Childhood exposure to violence and lifelong health ... · today's chUdren. worldwide birth rates...

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Childhood exposure to violence and lifelong health Clinical

intervention science and stress-biology research join forces

Q TERRIE E MOFFl1Tmiddotb ANO 1l-1E KLAUS -GRAWE 20 12 THlNK TANK Duke UilerJ if~ and K ing s CQf(ege Landon

A bstraLt

Many yOU S j)U)ple ho are miSIrmiddotllea by aJl J(JuL ictimized b~ bulJes criminally MgtaullOO or who llneJS domestic violence realLO Ibis vioknu e IXure h~ declltl ping behwomi emotio~ul lI r leamll)g prDbkms Whu js Iesgt C 1l kno n s thu h erse epuenos I~e violence expoure Cln 1euJ tO hddcn jl h ~skaJ Jterllions insne a dwd s body aJl~rarons lha rny havo lchene CIc LS o n ire lons he3lth We d__us v hy Ihis is Imponanl for tb lidd cf dc d Opn1Cf11I p~ydopuhoog~ and fuumlr sQoe ly and we recommend thll Slre-Smiddot bioogy reeanh and In tcren tioo c~cnce jun foltCS to c)Je

lhe problem Vc ctITlin lhe e d~nce bJ$C in ndon 10 ~-sn 5i li C m~asures for he bnd) Ci nfi atnenlIory Ilornnlt elomere elt~ n epif enenc

rne~h)Iltioszlig a nltl gcr~ ellpre ~sicn) Md bDilllmctlw disodergt neuroimaging and n~rchological lesung) We uso n v icw promm ni nlcrvennous [oc

rm lli~ couples and chtJ1Jren thll tIlve been desi gncd 10 rlaquoIuce lhe effe ts or chlldhood middotirlence expo~ue VC invite lllle[cntion scic rm gttS ard s~~s middot - bo logy reself1hcrs 10 colb bor-ae in Jdn g sITeSsmiddot bology mea~ure s 10 randomterl drt lct tri~i ci ifi retentons imelded in rWuce e ffeL~ of violerce exposw-e and olher uaumlS on )oung peup ~

Everyo ne knows violence is bad for children and adolescenLS - 11 is harmful for them to be mistreltHed 0 1 abused by an ltlduh (Q be vicuumlmized by bullies to wimess serious domestic vioshylence o r to be eriminall y assaulted Man ) young people

SupiXln for wning this an r le as provt(k d by ~ US Namponal Inititule of gmg (AGOj2281) and Ihc UK M~icJl R~mh Cmmcu (G IOO219Q and MRKOO3S IXj Ths w eh 5 a prod~t of lhe hin KJoas-Grlwe Thill k Tank meelng (luliC 23-17 10 1 (n aumlioz_ SWiLLerliliJ) UUU as ho seed by (he KJaus-Gr3wc-Foll1tJJiion Tbc FounduIQns purpnsc l ~ ro profOOSc Cishy

1 ceJlcnL i ntenE~ip ) Ul~Y am 11Ulo~-me reeMCh tfI-r i o l~ PS)choIOSYand psychohcrlPY and Iheir connca d di~pijoes in olck r 10 lmpoc pre co ton

and rretmcot of psyh()o~ icaJ problerns and disod r rs ~ U) dbsminue empirical1v $upponed prDsrams 10 th~ pub tluu gh 1 H Ir CI- of OumlUumlay ~ y~ems 10 indivdttalJ (OIIp )egt runi l i~ busineloC$ and imrilulOQ~ This lItlcJc briel)middot gtum mari ze 11 SCI O ~middot bnitlng p lpen wrlUumlcn for Ihe m~ring

Ili p jW W rncnii ~ aspi tMll~OnterW~IJUi -gmwe-thmk-wnk middot2U 1 2) 1be parshylicillJUS iR th group ~ lhc ioItoJini tm allh txucLI ordelj Looi~e AIshy~e~ru (Kingmiddot ~ ((jtkgc lonJmtl Don szligaocom CUOlcr lt)of North Carohna 3t Olap-I H11I A~llom CaipJ (Du~ Uniefil) iLIlll Klags College Lonshydon) Edth Cr~r Northweqem lmmiddotC ~ty) Andre Danese (Kings CoUege Lnndonr HeJeOl Filbn (Kings CoU~e Lw donl Kun Hl-eg (TechnioJhe Uni ef ~J1 Brampur~ttweig ) Nina Heinrdt (Uolverlta 5 Bidefeldt szligarbara Heiuigcc H1JdimUln (K1lus(jrawelm11ll Nr P~dlOlo~ iiChe Th~~)

M2r1 oum GrlweQc~r (KlausOrave_In)IIUl ffir PsydQ~uumlgi5Che n lfi3pe) Jonalhall iszligI (Kmgs CoU~ge Imdon) Gn~ry Mil ~ r lonhweSlem Umshy~rsi ~ ) Terne E -fomll (Duke Unlusuumly Jnd Kinfs CoI~ge LoOOclII) Carmiddot mite P-riante (KlItg ~ College Leudon) MOliI Snders CUniersiIY af Queeu5 htrul j ldan Sh lev iDuke UmvelSlty) S~ur ll-~ W3I IZo lUflersity orZunh) and 51udenl pmkipa1115 Ann-K3irln l ob (T-chnische L-Ill n~rs itar Briluli 5lhshyeig) ud ~-Esl Kupr-Yuron kJ IKlaus-Grlwe-lll5UDJt fiir PS)Chollogische

ThcrIpie) Addre~ oorespondencc and ~pri lll reqUeob 10 Tc~ Mor1i u Deparrshy ment ofPshology Duke Cni crsity Box 1()l4 10 1020 Voit M3in Snttt

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who are exposed to vio lenc~ reaci to Lhi s adverse experience by de eloping behaviorll emotional or leaming problems Whal is less weil known is lhm adverse experiences such as violence exposure can also lead [ 0 hidden physica1 alterat ions inside a child s body This artic le discusses why lhis is imporshytaIlt fo r the fj eld of developmenta l psychopalhology and for soc iel) examines the evidence base emd recommends thai slress-biology research and intervemion science join forces to (ackle the problem

When a child experiences violence adulLS tend 10 focus on the chi ld s leaming in school and anxiety depression or agshygressive reaclions because these Me pressing psychological neeU~ afte r the child is restored to safety However recent reshysearch indicates rn ere is also room forconcem lbout less visishyble ltldverse effects on a child s physical health for decades into his or her future (Krug 2002 Lupien Paulozzzi Melanshyson Simon amp Arias 2009 Shonkoff 20 J2 Shonkoff Gar ner amp the Commiuee on Psycho)Qcial Developmemal and Behavioral Pediauic s 20 12) These hidden effects are under srud y in ~Iress-biology research a rnulrid isc iplinary research area thai is rapidly gaining ground because of advances fo r measuring slress-sensil ive biomarkers in you ng people These biomarkers an imltres ling because in midlife adults these same biological aJlerations are known 10 be associaled ith elevaled risk fo r heart disease metabolic di seases imshymune diseases stcOke and even dementia (Danese amp McshyWCl 2012 Miller Chen amp Parker 2011 Taylor Way amp Seeman 20 11 ) Stress-biology research asks what biological (and psychological ) alLeraiions 10 brain and body can accOUnt l

for rne long -term connection between a SLressful childhood and ill heallh thaI only emerges 40 to 70 years Imer -bar

161 9

1620

is illhal chHngeS Here we look a po tential changes in oflenshysrud ied indicators o f th e hellrh of the bady (inflammatory Teshy

actions telomere eros ion epigenetic melhylaLion and gene expression) and brain (mental disorders neuroimaging and neuro psy(hological (e so ng)

Wh) is il importallt ro know that suess ful experiences durshylng childhood mighl Slart 0 child on the lang roJd 10 hean di sshyease or dememia Tltis infonnruion is lOlPOrtaszligt far developshymental sciemis ls because ir opens he door (Q earl) prevention which is imperalivc today because ur currem

demographie shifls Life expeclanc) is growing lange r and langer Demographie trends suggest the possibiJiry mar Ihe

euerent generalion oF c hildren will li ve an average of nearl)

100 years (Vaupel 20 10) Policymakers and cilizens are conshyce med that mese man y extrJ years of life should be health y productive and enjoYlble not ex tra years of disease d iS abi 1shyiry and depe ndence on ot hers Past medical research has shown thm u-eatlng adult palienlS afler lhey have conrracled illnesses such as cardiovascular disease diabetes or demenshytia genernlly does not fully res(ore Iheir guai() o f life (Jansshyson 2005 McG ill amp MeMahon 2003 Wellcome Trust 2006) There fore the hope of increasing children s lifelong productiviry health and well-being calls for research to idenshybull dfy prevenuumlol1 targe ts that can be lackled success fully in early life well be fore disease takes hold

At the same time hat life expee[ancy is growing Ion ger for todays c hUdren worldwide birth rates are dropping There

are fewer young people even in developing nauumlons Simulshytaneously baby boomers are beconting senior citize ns The ruio of young tO old is shifting heavily (oward older people The math is compelling soon each young persoD who is able 10 work will be depended on 10 support Ihe heathcare and soshycial securil) eosls of older people This is called the SlIPpOIl

ratio and it has beee changing aloegside the young 10 old demographie balance and I1 is expecled to cominue changing woridwide (hrrp Hen wikipediaorgwikiIPulenlOl_supporshy_muo) Thi s rJtio mCJns Ihm c hildre n are an increasin gy vashy

bull -J luable economic conunodity lnsuring the lifeloog health ltIOd proouctivi ry of each childmiddotcitilen is beeorrung more imporshy(aOt for the world economy than ever before We want todays

chi1dren co ha e life long good health because we love (hem hul we alsu Want lhem to be able [0 kee p (he economy going and suppon us in our ow n old age

GreaJ suides hJ middote beeo made loward design ing trealmen ts thru work for children and Jdolescenlo who have leaming cmccional and behavioral problems as weH as prognuns to premiddot ven( such problems among culdren at risk However loday only a small fraction of young people have acct=Ss to the se ershyfcclive rreatmenlS and preventions (Mihalupuulos Vos Pirkis amp Carter 20 11 National Reseanh CouDcil and lnstiwte of Medicine 2009) 1f preserving and promoLing the psychologshyical health of duuml ld ren were undejlcod (0 be essential for worldwide economic securiry ebild mental-health intervention might wc Ubecome a key weapon in lhe fight 10 improve qualmiddot iry of life over the emire life course Publi c awareness of lhe comlecuon be(Ween chi ldhood su-ess and adult physical healrh

T 1 Mofjitl tlnd he KlallsmiddotGr]fle 2012 Thillk TOllk

and age-related disease has the pOIential ro galvanize polioCJI wiH (Oward prevention and trealmeIl( (eg see Tuugh 20 11 ) In eontrast we have noneed mal uumliteners who see m inured 10

news o f maltrea1ed c hildren s emotional problems are surmiddot prised and faseinlled whe n told thal malrreated children have eleva[ed blood proteins that convey risk for heart disease

