,

dala, activation in INDIANAPOLIS, INDIANA. combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a large

ly—demonstrated difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-conce

s. The specificity of et al. (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray m

d top-down control predict poor response to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brai

f PTSD, Lanius et al. have been related to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a

etnam Twin Registry patients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et a

medial cingulate cortices (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies

nstrated that combat-exposed replicated this finding in PTSD, depression, and various other psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased h

ngulate and a larger response time brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other

o-twins. Finally, a proof-of-concept study reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical

her PTSD studies have shown that gray matter 5 hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction

d reprocessing (EMDR) therapy. In depression, brain shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subseq

emner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Sev

ot all, have replicated finding this in PTSD, depression, and variousand other psychiatric matterGray reductions PTSD have udies, but not all, havethis replicated finding in PTSD, depression, various other disorders. psychiatricGray disorders. matter in reductions in also PTSDbeen havedem als

d in other brain regions (e.g.regions anterior(e.g. cingulate). findings arefindings consistent a hypothetical model in which stress dysregulates hypothalami emonstrated in other brain anteriorThese cingulate).

These arewith consistent with a hypothetical model in which stress dysregulates h

utamate excitotoxicity, gray matter reduction.

Supporting this model, pilot studies have shown normalization of hippocampal stru -pituitary-adrenal (HPA) and axissubsequent and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction.

Supporting th

nctionhave following (Levy-Gigi et al., 2013;structure reviewedand

by Thomaes al. 2014).

A subsequent elegant twin study

by Gilbertson et al. (2002) has udies showntreatment normalization of hippocampal function et following treatment (Levy-Gigi et al., 2013; reviewed

by Thomaes et al. 201

mall hippocampus size as a predisposing factor PTSD, rather a consequence.

More recent work has presented a more picture egant twin study by Gilbertson et al. (2002) has for provided strongthan evidence for small hippocampus size as a predisposing factorcomplex for PTSD, ratherwher than

utcomes of work posttraumatic stressa (Sekiguchi et al.picture 2013). Reduced prefrontal cortex, but increased amygdala, activation into response to emotional pro ore recent has presented more complex wherein altered brain structures constitute both vulnerabilities and outcomes of posttra

see Phan et al., 2002), Reduced has beenprefrontal repeatedly—but in PTSD. Etkin ettoal.emotional (2007) therefore undertook a meta-analysis an ekiguchi al. 2013). cortex,not butconsistently—demonstrated increased amygdala, activation in response processing (see Phan et al., 2002), has

bnormalities.

The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control o ot consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities.

The specificity

ombined increased bottom-up emotional sensitization.

In contrast, the dissociative ofcontrol PTSD, Lanius et al.with (2012) found an increase ie efrontal with impairment to PTSD was also demonstrated, supporting a PTSDin model of reduced subtype top-down combined increased bottom-up

mbic inhibition the midlinesubtype prefrontal cortex.

Shin et al. (2012) (2011) found used the Registry to confirm previous suggesting that enhanc contrast, in theby dissociative of PTSD, Lanius an Vietnam increase Twin in limbic inhibition by the midlinework prefrontal cortex.

Shin et al.

ctivity in the dorsal anterior medial corticeswork (dACC/MCC) constitutes a familial risk factor, rather than state marker PTSD. In this 2011) used the Vietnam Twinand Registry to cingulate confirm previous suggesting that enhanced resting metabolic activity in the dorsalfor anterior and mestu

y,alShin et al. demonstrated that combat-exposed Veterans PTSD andthan theirstate unexposed significantly greater activation in the dorsa cingulate cortices (dACC/MCC) constitutes a familial riskwith factor, rather markerco-twins for PTSD.had In this study, Shin et al. demonstrated that com

e first eviden ce of nterior cingulate and a their larger response time difference scores on the Multi-Source Interference Task, as compared to and combat Veterans without decr eterans with PTSD and co-twins had significantly greater activation in the dorsal anterior cingulate a larger response timePTSD diff ea sedunexposed hippocampa l volume in PTSD, a brai ed this findi n region relate in PTSD yeBryant et al.ng (2008) demonstrated the possibleto utility of imaging in d predicting treatment response.

Other PTSD studies have shownet tha to mtheir Multi-Source Interference Task, compared combat Veteransbiomarkers without PTSD and a proof-of-concept study

by Bryant , depres emorco-twins. y and fearFinally, sionas , and various extinction. other psychi Several atric disord ons (e.g. an ers.(EMDR) terior(CBT) Gray mat cingul ehavior and eye and reprocessing therapy.

Inctdepression, brain studies structural deficits have ter reresponse. . (2008) therapy demonstrated the possible utilitydesensitization of imaging biomarkers in predicting treatment Other PTSD have shown thatbeen grayrelated matte ate) du . Thmovement ese fin ions in dings are co PTSD have al nsistent with so been d glial func a hy pothetical m tio n, le odel in (EMDR) adin oor response to serotonergic drugs, buteye enhanced response to glutamatergic antidepressants, suggesting presencebrain of a subpopulation of patie cognitive behavior therapy (CBT) movement desensitization and reprocessing therapy.

In the depression, structural deficits hav g to incr which st easeand ress dysr d glutamate egulates hy excitotoxici pothalamty, and subs zation of hi eqtreatment uent gray m ppoc ossible glutamate-based abnormalities leadingdrugs, to structural deficitsresponse and resistance serotonergic drugs (Abdallah al. 2014).ofBremner palresponse been related to am poor but enhanced to glutamatergic antidepressants, suggesting theet presence a subpo atter reduto stru cturetoanserotonergic ction. Supp d function fo orting this llowing trea model, tment (LevyGilbertson et gi et al., 2013 al. abnormalities (2002) vidence of decreased hippocampal volume in PTSD, adeficits brain region relatedGito memory and fear extinction.

Several studies, but not all, have replicate utamate-based to structural and treatment resistance to; serotonergic drugs (Abdallah et al.

2014).

Bremner et al (1 has provleading re view ided stro ed by Th omaes et al ng evidence . 2014). A for small hi as presente pp ocampus si dthe a mfirst ze as sorders.

Bremner eteal (1995) the first evidence of decreased hippocampal in PTSD, a brain and region related to memory and fear bu or avolume 95) provided evidence of decreased hippocampal volume in PTSD, a brain region related to memory fear extinction.

Several studies, co pred mplexprovided ispo pi sing cture where factor for PT in altered br SD, rather th ain structur an l. 2013). Redu es constitut ce d pr e Bremner xtinction.

Several studies, but depression, not all, have replicated this finding in PTSD, depression, other psychiatric Grayofmatter reduction efin thand plicated this finding PTSD, et al (1995) provided the disorders. first evidence decreased hipp ront vulnvarious al erab cortex, but and various other psychiatric disorders. bo ilities to an increased am d outcomes ygdala, activ of consistently ation in resp — on emonstrated inde other brain regions (e.g. anterior findings are consistent withreplicated a hypothetical model in which stress dysregulates se monst toall, PTSD, a brain region related to memory and fearcingulate). extinction.These Several studies, but not emhave rated ot ional proces this finding in PTSD, depression, and var in PTSD. Etkin sing (see Ph et al. (2007) an et al., therefore un impairment dertook a m to PTSD disorders. ypothalamic-pituitary-adrenal (HPA) axis and glial function, leading increased glutamate and subsequent gray matter reduction. et a-analysisexcitotoxicity, us other psychiatric Gray matter reductions in PTSD have to also been demonstrated in other brain regions (e.g. anterior cingulate).

These was also de and confirm monstrated, ed these ab supporting normalia PTSD mod n contrast, in el of reducestructure and function following treatment (Levy-Gigi et al., 2013; re thmodel, e dissoc upporting pilot have shown ofdysregulates hippocampal d top-down ndings are this consistent with modelnormalization in which stress hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading tivastudies ehypothetical control com su btype ofthe ¹Bremner et al ia (1995) provided first of decreased hippocampal volume bined with PTSD 6 , Laevidence nius et al. (2 increased 012) found ed the Viet an increase size inreduction.

PTSD, region related to memory and fearhave extinction. na m Twain udy

by Gilbertson etbrain al.

(2002) provided strong evidence forshown small hippocampus as a predisposing factor for PTSD, rather than a consequen ay matter Supporting this model, pilot studies normalization oflim hippocampal Re in gi stry tohas bic inhibitiostructure and function following treatment ( confirm prev n by the mid ious work su line ggesting th (dACC/MCC) at enhan c

veral studies, but

monstrat so been

ic-pituitary-adrenal (HPA) axis and glial function, leading to increased hypothalam-

ucture and pilot his model,

s provided strong evidence for 14).

A subsequent

rein altered brain structures constitute both vulnerabilities to and n a consequence.

ocessingstress aumatic

nd confirmed these s been repeatedly—but

of the

in emotional sensitization.

ced . resting metabolic

u

al mbat-exposed

DEAR PEOPLE:

D and their co-twins.

Finally, a proof-of-concept study ference scores on

at gray matter abnormalities predict poor response to cognitive

d to er abnormalities predict poor response

ents with

ropulation et al (1995) providedwith the first of patients possible

ed this finding in PTSD, depression, and various other psychiatric

ut not all, have

ns in PTSDvolume have also been pocampal

by Thomaes et al.

2014). A subsequent elegant twin geviewed to increased glutamate excitotoxicity, and subsequent

nce. More recent

7

g (EM and reprocessin volume in PTSD

epressa c antid glutamatergiother psychiatr

ent resis atm deficits and tre fear extinction

brain reg SD, ahave volume in PT PTSD also

iatric disorders other psychdysregulates h

stu on. Severalthis fear extinctiSupporting

dem also beenet PTSD have Thomaes al.

thalam es hypo dysregulatfactor for PTSD Supporting this

model, pi

14). A s

Thomaes et al. 20 factor for PTSD,

rather th

I’m told that you were probably never informed that I was anything other than “missing in action.”

“missing “missing “missing in in actio acti 8

glut possible nts with D, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various opulation of patie d hippocampal sence of a subp pre the g tin es idence of decrease ants, sugg vided the first ev pro ) 95 (19 al et er ric disorders. Bremner et al (1995) provided the firstBre evidence of decreased hippocampal volume in PTSD, a brain region relatedrio to memory and mn , and va us llah et al. 2014).

PTSD, depression ergic drugs (Abda d this finding in stance to seroton ate lic rep ve ha , t all but nodepression, s, PTSD, n. Several studies, but not all, have replicated this finding and various other psychiatric disorders. Gray matter reductions in studiein tinction. Several memory and mory and fear ex region related to in bra a , SD PT in gion related to me volume campal ased hippoThese o been demonstrated in other brain regionside (e.g. findings are consistent with a hypothetical model inns which stress of decrecingulate). nceanterior tter reductio in ed the first ev vid pro ) 95 (19 al disorders. Gray ma ric iat ych ps s. Bremner et er rious othglutamate excitotoxicity, and subsequent gray matter reduction. d va on, anto hypothalamic-pituitary-adrenal (HPA) axis and function, leading increased , depressi in PTSD g glial ess licated this findin del in which str rep ve ha , all t no a hypothetical mo udies, but consistent with are gs din fin e es s model, pilot studies have shown normalization of lat hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by e). Th gu tter reduction. (e.g. anterior cin bsequent gray ma er brain regions otoxicity, and su cit monstrated in oth ex ate tam d glu increase . 2014). A subsequent elegant twin study by cti Gilbertson etg al. has provided strong evidence for small hippocampus size as aed predisposing to (2002) , leadin by 2013; review and glial fun on (Levy-Gigi et al., renal (HPA) axis t ad en ryatm ita tre itu c-p ing mi low fol on cti fun d an complex picture wherein altered brain structures constitute both vulnerabilD, rather than a consequence. More recent work has presented a emore al structur sing tion of hippocamp size as a predispo shown normaliza all hippocampus ilot studies have evidence for sm g on str ed vid (2002) has pro th vulnerabilGilbertson et al. es constitute bo nt twin study by d brain structur ere alt subsequent elega in ere wh ture more complex pic has presented a More recent work e. nc ue eq ns co han a

g on� ion�

Chances are that you also failed to receive any of the letters I wrote from Germany.

That leaves me a lot of explaining to do.

9

region related (1995) provid

ed

in precis: I’ve been a prisoner of war since December 19th, 1944, when our division was cut to

cingulate). Th

ese

excitoto

predispo

ly—but not co

ribbons by Hitler’s last desperate thrust through Luxemburg and Belgium.

nsiste

ed, suppo

our divisi our divisi our divisi cut to ribbons cut to ribbons cut to ribbons Seven Fanatical Panzer Divisions hit us and cut us off from the rest of Hodges’ First Army. The other American Divisions on our flanks managed to pull out.