On the 25th annlversary of Development alld Psychopa lho(ogy there is an upponuniry for Ihe fietd uf developmenml psychopatholog y to bring together (Wo of irs strOngest sc ienshy lilie themes sLrCss-biology research and eLinical intervention sc ie nce If the hypothesis is true (hat su-e ssors sueh as vioshylenee thaI preci pitale psyeho lugieal problems fo r you ng peoshypie also undermine theu lifelong ph ysical health this would imply thaI the burde n of adult and lale-life di seases could be red uced by successfuHy improving the psychologieal health of children First first examine the evidence that violenee ex middot posure eJuses alteraxions in su-e ss biomarkers Ho gocd is il This is DOI an exhausuumlve technical review but_ ralher an overview o f evidence for causation Seeond we envisage w~ys thaI clinical intervention researchers co uld incorporale

suess biomarkers into their c1inical trials to discover if in vimiddot dious effecls of eh I ildhood su-ess can be prevenred o r even re ersed by psyehosocial rreatmems We nOle a handful of srudies lhal have reported pre- versus posttfearmenl o r trealshymem versus comrol group differences in suess-sensiLi ve bioshy

logical measures and make reeommendations for more sucb research Readers can frnd briefing papers with more in-deplh coverage of he seetions of this artice at hnpIwwwmoffinshycaspi comieonlentlklaus-grawe-think -[ltlnk-2012

Childhood Viole nce Exposure

Trus aniele focuses on viulenee exposure for four reasons First viulenee eposure is ooe of the moSt common and severe sou~esof human suess Seeond (he hypo thesis is thaI su-ess in genernl affects health and studying vio lenee exposuse in parshylicu lar prov ides a slrong test of iL Third violenee ex posure can he measured with fairly good reliabiliry and validit) which ~ is an ad vantage over many other adversi ties and srressors Founh violence victimizauon is already a dcar targel of pubshylicmiddothealth tnd law-e nfoCement prevention effons as weU as -

many clinical psychosoc ial interve noon progrnms providing opporrunities for research ioto reversibility of putative effects of violen ce on stress biology r o r mi s artiele we defmed vioshylenee exposure as personJ1 exposure (0 physical acts of intenshytional harm in the f1fS 18 years of life We coosideted physical o r sexual malcrearment by parenlS ur other eang ivers physical or sexual assIUII by other adults exposure tO parenlS or careshygivers dumeotic violence bullying by peers o r si bting s and violence wiltun the comexl of an adolescent roman uc relationshystU p These form s of vic timi zation can be defined according to recent comprehensive reviews (Gitben er al 2009) and guidemiddot lines (Leeb Paulolai Melanson Simon amp Alias 2008) Q2 Other (nonviole nt) adversines and forms of trnuma undoub(shydly have health implicmions bUI were omined (Boyce Sokoshyluwski amp Robinson 2012)

1621 Childhood eXJosufcgt 10 lulfla Gid lifelol J htollh

AboUI 25 of childrell expc ricnce som~ fonn of violcnce cxposure ltlS juveniles (Koenen Roberts Slone amp DUM

201 0) A comprehensive review of population-bascd sludies in devdoped eouOlries concluded lhal 5-J5 of children were f-Jhysically abused and 59(-30 of children were sexushyJly ubused whereas locc--20 had wilnessed dOlnesti c vioshy

Q2 lenee du ring ehildhood (Gilbert er al 2009) Subsequent nilshylional eSlimates agree A nutionally represeOlative survcy in the United States sought repons of exposure to vlolcnce (rom ehildren unde r age 17 and thdr pannts (Finkelhor Turner Onnrod amp Hamby 2009 Turner Fi nklehor and Ormrod 2010) Imcriean eSlimates for exposure across lhe duralion of childhood wen 20ck_19~ for bullying 2~-9 for dal ing iolence 5-19 for physicul malueatment 7ormiddot- 33 for physieal l$sauh 3-11 for sexuni mah reatshymenlassaulL and 13-27 for wime-sing ildul ts domestie violence This su rvey was repeated in Ihc Unied Kingdom yielding very similar prevalencc est immes (Radford e( al 2011) The World Heahh Organiuuion World Mental H~ahh Survey provided estimatc from 2 1 countries based o n retmshyspecti ve reportS of ad ul ts looking back to their childhoods Phy~icu l ubuse was rectlled by 59c-11 of respond ellls whereas 1-2~o reported conlaet sexual abuse and 49c---8 reporte-d exposure 10 family violence (Kessle r el al 2010) Varying raleS are panially due 10 differences bolween boys Jnd girls young children nd HJolescenLS and to vacy ing deshyfinilions and alteenai nment melhods aeross studie

Preva1cnce ratc) that cou nt vietims conceal the fact 111m chidren who are exposed to one incldent of vio lent victimishytmion are like ly 10 be repealedl) eKposed tO lhe same type of vi olence whieh is tenncd re llicrimiorion and (Q experi shyence multiple different types of viClJmizatiQn tenned polyshylliCl imiltlJliofl (Finkelhor Onnmd amp Turner 2007 2009) Funhermore juvenile ielimizmion increaltes o sk of udul[ violenee vietimization (Widom Czlja amp Dutton 20(8) Such long-tenn muhiple-exposu re patterns eonstilule cumushylali e Slress experiences Ihm exaeerbJ-te vic lims subseque nt mental hea hh outcomes (Appleyard Ege land va n Dulmen amp Sroufc 005 Teicher Tomoda amp AndCrsen 2006) Indi shyvidual vari~lion in these f-Janems of vioknce ex posu re should thus also bc eo nsidered in fUlure rescareh inlo effecLS on slress bio logy find hea lth Despile ind ividual heterogenei ty in the ex tent of violencc expo~ure and middotaliat ion in lhe population prevaJence eSlimales nll sources agree thul childhood vioshylence exposure is more prevalentlhan lt ought (0 be and sufshyficiem ly prevalent 10 be laken seriously) s aeomribuling facshytor in population herum und age-relmed discase lJurden

Hol Guod Js Th e Evidellce Film Childhoud Violmce Exposllre h~fluellces SressmiddotBiolagy kleasures

It may seem heartless (Q challengc 1he hypolhesis that vioshylence expos ure is harmful 10 lifelong hea lth as [herc s a moral imperati ve 10 prevenl iolenee agaills l cllildren HoUtshyever Lhere is also a scienlitie an(] soc ietal imperati ve 10 e alushyte Ihreallt 10 eausu inferen c~ Epidemiologisl e)kukue popshy

ukltion anributablc fraction~ 10 etimatc hmgt much of Ihe discltse burden in Ihe population eould be reduced jf certain causal factors were eradicated Por cxample ~ornc estimatcs suggest that er2dicat ing childhood advCf jLies could reduce psychialrie disorders by ncarly 30 (Kessler l1 al 2010) Such estim aLes are intendcd 10 mfonn public polieies and guide inl ervention efforts but (he popu lalion anribulable fI-action is of most use whcn lhe o sk faclorof imerest is cJearly cuu ~all ) related 10 the end poi nl (Rockhil1 Ncwman amp Weinberg 1995)I~ 1 possible (Q say that childhood violencc epuumlsure eauses paar heahh

Experimental researeh in nonhuman cmi mals has doeumiddot mened Ihal tres causes alterations 10 bad) and hrain meushysures In eontraSt thc requisile eidence for causmion in hushymun ch ildre n js wcaker Most sludies reviewed for lhis anicJe made an ltlcmpt (0 suppon causal infere nee by sWlisshylically eonLrolling for Olher risk faclors correlated ith vioshyle nlte exposure (sueh as low socioeconomie stalus or ramil ) slruCture) Ihal mighl have generaled abnormal scores on health measures HoUtc ver ehildren exposed 10 mahreatmem and io lenee are smListically likey 10 experience a whoJc host of additional admiddotersities thaI eould dimini sh Iheir heahh and il is difri cu ll 10 COntra) far al1 0 1 them (Cicchelll amp Talh 2005) Worsc yet beeause children inherit bOlh their genoshyt) pes and environments from Iheir parenls en viron mellwl ri sks such as lolencc exposllre are known to co-occur with gene lic predispositions 10 heahh Olllcome- lt uch ~ mentnl disorueTs and neuropsyeholog ical dysruncllonlt (Jaffee amp Priee 2007) 11 is nOI know n whelher Ilus gene-environment eorrelation eXlends to other heal lh ou(eomes or stress bioshymarkers but we should assurne (hat I1 does

Several srudy designs thai could ass ist wilh causaJ infcrene~ w o ff limitsO re scarthers who study ehildren For example (he hypothesized eausal e ffect of violencc ex posure on heahh could be eonfirmed by expenmenLaJ desigJls exposing children [0 violen ce (which is lmelhical) or by longirud inal de5igns lakshying bi omarker measurements before und after violence expuumlshysure 10 usc eaeh ehild as hi s own control (which is impraetical although not impossible)_ This CJusaJ hypOlhesis could also be (eslelt by comparing Ihe ~treslt biomnrker s(Urus of siblings who an discordam ror Ihe experience of violence ex-Uumlsure Twi ns are pnnicu larly good for this eonlr1Sl al though in mOSI tVin pai rs studicd as young childrcn when one lVin is mahrealed so i~ Ihe o tJler As a result o f these research limiulions we may nevcr bc abl e 10 ntle OUI the possibility Ihal biomarker ab shynonnalitiouml observed in violence-exposed ehi ldren were eaused by ~omeutheT kind 01 adversi ty Nevenhelcs s irve acshyeepl that lhe Wmiddot hypoLheis is Lhu ehildhood srress in general affecLS hcalLh lhen sludying violence ewosure in pan ic ular prov ides J Rasonable teSt o( lhi o hypothesis whelheror nOI efshyfcclscan be narrowed 10 violenee per se The main cau tion here is Ihat Ilus neid of inquiry is flf from beillg able tO slate how mueh of lhe diease burtlen in Lhe populuion could be reduced if lt111 violenee-ex posed child ren were successfully lreatcd Trealment ~tuutelt will be usefullo tackle this quesrion more abou( whlch appcars huer in Ihis artic1e

1shy

1622

Thc lleXI seelions of this anicle brieOy rei~w the ~tale of Ihe cvidence thai childhood violence eiposure affecS indicashytors of the health of the hOOr (inOummatory reactions lelomiddot mere erosion epigenelie melhylalion and gene expresion) and of lhe brain (menlal disorders n europ~ychologieal leSlshying and ncuroimaging) Thi gt set is not cxhlttustive fo r examshypIe slUdies of conisol (Gunnar amp Quevedo 2007) lttnd electroencephalogmphy (Cicchclli amp Cunis 2005 Polak 1005) in maltrealcd children are imponant but 1101 revi ewed here

ChildlOod vio~nce exposure and inj7ammarory ou(olfle~

InOammation is pan of the innme immune response a deshyfense mcchanism thai enablcs rccognilion of microorganshyisms antigens and tri ggers rapid reeponse againltl Ihern InshyOammation is lriggcred by inducers Vhich can be bOlh cxogcnous and ~~ndogenous (Mcdlhitov 1008) Exogenous induccr-s include microbial faclors and faclOrs such as allershyg~ngt imlams forcign boches and toxic compounds Endogshyenous inducers include biological signals prodmed by su-essed damaged or Olher-ise nlltll(unctioning ti ssuegt In reshysponse tO these signal s lhe innat lt immune l)slern develops 01

response in vol ving blood vessels white blood ccll s and Ihe so-co lied acutc-phase prolejns Ihe innammltltory response (Medzhitov 2008) A successful intlammatory re sponse achieves the elimination of the signal s thm originatcd the remiddot sponse Ihe resolution o f lhe respo nse and the repair of dashymagcd ti)sues