10

allah et al. 20 utamate-base 14). Bremner d abnormaliti d to memory et al (1995) pr es lea and fear extin ovided the fir ction. Sevethis st ev studies, but not all, have replicated finding in PTSD, depression, and various other psychiatric disorders.

Gray matter reductions in PTSD have a ral stu id ence of decre dies, but not as all, have replica ed hippocam d the first evid pal volume ted this finding ence of decre in SD, depr asregions ed hippoc ession, andmodel demonstrated in other brain (e.g.

These findings are consistentPT with a hypothetical in which stress dysregulates amanterior pal volucingulate). va rious other ps me in PTSD, a ychiatric diso brain region re finding in PTSD rders lated to mem , depr sion, oryand an and d fe ic-pituitary-adrenal (HPA)es axis and glial function, leading to increased glutamate excitotoxicity, subsequent gray matter reduction. Supporting ar vario ex tinction. Se us other psyc ve ral studies, bu hiatric disord e findings are ers. Gray matte t not all, ha consistent wi r reductions in th a hypothetof hippocampal structure and function following PTSD pilot studies have shown normalization treatment (Levy-Gigi et al., 2013; reviewed by Thomaes e have also ical model in been demonstr which stress ated in other oxicity, and su dysregulates brain bsequent gray hypothalamicmatby pihippocampus tuitary-adren size as a predisposing factor for PT terGilbertson subsequent elegant twin study (2002) has provided strong evidence for small reduction.et al (HPA) axis an Sual. pporting this d glial functio model, pilot stu (Levy-Gigi et n, lead dies have show al., 2013; revie n structures normalizatio wedhas

by Th a consequence. More recent work presented more complex picture wherein altered brain constitute both vulnerabilities to and ou omaes etaal n of hi ppocampal str . 2014). A subs ucture and fu equent elegan osing factor fo ncti t twin study by r PTSD, rather thanet Giactivation lbertson et a al. cons posttraumatic stress (Sekiguchi 2013). cortex, but increased amygdala, inal response to emotional processing (se equeReduced . nce. Moreprefrontal (20 02 ) ha s provided str recent work ha ong evidenc of posttraum s presented a atic stress (Se more complex kiguc pictundertook hi et 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore a meta-analysis and confirmed the ure wherein al. 2013). Redu altered brain ced prefrontal structures co ently—demon cortex, but in nstitu strated in PTSD creased amyg . Etkin etimpairment la, ac ties. The specificity of the prefrontal PTSD was also demonstrated, supporting a da PTSD model ofnreduced top-down control combined tivatio al. (2007) thto in respon erefore underto se to emotiona ok a meta-an orting a PTSD l processing alysis and confi model of redu ced top-do thesfound bottom-up emotional sensitization.

Inwn contrast, dissociative subtype of PTSD, Lanius et rm al. ed (2012) increase inhibition by th e abnoan controlincothe rm alities. Thine limbic mbined with sp ecificity of th increased botto e prefr m-up emotio nal sensitiza prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced metabolic activity in tion.

In contraresting st, in the diss ociative subt anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. dem

ion was ion was ion was ss

combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a large

difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-conce

et al. (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray m

predict poor response to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brai

have been related to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a

patients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al

(1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies

replicated this finding in PTSD, depression, and various other psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hi brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical

hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction

shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subseq

has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has prese

structures constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased 11 Gray matter reductions in PTSD have ... been demonstrated in other brain regions.

stay an stay stay an We were obliged to stay and fight.

12

nd fight y and fi nd fight Bayonets aren’t much good against tanks.

13

so we we ga we ga we ga we gav

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. S

also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dy

reduction. Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi e

Bremner et al (1995) pus size as a predisposing factor for PTSD, rather than a consequence. More recent work has presented a more complex picture wherein alteredprov bra

also been demonstrated amygdala, activation in response to emotional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTS 14 reduction.

Supporting demonstrated, supporting a PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, th in

as a cingulate predisposin Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anteriorpus andsize medial co

Our ammunition, food and medical supplies gave out and our casualties out-numbered those who could still fight

gave up ave up ave up ave up ve up

Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD

ysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matte

et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hip

vided the first constitute evidence ofboth decreased hippocampal in PTSD, a brain region related to memory and fearReduced extinction.

Several studies, butincrea not a ain structures vulnerabilities to andvolume outcomes of posttraumatic stress (Sekiguchi et al.

2013). prefrontal cortex, but

d inEtkin otheret brain regions (e.g. anterior cingulate).

These findings are consistent a hypothetical in which stress dysregulates hypothalamic SD. al. (2007) therefore undertook a meta-analysis and confirmed thesewith abnormalities.

Themodel specificity of the prefrontal impairment to PTSD 15 his model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed

by T n the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used

ng factor for PTSD, rather than aaconsequence.

More recent work state has presented more In complex picture altered brainthat structures constitute ortices (dACC/MCC) constitutes familial risk factor, rather than marker fora PTSD. this study, Shinwherein et al. demonstrated combat-exposed

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Se

also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dys

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTS

The 106th got a Presidential Citation and some British Decoration from Montgomery for it, I’m told

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Se

also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dys

16

everal studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD

sregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter

SD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various o

everal studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD

sregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter

In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex.

17

but I’ll be damned

18

if it was worth it.

19

ave also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress

atter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-G

mall hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has presented a more complex picture wher

ortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been repeatedly—but not consistently—d

mpairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined with increased bottom-up emotional

ortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal a

emonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cing

o-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment res

ovement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related to poor response to serotoner

utamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (19

ut not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Bremner et al (1995) provided the first evidence

nding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD have also been demonstrated in other brain regi

HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot stud

subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTS

The Germans herded us through scalding de-

lities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to

lousing showers. Many men died from shock

ook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a P

in the showers after ten days of starva-

TSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to

tion, thirst and exposure.

ten days of

onstitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD a

he Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et a

atter abnormalities predict poor response to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy

ntidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based abnormalities leading to structural deficits

olume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, an

elated to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric diso

ith a hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate

nd function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002

resented a more complex picture wherein altered brain structures constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguc

epeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities.

ith increased bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic in

esting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker f

ctivation in the dorsal anterior cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to comba

omarkers in predicting treatment response. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive beh

20 o poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of pa

014). Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extincti

s dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray

Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for

rein altered brain structures constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal

demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal

anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al.

gulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their

sponse. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behavior therapy (CBT) and eye

rgic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with possible

995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this

ions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal

dies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014)

SD, rather than a consequence. More recent work has presented a more complex picture wherein altered brain structures constitute both vulnera-

o emotional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore unde

PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the dissociative subtype of confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC)

f starvation

and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger response time difference scores on

al. (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray

y. In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced response to glutamatergic

s and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of decreased hippocampal

nd various other psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region

orders. Gray matter reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent

e excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structure

2) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has

chi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been

. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined

nhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced

for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater

at Veterans and theirith co-twins.

Finally, a proof-of-concept study by Bryant et al. (2008) Thesewithout findings PTSD are consistent a hypothetical model in hich stress dysregulates hypothalamic pituitarydemonstrated adrenal ( P ) the possible utility of imaging axis and glial function, leading to increased glutamate excitotoxicity, and subse uent gray matter reduction. havior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related ther PTSD studies have sho n that gray matter abnormalities predict poor response to cognitive 21 atients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. behavior therapy ( BT) and eye movement desensiti ation and reprocessing ( D ) therapy. ion. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. (dACC/MCC) constitutes a

h c dgruant tw CC/M gluim ductio, L d co fami e both vu et al taemdate nasnin gs, b in study er PTSD nfirm C iusPTeS lial r lnerabil(1995 TSD. Etk iffee ut en

by Gilbestud rexnccitotoxicity, C) const tD ities)to is ed in et al. al. (2 p ro iee e sco rt itute av hacingulate). and a (2007) th k fain niddeou(e.g. son ave also been demonstrated brain regions anterior These findings are consistent with hypothetical model in which stress ctoother s 0 n s 1 h u t tc c b 2 r a a s r sequean fa e d thomes of l.ve(2s002 ) fou erefore , rath t gm ontrast, e firs ) has pro es on th how posttrad respon nd a eo undert ra ro y i thkaan l i in the d e n u al ris t evi vid ni matic sse tof hippocampal Mult tha steata tronfunction atter reduction.is Supporting this model, pilot m studies have shown normalization structure following treatment (Levy-G den treo k fac t gra ed sand sociativ i-e ssg(S ge te-a So luetk ce o vid e subty mnaarly tor, r y nu aig rcfo ce mu al cingu f dec e Irnt kesrisf and confirm pe of PT atcehriget al. 20 matter athe late cort r o e e S ed theasse 13). Rpresented rt D, Laniu r PTS rfere picture wher ic awork bnor a more complex icessize mall hippocampus a predisposing factor for PTSD, rather than More recent edua e adbhnio ntid has se ce nce (dAas D a consequence. mfr t al. (2 d pre CC/MCC aloitnie prm ep poc Task aalities.

012) fou. In this respons ) consti taslp , as c mpa The specressants nd an instud tutes a e time d r e d o creay(see ictconsistently—d city orepeatedly—but volu hasifibeen familial to emotional processing sugg ortex, but increased amygdala, Phan et al., l2002), not iffere s,eSh poor f , th inin nce sco activation in response m liemt bic in risk fac e pre esfr tio res on th resp studies tor, rath nn al. d hibitio e in PTS gta thle p onse e Multier than have sh n e D b m y , th onstcombined a bincreased Source rese emotional e mwith mpairment to PTSD demonstrated, supporting a PTSD model of reduced bottom-up ownwas statetop-down idli thatalso marker control nerapire Inte nce n rfreog gray ma rference for PTSD rated th of a ced res n tter abn iota Task, as nlrel . In this at co subp ponse to o rm c o m a a s m ortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity the dorsal li oa tu ted in glutam ties pre pared to b d y, a S t h t in atergic dict poo o me etxa c e o m p l. b o a antidep evidenc t Vetera r respon s m e o d r re e n with activation in the Vedorsal se to cco-twins of d ssanwith an teran anterior ycing ecrecombat-exposed emonstrated that Veterans their unexposed ts, suPTSD ognitive had significantlysgreater out PTS ased hip ggesand s wit D and th ting the behavio pocamp mpal vo h PT eir presenc r therap al volum lu S m e y e in aPT (CBT) biomarkers of a sthe o-twins. Finally, proof-of-concept study by eBryant (2008) demonstrated utility of imaging in predicting treatmentDres an in PTSet ubppossible and eye SD, a bra D, al. opulati a brain in regio on of pa ulate). T region re n relate ti h e e n la s ts e te d finding with prelated to memtherapy. In depression, dbrain ovement desensitization reprocessing (EMDR) to mstructural ossibleto poor response to serotoner emory a deficits have been s are cand ory and onsiste nd fear fear exti lization nt with extincti nction. resistance to serotonergic of hipp abnormalities leading a o h n utamate-based to structural deficits and treatment drugs (Abdallah et al. 2014). Bremner et al (19 y Several potheti . Severa ocampa cal mod l studie studies l structu , but no quence s, el in wh re and fu . t M ic all, hav et al (1995) provided the first evidence re recreplicated ction depression, stresspsychiatric ut not all,ohave and varioushother e replic ent work this finding innPTSD, followin dysregu disorders. Bremner a te g treatm has pre lates hy d this see Pha sente pothala ent (Lev nPTSD, et al.,depression, a mopsychiatric mic y-Gigi ereductions in PTSD nding in and variousdother disorders. Gray matter have also in other brain regi -pitbeen re comp 2002), h uitarydemonstrated t al., 20 lex pictu as been -a d 1 renal 3; revie op-dow re where repeate wed by n d c in ly o T ntr —but nglutamate excitotoxicity,alt homaes Supporting this model, pilot stud HPA) axis and glial and subsequent ol cofunction, ered ot cons mbined leading to increased brain str gray matter reduction. et al. 20 istently with inc uctures 14). ggestin —demo reased chippocampus o g thatelegant n s ti n s tu b subsequent twin study by Gilbertson et al.