If Ihe indu cers become chronic UIld Ihe rcsolulion phalte cannot QCcur lhe olherwise protcctimiddote acute inOaml1latof) response can become a delrimental chronic inOa mmarory slate Because hc inOammatol) response is nonspceilic il does nOI discriminate between inflall1mltilion inducen (~g invading microorgani sms) and sUTTounding lissues Co llatshyeral damage during chronic inllammatory Slales may Ih ereshyfore lead 10 significam lissue damage leading 10 agemiddotrelaled diseae such as cardiovascuar disease Type 2 diabetes and dementia (Holarnisligil 2006 Nguyen Julien amp Rivc-sl 1002 Ross 1999) In hurnans a meta-analysis o f longitushydinal-cpidemiologic al swdies $ugg~sls that even mild e1c vashylion in plasma innammatiOn biomarkers such as C-r~xlive

prolei n fibrinogen and white blood cel count predicis eleshymiddotalcd risk for card iovaltcular discltlse (Danesh Co llin s Apshypleby amp Pelo 1998) Elealed innammmion le vels huw also been linked 10 ri sk for psyc hopalho logj (Soc2)n-ltka Zang Kennedy amp Mclntyr~ 2012) Although innammlttli on has be~n agtsociated with severnl psychinuic disorders a eau~a1 relation is most establiohed with regard 10 deprc-sion where evidenee comes from mcta middotanaIY$ls randomized conshytrotlcd uia ls and experimental animal model ~ (Dantzer OConnor Fn=und Johnson amp Kelley 2008 Howrcn Lamshykin amp Sills 2009)

Many experimental findings from animal model s docushymenllhe effccls of early life strcslt on long-tcffi funct io ning 01 the immune system and panicularl y inJlammation Obsershy

vmiollal sUdies of humam also shov lhat juvenile vio lence vicrimization is linked 10 abnoffilal immune system funclionmiddot ing Vilh elcvaled inOamlnation levels (Danese- el aL 201 J Danesc Paruumlmte Caspi Taylor amp Poulton 2007 KiecolishyGlaser el al 20 I J Shincliff Coe amp Pollak 2009 Slopcn el ltll 1010 Sunecs el al 2003 Widotn Czaja Benlley amp Johnson 10 12) For exumple in lhe Dunedin Study child ren who had been ex p05ed (0 matemal rcjection hmh parenting disrupuve caregi ver changes physkal abusc or sexual nbuse were almosl rwice as likely ai nonmahreated children O lhow eeloaled levels of muluple clinically releunt inOammation biomarkers such ltlS C-reaclive prolein fiblinogen and whitc blood cell count in adullhood (Danese et aJ 2007) These frndinge wen independent of lhe innuencc of olher co-occurshyring early-lifc adversilies su-ess in adulthood adult nealth and health hehavior and CUTTen actlve infections Among 12-yeas-old panicipams of he UK En vironmemal Ri sk (EshyRi sk) Longitudinal Twin slUd) physicall) maltrcaled chilmiddot dren cxpericnting current depress ion alread) exhibiled eleshyvaled innammalion levels in childhood (Danese el aL 10 11) This frnding 100 could nOl be explained by potemiaJ confounders such 3- famil socioeconotnic circulllstances obe~ ity or current infections Another sludy reponed thal bOlh postinslifUlionalized c hildrcn living in adopli~ hOllles and children with substantiated cases of ph)sical abuse slill rcsiding with meir familics showed elevatcd seC~lor) immushynoglobulin A for herpes simplex virus compared 10 cOnlrolgt indicating impainncll in Ihe aequired immune respOnse Ihat nonnall y conwins lhe reacli valion of lhis alem virus (S hirtshycliff ct Oll 2009)

This ffect of juvenile violence viclimiwtion Oll inflamshymalion ha thugt been rplicalcd in independent studic~ ttpmiddot pcars 10 be independent of con-elaled risk factors and is preshysent when ictimizalion i$ altcenained prospccliely during childhood Furthennore the inl1ammaory alterationgt of juveshynile vlolence viclims ha v been observcd 10 onse t in duldshyhood und al ~o to be prcsenl in dult life Some studics suggest thai theconncctiongt between childhood stress ltlnd innammashytion measures are Irongest among individuals Vith depresshysion tDancsc el al 2001 100S) Becausc juvenile violence QJ viclimizltllion could innuence long-tenn di scale outcomes through the meehanism of elevution in innammation le vels Ivcrsing the effecl of victimizalioll on inOammalion cou d pore mially reduce health burden

Childhood Iole llce e)pO~ffre and relomta erosion

Telomercs an Ihe repetili lo e 1TAGGG sequences thai cap and prOlecl he ends of chromosomes Thc) plny a major roje in regulaling cellular replication and shonen progressively wilh cadl cdl divi sion in repticaling human lissues Upon reaching a crilica lly shon length ecHs emcr a stille of replicashyiw arreSl callcd senescente [n reccnl y~ lelomeres hae emerged as a promi ~ing new cand idac in epidemiolog1cal reshysearc h Shortcr Itlomcre lengln and increased erosion rate are bOlh associmed with higher risf- of morhidity and munality

CdfdlUlod ( IlOSUre 10 vl leTl(e und lift lolI~ h~ ith

(CawLho n Smilh QBrien Sivalchenko amp Kcrbcr 200 Ehrlenbach el al 2009) Studies in animal models have promiddot vided suppon fOT th- pred icli c UIility of lelomere cnglh eru-ly in li fe o n lhe animals subsequenl Jifespan IHcidinger ~l al 2012) The adve nt o f high-lhroughpul and cosl middoteffecmiddot live laborarory rechn iquc thnl measure telo mere lengLh in

bu ecal lte l1 s or pcripheral blnod eells opened Ih e gate 10 new studies linkjn g shoner [elomere knglh wi lh a broad range or risk factors that predict di sease morbid il Y inc1uding smoking obesiry (Bux ton CI al 20 11 Nurdtjall el al 2003 Valtles el Oll 2005) schizuphrcnia (Yu Chang Lin amp Chu 2003) moud di sorder (Simo n et al 2006) and p~yehoioeial

stre ss (Epel el a1 1004 Kiccoll-(jlaser et a1 20 I) In the past 2 yeafs studie have pTUided iniial suppon for

an associltion berween chi ldhood lress and le10mere lengul Adult pJI1icipants who repontd physicltll abu lte emotional negleeL ororher ad verse life even lS in ehild hood had signifishy

cantl y shorter te lome re l en~ l h reganllcss of key pOlenlial confounding faclOrs such as age Sex smoking or body mass index (Kananen et Oll 2010 Kieeolt-Glaser CI aL

201 J ODonovlln Epelm el al 201 J T)rkn el al 2010) Howeer one slUcl y faiJed to replicale [he aSiociarion beshytveen le lomcre length and reLrospecti ve a~essmen o r physshykaI and sex ult11 abu se in c hildhood in a large cohun of altull lwins (Gas~ Pans Knowles Aviv amp Spec[or 2010) in the first srud y or ehildren inslilUtio naJ care was s ign ific antly assoc i3led with shoner lelomere lengLh In midcl le ehildhood (Dmry el al 201 I) in addition Ihe EmiddotRi sk Sludy reponcd that ehildren who experienctd two 01 more kinds of violenee exposurc showcd signiflcanlly more lelomere erosion beshytween age 5 baseJine and age 10 ro10V-UP meas urments (Shalc et aL ~012) Thi lt frnding provided lhe fi rs t evidencc that siress-rd ated acceleraled lelome re erosion berwcen tVo repealcd IIlcasures (as opposcd 10 telomcre lengI]) al o ne time point) can be observed 31 a young age while ehildren Me egt~riencing stress anlt welt berure they dce lop poor hnhh lt1S adults

Telomere lenglh mealt uremenl is lOW offered as a diagnosshytie 1001 (Q monitor hcalth ~Uld predicl diseasc risk (Wulinsky 2011) However recent findings from slud ies wilh repeJlcd Ielomere mcltSuremeJlts indieate (auuon bccause the lempomr process or lelomerc erosion IS more complex Ihan initi ali) asshysumed Fuumlr example telomere englh is hig hly vari-ble across dirferent age groups there is s ignificlt1fll intraindividual Cl ria middot bili() lelomere erosion is invcrel y conel alcd w ith baseline Iclshyunlcre leng lh Md al so in sa me in di viduaJs lelomeres lengthen over timc (Avi el lt11 1009 Epel el al 20091 In aJ middot dition Ihe re are eonLrQmiddotersi~s regarding the beSl wa)s to meamiddot sure tc)omere lengLh Finn lly anather mClhodolugical questia n eoncems the measuremelll of telamere Icngth in d ifTcrenllisshysucs (Shalev Cl 0112012) Because or cthical difllculfies obshylaining blood front ehildren in the community most studies in childrcn havc used buecal cells in~cad of the fX riphu al b lood ceUs more commonl y used in studie of adull$ This difshyrerence mUSl mise Iht questioll o r Io helher ti ndi ngs will genermiddot alize aeroS$ age and lissuc type Extreme camion should be

raken as more resemh is needed tO c1arify lhe mechanisszligls thm govem lelomere lenglh dy namilts

Childllood vivellce e11Qsure alld epigellelic Ollcomes

Sitting above Ihe DNA scquence i5 a second luyer of inronnnmiddot lion (he epig elJomeJ lhal regula1e s 5C middoteral genomic func middot lions inc luding when and whre genes MC actively expresscd Epigeneties refcrs 10 lhe reversi ble regulalion of various genomie funclions occurring i ndependent Iy or Lh e DNA seshyqucnce mediated principally Ihrough bioche mical changes in DNA methylalio n und chromatin $ructure Epigenetic pro shycesses are essemial tor noml al cellurar developmenl Md regshyul~lion of gene rUllCl io n (Feinbe rg 2010) DNA mehyl alion

is perhaps [he best underlood among severu l kind or epigeshynelie Illodirieat ions Unlike Ihe DNA ~equence wh ich i ~

stable and robust epigenelic processes are orten ti ssucshyspecific devdoplllentally regulated and high I dynamie A

growing bad) or ev idence shows thaI the ep igenome e hanges over the life cou~e and is eorrdaled with age an imponanl obscrvalion given th at Lhe prevalence or man) chronic diseashyses inereilSes wih adancing age (Bjoms~on el a1 2008 Bock landt Cl aJ 2011 Christensen el 011 2009 Flanagan ct al 2006 Fraga el al 2005) There is aJso moun(ing evi middot dence thaI epigenetlc proecsses are infiuenecd by faclo rs in lhe cnvironment DNA methylalion for ex ample has been shown 10 vary a5 a fUllelion of nutritional chemical phys ical and pi)cho social ractors Epigellelic mechanisms lherero~

repre sent 01 poteil lini link ber een genC$ and lhe en vironmenl and Lhis hypolhesis is supponcd by observalions lha monomiddot zygotic lw ins can differ in DNA meth ) lal ion (fraga CI al 2005 Wung ct aJ 20 I 0) Ir wasrcce ntl) proposed that epige nelie mechani sms play 01 piLlotal role in humM health and di ~ middot

eaie wll h incrcas ing evidence for Lheir involvernenl ncross Ihe broad spectrum o f chronic eompkx illnes-cs jnclud ing physica l physio logiea L and mcntaJ d isorder (Feinberg 2010 Pelronisl0 10)

Changes in DNA mclhylation rollow ing early lire stress IlJ C been asoeiatcd wilh long-term lthanges in gene cxpresshysion and behavior and Lhere is init ial e middotidence lhat lhey eO llshytribute 10 bOlh psychiatric disordc[$ and rh ys iologieal diSlurshybances laler in lire (Champagne amp Curley ~009 G luckman Hansan amp Reed le 2007 Runen amp Mill 2009)