(2002) has provided strong evidence for small tr ottom-u te bothsize as a predisposing factor for PTS enhanc a te d in ed resti p emoti vulnera PTSD. E n tkin et onal se g metab ins had nsitizati l. (2increased olistress ignifi 007) the amygdala, activation in response to c activit lities to sand outcomes (Sekiguchi prefrontal cortex,abut on. In cantly g of posttraumatic y in the et al. 2013). Reduced refore u contras reater a d n o d t, rs e in c ra tiv on possible l anteri the diss orof inabnormalities. o PTSD utility o and confirmedati anthe the dors ook a meta-analysis these The specificity also demonstrated, supporting a P d mprefrontal tive was edial cin impairment tocia f imagin s u a b l ty a n p terior c e of g bioma gulate c tural de ingulate ortices rkers in ficitsetha and a la (dAC(2011) pin TSD, Lanius al. found an increase prefrontal the Vietnam Twin Registry to relimbic dictinginhibition by the midline C/MCCused ve(2012) rger res cortex. Shin et al. been re ) tr e a p la tment re onse tim ted to p o seroto sIn oorthan e p o d nerg n if re s fe e s onstitutes a ic familial risk factor, rather state marker for PTSD. this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD a . re ponse to Other P nce sco drugs (A TSD stu res on seroton bdallah dies ha ergic dru disorde e t a l. v e 014). Bre to combat Veterans without shoFinally, gs, but PTSD and their co-twins. rs. Brem Interference Task, as2compared wn thaa he Multi-Source study by Bryant et a enhanc ner et a mner et t gproof-of-concept ray ed resp l (1995) al (1995 onse to s in PTS provide ) p ro v g id d theto lutama D have ed th atter abnormalities poor response cognitive (CBT) eye movement desensitization firs e firsand tergic and reprocessing (EMDR) therapy also bpredict t eviden behavior therapy t eviden een dem ce of de ce of de onstrate nt gray creased c re a m d s atter resuggesting the presenceinofoathsubpopulation ed habnormalities ntidepressants, of patientshwith leading to structural deficits ippocpossible ippocam er brain duction ampal v glutamate-based pal regions . Suppo olume in e for sm rting th (e.g. an P T S D te is , a olume inall PTSD, a brain region related to memory and fear extinction.

Several studies, but not all, have replicated this finding in PTSD, depression, an ri model, hippoca brain re or cingu pilot stu mpus s gion late). Th ize as a dies ha e s ntal cort e fi n v p d redSeveral ings adepression, show isposin studies, but not all, ehave elated toex memory replicated and various other psychiatric diso , but incand fear extinction. re cons n norm this finding in PTSD, g factor reased istent alizatio for PTSD amygda n of hip l impair , ra la p th o , a c er than ctivadysregulates ampglial ment to ith a hypothetical model in which stress hypothalamic-pituitary-adrenal (HPA) axis and al strfunction, tion in a conse PTS ucture leading to increased glutamate respons D was a quence e to em lso dem . More re al corte o ti o n o c s n x ent w trateet . Shfollowing al proceet al. 2014). A subsequent nd function reviewed by Thomaes elegant in et al. treatment (Levy-Gigi d, al., ork hastwin study by Gilbertson et al. (2002 sup2013; ssing (s porting (2011) u ee Phan a PTSD sed the demons et al.to mconstitute Vietnaaltered o d , traate 2 e resented more complex picture wherein brain structures both vulnerabilities and 002),outcomes l of red m Twin d that c has bee of posttraumatic stress (Sekiguc uced to Registry ombatn p-down expose to c r co-twin o c n o firm pre therefore undertook a ntr d Vetera ol comb epeatedly—but consistently—demonstrated meta-analysis and confirmed these abnormalities. s. Finanot vious w ns witinh PTSD. Etkin et al. (2007) in lly, a pro e d ork sug PTSD an of-of-co gesting d their ment d ncepsensitization. thaLanius u dissociative t study esensit bottom-up emotional t enhanet al. (2012) found an increase in limbic in ith increased subtype of PTSD, xposed

by BryaIn contrast, in thene ization ced c o -t n w and rep t in e s t h a l. a d (2 rocessin sed abn s 0 ig 0 8 n ) ifi d c e antl ormaliti activity in the dorsalganterior m esting metabolic and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker f (E o M n y s D g tr R re ated th ) therap es lead ater e possib ing to s y. In de pressio tructura le utility e replic n ate l ctivation indthe dorsal anterior cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to comba , of imag brain str deficits this find ing and tre uctural ing in P atment deficits TSD, de eater ac re ave bee istancshown pressio Other PTSD studiesshave omarkers predicting gray matterhabnormalities predict poor response to cognitive beh tivain e to sethat n relate tio n, and v n in the treatment response. rotonerg d arious o dorsal a ic drugs ther psy 22 nterior (A chiatric bsuggesting dallah e o poor response to serotonergic drugs,cin but the presence of a subpopulation of pa guenhanced late and response to glutamatergic disordantidepressants, t a l. e rs. (dAC a larger C/MCC) respons co 014). Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, anbrain region related to memory and fear extincti e time d stitute sa ifferenc e score

But I

e. Ot and 014) 2) ha oton nse ic st PTSD al (1 . Bre subs her P ress t ergic s pro 995) have mne eque (Sek TSD vide drug prov also r et excitotoxicity, iguc naxis stu d str ided s,and t graand glial function, sthdysregulates hypothalamic-pituitary-adrenal (HPA) leading to increased glutamate subsequent gray ese b a b d h e l u i o e i en d (199 t enh abno y ma the fi ng e sh et al emo 5) pr vide tter rmal ance . 201 rst e nstra ovid nce redu twin study ireviewed 3). R et al. 2014). vid d resfor ties. increet al., 2013; edstrong ence has provided Gigi A subsequent elegant

by Gilbertson et al.

(2002) evidence for s ted i ction educ p The by Thomaes t ase o h n m e firs n ot of de se . Sup ed p spec all h in lim her b t vi refro crea port ippo ificit bic i rain denc sed Reduced eprefrontal ing t ntal cam y of both vulnerabilities thanaltered brain nhib rein structures constitute hipp regio et al. 2013). e of his mstress (Sekiguchi pus of posttraumatic corteto and outcomes the p state ition ocam de size ns (e x, bu refro odel mark by h as a pa v .g n , pilo t inc n l e(2007) r for Etkin et tal. pred omp olum midl thereforetaundertook reas terio impa demonstrated inePTSD. a meta-analysis The. aspecificity of thelprefrontal t stu ared ispothese abnormalities.

PTSD ed a and confirmed ine p r e d i r c i i m e i n sing ngul s ha to co myg . In t ent t P refro ve sh ate). facto dala h s mba o PT ntal of PTSD, Lanius , acan Thes oby In contrast, in theisdissociative subtype al. (2012) found in rlimbic midline prefrontal tsensitization. tudy Set t Vet o co wnthe corte for P inhibition Dw tivaincrease e , Shi n eran gnit a T o x fi s t S r i . n a o m D, ra Shin n et d ive b lso d n in s wit aliza ther al. dconstitutes resmarker ehav cingulate em hout t al. tioet pons for PTSD. and medial cortices ae familial risk factor, rather Inththis onst than state emo oanterior n oal. pula ior t (201 PTS(dACC/MCC) an astudy, Shin f hip rated e to nstra hera D an tion 1 c ) p o u e o nseq , sup ted t sed py (C m t d th of pa the Task, iona port to combatoVeterans uencand their eir con the Multi-Source hat c Interference BT)difference tientresponse time ngulate scores Vietn as compared d fea and a larger ing a l prowithout PTSD and o-tw e. M omb s wit eye am T ore r cess ins. F r ext at-ex P h T S m p i D mo win e incti ng (s inall ossib ovem osedresponse to Regi oPTSD y, a p predict ppoor eeye del o (CBT) and leshown n. Se studies have e Ph sponse.

Other matter cognitive ent d abnormalities n Vete glut that gray stry behavior therapy d th roof f red vera an e esen rans ama to co eir u -of-c u l stu t c a s t w e nexp e l i n tizat d top it P once -bas firm dies ion suggesting ed aantidepressants, TSD , buto rgic drugs, butoenhanced response theptpresence of ah subpopulation of patients with possible -dow prev sed stud and t nglutamatergic bnor and co-tw ious n co ot al y by repr mali their w ntr ins h l, ha o o B r c ties ryan k sug e u adof v s n e s e i 995) provided the first evidence decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction.

Several studies, l t ng (E repli xpos eadi sign g e e t s a t ifica ng to cate l. (20 ed c ing t M D R ntly d th o-tw hat ) the 08) ructu is finto memorystand ireplicated ns h reate region related emonot all, have py. I studies,dbut of decreased hippocampal volume in PTSD, agbrain fear Several ral dextinction.ra ding ad s this nstra r act n de efici ignifi in PT ivati t p e r d t e s ca ssion SD, d the p on in and epre in which stress treadysregulates , bra ossib ions (e.g. anterior cingulate). These findings are consistent with athypothetical model hypothalamic-pituitary-adrenal he d tmen ssion in st le ut orsa ructu t res , and i l ant l i t yo istan ral d et al. 2014) vario et al., 2013; eritreatment dies have shown normalization of hippocampal structure and function following (Levy-Gigi reviewed or ci efici ce to by Thomaes us o ngul ts ha ther sero ate a v t p e o s b n ychi nd altered ergiboth a lar brain structures SD, rather than a consequence. More recent work has presented a more complex picture wherein atric constitute c druvulnera- e ger r diso gs (A espo rder bdal s n . (dtherefore o emotional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD.seEtkin unde ACC/ timeet al. (2007) M diffe C C ) c renc nst e sco subtypeoof PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the dissociative res o n th e Mu confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC)

didn’t.

and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger response time difference scores on

al. (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray

y. In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced response to glutamatergic

s and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of decreased hippocampal

nd various other psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region

orders. Gray matter reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent

e excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structure

2) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has

chi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been

. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined

nhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced

for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater

at Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging

havior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related

23 atients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al.

ion. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. (dACC/MCC) constitutes a

mn

er

ov id

de

ed

nc eo f po ca mp al ab rai nr eg an ion df ea r ex ot tin all cti ,h on av er . es ep sio l i n, ca Under the Geneva Convention, Officers and a t ed nd ma tte va Non-commissioned Officers are not obliged rio rr ed us eg uc oth ion tio to work when taken prisoner. I am, as you er ns s( e.g mo in know, a Private. .a PT de nte SD l rio ha de in w rc ve hic g tcre ing als o ase hs ula ob tre bra incred te) ee ss as av in .T n dy e s reg ed he sre se t n howion glut g ula fi rel 20 ot a n n din 14 all no ate ma tes t ) , r gs hy ra . A hav ma d to e ex are po cit ngy ma subs e re liza mem t ha fac tte equ plic tion or otox l a r a y mi to r e a o t a ic c-p titre co r fo educ nt el ed thf hip nd ity, a itu ute ns r P tio eg is p nd o T ita i fi a n s c S nd am su , le bot ten D, s in nt rybs tw ing p ala adi h v t w rat ad P eq ren , a ng t uln ith her TSD in st in aPl st ue TS ruc rm ctiv o i er a h th ha ud al nt a v D a n gra , dteur kin liza atio cre bili ypo an a e ayl by ym so Gi pe et tion n in asedties thet co asn r e l b a n ic se t a eeber sido fu t tte n dts waeleg l. (20of hi resp gluto an al m q n, nac rr on em oduen ed s an 0 pp on am d ntdio uc onet n the also t tw 7) th ocamse t ateoutc el icne. tio a s f i M e o t e o n l. ( ra whor llo n. ntr r tha dem stu refo pal em xciotme 2 t e e i 0 w c o s d d n a s o 0 h rse tox o ing 2 i t n tie st, i a c nst y byre u truo i c ) fp on treen c i o h t c n t s t n t on rat t u a ityos rea sst w hse r al l. ( o a he seq ed Gilbder , atntr rprbo dyo tm e t o e anpdro 2 a srke rvaii en e t 011 nd o diss uen,csup rtso onk a fcuenss d suumba ner h d g t (L u ) o a u p o e e s d l et m . M ort i s c d m em use tcomcia t a n g i e t ev p t s cus iogn ( io eta q e a o r t i t o d s l e r y-G n r n i e . e ons soe etrne s h (20-a f e nd dia tion the s ove s e reg a y eloP igi ge npte tssg l n 0 f c a e l o u P a V e 2 po bt r t ed rto cin l pr ie w T ( l h v n ) a d h S y S i a y h t i st y ekm de nng o aalm o t assis wD g t am igaut orm nc ettr pp hat k a mulat cesnsam trapuemo parno o k i o eaal tcehr e rec-p dvic hd .t,m aftPi T ae d a ortincom eta-e co ing T(win i reed coitu doen s lpo 20en c Ss D s b mpt auc dfisr f sre 02t re tr,eLa cia larg g a Pat-e anarltyice ee R e l t t ( m ) l P .

L g r i , d e oend ssni 20on haist T xp nutec t heavy e s s d gt e n ery (Sues 13. Su x sb ns ive s r res SD m os is a(n eda -Gi d A hevi ). pp . keigt u t ato eegi dCcC/ tm sdeen opo on odeed V l ort c m Fina btyp e u a n .

M o , o t l c p e -rdeo 20nfi abce nfiCC .h(i2 repal T l e ose t l of ter 02rm cwo ., 2 rm) c nofo e 0 r . O win lRy, a e f a i t e 1 m ) m ate01 n cp ns PT e rs , hpa edon r d a 2 p m t u l e ) h r . ma 3; SD d l c gis oo s r tic er a o w t f d 2 e s e e h o t l n x 0 i i , f itiell vieo d itth b etsue u1n3 e t f tropic euns opPT te d).aR en s (dPTS ry t-oof- Lanfeiuren s.hipp l ctu asb -dSoD rw re om eo neidu s ece on naof oVe sitiz ACCD/ stu cocn pre wn w n r t asc cr e ter at a a c MC di b m a fi k ste cre mai ed ncd inh l. o( r mpt C) es rei on ee udgly l a p bu ans ion 2 i t e t d s p a s r h c i 0 s12o n h treoi retvud ge—b lersi. e iefr dift en withand onsatvi e rl u stiut n on )nfot sT ioyub co khf e f h tal t P r ngno nm huen s ywB acsp exb no erenanc24 TSeDpro ustehsow t d t M t p i r o e h o aun onsed rykan a nf t a c atcon r, crifi d nc rma ce e ltiin edw sut am sis ep lit scores ndesth atchit ha sin -Scor gegt ten re p t i cioth iltiag eig eyr of ueracs easlt r u(E i r tl ev stueds le s oonnse t n a . i(n the wi cr e r e M y i n y b ad 2 s ha ide i g theto exDR nsea Innt l kmfa 00t v n y i p s

IIwa wa I wa

as their leader as their leade as their leade One-hundred-and-fifty such minor beings were shipped to a Dresden work camp

on January 10th. I was their leader by virtue of the little German I spoke.

25

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. S

also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dy

et al studies (1995) provided the first evidence of hippocampal volume in PTSD, a braintreatment region related to mem reduction. Supporting thisBremner model, pilot have shown normalization ofdecreased hippocampal structure and function following (Levy-Gigi e

been in other brain regions (e.g.recent anterior cingulate).

These afindings are consistent a hypothetical pus size as a predisposingalso factor fordemonstrated PTSD, rather than a consequence.

More work has presented more complex picture with wherein altered bra

reduction. this model,(see pilot studies have shown normalization of hippocampal structure and function followi amygdala, activation in response to Supporting emotional processing Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTS

size as a predisposing for PTSD, rather than awith consequence. recentemotional work has presented a more complexin p demonstrated, supportingpus a PTSD model of reduced factor top-down control combined increased More bottom-up sensitization.

In contrast,

amygdala, activation response to emotional processing (see Phanactivity et al., 2002), been repeatedly—but not consisten Vietnam Twin Registry to confirm previous workinsuggesting that enhanced resting metabolic in thehas dorsal anterior and medial cingulate co

demonstrated, a PTSDgreater model activation of reducedin top-down control combined with increased bottom-up emotional se with PTSD and their unexposed co-twinssupporting had significantly the dorsal anterior cingulate and a larger response time difference

Twin Registry confirmbiomarkers previous work suggesting that enhanced resting metabolic activity in shown the dorsal et al. (2008) demonstratedVietnam the possible utility ofto imaging in predicting treatment response.

Other PTSD studies have thatanterio gray m

with PTSD have and their co-twins had significantly greater activation in the dorsal anterior cingulate and a larger depression, brain structural deficits beenunexposed related to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepres

al. (2008) demonstrated theBremner possibleetutility of imaging biomarkers in predicting treatment response. Other PTSD studie resistance to serotonergicetdrugs (Abdallah et al. 2014). al (1995) provided the first evidence of decreased hippocampal volume in PTSD,

depression, brainprovided structuralthe deficits have been to poor responsevolume to serotonergic enhanced to psychiatric disorders. Bremner et al (1995) first evidence of related decreased hippocampal in PTSD, drugs, a brainbut region relatedresponse to memory

resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of decreased hipp

psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain.g ions (e in reg her bra t o in odel d this m strate emon orting d p p n u e S e . ob ion ve als reduct SD ha s in PT n io t c r redu matte

It was our misfortune to have sadistic and fanatical guards. We were refused medical attention and clothing: We were given long hours at extremely hard labor.

26

Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD

ysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matte

mory fear extinction.

Several studies, but A not all, have replicated thisstudy finding PTSD, depression, andhas various otherstrong psychiatric disorders.

Gray m et al., and 2013; reviewed

by Thomaes et al. 2014). subsequent elegant twin byin Gilbertson et al. (2002) provided evidence for small hip

lain model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function,et leading to increased glutamatecortex, excitotoxicity, an structures constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguchi al. 2013).

Reduced prefrontal but increa

ingEtkin treatment (Levy-Gigi et al., undertook 2013; reviewed

by Thomaesand et al.

2014). A subsequent elegant twin

by Gilbertson et al. (2002) has provided stro SD. et al. (2007) therefore a meta-analysis confirmed these abnormalities.

The study specificity of the prefrontal impairment to PTSD

picture wherein altered brain structures constitute both vulnerabilities outcomes of posttraumatic (Sekiguchi etShin al. 2013). pre n the dissociative subtype of PTSD, Lanius et al. (2012) found an increasetoinand limbic inhibition by the midlinestress prefrontal cortex. et al.Reduced (2011) used ut no dies, b tu s l ra ntly—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis andInconfirmed The specificity of the prefro ortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. this study,these Shin abnormalities. et al. demonstrated that combat-exposed e Sev i ction.

PA) ax extin nal (H study ensitization.

In contrast, in the dissociativeTask, subtype of PTSD, to Lanius et al.

(2012) found an PTSD increase limbic inhibition by the midline prefrontal cortb -adre e scores on the Multi-Source Interference as compared combat Veterans without andin their co-twins. a proof-of-concept d fear Finally, n ry a a it ry u e s memo mic-pit homae y Tdemonstra hala ted to lastate d bal. or and medial cingulate cortices constitutes familialtherapy risk factor, rather than marker forsPTSD. this potIn matter abnormalities predict poor(dACC/MCC) response to cognitive a behavior (CBT) and desensitization andstudy, reprocessing (EMDR) therap n removement ieweet vShin te hy gioeye com re la re ; u 3 re g in 1 o sre l., 20 D, aasbra ss dyabnormalities ted a m et aPTSD Spossible n re i T rssants, response time difference scoresof ona the Multi-Source Task, compared to combat Veterans without and their co-twins.

Finally, a e t P suggesting the presence subpopulation ofInterference patients with glutamate-based leading to structural deficits and trea s s ig h re in -G p whic lume ut in t (Levy rk has pal vo odel in rtex, b atmen (CBT) and eye nt wodepression, ovarious mcognitive e c re l c t l a a re g have shown gray abnormalities predict poor response to behavior therapy movement desensitization and re ic t ,es a brain region that related tomatter memory and fear extinction.

Several studies, but not all, have replicated this finding in PTSD, and oth t n in re w the ns prefro ce. Mo n follo a hypo not co duced equen ut Gray functio t withreplicated nhave conspossible 13). Repsychiatric tepresence oy glutamatergic antidepressants, suggesting of a subpopulation of PTSD, patients glutamate-based abnormalities to s ly—bleading and 0other and fear extinction.

Several studies, butconot this finding in depression, and various disorders. mat isall, d n awith 2 sthe re a te n l. u h a a t t e c t r e rep s are , rathe pal stru iguchi nding r PTSD pocam ss (Sek but not all, have replicated this finding in PTSD, de pocampal volume in ).PTSD, a fi brain region related andcto fear Several studies, ese r foextinction. of hip to memory ic stre fa t n te Th a g io la t m in u a s u g liz po tra osthave or cin norma predis studies, but not pall, replicated this finding in PTSD, depression, and various other psych . anterirelated tovmemory as aSeveral gregion hown and fear extinction. us size ha e s p s m ie a d c o tu p s t ip o h il l, p small

each day each da

Our food ration was two-hundred-and-fifty grams of black bread and one pint of unseasoned potato soup

27

After desperately trying to improve our situation for two months and having been met with bland smiles I told the guards just what I was going to do to them when the Russians came. They beat me up a little.

they be be be

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear Bremner extinction. et al (1 S

but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSDbut have not also all,been have

in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates inhypothalamic other brain re

nal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supporting this nalmodel, (HPA) axis piloa

shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). shownAnormal subseq

twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather twin study than aby con Gi

recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and outcomes of posttrauma recent wo

(Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al.,(Sekiguc 2002), h

repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these repeatedly—but abnormalitie n

of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined with increased of the bot p

emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibitionemotional by the midline sensitp

Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the Shin dorsal et al. anteri (201

cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstratedcingulate that comb co

Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a largerVeterans responsewith timePT d

on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study on the byMulti-S Bryan

demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray demonstrated matter abnor th

poor response to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression,poor brainrespon struct

have been have presence been relat of a 28related to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the

of patients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah of patients et

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear Bremner extinction. et al (1 S

eat me me up eat eat me

Several 1995) provided studies, the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies,

ne demonstrated replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD have also been demonstrated

c-pituitary-adreegions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adre-

ot and studies glial function, have leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have

quent lization elegant of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant

nsequence. ilbertson etMore al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More

ork atichas stress presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and outcomes of posttraumatic stress

chi haset been al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been

not es. The consistently—demonstrated specificity in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities. The specificity

prefrontal ttom-up impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined with increased bottom-up

prefrontal tization. Incortex. contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex.

11) ior used and medial the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and medial

bat-exposed ortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed

difference TSD and their scores unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger response time difference scores

nt Source et al. Interference (2008) Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008)

rmalities he possible predict utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray matter abnormalities predict

nse tural todeficits cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced response to ated subpopulation to glutamatergic poor response antidepressants, to serotonergic drugs, but enhanced response to glutamatergic suggesting the presence of a subpopulation 29 suggesting the presence of a subpopulation of antidepressants, patients with possible glutamate-based

st al. with 2014). possible glutamate-based abnormalities leading to structural deficitstoand treatment drugs. resistance to serotonergic drugs (Abdallah et al. 2014). abnormalities leading to structural deficits and treatment resistance serotonergic

Several 1995) provided studies, the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies,

30

PTSD, a brain region r

have replicated this fin

Gray matter reductions anterior cingulate).

stress dysregulates hyp

to increased glutamate

this model, pilot studies h

following treatment (Lev

elegant twin study

hippocampus size a

recent work has pr

constitute both vulner

2013). Reduced pr

emotional processing (s

demonstrated in

confirmed these abnor

also demonstrated, supp

increased bottom-up e

PTSD, Lanius et al. (201

I was fired as group leader.

cortex. Shin et a

suggesting that enh

cingulate cortices (dACC/ PTSD. In this study, Shin

their unexposed c

cingulate and a larger

Task, as compar

proof-of-concept study b

biomarkers in predict

matter abnormalities p

movement dese

structural deficits have b

response to glutamatergi

patients with possible

treatment resistance

provided the first ev

related to memory an

finding in PTSD, depres

provided the first ev

related to memory an 31 finding in PTSD, depressio

in PTSD have also been de

findings are consistent

rders. Gray matter reductions in PTSD

rior cingulate). These findings are

ates hypothalamic

eased glutamate excitotoxicity,

, pilot studies have shown

ng treatment

sequent elegant twin study by hippocampus size as a recent work has presented a

tute both

guchi et al. 2013). in response to emotional

Beatings were very small time: one boy

ot consistently—demonstrat-

starved to death and the SS Troops shot two

lysis and confirmed these

for stealing food.

PTSD was also demonstrat-

mbined with increased

On about February 14th the Americans came

ative subtype of PTSD,

over, followed by the R.A.F. Their combined

he midline prefrontal cortex.

labors killed 250,000 people in twenty-four

evious work

hours and destroyed all of Dresden

rsal anterior and medial

, rather

ated that combat-exposed

antly greater activation in the

e scores on the

ns without PTSD and their co-twins.

strated the possible utility of imaging

ies have shown

tive

d reprocessing (EMDR) therapy. In depres-

nse to serotonergic drugs, but

ting the presence of a subpopulation of patients

tural deficits and

14). Bremner et al (1995) provided

a brain region related to memory and fear extinction.

D, depression, and

ded the first evidence of decreased

ry and fear extinction. Several studies, but not all, have

psychiatric disorders. Gray matter reductions in PTSD have also been demon-

ndings are consistent with a hypothetical model HPA) axis32 and glial function, leading to increased glutamate excitotoxicity, and subsequent

ve shown normalization of hippocampal structure and function following

014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small

possibly the world’s most beautiful city.