Research using rodenl mooels provides ditect evidence for Ihe rore o f etrly li fe Stnss on lhe epigenome a number u f dmiddot lailccl revicws have becn ncently published on Ihis subjec t (Champagne amp Curley 2005 2009) Perhaps Ihe best known example is a repon that variation in mruemal eare in rotS allen DNA methylatiun and hi stone acecy lat ion neM the glucoconishyco jd receptor gene tnuclear rcceplOr subfamily 3 group C membcr I ) in the hippocampus of the offspring directly atlc-clmiddot ing tr1Ilscription and subsequenl stress respon~ in adulthood (Weaer ct OlL 2OQJ) A crossmiddotfostering design was Ilsed 10 inshyrer a causa relation ship beI ween materna carc and pigenelic dinmiddoterences and i was also discoven~d Ihat tbc chang~lt in DNA methylmion eould bc reversed us ing epigcnelic drug

_I 1624

trealln~nLs Despie slimulaling resarch imo the epigcnetic consequence of early-life adersil) these seminal fmdmgs lt1wail conincing ctCCumulation of positi e replicarion resulls

Research on epigenomic changes in humMs occurring in response 10 early-life ad crsil) is considcrably more limited

and the rc sults marlen difficuh 10 interpret given lhe b iologshyie rechnical and mClhodologicul iS$ues inhcrent in how the srudielt have been implemcmed (Beach Brody Todorov Gunter amp Philihen 2010 Heijmans amp Mill 2012 MeGashymiddotan el aL 2009 Tyrka Price MarsiL Wallers amp Carpeller 201]) The few human sludics are a1l characlerized by relashytive) srnnll ehanges in DNA mClhylmion and Ihe biological significancC of lhese changes is )Cl 10 bc eswblished ur parshyti cu lar intercst are Jepons of differential DNA melhylation in genes relmed to immune funct ion and innammalion in POIshytmummie stress disortler (PTSD pati en l~ Smith et al 1011 Uddin et a1 010)

A[lhough [her is mounting intcrest in cpigene[1c epidemiddot miology the field is sllll in ilS infaney Splcific re search inlo the epigenelic consequcnces of ehildhood vioJcnee vicshytimilation in humans is I--k ing allhough research using roshydem models suggesls polent inl links between earl)- life advershysity and epigcnomie plaltticilY To date vinllall) aU research into the epigenclic eonsequences of early-life adversiiy halt foeu sed on DNA m~hylalion changes near a priori candidme genes thoughl 10 be in volved in mental disorders Slre~ -remiddot

sponse pathways or neu ral plaslicity lt is thcrefore uncear how applieable the nsuILlt are fo r underslandin g physical health Howevcr recem advanees in genomic lechnology make it feasiblc lO undenake unbiased whoe genomemiddotseale studies of DNA melh)lalion in response 10 early-life suessors such as violenee victimizal ion As research Slill1S (Q identify epigenelic ehanges relming 10 earlymiddot life advell ity and ph) sshyeal health je will be imponanl 10 question (ause and effect disease-associated differemially Illthylmed regions may anse prior to illness and comribuLe 10 the disease or could be a seeondary effccl of the di e1Se praeess orofthc medieashylions used in trealment Hc ijmans Tobi lumey amp Slagshyboom 2009) I1 may be difficult (pernaps impossible) 10 obshylain eausal e idence linking childhood lrauma 10 altered DNA methylalion and ~ ub)cquent di sease given Ihe elhical issues involved in 10lpleOlenllng causa sludy design s Large 10ngilUdinaJ epidemiologieal eohons are an ideal resource for epigenelic re search but in such sludics wbole blood 0 1 bllCCfl l ce l1s ure usually Ihe only bio logicul materia ls archi ved whieh is problemalic because DNA melhylation differences could be co nfounded by difference$ in the ce llular composilion of sampies from different lissue sourees Another key queslion concems ehe exterll 10 which erlsiy accessible issue (such al blood) can be used lO ask qu estions aboul inaccessi ble tisshy$ues sueh as Ihe brain and olher intem31 organs lDavies CI a l 0 12) Finally b~crluse there is a considerabk interesl in epimiddot genelic research in both the seicmific and popu( press il is

imponant thai epigene tics should avoid hype and unreali slic promises and keep in mind [hat optimal research melhods are slill ver) much under construction

T E HoffiC (lId ( Kla5middotGra~middot1 201 2 TIulIk Tonk

Chifdllood iolence exposure arid gene ep renioll outcomes

PeripheraJ blood gene ex pression is an interesling recen deshyvelopmem in stress bio marker rouml eanh wi Lh opponunilies for hoth hYP(gtihesis-dri v~n researc h md for hypothesis-free discovery (Sunde 2010) Blood ce l mR NA expression can be meas ured ei ther Ihrough lhe cilndidate-gene approach Ihm iso in one ge ne at a time through [he whoJ genome transhyseriplomie approltleh using array syStems cr through the si shylIlultan~o us analysis of 30 to 100 related genes ~deeted 10 ~prsenl ltl biolog ical SSlem (Sunde 2010) Two main biomiddot ogleal ~yslems involved in Ihe stress reSplln~e the hypOIhal amie-plluitary-adrenoconica (HPA ) axis and tbe innarrullilshytory system have been tllc foeus o f smilll number of shldies in l1umans thaI hrlmiddote examincd peripheral blood gene expresshysion (olOvi ng ex posurc lO severe stressofi These sludi es have lended to examine adul Pilii~nts with PTSD or oLher slressmiddotrdated [omls of psychop2lhology wllo had eXJXrishyenced recem lraumalic stressors such as the evcnlS of 91 I mililary com bat or assJU)[ (Mondelli el al 1011 Sarapas el aL 2011 Segman 11 al 1005 Yehuda et al 2009) Olher sludies have idenlified gene express ion diHeren ees assoeialed wilh more cluonic adverse e(perience~ ~ ueh as malernal sepshyaration in rhesus mon~es (Cole ct al 2012) or poveny longshyteml caregjvjng and loneliness in humans (Chen Miller Koshybor amp eole 2011 l-li11er el al 20GB r lil1er Rohlede r amp eole 2009 ODonovan CI a l 2011 ) The emerging literalu re Q4 indicilles a roje for gene expression in mediating lhe effecLlt of stress exposure on the immune system and Ihe sympalhelie nerous system However st udies of children linking gene expression 10 violenee eltposure ltIre fe ltLabome el aL 201 2) This research arca is )e 10 be devcoped

Childhood dolelee expowre al1d meltal hea fllt OUCOflles

Although menlal health is nOt a direet su-ess- physiology meashy~ure we incJude il here because il is one indicator of the health SIJIUS of Ihe brain (lupien et al 2009) and cvidence is mounling thai mental disorders invol vc ph)siologieal changes such as elevaled innammnlion (Soczynska lang Keuned y amp McIntyre 2012) Moreover sa nte research sugshygCSLlt thai iolcnee el posure has iLs greatltsl cffect s on future health amon g the subsei of middot iolence-exposed indi vidual s who deveop meniaJ disorders fOllowin g vi olenee cxposure (Danese et aJ 2008 201 Heim CI al ~OOO Vythilin gam el al 2002) Thc disabilil) causcd by psyehialrie di sonlers is growing panicularly in deeloped Wcstem nmions where fhe burden of eo mmunicable di seases is now reduced and psychiatrie conditions aecounl for over 409 of all years li vw with disabilit) according 10 Ihe World Health Repon (World Health Organimlion OO) Associalions beleen ehildhood victimizalion and adull mental disorders have been reponed in relation to expos ur~ tO domeslic violcnce_ phsieal abuse exuaJ abusc emorional abu se and neglcel (Kessler el al 201 0) Research hls al so chalenged Ihe

Chifdhood erpU5Ure 10 IiO(IlCt lIlliftiollg helIIII

view Ih t buJlying viclimization is hannl~s by shO ing thai il increases Ihe risk of psychiatric plUbJcms (Arsenclult Bowes

amp Shakoor 2010 Fishe r Ma ffitL el al 2012 Fisher Schreshy

ier Cl al 20 l~ Win spcr Lcreya Zanarini amp Wolke 2012) Taken together the cvidencc shows Ihat childhaod via middot

l e nc~ vicumizaliuumln i$ U5soci ated with risk for (a) man) differmiddot ent kinds of psyc hiatrie disorde rgt (b) como rbid lry (e) ul1fashyvorable course of illne s and (c) poor [reJuncnt response 1t is dlfficuJI to idenlify a d isorder 10 ohicn childnood viclimizashylion is not linked h is signifieamly altsocimed iln mood disshyo rders anxiel Y disorders behaviordisorder and sub$tallceshyuse disorders and with an indivi(jual havmg nlore lhan one of Ihese disarders simultaneously (Gree n et a 2010 Ke$I-r Cl al 2010 Seot McLaughlin S milh amp Ellis 2012) A reshycent discovery is lhat childhood vjul ence victimizillion is al so linked 10 schizophrenia psychosi s and p ~ychOlie- like sy mpshyIOms (Areneauh el al 0 1 L Toth Piekreign Strenach Roshygoseh Caplan amp CiccheHi 2011 Vareseet al ~O I 2) In re middot rillion 10 coursc o f illness il mcta-analysis revenlcd thal childhood maltroltment pndicis an unfa vorable eou~ of de shypression as defined by both recurrence and pe~iSlence

fNanni Uher amp Danese 201~) Le$s evidcnce is available aboul the course of other disorders but in tnalyses undershytaken for (his anic c in the Dunedin sludy childhood mal middot treatment significanlly predi etcd a more reCllrrent ca urse o f majordepreltivc disordef5 anxiet) di sorders alcohol-depenshy

dence di~orders and dng middotdependence disorders In relation 10 treatmcnt rspon se a metamiddotanalysis o f clinicill triltll~ reatmiddot ing (jepression showed th ai childhoa d maltremiddotumenl was assoshycialed with clevalcd risk o f nonresponse or relapse during trealmem (Nanni CI al 201 2)

Ho good is the e vidence and how sl long is the conneeshytion As usual il depends on stud y melhodo logy Toda) ehi ldhood iolence exposure is a widel) accepled cause o f psychiatnc disorder Hoever his is arecent hi storicI deshyvelopment ThiIly years ago childhood maltreannent was nOl included in mo sl etiological theories 01 mental di sorder in part because man) fo rms of mallreatmenl wert considered to be 100 rare tO account for population prevalencc r2leS of psychiatrie co ndilions Fuumlr his reason 10Ilgit udinaJ-epidemi shyologieal $lUdics launched ns laie il S the I 970s did nOI s)sl~mshyalically inquirc abOUI violcnee ex posure As a resull much of our information linkin g childhood violence viclimization O

adull psychi atrie diSuumlroer relies on un weIJ adults retrospecmiddot tivc repons of Iheir vicumizalon Year$ in lhc pas il mClhod known O introduce bias (Susser amp Widom 2012) Oie danshygers of I1trospeelivc data are kfIown normal fo rgelling re vi shyStOUiSl recal bias by respondems knowleJgc of subscquent d leilSC oucome bias from responrJents cogniti ve dys fullcshylion or allered mood and lelcscoping of ncalled cvenlS Oeshyspile Ihis reaon forcaulion pc~ua$ i e studies Viirh prospccshyli ve measurcs of ia lence exposure and s tudics o f siblings diseordanl for viulcnec have lendcd 10 confirm lhal child shyhood violence cxposurc leads to poor menta l hcalth in ado lt- cence and adulthood (A~enlilult et al 2010 Gitbert el a1