33

But not me.

34

B Bu B B But Bu B B Bu But n

But not me But not me m ut not me But not me But not me But not m But not m t not ut notme me But not me But not me But not me But not me ut not me not me

Bremner et al (1995) provided the first evidence of decreased hippoc

related to memory and fear extinction. Several studies, but not all

depression, and various other psychiatric disorders. Gray matter reductions i

in other brain regions (e.g. anterior cingulate). These findings are consisten

stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial func

excitotoxicity, and subsequent gray matter reduction. Supporting this model

tion of hippocampal structure and function following treatment (Levy-Gigi et

2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided

pus size as a predisposing factor for PTSD, rather than a consequence. More recent

picture wherein altered brain structures constitute both vulnerabilities to a

(Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala

processing (see Phan et al., 2002), has been repeatedly—but not consistently—dem

therefore undertook a meta-analysis and confirmed these abnormalities. The speci

PTSD was also demonstrated, supporting a PTSD model of reduced top-down control

emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et

inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Tw suggesting that enhanced resting metabolic activity in the dorsal anterior and

constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin

posed Veterans with PTSD and their unexposed co-twins had significantly greater activ

and a larger response time difference scores on the Multi-Source Interference Task, as c

PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demons

biomarkers in predicting treatment response. Other PTSD studies have shown that gr

response to cognitive behavior therapy (CBT) and eye movement desensitization and reproc

brain structural deficits have been related to poor response to serotonergic drugs, but

antidepressants, suggesting the presence of a subpopulation of patients with possible gluta

structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). B

evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear e

have replicated this finding in PTSD, depression, and various other psychiatric disorders. B

evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear e

have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matt demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with

dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glut

gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocam

treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by

strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequen

more complex picture wherein altered brain structures constitute both vulnerabilities to and outcomes

al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional proce

repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook

abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, supportin

control combined with increased bottom-up emotional sensitization. In contrast, in the dissociative subty

an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Tw

suggesting that enhanced resting metabolic activity in the dorsal anterior and medial cingulate cortices

factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Vet 35 co-twins had significantly greater activation in the dorsal anterior cingulate and a larger response time

Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of

demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD

Bremner et al (1 but not all, have in other brain re nal (HPA) axis a shown normal twin study by Gil recent wor (Sekiguch repeatedly—but n of the pr emotional sensiti Shin et al. (201 cingulate co Veterans with PT After that we were put to work carrying on the Multi-S demonstrated th corpses from Air-Raid shelters; women, poor respons children, old men; dead from concussion, have been relat fire or suffocation. of patients Bremner et al (1 but not all, have hippocampal v and various other are consisten mate excitotoxic following t evidence f wherein alter increased am Etkin et al. (200 strated, su subtype of PT confirm previou risk factor, rath significantly grea combat Veterans in predicting t eye movement d but enhanced r leading to stru hippocampal v and variou memory an reductions in PT stress dysr reduction. reviewed b These axis and 36 findings are consistent with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) predisposing fact glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. vulnerabili emotional

we carrie we carried we carried

1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, e replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD have also been demonstrated egions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adreand glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have lization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent eleganti lbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. Moren rk has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and outcomes of posttraumatic stresss twin hi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been

not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities. The specificity refrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined with increased bottom-up repe ate ization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex.

11) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior andemedial mot ion ortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Shin et TSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger response time difference scores cing Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryant etVal. (2008) u eter ans he possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray matter abnormalities predict w on t he M se to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural demdeficits onst ted to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation rat poo r res s with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah het al.

2014). p ave been 1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, re of p a e replicated this finding in PTSD, depression, and various other psychiatric disorders. Bremner et al (1995) provided the first evidence Bof redecreased mne tien r et volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, but al not all, h r psychiatric disorders. Gray matter reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These hipp findings av o cam nd v nt with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading toaincreased pal v ario glutau s othe city, and subsequent gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structurearand function e co r n is maprovided treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has tent te ex sstrong w cito toxi for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has presented a more complex city follo picture wing but red brain structures constitute bothcursed vulnerabilities to and outcomes of posttraumatic cortex, Civilians us and threw rocks as we car- stress (Sekiguchi et al. 2013). Reduced prefrontal trea evid en mygdala, activation in ried response to emotional processing (seepyres Phan etin al., 2002), has been repeatedly—but not consistently—demonstrated incePTSD. whe for s bodies to huge funeral the city. rein ltere 07) therefore undertook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD iwas ncrealsoademondb ased Etkin upporting a PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, dissociative a inthe myg et a da l . (20 TSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the VietnamsTwin 07) t to trate Registry her d ,asfamilial subt us work suggesting that enhanced resting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes upp ype ortin confi of P her than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed TSD had rm p co-twins , Lan revio r i s k fac as compared ater activation in the dorsal anterior cingulate and a larger response time difference scores on the Multi-Source Interference Task, us w toi tor, r ork s sig abiomarkers u ifiimaging ther s without PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility nof cant than com ly gr b e at Ve treatment response. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behavior therapya(CBT) andst t e r activ tera in p ns w drugs, at red desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related to poor response to serotonergic itho ictin eye ut P g m trea T ovem abnormalities response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based t men en but t re eevidence nhan t d uctural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first ofesdecreased ensi c lead tizat ed r edepression, ing in PTSD, io volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding spon to st se to hipp ruct related gl us other psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, aobrain to cam region ural pal v d efici anddisorders. oluGray ts nd fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric me matter va mem rioumodel PTSD s oth ininwhich TSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical redu ory a er p sych ctio nd f nsubsequent eagray regulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and iat s in r extmatter PTSD inct stre (Levy-Gigi h ion Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatment et al., 2013; ss d ave y a sreg lso b redu ulat size

by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small cthippocampus ion. es h aseean revstructures otha iewe Supconstitute port37 ypboth predbrain tor for PTSD, rather than a consequence. More recent work has presented a more complex picture wherein altered l ing d by ispo this to sinactivation Thin ities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, omresponse g fac mo aes tor f vuln etaameo erab processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook l. 20 ilitie r PTSD, r emo at s t

ed bodies dd bodies bodies

xtinction.

Several studies, Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. S ebut also been not all, demonstrated have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD have also been pothalamic-pituitary-adrein other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates hypothalamic model, pilot studies havefunction, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilo nal (HPA) axis and glial 4).

A subsequent elegant shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subseq than consequence.

Moreet al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a con twin astudy

by Gilbertson posttraumatic stress recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and outcomes of posttrauma al., 2002), has (Sekiguchi et been al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), h bnormalities.

Thenot specificity repeatedly—but consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirmed these abnormalitie reased bottom-upimpairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combined with increased bot of the prefrontal eemotional midline prefrontal cortex. sensitization.

In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline p orsal and used medial Shin anterior et al. (2011) the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anteri that combat-exposed cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that comb onse time with difference scores Veterans PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger response time d dy Bryant et al. (2008) onby the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryan atter abnormalities predict utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray matter abnor demonstrated the possible rain poorstructural response deficits to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain struct sence of a subpopulation have been related to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a Abdallah et al.

2014). of patients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et xtinction.

Several studies, Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. S rst of decreased butevidence not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Bremner et al (1995) provided the first evidenc ing in PTSD, depression, hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD orand cingulate).

Thesepsychiatric findings disorders. Gray matter reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate various other ding to increased glutaare consistent with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to incr pal structure and function mate excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structu has provided strong (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provid following treatment ore complex evidence for picture small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has presented a more comple dwherein prefrontal cortex, butstructures constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefronta altered brain demonstrated in PTSD. increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstra to PTSD also demonEtkin et was al. (2007) therefore undertook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD wa t,strated, in the dissociative supporting a PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the dis ietnam Registry to et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twi subtypeTwin of PTSD, Lanius MCC) constitutes a familial confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC) constit unexposed co-twins had risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed rence Task, asgreater compared to significantly activation in the dorsal anterior cingulate and a larger response time difference scores on the Multi-Source Interference Task, lity of imaging biomarkers combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imag havior therapytreatment (CBT) and response. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behavior ther in predicting nse serotonergic drugs, eye to movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related to poor response to sero ate-based abnormalities but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based st evidence of decreased leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence ing in PTSD, depression, hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD ain related andregion various other to psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region isorders.

Grayfear matter memory and extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. G pothetical in have which reductionsmodel in PTSD also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical sequent gray matter hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gr stress dysregulates Levy-Gigi etSupporting al., 2013; this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi e reduction. ppocampus as a et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus reviewed bysize Thomaes structures constitute predisposing factor forboth PTSD, rather than a consequence. More recent work has presented a more complex picture wherein altered brain structures ation in response to outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in re vulnerabilities to and fore undertook a me- (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undert emotional processing a PTSD model reduced these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD mo ta-analysis andofconfirmed et al. (2012)control found an top-down combined with increased bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012 suggesting that enhanced 38 increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggestin tate marker for PTSD. In in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marke resting metabolic activity tivation in the this study, Shindorsal et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in without and their anterior PTSD cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PT

B B But But But not

Several studies, n demonstrated c-pituitary-adreot studies have quent elegant nsequence. More atic stress has been es. The specificity ttom-up prefrontal cortex. ior and medial bat-exposed difference scores nt et al. (2008) rmalities predict tural deficits a subpopulation t al. 2014).

Several studies, ce of decreased D, depression, e). These findings reased glutaure and function ded strong ex picture al cortex, but ated in PTSD. as also demonssociative in Registry to tutes a familial d co-twins had , as compared to ging biomarkers rapy (CBT) and otonergic drugs, abnormalities e of decreased D, depression, related to Gray matter model in which ray matter et al., 2013; s size as a s constitute both esponse to took a meodel of reduced 2) found an ng that enhanced er for PTSD. In the dorsal TSD and their

When General Patton took Leipzig we were evacuated on foot to (‘the Saxony-Czechoslovakian border’?). There we remained until the war ended. Our guards deserted us.

On that happy day the Russians were intent

But no But not me But not me not me t not me But no t me on mopping up isolated outlaw resistance in

our sector. Their planes (P-39’s) strafed and bombed us, killing fourteen, but not me.

39

But no

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinc reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypoth excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structu Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequenc outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emoti undertook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) use medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrat cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD predicting treatment response. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behavior t to poor response to serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulatio (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to m disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and f matter reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a glutamate excitotoxicity, and subsequent gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocam

by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a conseque outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emoti undertook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) use medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrat cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD predicting treatment response. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behavior t

40

ot me.

ction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter hetical model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate ure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study by ce. More recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and ional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore supporting a PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the ed the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and ted that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior D and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related on of patients with possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased mpal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thomaes et al. 2014). A subsequent elegant twin study ence. More recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to and ional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore supporting a PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the ed the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and ted that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior D and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related

41

Eight of us stole a team and wagon.

living li We traveled and looted our way through Sudetenland and Saxony for eight days,

Bremner et al (1995) provided the first evidence of decr reductions in PTSD have also been demonstrated in othe excitotoxicity, and subsequent gray matter reductio Gilbertson et al. (2002) has provided strong evidence outcomes of posttraumatic stress (Sekiguchi et al. 2013 undertook a meta-analysis and confirmed these abnorma dissociative subtype of PTSD, Lanius et al. (2012) found medial cingulate cortices (dACC/MCC) constitutes a fam cingulate and a larger response time difference scores o predicting treatment response. Other PTSD studies ha related to poor response to serotonergic drugs, but enhan gic drugs (Abdallah et al. 2014). Bremner et al (1995) psychiatric disorders. Bremner et al (1995) provided th disorders. Gray matter reductions in PTSD have also been increased glutamate excitotoxicity, and subsequen elegant twin study by Gilbertson et al. (2002) has pro vulnerabilities to and outcomes of posttraumatic stress (S Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et a al., 2002), has been 42 al. (2007) therefore undertook meta-analysis and confirm ampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depre In contrast, in the dissociative subtype of PTSD, Laniu repeatedly—but not consistently—demonstrated in PTSD. ns (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates hypothalamic-pituitary-adrenal (H dorsal anterior and medial cingulate cortices (dACC/MC model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Tho the dorsal anterior cingulate and a larger response t ampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has presented a more complex picture wherein altered

ike kings The Russians are crazy about Americans.

The Russians picked us extinction. up in Dresden.

We but not all, have replicated this finding reased hippocampal volume in PTSD, a brain region related to memory and fear Several studies, er brain regions (e.g. anterior cingulate). These findings consistent hypothetical model in which rode are from there with to athe American lines at stress dysregulates hypothalamic-pituit on. Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 201 e for small hippocampus size as a predisposing factor for in PTSD, rather than a Ford consequence.

More recent work has presented a more complex pictur Halle Lend-Lease trucks.

We’ve 3). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), has been repeatedly— since been flown to Le Havre. alities. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combin d an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work sugge milial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unex on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept study by Bryan ave shown that gray matter abnormalities predict poor response to cognitive behavior therapy (CBT) and eye movement desensitization and reproc nced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based abnormali provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but n he first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregulates nt gray matter reduction. Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatme ovided strong evidence for small hippocampus size as a predisposing factor for PTSD, rather than a consequence. More recent work has presented Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional processing (see Phan et al., 2002), ha 43 top-do med these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced ession, and various other psychiatric disorders. Gray matter us et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm p HPA) axis and glial function, leading to increased glutamate CC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with P omaes et al. 2014). A subsequent elegant twin study by time difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-ofd brain structures constitute both vulnerabilities to and

I’m writing from a Red Cross Club in the Le Havre P.O.W. Repatriation Camp. I’m being wonderfully well fed and entertained.

The state-bound ships are jammed, naturally, so I’ll have to be patient.

reduce studies, found a demonstr that e lamic-p ma model, pil activation 2014).

A suP without rather th t outcomes moveme (see but Phan et enh these ties combined decrease inhib depressi metaboli related to study mat anterior cing model in w co-twins gray matt Other PTS and reproc glutama defici volume in P other psyc fear extinc PTSD ha dy reduction reviewed predisposi both vulner to emot meta-ana reduced found an i that enh marke activation in without PTS trea movement but enhanc ties lea decreased h depression related to me matter model in wh gray matter

21 600 21 60 21 21 600 600 600 60 60 60

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinction. S been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysregu Supporting 44 this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; predisposing factor for PTSD, rather than a consequence. More recent work has presented a more complex picture wherein altered brain structures in response to emotional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) th supporting a PTSD model of reduced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the dissociativ to confirm previous work suggesting that enhanced resting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC) cons

ced top-down control combined with increased bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (20 but not all, in have replicated thisby finding in PTSD, depression, andShin various other psychiatric GrayRegistry matter reductions PTSD have been an increase limbic inhibition the midline prefrontal cortex. et al.

(2011) used thedisorders.

Vietnam Twin to confirm in previous workalso suggest rated in other brain regions (e.g. anterior cingulate).

Theseand findings arecingulate consistent with a(dACC/MCC) hypothetical model in which stress enhanced resting metabolic activity in the dorsal anterior medial cortices constitutes a familial riskdysregulates factor, ratherhypotha than st pituitary-adrenal axis and glial function, leadingthat to increased glutamate excitotoxicity, and subsequent gray matter reduction.

Supportinggrea thi arker for PTSD. In(HPA) this study, Shin et al. demonstrated combat-exposed Veterans with PTSD and their unexposed co-twins had significantly lot haveanterior shown normalization oflarger hippocampal structure and function treatment (Levy-Gigi et al., 2013; reviewed by et a n instudies the dorsal cingulate and a response time difference scoresfollowing on the Multi-Source Interference Task, as compared toThomaes combat Veter ubsequent elegant twin study by Gilbertson et al.

(2002) has provided strong evidence for small hippocampus size as a predisposing factor for PTSD PTSD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in predict han a consequence. work has presented more complex wherein altered brain structures constitutebehavior both vulnerabilities and treatment response. More Otherrecent PTSD studies have shown a that gray matter picture abnormalities predict poor response to cognitive therapy (CBT)toand s ofdesensitization posttraumatic stress (Sekiguchi et al. 2013).

Reduced prefrontal cortex, but increased amygdala, activation in poor response to emotional processing ent and reprocessing (EMDR) therapy.

In depression, brain structural deficits have been related to response to serotonergic dru al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al.

(2007) therefore undertook a meta-analysis and confirmed hanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based abnorm es abnormalities.

The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down contro leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence d with increasedvolume bottom-up emotional Into contrast, thefear dissociative subtype ofstudies, PTSD, Lanius et all, al. (2012) found an increase in limbi ed hippocampal in PTSD, a brainsensitization. region related memoryinand extinction.

Several but not have replicated this finding in PT bition by various the midline cortex.

Shin et al. (2011) used theprovided Vietnam Twin Registry to confirm previous work suggesting that resting ion, and otherprefrontal psychiatric disorders.

Bremner et al (1995) the first evidence of decreased hippocampal volume in enhanced PTSD, a brain reg icmemory activity and in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In thiG fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. y, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsa tter reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothet gulatestress and a dysregulates larger response time difference scores on the(HPA) Multi-Source Task, as compared to combat Veterans without PTSD thei which hypothalamic-pituitary-adrenal axis and Interference glial function, leading to increased glutamate excitotoxicity, and and subsequ s. Finally, a proof-of-concept by pilot Bryant et al. (2008) demonstrated the possible utility of imaging in predicting treatment (Levy-Gig response ter reduction.

Supporting thisstudy model, studies have shown normalization of hippocampal structurebiomarkers and function following treatment SD studies have shown that gray matter abnormalities predict poor response to cognitive behavior therapy (CBT) and eye movement desensitization cessing (EMDR) therapy. In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced response to atergic antidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based abnormalities leading to structura its and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of decreased hippocampa PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and variou chiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and ction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in ave also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stres ysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matte n. Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013 d by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a ing factor for PTSD, rather than a consequence. More recent work has presented a more complex picture wherein altered brain structures constitute rabilities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response tional processing (see Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a alysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model o top-down control combined with increased bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012 increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting hanced resting metabolic activity in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state er for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greate n the dorsal anterior cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to combat Veteran SD and their co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in predicting atment response. Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behavior therapy (CBT) and eye t desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits have been related to poor response to serotonergic drugs ced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with possible glutamate-based abnormali ading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence o hippocampal volume in PTSD, a brain region related to memory and fear extinction. Several studies, but not all, have replicated this finding in PTSD n, and various other psychiatric disorders. Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region emory and fear extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gra r reductions in PTSD have also been demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetica hich stress dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequen reduction. Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi e

days recupera dollars back p days furlough I hope to be home in a month. Once home I’ll be given twenty-one days recuperation at Atterbury, about $600 back pay and — get this — sixty (60) days furlough.

Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD ulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter red reviewed by Thomaes et al. 2014). A subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus 45 s constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdal herefore undertook a meta-analysis and confirmed these abnormalities. The specificity of the prefrontal impairment to PTSD was also demonstrate ve subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the midline prefrontal cortex. Shin et al. (2011) used the Vietnam T stitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated that combat-exposed Veterans with PTSD an

monstrated inBremner other brain (e.g. anterior These findings are consistent with a hypothetical model in which stress dysregulates hy et alregions (1995) provided the cingulate). first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fea mic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter Supporting studies, not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders.

Grayreduction. matter reductions in odel, pilot studies havebut shown of hippocampal structure andThese function following treatment (Levy-Gigi et al., 2013; reviewed

by Thoma demonstrated in normalization other brain regions (e.g. anterior cingulate). findings arefor consistent with a hypothetical model in which stressf 14). A subsequent elegant twin study by Gilbertson et al.

(2002) has provided strong evidence small hippocampus size as a predisposing factor lamic-pituitary-adrenal (HPA) axispresented and glial function, leading picture to increased glutamate excitotoxicity, and subsequent matter reduc her than a consequence.

More recent work has a more complex wherein altered brain structures constitute bothgray vulnerabilities t model, pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; rev tcomes of posttraumatic stress (Sekiguchi et al.study 2013).by Reduced prefrontal cortex, but increased amygdala, activation inhippocampus response to emotional proc 2014). A subsequent elegant twin Gilbertson et al. (2002) has provided strong evidence for small size as a pred e Phan et al., 2002), has been repeatedly—but consistently—demonstrated in PTSD. Etkin et al. wherein (2007) therefore undertook a meta-analysis and rather than a consequence.

Morenot recent work hasto presented a also more complex picture altered brain structures constitute both ese abnormalities.

The specificity of the prefrontal impairment PTSD was demonstrated, supporting a PTSD model of reduced top-down con outcomesbottom-up of posttraumatic stress (Sekiguchi et 2013). Reduced prefrontal subtype cortex, but increased amygdala, activation in response to mbined with increased emotional sensitization.

Inal. contrast, in the dissociative of PTSD, Lanius al. (2012) found an increase in Phanprefrontal et al., 2002), has been repeatedly—but in PTSD. Etkin et al. et (2007) therefore undertook a me hibition by the(see midline cortex.

Shin et al. usednot theconsistently—demonstrated Vietnam Twin Registry toalso confirm previous work suggesting thatmodel enhanced resti these abnormalities.

Theand specificity of(2011) the prefrontal impairment to PTSD was demonstrated, supporting astate PTSD of reduce etabolic activity in the dorsal anterior medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than marker for PTSD. with that increased bottom-up Veterans emotional sensitization.

In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) udy, Shin et al.combined demonstrated combat-exposed with PTSD andused their unexposed had significantly greater activation in the foun dor inhibition by the midline prefrontal cortex.

Shin et the al.

(2011) the Vietnam co-twins Twin Registry to confirm previous work suggesting that terior cingulate and a larger response difference scores on Multi-Source Interference Task, as compared to combat Veterans without PTSD activity instudy the time dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state m twins. Finally,metabolic a proof-of-concept by Bryant et al.

(2008) demonstrated the possible utility of imaging biomarkers in predicting treatment resp study, Shin et al.that demonstrated that combat-exposed Veterans with PTSD and theirbehavior unexposed co-twins had significantly greater activ her PTSD studies have shown gray matter abnormalities predict poor response to cognitive therapy (CBT) and eye movement desensi cingulate and a larger response time difference scores on the Multi-Source Interference Task, as compared to combat Veteran d reprocessinganterior (EMDR) therapy.

In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced resp co-twins. Finally, a proof-of-concept study by Bryant et al. (2008) demonstrated the possible utility of imaging biomarkers in predictin utamatergic antidepressants, suggesting the presence ofmatter a subpopulation of patients with response possible glutamate-based abnormalities leading to struc Other PTSD studies have shown that gray abnormalities predictet poor to cognitive therapy (CBT) and eye mo ficits and treatment resistance to serotonergic drugs (Abdallah et al.structural 2014). Bremner al (1995) provided the firstbehavior evidence decreased hippocamp reprocessing (EMDR) therapy.

In depression, brain deficits have been related to poor response toof serotonergic drugs,and bu ume in PTSD, and a brain region related to memory and fear extinction.

Several studies, but not all, have replicated this finding in PTSD, depression, antidepressants, suggesting the presence of a subpopulation of patientsvolume with possible glutamate-based abnormalities her psychiatricglutamatergic disorders.

Bremner et al (1995) provided the first evidence of decreased hippocampal in PTSD, a brain region related to mem deficitsstudies, and treatment to serotonergic drugs in (Abdallah et al. 2014).

Bremner etother al (1995) provided the firstGray evidence ofreduc decre r extinction. Several but notresistance all, haverelated replicated this finding PTSD, depression, and variousbut psychiatric disorders. matter volume in PTSD, a brain region to memory and fear extinction.

Several studies, not all, have replicated this finding in PTSD SD have also been in otherBremner brain regions (e.g. anterior cingulate).

These findings are consistent with a volume hypothetical model in which otherdemonstrated psychiatric disorders. et al (1995) first evidence of decreased hippocampal in PTSD, a brain regions sregulates hypothalamic-pituitary-adrenal (HPA) axis glial provided function,the leading to increased glutamate excitotoxicity, and subsequent gray matter fear extinction.

Several studies, not and all, have this finding in and PTSD, depression, and various other psychiatric disorders.

G pporting this model, pilotalso studies have shownbut normalization ofreplicated hippocampal structure function following treatment (Levy-Gigi ethypothetical al., 2013; rev PTSD have been demonstrated in other brain regions (e.g. anterior cingulate).

These findings are consistent with a m omaes et al. 2014).

A s Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to subsequ memory dysregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and tinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders.

Gray matter reduction reduction.

Supporting this model, pilot studies have shown normalization of hippocampal structure and function following treatmen SD have also been demonstrated in other brain regions (e.g. anterior cingulate).

These findings are consistent with a hypothetical model in which s reviewed by Thomaes et al. 2014).

Aaxis subsequent twin studyto byincreased Gilbertson et al. (2002) has provided strong evidence formatter small sregulates hypothalamic-pituitary-adrenal and glialelegant function, leading glutamate subsequent gray predisposing factor for PTSD, (HPA) rather than a consequence.