Q2 2009 KcnrJler CI a1 2000 Nelson Cl ar 2002) Hoveve r

1625

in gene ral relrospe(ivc viclimi zati on is mo re strengI) as somiddot eiated Wilh disordcr man prospect ive viclimi7alion a differshy

e nce Ihal is e idcnl in wihin -sludy comparisons as wel as

in belween-stud y eompari$Ons (Gilben el a1 1009 Susser amp Vidom 20 2 bUi sec Seoll et ltll 201~ ) As ~uch it i ~ Q2 wi se 10 be caulious when estimating how much oflhe p~y chishy

illnc discase burJen in the population could bc reduced if all iol ence middotexposcJ children were successfull) treatcd Final1 y allhough viol - nce ictimizalion is a pOlent ri sk ractor fo r deshyveloping psycnhmic di sorders Ihere an markcd indiidual Jifferen ces in reltponse and many thildren who are victimized rcmain healthy (Ciccheui 2013 Ciccheni amp Ragasch 2009)

Childhood d ueIce etpOSllre alld nearopsyrhological heltdth olfcomes

Neuropsyc hologicaltes$ aJl ~ens jli ve indiCalOrs of integnty u f the brain and it ~ mental funelion~ An aggregate of an ind lshyvidual s neuropsyeho logical abilillcs (hc IQ) is a pmven relishyable pocdiclor of life-Iong health all-cau se morbiJi ty laIe -life fraill y and early mortillil Y (Oeary Whit-man Starr Whnlley amp Fox 2004 Gonfredson 20] - ) Moreover the rQ is he best p redielOr o flife suceess oUlCome~ Ihat enhance midlife Ilealth cducilti on occupationa auainmenl ami job performance (Scnmid r amp HUnler 2004) A bird s-eye view of heory linkshy

ing c hildhood stress 10 bmin heath includes a scquenti al chain in which earl y- life ehrom e stress di srupls Ihe homeo swsis of -tress-biolog) sY~lems (includillg illflammaton anJ HPAshyax i$ hormones) which in turn disrnpts nonnal deelopmem of brain S ITI1Cture~ whi ch in lurn produces observable defrcits in stress-exposed inrJi idua l ~ leSied leaming memory and alshytenlion capaciues (Daneseamp McEwen 2011 kEwen 2012 Sapotsky 1996) Al o f these (hoorelical sleps in Ihe causal chain hVe been we il worked oul in ammal s1ress research parshylicularty in rodenl modcls (Millan el al 201 2 Shors 2006 Teicher Tomodil amp Andcrscn 20(6)

A handful of SlUdies have compared maltreated ehildren 10 tompariso n children and delceLed defieits in the omnibus IQ ilS weil as lests o( memory exccul ve functions artellion and conc cntmtion (revieweJ in Wilson jilnscn amp Li 20 11) The hallrnark longitudinll follow-up of 413 ofli ciall) substamishyaLed ehild mallreat mem victims showed Ihat as aJults Ihey scored on lvernge 10 IQ points belo tnalched commis (Perez amp Widom 1994) Chroniciry 01 exposure is imporTilnt a Sllldy of 1777 childnn registercd with Child Prolecli ve Sershyvices reporTed thai ehidren viclimized chronically aeroS$ multiplc years had lowcr IQs (han children who were s ituashytionally multrtjtcd (Jaffee amp Maikovich-Fong 1011 ) 10 Ihc E-Risk Longitudinal S tudy of a nationally represenlauve UK birth cohon o( 2232 children physieal mallrealm-nl freshyquent bul1ying victirniz3lion anu uomeslie vio lence cIiposure were each independently associaled with a general neuropsymiddot chologicil l dcfi c il cf 4 10 8 fQ pointlt (Jaffee Caspi Moffill PolomiddotTomcis 8 Tayl or 2007 Koenen Moffill Caspi Tay shylo r amp Purce 2(03) Jn an alyses undertaken for thi s lf1icle in thc Dunedin longi tudinal sllIdy maltreated childrcn scorcd

1626

on awrage 5lQpoints Jower Ihan cohon peers as adolescents hUl when the same children were reteslcd 25 years taLer lhc defie1 had worscnOO 10 8 poi rns und neuropsychologiealieslshying revcaled Ihal formcrly mallreated children had delicll in working memory visual-spruial perceplual reasoning ltlnd vetbal comprenension as lare as age 38 Disrupled homeOst3shyltis of SlIeSS homlone bull md innammltllory systems is thoughr 10 aller the brain devclopmenl neces--ary for heatlhy neuropsyshychologiea] funClions slIggesling Ihe hypolhesis Ihm trejlshyments ablc to TCestabJish homeoslaltis in melte sysems may enhanee menta] abili ti es

Childwod Iioellcf (fJOsure (lIId neliroimogillg OlfIcom(5

Neuroimaging measures atJow inferences aboul Ihe SlruclUrIIl andlor funclional inlegrilY of lhe brain StrucJUloll measures such as Ihe size of specitic brain regions and volume or grc) and while maller are 1s~essed Viilh siructural magnetic resonanee imaging (MR t) In COnLraSI funClional MRI (fiIRI) relies on changes in mc blood oxygenalion level ~ a eonsequence of nellfona aClivalion and Ihus measures neushyronal actvit) indirec tly and with a delay of ~eernl seeonds bUI -ith a high spmial resolution Participants in fMRJ studies are l)pietlIy administered tasks 10 measure brain activation POSilfOlI emi~sion tomogmphy me1Sures changes in lhe bJood now tO re eal aclj ve brain regions Diffusion tenlor irnuging gscertains integrilY of vhite rnaLer trocLS connecling brain remiddot gion s A considerah le number of neuroimaging sludie using these tcch nologies havc invesligatlaquol assoc imion~ WiTh ehiJd mahrealmenl Bccausc of chalJcnges in undenaking neuroshyimaging of young childrcn most tudics havt examined adult patients with lrduma-related psyehiallie eonditions (eg Anshyd~l$en amp Tomada 1003 Weniger amp Lange 2008) or adults who retrospectvely reponed mallTCatmcnl (eg Cohen amp Grieve 2006 Dannlowski amp $Iuhrmann 201 2) Because of Ihe dlffieullY or lesting children wilh fu nctonal activmion paradigms mOSI sludics of children have reponed only strueshyturnl MRI measures Two reeenL exceHeni and eomprehenshysive re iews have summarized and criliqued Ihe neuroimagshying literlture on ehild violenee exposure (Han amp Rubia 2012 McCrory lJe BrilO amp Viding 20 10) concluding thaI structura and funciional finding~ have eonsislcmly apshypeared in lhe cireuitry of the frontal and limbie reeions of the brlin which include slructure~ such as the hjpp~arnpus am)gdala snimulll prefromal conex orbitofrOnt a conex and anterinr cingulae gyrus

Cerrain nOlanle palterns Javlt e1nltrged (rom Ih e many imngi ng sludics ~ported _ The hippocampus hJS been a Slal Cshyillre 01 spe(jal focus because animal models have shown Ihal stress middotinduced high levels of glueocorticoids over prolonged pe-riods of time ean impede hippocamp31 dcvelopmem und impir Illemory A meta-malysis of stru(lurnl im3ging sludies eoncluded mal hippocampa volume is smaller in auuts (Cshy

poTting 1 childhood maltreaLment history bUI nOI in 1nlltrealed el1i lulln proznpting Ihe h)polhesis That chi ld hood SIItSS may cause abnom1al hippocampal developmem Iha on becomes

T E 4of lind fflt KlolIsmiddotGlmH 202 Fhlllllt Ttm

deteelable in Ihe mature bmin (Woon amp Hedges 200~) A cau shylionary note has beeo raised by the fincling that hippocampi were small in nontraumamiddotc-xposcd monozygolic twillS o( PTSD pmien1~ suggesling the possibiliry timt inherlled small hippocampal volume anledmcs nlutna exposure and poses risk for PT$lJ (Gi lbenson el al 2002) The ammiddotgdalfl has QS also been a frequem suhjcci 01 study because it is involved in rear conditioning amI negative emouonalilY and resea reh suggcsLS stress eiln enargc 11 ltDavidson amp McEwen 2012) ArThough Ihere are a few funclional findings u meta-lIlalysi~

did nol yicld consislem s[rucluml differtnces in amygdala volshyume (Woon amp Hedge~ ~OOS) Another brnin Slnleture thai has reeei vOO much attenLion in sruclies o( maltreatmem ~ lhe prcshyfrontal conex of intec-si becausc it matures laie and may (hus be especially vulncrilble tO e~ly stress and becaust it is inshyv(lJved in emolion regulation Siruciural abnonnalitiouml in thi~ region have beeil reponcd for maltreatcd juvenJics (Anshydersen amp TOfllada 100~ De BeJlis amp Keshavan 2002 Edshymistoll el al 20 11 Hanson CI aL 2010) as have a few funeshylional findings Thi~ lilemluw alw contains scaTlered findings involvll1g lhe cerebellum (De Bellis amp Kuchibhalla 20(6) wh ite maller mets (eg De B~lIjs amp K~havan 1002) and omer brain 3ltas in relation 10 ehi ld maltrealmenl

As a calloon the ncuroimaging litermure is Far trom add~sshy

ing me question of caUsaJiLY as it lacks cquivaJen measures in eXpltrimcnlJ an imal models locks difTerentiai imaging findshyirtgs omong siblings diseordant (or childhood vioene~ exposhysure rmd also lacks pruspecue studielt shoving withi n-individshyual change in imaging mea~lUes from before 10 after violence exposmc In particuJar sampIe siles are gentraly far 100 small to Juempt indoding swlistical conlTUumlls for lhe lio$l of co~Jaled factors known 10 be a5sociated wilh chi ldhood violenee expomiddot sure and ils eOllsequent psychialrie condil ions

Inlen entions for Childhood Violenee Exposure

Jr middote presume mal childhood vioJenee exposure is comnlon and thai i ean alter ietims- Sires biology to eenwally inereasc adult disease szliglorbidiry and mOtlliF) Ihe quest ion arioes what mighl be done ahout this Prominent questions concem prevention nnd r~yersib i liLY (an physicill harm 10 booy and brun be redueed by fam i) programs that prevenl chitdhood iolencc exposure Catt hann be reversed by individual psyshychosocial treatments Iht1 reverse Ihe psychologieal sequelae of mahrtatmem In Ihis seetion we brielly note imerentions mal hae been scienlifically 1e5led and dcclared promi5ing for preventing 01 nverling outcomes of ps)chologieaI hann Gur sllggcsLion is that slress-biology measuICS ougbl 10 be added (() oials of imcrvelluons likc these 10 lesl wheJher mey mignt a l ~o prevent or ree~e phy~icaJ hann 10 body and brain

lIleelll iollJfor chidrell 1110 haFe erperienced oeJceshyrelared IuUIliO

Sevcral rev iews have evaluared psychologieal inlcrvelllions for posuroumatie r~aelions in children ineluding bUI not limshy

Cliifdhood er(lOJIIt IU Iioleure und I(Molig henilh

iled to violcnee-indueed u-auma (Cohen Berliner amp Mannarshyino 2010 MacMilian et al 009 Penin Smilh amp YuJe 2000 Robjanl amp Eucl 2010 Rodellburg Benjamin dc Roos Meijer amp Siams 2009 Rolfsnes amp 11I~oe 2011 Stalshylard 2006) These posnrnuma reactions 3re nOl eonmained 10 PTSD symploms but inc1ude a hosl o( emotional and behashyiora1 sequelat (Camon amp Klcller 2012) The evidencc ba~e has been criticizcd (ur the usua melhodoogi C 1 shoncomshyings known 10 bcdev il treatment research (Mikton amp BuIChshyan 1009) Nevenheless meta-analyses and systcmatic reshyvie s of randomized elinical trials idenuumlfy cognili ve behavior Iherapy (CszligT) approacht~ as efT~lie spec ilicltll1y

trauma-foc used C szligT (fF-CBT Kowalik Weller Ve nter amp Drach man 1011 Rolfsnes amp Idsoe 2011 Slal13rd 006