More recent workand has presented aexcitotoxicity, more treatment complexand picture wherein bra pporting this model, pilot studies have normalization of hippocampal structure following (Levy-Gigi et al.,altered 2013; rev both vulnerabilities to andshown outcomes ofbyposttraumatic stress (Sekiguchi et al. function 2013).

Reduced prefrontal cortex, but increased amygda omaes et al. 2014).

A subsequent elegant twin study Gilbertson et al.

(2002) has provided strong evidence for small hippocampus size as a predist to emotional processing (see Phan et al.,work 2002), has been repeatedly—but notpicture consistently—demonstrated in PTSD. Etkin et al. (2007) tor for PTSD, rather than a consequence.

More recent has presented a more complex wherein altered brain structures constitute both meta-analysis and confirmed these abnormalities.

The specificity of the prefrontal impairment toamygdala, PTSD was activation also demonstrated, suppo ities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013).

Reducedemotional prefrontal cortex, but increased insubtype response reduced top-down control with increased bottom-up sensitization.

Inet contrast, in therefore the dissociative of to PTe ocessing (see Phan etanal., 2002), has beencombined repeatedly—but not consistently—demonstrated in al.

PTSD. Etkin al. undertook a meta-an foundabnormalities. increase inThe limbic inhibition by the midline prefrontal cortex.

Shin et (2011) used the(2007) Vietnam Twin Registry to of confirm pr d confirmed these specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model reduced that enhanced resting metabolic activity in the dorsalIn anterior and cingulatesubtype cortices of (dACC/MCC) constitutes a familial fa ntrol combined with increased bottom-up emotional sensitization. contrast, inmedial the dissociative PTSD, et al. (2012) found risk an inc for PTSD.prefrontal In this study, ShinShin et al. demonstrated that combat-exposed Veterans with PTSD and Lanius their unexposed co-twins had s mbic inhibitionmarker by the midline cortex. et al.

(2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhance activation in theanterior dorsal anterior cingulate andcortices a larger(dACC/MCC) response time difference scores on the Multi-Source Interference Task, as com etabolic activity in the PTSD dorsal and medial cingulate constitutes aal. familial risk factor, rather than stateutility marker for PTSD. without and their co-twins.

Finally, a proof-of-concept study by Bryant et (2008) demonstrated the possible of imaging udy, Shin et al.treatment demonstrated that combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dor response.

Other PTSD studies have shown that gray matter abnormalities predict poor response to cognitive behaviorPTSD thera terior cingulate and a larger response time difference scores on the Multi-Source Interference as compared to combat Veterans without desensitization and reprocessing (EMDR) therapy.

Inthe depression, brainTask, structural deficits have been related to poor respon twins. Finally,movement a proof-of-concept study by Bryant et al. antidepressants, (2008) demonstrated possible utility ofofimaging biomarkers predicting resp but enhanced response tomatter glutamatergic suggesting thecognitive presence a subpopulation of in patients withtreatment possible gluta her PTSD studies have shown that gray abnormalities predict poor response to behavior therapy (CBT) and eye movement desensi ties leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al.

2014).

Bremner et al (1995) provided d reprocessingdecreased (EMDR) therapy.

In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced resp hippocampal volume in PTSD, of a brain region related to memory and fear extinction.

Several studies, but notleading all, have replic utamatergic antidepressants, thepsychiatric presence a subpopulation of patients with possible glutamate-based abnormalities to struc depression, andsuggesting various other disorders. et al (1995) provided first evidence of decreased hippocampal volum ficits and treatment resistance toand serotonergic drugs Several (Abdallah et Bremner al. 2014).

Bremner etreplicated al (1995) the provided thein first evidence of decreased hippocam to memory fear extinction. studies, but not all, have this replicated finding PTSD, depression, anddepression, various other ume in PTSD, related a brainreductions region related to memory andbeen fear demonstrated extinction.

Several studies, but not all, have this finding in PTSD, and matter in PTSD have also in other brain regions (e.g. anterior cingulate).

These findings are consistent her psychiatricmodel disorders.

Bremner et al (1995) provided the first evidence of decreased in leading PTSD, a brain region related to mem in which stress hypothalamic-pituitary-adrenal (HPA)hippocampal axis and glialvolume function, to increased glutamate exci r extinction. Several studies, but notdysregulates all, have replicated thispilot finding in PTSD, and various psychiatric disorders. matter reduc gray matter reduction.

Supporting this model, studies havedepression, shown normalization ofother hippocampal structure andGray function followi SD have also been demonstrated in other brain regions (e.g. anterior cingulate).

These findings are consistent with a hypothetical model in which sf al., 2013; reviewed by Thomaes et al.

2014). subsequent elegant study by glutamate Gilbertson excitotoxicity, et al. (2002) has provided strong evidence sregulates hypothalamic-pituitary-adrenal (HPA) axis andAglial function, leadingtwin to increased subsequent gray matter size as a predisposing factor for PTSD, rather than a consequence.

More recent work hasfollowing presented a moreand complex picture wherein a pporting this model, pilot studies have shown normalization of hippocampal structure and function treatment (Levy-Gigi et al., 2013; rev constitute both vulnerabilities to and outcomes of posttraumatic stress (Sekiguchi et al. 2013).

Reduced prefrontal but increas omaes et al. 2014).

A s Bremner et al (1995) provided the first et evidence of decreased hippocampal volume in PTSD, a brain region cortex, related to memory in response to emotional processing (see al., 2002), has been repeatedly—but not psychiatric consistently—demonstrated in PTSD. Etkin e tinction. Several studies, abut not all, have replicated thisPhan finding in PTSD, depression, and various disorders.

Gray matter reduction undertook meta-analysis confirmed these abnormalities.

The findings specificity theother prefrontal to PTSD was also demons ve also been demonstrated in other brainand regions (e.g. anterior cingulate).

These areofconsistent with impairment a hypothetical model in which stress model of reduced top-down control combined with increased bottom-up emotional sensitization.

In contrast, in the dissociative subt es hypothalamic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reductio (2012) found an increase limbic inhibition by of thehippocampal midline prefrontal cortex.

Shin et al.following (2011) used the Vietnam Twin et Registry to con pporting this model, pilotthat studies havein shown normalization structure and treatment (Levy-Gigi al., 2013; suggesting enhanced resting metabolic activity in al. the(2002) dorsal anterior andfunction medialevidence cingulate cortices (dACC/MCC) constitutes arev fam omaes et al. 2014).

A subsequent elegant twin study by Gilbertson et has provided strong for small hippocampus size as a predis than state marker for PTSD. More In this study,work Shinhas et al. demonstrated that combat-exposed Veterans with PTSD and theirconstitute unexposedboth co-t tor for PTSD, rather a consequence. recent presented a more complex wherein altered brain structures greaterthan activation in the dorsal anterior cingulate and abut larger response timepicture difference scores on the Multi-Source Interference Task ities to and outcomes of posttraumatic stress (Sekiguchi et al.

2013)., increased amygdala, activation in response to emotional processing (see Veterans without PTSD and their co-twins. Finally, a proof-of-concept study

by Bryant et al.

(2008) demonstrated the and possible utilityth of 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin etgray al.

(2007) therefore undertook a meta-analysis predicting treatment response.

Other PTSD to studies have shown that matter abnormalities predict response to confirmed cognitive beh normalities. The ofdesensitization the prefrontal impairment PTSD was also demonstrated, supporting a PTSD model ofpoor reduced top-down control co eyespecificity movement and In reprocessing (EMDR) therapy.

In depression, brain structural deficits have been relatedinto poor in res th increased bottom-up emotional sensitization. contrast, in the dissociative subtype ofthe PTSD, Lanius et aal.subpopulation (2012) found an increase limbic drugs, but enhanced response to glutamatergic antidepressants, suggesting presence of of patients with possibl bition by the midline prefrontal cortex.

Shin deficits et al. (2011) used the Vietnam Twin to confirm previous work suggesting that enhanced resting malities leadinganterior to structural and treatment resistance to Registry serotonergic drugs (Abdallah et al.

2014).

Bremner et al (1995) prov tabolic activity in the dorsal and medial cingulate cortices (dACC/MCC) constitutes familial risk factor, rather than state marker for PTSD. hippocampal volume in PTSD, a brain region related to memory andaco-twins fear extinction.

Several studies, but not all, have replic udy, Shin et al.decreased demonstrated that combat-exposed Veterans with PTSD and their unexposed had significantly greater activation inPTSD. the dor depression, and various other psychiatric disorders. (dACC/MCC) constitutes a familial risk factor, rather than state marker for In terior cingulate and a larger that response time difference scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD demonstrated combat-exposed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dors twins. Finally,aalarger proof-of-concept study by Bryant et al.

(2008) demonstrated the possible utility of imaging biomarkers in predicting treatment resp response time difference scores on the predict Multi-Source Interference Task, as compared to combat Veterans without PTSDdesensi and th her PTSD studies have shown that gray matter abnormalities poor response to cognitive behavior therapy (CBT) and eye movement study

by Bryantbrain et al.structural (2008) demonstrated the possible utility of imaging biomarkers in predicting treatment respon d reprocessingproof-of-concept (EMDR) therapy.

In depression, deficits been related to poor response to serotonergic drugs, but enhanced resp have shown that gray matter abnormalities poor have response to cognitive behavior therapy (CBT) and eye movement desensitiza utamatergic antidepressants, the presence of apredict subpopulation of patients with possible glutamate-based abnormalities leading torespo struc (EMDR)resistance therapy.suggesting Intodepression, brain structural deficits have been related to (1995) poor response to serotonergic drugs, but enhanced ficits and treatment serotonergic drugs (Abdallah et al.

2014).

Bremner et al provided the first evidence of decreased hippocamp suggesting the presence a subpopulation of patients possible glutamate-based abnormalities leading to str ume in PTSD, antidepressants, a brain region related memory anddrugs fearof extinction.

Several studies, butwith not haveprovided replicated this finding in PTSD, depression, an resistance totoserotonergic (Abdallah et al. 2014).

Bremner et alall, (1995) the first of decreased her psychiatrictreatment disorders.

Bremner et (1995) provided the first evidence of decreased hippocampal volume inthis PTSD, aevidence brain region related tohippoc mem brain region related to al memory fear extinction.

Several studies, but not all, have replicated finding in PTSD, depression, and v r extinction. Several studies, but not all, haveand replicated this finding in PTSD, depression, and various other psychiatric disorders.

Gray matter that reduc disorders. (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demonstrated cs SD have also been demonstrated other brain regionshad (e.g.significantly anterior cingulate).

These findings are consistent with a hypothetical model in which with PTSD and theirin unexposed co-twins greater activation in the dorsal anterior cingulate a larger response tim sregulates hypothalamic-pituitary-adrenal (HPA) axis and glial function, to without increased glutamate excitotoxicity, andand subsequent gray matter the Multi-Source Interference Task, as compared to combatleading Veterans PTSD and following their co-twins.

Finally, a proof-of-concept stud pporting this model, pilot studies have shown normalization of hippocampal structure and function treatment (Levy-Gigi et al., 2013; rev demonstrated theet possible utility of imaging biomarkers in decreased predicting hippocampal treatment response.

PTSD studies haverelated shownto that gray omaes et al. 2014).

A spoor Bremner al (1995) provided the first evidence of volumeOther inand PTSD, a brain region memory predict response cognitive behavior therapy eye movement desensitization reprocessing (EMDR) therapy.

In dep tinction. Several studies, but not related all, to have this finding in(CBT) PTSD,and depression, and various other psychiatric disorders.

Gray matter reduction deficits have been toreplicated poor response to serotonergic drugs, but are enhanced response tohypothetical glutamatergic antidepressants, suggesti o been demonstrated in other brain regions (e.g. anterior cingulate).

These findings consistent with a model in which stress dysre subpopulation of patients withglial possible glutamate-based abnormalities leading to structural deficits and treatment resistance to ser pothalamic-pituitary-adrenal (HPA) axis and function, to increased glutamate excitotoxicity, and gray matter reduction.

Su al. 2014).Bremner et al (1995) provided theleading first evidence of and decreased hippocampal volume insubsequent PTSD, a brain related to by mem s model, pilotet studies have shown normalization of hippocampal structure function following treatment (Levy-Gigi et al.,region 2013; reviewed Th Several studies, but not all,by have replicated this finding in PTSD, depression, and various other psychiatric disorders. (dACC/MCC) const 2014). A subsequent elegant twin study Gilbertson et al.

(2002) has provided strong evidence for small hippocampus size as a predisposing facto factor, rather thanrecent state work marker forpresented PTSD. In this study, Shin etpicture al. demonstrated that combat-exposed Veterans with PTSD and their un her than a consequence.