Q6 Wethinglon el aL 2008) TF-C BT combines parent and child skill s-bascd componenls wilhin ltl framevork of a rrauma model These compone nt s inelude ps)chueducation (infor mltlLion about lrauma and trauma reaetion l pareszligling sj ill~

(ie behavior managell)enl skllls) relaxation skil1s (to manshyage phyltiologicaJ rcaclions 10 tIltluma) lt1fleclive modulation skill s (10 manage affective re$ pon se~ (0 trauma) cognilie coping skills (10 exp10rc ltlnd discU5S connecrions betw~n

though tS feeling and behuviors) LrrIuma narrative and proshyccss ing (to COITeCI cognitive distonions realed to trauma 10 reorganize memories) in vivo maslery of trIuma reminders laquo(0 oe rcome generalized fear reluted to lrauma) ami ~are) planning fuumlr the fUlUre These component$ are laughl in parshyallel purenl and child session as wcH as in eonjoint cbllushyparem sessions The number of sessions vmies b~lwcen 11 und 16 TF-CBT appears (0 reduce PTSD-related symproms and gen er problem behaiors Rece-nt srud ies on TF-CBT not yet included in mcta-anal yses or re iews suppon the premiddot vious conelusio ns bul also add new insights A trauma narmshytive is nOI nece~saril y needed (Deblinga Munllanno Cohen Runyon amp Sicer 2011 Salloum amp Owrsuc bull -1 2011) aud TF-CBT also works wilh children of different ilges from preshyschoullo high ~chool (Nixon SlC rk amp Pearcc ~Oi 2 Selle~ rshy

ing~ 7eanah Drell amp Lameu 2011) Olher IreatmenL for violence-cxposed childrcn an tnder initial c-uuml luation for exshyamplc Eye Mo vement Ocsen$itization ami Reprocessing (Rodellburg CI al 2(09) ami Narrative Exposurc Therapy for Children and Adokscenls (Robjant amp Fazd 201 0)

InfCnenrionsjorOll1iJies to redlee chidrels vioence etlJDsure

In addition 10 interventions thai direety rreal child viclims there are ltl number of uther psyehosociallszligtercnlions availshyable 1O enbancc ehildren s psycho~ociul adjuslmcnt in the contet of violence exposure by working wi th parcms or with parcnLS and e bildren logether These inc1ude intervenshytion progroms intended 10 rcduce iolence cltposure and pre~

vent child maltrealmenl by pnwiding edueation and supen ishysion 10 paremgt of ver) you ng children Nurse-Farnily Pannership and early Slan are cxaOlpll~ of IWO home- visitshying progrJOlS with bi aim thai hnvc been cvalualcd as effecshy

1621

li ve (MacMillan el al 2009) Iso among the leader are inshytervention to reduce mk ofchild maltrcalmenl by improving parenting such CiS Projecl SUPPUil (Jourilcs et aL 2010) and Pathways TripIe P (Prinz Sanders Shapiro Whilaker amp LUllker 2009 Wiggin Sofrano amp Sanders 2009) and trealmonlS aitning to slrengthen inrant-p~lren attachmenl in familie al risk for mahreatment (Ciccheni Rogosch amp TOlh 2006) For examplc Project Suppon is n family intershyvention to provide in st rument and emotional suppon 10 mothers and teach Ihem chi1d-managemenl skils TI was origshyinally developed 10 red uce eo nduct problems in chidren from familie s u5ing domestic viocnce shelters As another examshypie parent-thild interaction Iherapy (Chafrin el ru 2()()4 Chaffin Fundcrburk Barr Valle amp Gurwitch 20) works with bOlh Ihe violencc-expused chUd and Ihe (nonoffending) parenl ltti ming 10 impromiddote paremaJ skills and mOlivalion 1nd enhmce parent-child imerac tion s This is aeeompli shed by direct coaehing of parent- and direct prJclice o f skills in dyashydie parem--dild sessions Preiminary evidence points 10 the $ignificilncc of an additionltll module (six motivational sesshysion s) when working wilh families in child welfare fo r child mahreatmen l

The TripIe P syslern WltlS ealualed using a cluster doumlig n 10 randonnze eighteen counti es in South Carolina 10 cither Triple p s soc ialleaming-based pmgram or 10 a care-as-usuaJ cOnlro l condil ion Following intervention the TripIe P counlies obshyserved lower rates of found cases of child maltrealnlenl hospishyralizations and injuri cs due to maitrealmenL and outmiddotof-llOme pRCemenL~ dlle 10 malrreatme nt (Prinz Cl aL 009I Thls was Ihc rmt time a public hcallh parenring intervention has shown posili e population-level eflects on child maltremment in a ranuo rnized dC5ign with coumy as lhe unit of mndom asshysignmenl BOIh ex perimema and clinieal reseanh havc demshyonstrared that stnlClured parenling programs are among the mO$t efficacioll s intervent ions ltlvrulable 10 promotc Ihe menta] health and we ll -being ofehildren paniculary in families who are ar risk of malrreatment (Mihalopoulos CI al ~O J I Nat ional Re~earch Counci ami In litute o( Mcdicine 2009)

Intel1tntions f or coupes 10 redllfe chid rCIlS vioef(middote emiddotlJosure

Cllildren are psychoogltull y harmcd by exposurc 10 intimate partner violence bctween adullS in Ihcir lives a~ weH 8$ by conflici belveen their parcnts fBuehcr Cl Oll J 997 Cumshymings amp Daies 2010) Moreoer research h~lt further shown Ihal inrimatc panner violence among adu11s coincides with phys icltll mallreatmcnL ofchildren in Ihe horne al rates far beyond ch1nce (Usofsky 2003 (i)verlien 20 10 Tayor Gu~

temlan Lee amp Ratllouz 2009) Given these tWO flndings inshyterventions effeclive ar slrengthening eouple relalionships and redncing cuuple conflici mny Iso hnve he unepeelcd bellcHt of rcducing childhood middotiolcncc exposure and psychOshyogiea l hann Treating patents ma kes sense becnusc the youngcr u child is the more like1y Ihal middotklimization is perpcshyirntcd by pltlrentlt (Finkelhor 199)

1628

Over rhe last 30 years approximat~l y 100 clinical trials have denlonstrarcd Ihe efficacy and effeclj vcness of cognilive behavioral couplc inlerventions 10 reduce connici am prevem relalio nship dislress and diorce (Hahlweg Saucom GraweshyGerber amp Snyder 2010) Allhough couple progrnlTIs scem La bc effeclive in reducing conOicl ev idcnce is lacJing Ihallhey areeffeclive after a couple has heconle physicall y violent and thus most programs aim at prevcnlion eltlIl y in rclation ship s Forexample skills-based couplcs programs SLlch as Pre marshyilOl Relation ship fnhanc~mcnt Progrnm (Markman Floyd Stanlcy amp Sloomsli 1988 Markman Renick A o yd Sanley amp Clements 1991 ) Premantill Prepanll ion-A Coupks Le1rning Program (Hahlwcg Markman Thurrnair Engl amp Ecken 1991$ Thurmaie r Eng amp Hahhl-eg 1(99) or Freishyburger Stress Prevcntions Program (Bodenmann 2004) hae dcmon slrat~ effectiveneslt Moreover Ihe Prernanral Relashytionship Enhanc~menl Program and the Premarital Prcparashylion-A Couples Lcarni ng Program eourlelt have shown sigshynificanl improv~ outcome ~ an~r 5 -ycltJr follow-up Given diorce rltcs of about 50- ac ros ) countries anel knowledge thar couple conflict and separalio nldivorce ru-e altsociued with increascd d sk for children s violence victimintion early inte entions 10 enhanee coupl~s relJtionship sJtisfacshy

ti on may be an imponam slrmegy 10 rcduce ehild harm (Hahlshy eg CI al 2010)

Bringing Strcss-Biolog~ Researcb and Clinical Inlenention Scicncc Together

As implied by Ihe title thi s anicJe invi tes interventio n scienshyri ss and stress-biology researchers 10 collaborare in adding slress-biology mcasures 10 randomizcd clinicallfials of intershyventions ililended 10 reduce effeets of middotjolence exposure on children Doing so would filllWO scienlilic gaps

The lirst gap eonccrns a potemial benelit for treatment trials objccrive meaiures o f imponam treatment outeome jtmiddotlost psyehosoeial intervention trial s collcct on I) a narmw se i of outeome da1a limiting themsclves tO such targets as children s PTSO symptoms aggr~ion emotional problems school aehievemem or relat cd psyehosocial meas ures Such asscssments entail me thodologiea l chrukngcs suh as [he need for objecti ve raters ho are hlind to trearmen l In ilddishylion behavior ratings can be insensitivt as c hangc indicators ltlnd agreement belween adult reponelgt is ofren welk In conshyIrl5l beforemiddot- and afler-trealm01 meltture s such as fMR L inshyOammation conisol naclivit or ne uropsychologieal tests of art~nti()nul vigilanee are inherently objcctimiddote and miglll prove sensitive 10 treatment cffee ts In any case it is fundashymentally imponant w lind Out if psyehosoe ial intervent io ns actually can sruft slreSsbiology indicawrs

The seco nd seientitic gap coneems a potemial bellefit for s-1ress-bioJogy research nc answers 10 the thorn y queslion of

cau~ti on Our review aoovc re ea led that alrhough Ihere i~ rnuch exciremenl aboul SLreSS biomarker research evidencc of simple association in human ehildrcn is very sparse and therefore testlng for stress-biomarker abnonnalities in sam-

T t 4o)ji l arulhe Klals-Gml t 2012 ThjJk Tank

pies recru itcd for vioknce-exposure treatme nt trials would add bad I) necded basic descriptivc data We funher noted Ihat elhicaJ and logi slieltll ehal1enges havc made I1 diflicuh to test -hether psychosocial stre ssors wly ca use alteraions in body und broin lJ1~nsllrcs in humltln children therefore the eide nce base foreausmion remains moslY observmional 8y themsel vcs intervention studies that generale pre - versus po~1treatment or lreatme nl -ersu s control differences in chilshydreumiddot - in narnrnatio n telomere erosion or cxecUlie funcLion by treati ng vio lenee exposure would nOI uncontrovenibly prove Ihat vio lence exposure damages health (jusl as nducshying feve r wilh aspi rin does not prov~ that aspirin dcfieiency eause- ~ feve r) Howevcr intervention ui~ls wlth rolldom lt15 shy

sig nment co uld add nowmiddotmissin g experimemal cvidence ro augme nt causa inference Same c hallengcs tO and the eonshysiderablc benelit s o r integraing biological m~urernenlS

into inrervcn iou studies have been di se ussed previously (Cicchelli amp Gu nnar 2ooS) A ver) sma11 num~r of vioshylence-relared Lrcatmeszligl trials have ltlIready incorpornlcd stress-biolog y mc~ures and we inlroduce examplcs ot Ihem beimgt The nex[ seclion al so makes rccommendntion~ for research designs

TreQll1Ienr Tri(lls incorporafillg stress-bioag meawres

Ar leaslwo reportlt o f successful small- scale clinieal rri als o f interventions for maltremed pn iehool c hildren have reponcd thaI on averoge lrealmcnl normali zed leve ls of he stress horshymon e coni sol (Ciccheui Ragasch TOlh amp Srurge-Apple 20 I I Dozier Peloso Lewis Laurenceau amp Lev ine 2008 Fisher Gu nnar Chamberlain amp Reid 2000) In ad dition o ne neuroimaging study co mpared psychoeducmional and cognitive behavioral group lreaune m versus u$ultll rreatmcnt for l1lahreated children with PTSD Treatment indueed changes in (he nctivauumlon of the aJl(erior cingu late gyrus and inSlIla thai we re detecled by f1RI during a Stroop intcrfershyence lask The changes v cre interpreled as renecring inshycreased selecti -c aue ntion and 10er emorional arousal after Lrclttrment (Tho maes amp Dorrepaal 20 12) There is alo ershydenc~ from neuroimaging studie5 in adult s Ihut treatment of rTSD induees changes in brain lunetio n on fN1RI (eg Fel shymingham el aL 2007) Finally a 3-moszliglh mediwtion inrershyvention has been reponed 10 be assoc iated with highcr teloshyrn emse aellvity whieh could lengthcn lelolllens (Jacobs et al Ol l)

In addit ion (0 thi s smalJ sel of treatment studies there are olher illuiguing indicalions Ihat ilHcfentions of varying types might be able to reverse Ihe cffccts of violence exposure on srres s biology (Oavidson amp MeEwcn 2012) With respeci 10 telomere erosion evidence from a gcnclically modified mouse model shomiddot~d thai pharmacologieaJ activ ltI lion or tel shyomerJse reversed indicators o f mouse ltlging (Jnskelio ff Cl al 20 11) In humln studies healthy diel and high sociaJ suppon ltll1enuared 1he relalionsrup belween shon telomere length and presence of heart d isease (Dia7 amp Samuni 2010) a od reducshylion of psychologie1 disrress walt iJssociated wilh increased

1629

_ I Chifdhnod eWOSl11 10 liolillre ond life lollX henllh

Q7 lelomerJse aClivity (DaubenmitT et al 2011) Wilh respcllO epigenelic change epigenelic di sruplion is pOlenlially revermiddot sible and thus is a realistc target for phannacoogical undor behalioral imerven lions Numerous agems hnvi been discoshyercd to nltcr DNA melhylltllion aod histone modificltllions and scveral are beiog testelt in ongoing clinicallrials So-caled epigenetic drugs are beiog devcloped for a range of disorders nlOSI notabl) cancer (Kaiser 2010) and many cumnl ly u~ed psychiatrie medicalions have effccls on lhe epigenomc (BOKS Cl fit W12) One potential obslaclc is (bat drugs that rargellhe epigenome globally can have unexpecled (anti pOlcnually rashythogenic) enecls on Ihe llilnscription of genes lhat are notrne desired targe With respcct 10 chronic intlammmion levels sevcrul effective lrealmems could reduce thein In an initial study of ralS lubjected 10 malemal-$eparation stress lhe egt shypeclcd work ing-mcmory deficit was prcvented hy prophylacshyti e adminisumioll of nonstcroidal ~nli - innammlIory medicashylion (Bnnhou~e amp Andersen 2011) Seveml classolt of medicat ions hltlv~ ami-innammalOry elfects lneluding the frequently used nonsteroidal ami-inflanlnlalory drug~ Exoshygenous glilcoconicoid hormones are allo potem steroidal anti-jnflammatory drugs and same alllidepressant medicashytions also have ami-innammatol) effects (MilleI 0la letie amp Raison 2009) AnimiddotjnOammatory efCects have been claimed for diet1ry omega-3 pol )unsaturatw fltlt) acids physieal cxenisc acupuncture and meditation (Handsehin amp SpeigJeman 2008 Kiecolt-Glaserel al 2010 Oke amp Trashycey 2009 Zhang amp Spite 2012) Finally_ one sludy sugshygested lhat engag~ment in cognili vely based compassion mJining is assoc iated Vilh progressive reduction in sal ivaI) inOammmiun biomarke~ among ad o le~cents in fosler can (Pace et al 2012) These potential reversibility effecls rcmain speculaltve until replicated and long-tenn tollow-up will be required to ascenain whether these changes ltlJ1 maintalned and lranslate into improwd healih oulcomes (Millcr amp Cvmiddot hen 2001)

ReCOlllmelldatiOIlS for research designs

Unforeseen melhodologicaJ challengc~ muSI be solved (j luumlng (he way in the course of any ne rese mh endeavor Nevershylhelelts we offer some stariing recommcndali ons for reshylteru-c he who wi~h 10 add itress-biology mcasures 10 raJlshy

dOll1ized dinielll trinls 01 intervenLi ons intended 10 redu~ effcc(s or violence exposure on chidren

fin-t there are logistic considerllion~ Allow rlen1y of time ami faCe-IOmiddotroumlte cOnlltct for imervenuon ~eienliS(s and stre~s

biolog-isis 10 build iIl cffeclivc collaborlll ve leam The5e IWO profession conrluct scierce under markeJly different sels of assumplions and carl clti ly misunderstand each other Anlicipate mal Ihe usual chnllenges in relation 10 ethical reshyview panicipMI recOlitmenl retention and infonned conscnt may be magnificd by the addition of biomarker dala collecmiddot lion We have found th~ fami l ie~ Md children enjoy biomarshyker data collcclion even blood phlebolomy (Iod they gene rshy(lHy like Ihe nOlion that they are engageJ in real $ciencc

(Howevcr I1 can be cJifficult 10 p-riuade cau(jous ethical reshyview panels of this in advMce) Plan to provide exlra conllshydenLialily rrolect ion for biolllarker dala Engage Ihe therapeushyLic slafr hy insuring they undergttand lhe project rully and have a chance 10 give real inpul to the cJe~ign Learn aboul tbe logisshytics of biomarker dltlamiddotcoleclion FOr CXtlJllp1c for wet llleashysures there are three scparate 51ages initial (igtue collection ussue siorage and taler assay Tissue collection Ilt Orien enLimiddot ci ngl y incx rensi vc wherc-a_ storage space and ~says orten emai l larger hidden COls Con idcr Ihe pros and cons of givshying familiegt feedback on biomarker $latus Ihe) mry epecl a lab repon as is Iypieal after a doctor visil_ but nsearch meashysures are differenl tTuOl clin iltl tCSLlti in [undafllentaJ ways E labli sh in advance wha if an ICel of biomarker elevauon IoulcJ be su fficiemly alarming to warra nt a medicaJ rcfemlI For example neuroimaging has lhe potential 10 deicc I somiddot callcd ineid~ntal findings of neurological diseltse

Sccond Ihere are de~ign rccorllmcndations SeiccL a lreatshyment prolOcoithai is a good bel_ one Ihal al111dy has sirong evidellcc of behuvior-change cffectJvcneltis such as TFshyCBT 00 nOt allo the addit ion of bio marker measuremem lO aller or di srupt Ihe treatment protocol for eoample do not have the CBT thcrapisls dmw blood sampies or give neushyrop~ychologicar le S(s SeJect a ~Iress bio marker outcome meashysllre Ihal is likewise a good bel_ one lhal has slfOng apriori evimiddot dence Ihal it is aJlercd by psychosoeial stress and one Ihat is capable of changing on a tillle scaJe mal rns the inter ention Common sense recommends Slaning wilh biomarkers that arc inexpensive nonin vasi ve repealable and low LeCh Leam aboul lhe distribution of the selected biomarkcr acros age and sex and rccruit a sanlple that can mitigale or aCCQllUnoshydale any such heterogeneity Rccruit a sam pIe of paLienLlt 10 be mndomly assigned to treatment ve~ u s contml who have well middotcharJCtelized and documenled violence-exposure hi slorshyies Onc element thai requires Ihought (and more informalive cJala) js whether to eltroll in intervenuon research only the submiddot sei ofviolence-cxposed young pcor1e who exhibit consequent mental heahh difficulties alti 0pp0oed 10 any viocnce-exposed yo ung people Ad11iniMer psychosoci11 measuremenlS and bjomarker measurem~ms m Ihe ame time Take 3 basehne biomarker szlig)ea$ure beforc randomiation to avoid contamlshynating baseline ilh Ihe palienls knowledge of th~ir group asshysignmenl Repeal biomarker meruurcs frequentl) at lealtt al ba~e line start midpoint and discharge 10 allow rorascenainshyment of Imjeltlories of chan ge across Ihree or more measureshyment points Use a care-asmiddotusual COJllfQl condiuon instend of wail-lisl comrols who are cVl n[ually given the treatment as care-asmiddotusual cOnlroJs enable a long-tel7Tl follow-up comparishyson Oigtcuss (he pOlemial rcputlt1tional COSIS of null findings to bolh intervention sc ie ntiL~ and $tress bi ologislS and agree in advance how an) null findings 111 be rcpuned

Thc need for gllidil~ fheOl)

Man) fundamental quesliolls of a Iheorctical nature need 0 be answcrcd (0 explain how and ho much childhood

1630

vic timizalion contribules 10 heallh problems across lhe lifeshyspan Although a lhorough lrellmem of th eory is beyond Ibe scope of Ihi s article we poin t (0 ( WO k~y areas in nced of lheory deve lopmem (M ill er e hen amp Cole 009) Onc key lheore tical queslion has 10 do wi th Ihe natu re of violence ex posure itselr Are a11 forms of vicljmizauoll (hul lyi ng mal shyLrealmenl domesLic i ol~nce) expecled to havc thc sameco nshysequence5 for hcahh lfsotheory mUSl spcify a psychobioshylogical common denominator these exposures ~hare perhaps a generic cognit ive appra isa l OfT hrea or enhanced perceptuul sen ilivy 10 lhreal-re JaJed cues If nOL lhen perhaps wtlal is epecially damaging for childrens biologica l systems is the profound viol3lion oftruslthat follows parental maltreatmem lhe social rejeclion inhcrent in chronic bullying or pcrsi steszligl f~ nboul safeLy that accompany exposure 10 odult domestie doknee However iL would be necessary 10 explain whal mechanisms allo different exposurcs 10 produce similar (or different) physiologieal effects This issuc becomes even more impol1an l when askin g wh~ther Of noL mechashynisms (o llowin g violenee exposure differ from tllOse arising from olher adversilies such as poveny or parental Joss

Another ke Iheort li cal question has to do wilh mind -body mechani~m s How does vio lence gel under the skin aL Ihe level or tissues and organs to pu sh forward thc pmhogenesi s or di sease Thallks 10 man) years of research il is known in some detail how Ihrcats that elllamlle in Ihe sodal o rld acshy

Ref~rtnees

Andtltll S amp Torndl l - (~~t ~ r11 mlI~ c rJelUt r re-nsluf ptmiddot nob In lhe e[fecr o( chikllillod sexual Ouw 01 ~~1ltIn Iltriouml J eClLgtpshyme1 Juumcrl o vIJl ropl)thivry CllIwr NrljroKTfltmiddott 10 292shyUH

Appll)ard K Egcb 1d R van Dulmcn M H M amp SIU fc L- I ~Wj bull Whcn more is nOl beuer Tht roje Of CU lllulal le ri~ 1 b cbUrJ behJliol oUlcome~ j urm(ll gtjCh ild P~cvJY Pf-middotchi1r 6 235- 245

Arseneaull L BO1lte L amp Sil JIO S 201 0) szlig ufl ) lflg vKI rnltatiol in youlhs and menl] hellth prij)~ lc la Mut h do abc-llI szligotlling PSodlltj shyIV81rl MrdCllii 40 711- n9

ArscocraulL L CannOll M Fitler H L PlanCl)k G Mo(li ll T E amp Casrti A (2011) Childh)lltj ITJ UlTla aUI chiid~l~ ncrciag PSYC hOLl C sympiom A ~ene l tC3ll) e ll~ill~ ~tTud l n p l t-ampUrt rod~ mr Tlct1n Joum il f 0 P~-dlj1l0 1 60~ 65- T