More has aanterior more complex wherein altered brain structures scores constitute both vulnerabilities t significantlystress greater activation dorsal cingulate and abut larger response time difference on the Multi-Source Inter tcomes of posttraumatic (Sekiguchi et in al.the 2013).

Reduced prefrontal increased amygdala, activation in response to emotional proc to combat Veterans without PTSD and their co-twins.

Finally, cortex, a proof-of-concept study

by Bryant et al. (2008) demonstrated the possib e Phan et al., 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkinthat et al.

(2007) therefore undertook a meta-analysis andto biomarkers in predicting treatment response.

Other PTSD studies have shown gray matter abnormalities predict poor response ese abnormalities.

The(CBT) specificity of movement the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down conr therapy and eye desensitization and reprocessing (EMDR) therapy.

Inof depression, brain structural deficits been mbined with increased bottom-up emotional sensitization.

In in the antidepressants, dissociative subtype PTSD,the Lanius et al.

(2012) found anhave increase in serotonergic drugs, but enhanced tocontrast, glutamatergic suggesting presence of a subpopulation of patie hibition by theto midline prefrontal cortex.

Shin et al.response (2011) used the deficits Vietnamand Twin Registry to confirm previous work suggesting that enhanced restin glutamate-based abnormalities leading to structural treatment resistance to serotonergic drugs (Abdallah et al.

2014). ow etabolic activity in the dorsalpredict anterior andresponse medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for(EMDR) PTSD. abnormalities poor to cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing udy, Shin et al.brain demonstrated that combat-exposed Veterans withresponse PTSD andtotheir unexposed co-twins had significantly greater activation in the dor deficits have been related to poor serotonergic drugs, butas enhanced response to glutamatergic antidepre terior cingulate andstructural a larger response timeof difference scores on the Multi-Source Interference Task, compared to combat Veterans without PTSD of a subpopulation patients with possible glutamate-based abnormalities leading to structural deficits andtreatment treatment re twins. Finally,presence a proof-of-concept study

by Bryant et al.

(2008) demonstrated the evidence possible utility of imaging biomarkers in predicting resp drugs (Abdallah et al.

2014).Bremner et al (1995) provided the first of decreased hippocampal volume in PTSD, a brain region her PTSD studies have shown Several that gray matterbut abnormalities predict poorthis response toincognitive behavior therapy (CBT)other and eye movement desensi fear extinction. studies, not all, have replicated finding PTSD, depression, and various psychiatric disorders. (d d reprocessingfamilial (EMDR)risk therapy.

In depression, brain structural deficits have been related to poor response to serotonergic drugs, but enhanced resp factor, rather than marker PTSD. In this of study, Shin with et al.possible demonstrated that combat-exposed Veterans with 46 antidepressants, utamatergic suggesting the state presence of afor subpopulation patients glutamate-based abnormalities leading toPTSD struc co-twins had significantly greater activation in theetdorsal anterior cingulate and a provided larger response time difference scores on the Mult ficits and treatment resistance to serotonergic drugs (Abdallah al.

2014).

Bremner et al (1995) the first evidence of decreased hippocam as region compared to combat Veterans without PTSD and their studies, co-twins.

Finally, a proof-of-concept study

by Bryant et al.

(2008) demon ume in PTSD, Task, a brain related to memory and fear extinction.

Several but not all, have replicated this finding in PTSD, depression, and of imaging biomarkers in predicting treatment response.

Other PTSD studies have showninthat gray matter abnormalities her psychiatricutility disorders.

Bremner et al (1995) the first evidence of decreased volume PTSD, a brain region related topredic mem cognitive behavior therapy (CBT)provided and eye movement desensitization and hippocampal reprocessing (EMDR) therapy.

In depression, brain structural r extinction. Several studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders.

Gray matter to poor response to in serotonergic drugs, but enhanced response to These glutamatergic antidepressants, suggesting the presence of which a reduc subpo SD have also been demonstrated other brain regions (e.g. anterior cingulate). findings are consistent with a hypothetical model in possible glutamate-based abnormalities leading to structural deficits and treatment resistance to serotonergic drugs (Abdallah et al.s

ypothaar extinction.

Several g PTSD this have also n been aes et al. hypothasfor dysregulates PTSD, ction. this to andSupporting viewed by Thomaes et al. cessing factor for PTSD, disposing confirmed h vulnerabilities to and ntrol o limbic emotional processing n eta-analysis and confirmed ing ed top-down control In thisincrease nd an in limbic rsal tand enhanced resting their marker for PTSD. In this ponse. vation in the dorsal itization ns without PTSD and their ponse to ng treatment response. ctural ovement desensitization palenhanced ut response to d various s leading to structural mory and eased in hippocampal ctions D, depression, and various stress n related to memory and r reduction.

Gray matter reductions in viewed by model in which stress y andgray fear uent matter ns in nt (Levy-Gigi et al., 2013; stress hippocampus size as a rain reduction. structures constitute viewed by ala, activation in response sposing therefore undertook a vulneraorting a PTSD model of emotional TSD, Lanius et al. (2012) nalysis revious work suggesting d top-down actor, than state creaserather in significantly greater ed resting mpared Veterans In thisto combat grsal biomarkers in predicting apy (CBT) and eye and their nse to serotonergic drugs, ponse. amate-based abnormaliitization the first of ponse to evidence cated this finding in PTSD, ctural me in PTSD, a brain region mpal rdpsychiatric disorders. Gray various t with a hypothetical mory and itotoxicity, and subsequent ctions in ing treatment (Levy-Gigi et stress small hippocampus rfor reduction. altered brain structures viewed by sed amygdala, activation yetand fear therefore al.PTSD (2007) ns in strated, supporting a PTSD dysregutype of PTSD, Lanius on. previous work et al. nfirm viewed by factor, rather milial risk sposing twins had significantly vulnerak,Phan as compared to combat et biomarkers f imaging in hese havior therapy (CBT) and ombined sponse to serotonergic le glutamate-based abnorg vided the first evidence of In this cated this finding in PTSD, rsal this study, Shin et al. and their sal anterior cingulate and ponse. heir co-twins. Finally, a itization nse. Other PTSD studies ponse to ation and reprocessing ctural onse pal to glutamatergic ructural deficits and nd various campal volume in PTSD, a mory andother various psychiatric ctions in combat-exposed Veterans stress me difference scores on rdy reduction.

by Bryant et al. (2008) viewed by matter abnormalities ypression, and fear brain structural ns in the have ing presence of a egulates rotonergic drugs (Abdallah upporting mory andet fear extinction. homaes titutes a familial risk or for PTSD, nexposed co-twins had to and rference Task, as compared cessing ble utility of imaging confirmed o cognitive behavior ntrol to poor response nrelated limbic ents with possible ng wn that gray matter this ) In therapy.

In depression, rsal essants, suggesting the and their esistance to serotonergic ponse. n related to memory and itization dACC/MCC) constitutes a to unexposed Dponse and their ctural ti-Source Interference mpal nstrated the possible d various ct poor to mory andresponse deficits have been related ctions in opulation of patients with stress . 2014).own that gray

I’ve too damned much to say, the rest will have to wait, I can’t receive mail here so don’t write.

May 29, 1945

Love, Kurt - Jr.

47

K

Kramer Press

Head Trauma was designed, printed, and bound by Brie Kramer for Kramer Press in February 2017.

This sole copy is printed in PT Mono and PT Sans.

TSD, a brain region related to memory and

sion, and various other psychiatric disorders.

g. anterior cingulate). These findings are

ary-adrenal (HPA) axis and glial function, leading to

this model, pilot studies have shown normalization of

d by Thomaes et al. 2014). A subsequent elegant twin

ze as a predisposing factor for PTSD, rather than a conse-

Bremner et al (1995) provided the first evidence of decreased hippocampal volume in PTSD, a brain region related to memory and fear extinc studies, but not all, have replicated this finding in PTSD, depression, and various other psychiatric disorders. Gray matter reductions in PTSD demonstrated in other brain regions (e.g. anterior cingulate). These findings are consistent with a hypothetical model in which stress dysreg ic-pituitary-adrenal (HPA) axis and glial function, leading to increased glutamate excitotoxicity, and subsequent gray matter reduction. Supp pilot studies have shown normalization of hippocampal structure and function following treatment (Levy-Gigi et al., 2013; reviewed by Thom subsequent elegant twin study by Gilbertson et al. (2002) has provided strong evidence for small hippocampus size as a predisposing factor consequence. More recent work has presented a more complex picture wherein altered brain structures constitute both vulnerabilities to an posttraumatic stress (Sekiguchi et al. 2013). Reduced prefrontal cortex, but increased amygdala, activation in response to emotional process 2002), has been repeatedly—but not consistently—demonstrated in PTSD. Etkin et al. (2007) therefore undertook a meta-analysis and confirm The specificity of the prefrontal impairment to PTSD was also demonstrated, supporting a PTSD model of reduced top-down control combine bottom-up emotional sensitization. In contrast, in the dissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibitio prefrontal cortex. Shin et al. (2011) used the Vietnam Twin Registry to confirm previous work suggesting that enhanced resting metabolic act and medial cingulate cortices (dACC/MCC) constitutes a familial risk factor, rather than state marker for PTSD. In this study, Shin et al. demon posed Veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and a larger res scores on the Multi-Source Interference Task, as compared to combat Veterans without PTSD and their co-twins. Finally, a proof-of-concept s demonstrated the possible utility of imaging biomarkers in predicting treatment response. Other PTSD studies have shown that gray matter cognitive behavior therapy (CBT) and eye movement desensitization and reprocessing (EMDR) therapy. In depression, brain structural deficits serotonergic drugs, but enhanced response to glutamatergic antidepressants, suggesting the presence of a subpopulation of patients with p structural deficits and treatment resistance to serotonergic drugs (Abdallah et al. 2014). Bremner et al (1995) provided the first evidence of d

Head Trauma

structures constitute both vulnerabilities to and outcomes of

mygdala, activation in response to emotional processing (see Phan et

. (2007) therefore undertook a meta-analysis and confirmed these

ated, supporting a PTSD model of reduced top-down control combined with

f PTSD, Lanius et al. (2012) found an increase in limbic inhibition by the

ous workmo suggesting that enhanced resting metabolic activity in the dorsal ry and ed to me

state marker for PTSD. ers. In this study, Shin et al. demonstrated that combat-exposed psychiatric disord

anterior cingulate and a larger response time difference scores on the Multi-Source hese findings are

-concept study on by, Bryant leadingettoal. (2008) demonstrated the possible utility of imaging and glial functi of es predict poorno response toncognitive behavior therapy (CBT) and eye movement desensitizarmalizatio es have shown

By Brie Kramer

Brie Kramer

twin nse to serotonergic drugs, enhanced response to glutamatergic antidepressants, suggesting gantbut nt ele 014). A subseque a conse-to serotonergic drugs (Abdallah et al. 2014). Bremner et al al deficits PT and treatment resistance rather than actor for SD, s ofnot all, have replicated this finding in PTSD, depression, and tcomebut and fearlne extinction. studies, to and ou rabilitiesSeveral both vu e Phan et ssing (seto procerelated olume in PTSD, a ot brain memory and fear extinction. Several studies, but not all, have ionalregion n response to em ese th ed rm D have also been in other brain regions (e.g. anterior cingulate). These findings are alysis and confi andemonstrated dertook a metad with rol combine down contglutamate glial function, leading top-increased excitotoxicity, and subsequent gray matter reduction. uced to red of l de mo SD n by the inhibitio limbic eatment (Levy-Gigi et al., 2013; reviewed

by Thomaes et al. 2014). A subsequent elegant twin study by se in increa (2012) found an l ity in the dorsa c activwork tabolirecent ather than a consequence. has presented a more complex picture wherein altered brain resting meMore g that enhanced posed that combat-ex nstratedactivation refrontal cortex, increased amygdala, in response to emotional processing (see Phan et al., 2002), et al. demo Shin ,but SD. In this study -Source res on the Multi difference scoThe lysis and confirmed specificity of the prefrontal impairment to PTSD was also demone timeabnormalities. nsthese po res r ge lar a and imaging ssible utility of trated the po zation. In contrast, inmo thensdissociative subtype of PTSD, Lanius et al. (2012) found an increase in limbic inhibition by de ) 08 (20 al. zaBryant et ment desensiti T) and eye move erapy (CB vior thactivity at enhanced resting metabolic in the dorsal anterior and medial cingulate cortices (dACC/MCC) constitutes a ha be ve iti gn sponse to co s, suggesting c antidepressant rgi ate tam glu ponse to co-twins had significantly greater activation in the dorsal anterior cingulate and a ns with PTSD and their unexposed ed res hanc et al c drugs, but en

An original letter by Kurt Vonnegut with research from the National Center for PTSD