1 1110 A eilen W Gl1ililI~r J P 1oJ1il M Brinamp-onbe M ClJ X e ~1 (2000) Leukoc le l e~ollirc ll )rnmiC5 L(m~iru jl d fioojn~s

among )QU ng ad~ 1S in Ih~ szligogillusa HtU1 SuJ) -lnrNlc1II JOllm ul (f EpidcmlmQiJmiddot 169 323-329

Bar lif n J (Im) f~Ul and ifiIll QrhlfItadJlJI dsfUumlllt LodMl I3 rilshyist- Medic-t Jou11Ql

Boaoh SR BnJd) G H Todlrol A A Gunter T 0 amp Phili tgtrtR - (2010) Mlthylatiol mSLCnA4 i ~ linke mirmJ) h ~ ~IQ) ofclllid jbuoe In cxami1 al~ ur Ihe (0 11 AdOt ~amr~- crnTf Jml mo (f( Mrdshylcol G~(IICS Porl 6 Nturop f) drl1tt1c C ~IItf 1538 1 1IJ--11J

szlig jom5son H T_ Siu rd s~ M I F-l1lill_ M D Inzany RA Aspduml T_ Cui H CI a1 [20051 InU-IuJn niual I~mge oCr llme in D)A mct11ylal i ~n jlh ianuhOl chlttcrin j utrmgl (( Ih( 4mlfinln ) (( JUroNalll 199 2s77- 288J -

BICImdl S LI W Sehl M E S1szligCbr F 1 Sin~heiOkr J S HOl-aih S I 11 (201 I) Eplgcndllmiddot pralkwrs Of j~c 1lJS ONE 6 clJIt 1

szligrxlmrrnn G i ~OOJ Vf nyJfJcl1fJh~mp rc nhT PmTm B rI ~ itll dtcrJpy ~ Ih co~e-s BCMI Swiu r ~ Huber

Boh M P de Jen j 1 M Ka M l VIll~szlig r H Fcm~dcs C Kahfl R S Cl a1 1201 ~ I C UITCnl )31Wi ~f1IJ fu rore Plpt~ r(l(cpifenCli~ p~shythophlln~ology EpiSflICIS_ 7 20 2K

T F Hoffil fild Ihe KluuJ-Gmle 20J2 Think Tank

UumlVate the neural eircuiuy regulaling the au tonomie nervous system and th e HPA ali and how the oulOow o r Ihese t o S)~lems affec ls cGrdial vascu lar immune and metabolie sysshylems A much thomier isw e arises when oe Ionsider the lemshypOrl1 (em ures of lhe conncclion beLieen ehidhood middoticlimi shyzation tnd adult health Most mechani stic kno ledge or slress penains to it s immediate biologieal (middotonsequcnees There is so some undersl anding from work Oll PTSD or how SIJe SS syslems look in situations where the precipilaling stimulus has dissipmed bUI a subjecl ive sense of Ihrcol Hnshygers However the period o( incub aJ ion between child malshyIrcatmell l 3ml eoronary hcan di sease i~ approximalely 40shy70 years Ta bc sueeessrul research anlt Iheory wi i n~d 10

bridge lhat temporal gap in a manner Ihat is psyeholog ieally laquond biolorica1y plausible Does childhood iolence exposhysure seL young people on pathway in whi ch each ad vers ity bese~ fUl1her adversi ties and Ihe cumulali ve efrecis of srress ex pmures sustain risk for laler health problems as proposed in life-course Iheo r) (PoJli ll Rose amp Kau rman 20OS) Is early- life stre ss programmcd ioto physiology during a sensishyli ve period o r ehid dee lopmenL in a perrnanenC irrewribJe manner as argu~d in thc reta] origins hypolhesis (Barker 199)1 TIlese and other big queslions need Iheoreical and empirical anenlion if we are to argue th allhc popularions burden of discase could be reduced j ( a vi olence-exposed chidren were successfull y treated

Boyce W T Sokoklski M T amp RotI I~1L G E (20 12) Tow~rd a lew hioJoumll ) llf ~1i 1$ I~r) l () P rrJfr ll1181 (JI~ NIJI~rJl -n~m v Sc ishy~nNj UN 171middotlt n 14S dodO IlJJJplll~ I I ~ Il6- l09

BnI~1U lle H camp ~n lerlttfI S L UOI ] ) 1OiISI tTOldd ~ l ll lszlignamilliI (H)

lrtllmtTl prew nL Ut-II) OO t f(ccl ~ o( e3 1 1~ lUe ltC~ In rJ L~ n(lulrnl Pflhitllllmiddot 70 -1 J~-+n

BlJlthltrCbull AtllliOay C Kn hnullllllJ - SIOCle G Gcrlnl J amp Pemlxrmiddot ICltl S (1 991 ) ln t~rparen ll arrt~ict a1 J )u ulh rrobl~ m bclt3Vl A IfICUI - lysi jou nr 0 Ch~ ld d FmlUly Sn(uumlr 1) 233-247

Button J L WaJl~rs R G Vi$ ikis-Si e)1 S Meyre D Frn~ue l P amp Blilimltllt A J (20 11 1 Chd dhQod obcn k amp$ ~(( td illi f()I1ef

lelloc)lc le~ I(n~lh loumtJI (gt(0111 1lt 11 fmIlaquorJw~yMII IOIxJIa mo Sf6 1500- 1505

Cmio~ V 0 amp Kkil~f H C 102) T~~ m~11 of lrumall we~s digtoumlr~kr in hilreand dQescrnl Assessmc-lt iUId ITe3lJnent trJ1cgio Pryc i middot n c T1ml~ 29~dall(C onhn~ pYhlarwn

C311 Rol R ~ I Smith K R_ 0 Brien E SI llthtnlo A amp Ke ~r R A tfKH f I $gtocilli1 n bet~~ ldomen lerlglh lszlig hlood aG lilonaHly In pllt~ ed 60 )car 0 nloder Usm o 1~ 39-395

ClolIfTi [l_ 01 FUIloleTOO rl B SarI D -jJk L A amp Gnrwilch R (lI I) A lornhirreci lOOli vJ iun ~nd pilIiI ~ l -drnd InICrwlloll Itzr ry prb~c ~ dUn oh iJII Qoetfar lt Illl i~m In 3 ruI iklnrimiddotu J 1hilllVl tr l) iield ub l JOll r7lfl l CiJrwllIIS amp Ciir1rrof P~t 111ftgt 9_ ~95

Claiiin M Sito ~ ) 1 F Fun~lrk B aIl L A_ BreSWl E v amp Bilili(h a T f201)n 1ltIft~T-lthIM inl~rlCfi (ln fle12PY o llh rh)sKaJ~ abu~he Plirl1W Effi~y for _ ftumiddoting furun ~hu~e reporu Jou mrJ oj Clt7tJS~ltiilS Clmi( PjydwOKI 72 5(l-SIU

ChJmp~ F 1 amp CUIIe J P 2005) How SOltU cxpc ri C l)le~ mOII(JlCC Iht hnin Crrent Op iliuszlig in NtTj~lilt4uSY 15 7()J-109

O amp3gnc FA amp Curiy 1 P (2009 Er igenetic lnclfli~rrgt~ med ~ras

h( JUIlitnn e ff~lgt Ul m~(~rtal Clle on llemiddottllgtr mc nL N~lltm f~l~ r d 8iophanonrJ RtIifo s 33 591 (l(Xl

Che n E Mil lt-( G E Kobl)r M S amp CoS W 201 IJ MimAi JInl lh ouif~~ he effelS of lu earlr-lif- tgtmiddotl tICCQomk St3f~ t pro-mflamshymltllOlY ~i~n~h llg in ad utlKol WQlf c iiJr f)rhior-rymiddot J6 729- 73 7

Clrildhood eXIOslIIe 10 dalelee i1mllff lolIg Inllh

(hriSle illt-fl B C Hou~lJQn E A ol arsL C 1 Zht n~ S Wrensch middot1 R Wie nI1Js J L d a f ~~l A ~m and eOllflmFl1e tl fmiddotIt5IHC~ 1t Cr 11~ ut~lfi c DIA nlCmtmm IkrxndclII upon CpG _111 CClltX t

QS fLo) G(lI(i~ 5 e lC(llJ(]Ol Ctd~IIi D f~nt Anllml ~~tMC~ rejew Roumlil itJ1 funfii~llIp 11 mumiddot

1~L[lt1 cfliJdrc~ fJ l rret tJI uHJ lut1l~ pmpeclic~ h rl m J tlj CiIiM PSjm~ amp P~~~Y1 JI U 1111) ~)_76[020 1 2 02amp1b_

)l2 Ckdeur D ouml Cuni~ W J (1001) ~fl cvcnlmiddotrLICd poIcnuoj ~lUU~ er lh~

o-$Si n1 i I fteIIC f-la ClpreltSiOh In YJ Ufij Ii ~l who cxp-rishy-ncJ matlttllnenl Junng 11~ fi N ~cJro(lire OJImrfumd p~bull IImiddot plt I tgr 17 64 1- 77

CIftI c-ui D amp Gllnnar ~I R aCX rS ) Inl ~r~ Lmg bolllpd llXJSU ~ ir ln lhc J~ iJ n IIrJ clIluJ lion of pnlin LfVe 1nlcrcmil D P rUll i nd 1 ) (lI lIJv) 20 137- 74

Clcmiddothell i D amp RwsdI F A (2(1091 Altloptie clPir~ umlrf Ctgtndai of Clllcmc ~~~ ~1uJti~ C mfiucDlmiddotHgt l Ih~ dCf~n -IIJl15 of II~ilkHCC In

maltrealld chil~I Clr OiflCiWfS m CJrdd w rtf AJfIlmiddotel oT -JIJPmiddot mrnr 12d 7-59

Ciccheui D Rv~ostl I A amp Toth S L t 100(n Folerillg S~Ull mlChmiddot m~nl in IIlfI~ in nmiddotllmIIIIlnf fll1ks lhrou~h pn enli~ inrmiddot~nI ~I IJelflflIllt I ulld phnrgtrh lIJX) 18623-6gt9

Ciuhell i D Rvgo~h F Turn S L amp Slurgcmiddot-ppk M tO I J) 1 l) fmiddot

n14li1lng Ih~ tlcIC]llr-ment oIl(Ii-ut trgulwn 11 m11JclIN tnrlI1l~ lhlll-=h P= c1 li middotc inletlColI n 0 1 fPIIOII 111 P~rh IJ tr(lI) 23 n~middotmiddotsoo

C icchcru D amp TOIh S 1 OO5 Ctld 1Tl1[relltle nt middot wHll r H fr r-f rUmcul l(middotirnv (Vol I pp ~W-4lt ~ t ~ ) Aiw C- Annual Remiddot view$

Chen J A szligedinu L amp MnlMi lluuml A ( ~ot traquo) Trau1Ja fOCll~- CRT [ r d llldnlI tth cO lllaquourio g IraulJ ~ all tl ~hll lor pn ltm_ Child AblHe amp N1I-I 14 215 12middot1

Cohelt1 R OumlL Gr c A S t ~OO6) Ettl ~ li fe -Ir tlJ rro rphonxUj of Ihe ~I uh ncrir c it gu l~~ne~ lnu lmiddotludlt nud d szlig)~io middotd PsmiddotclImmiddot 59 915middotYS2

Co~~S W CO~lI G AI I Ibull J M G RII~S1ero A M HcdmlO J_ J amp Suo ml S J (~ll 2 TmrucrrprlOtJirJ modllrllo ll iJ 11 dtl~(Pir~ mrmiddot IrIllnr spum r(lrr lijlt rtJ~rf Itfl~I ~ fmr ~I~mlf s oilffll lltl1

In Ir bullbull rml(otliH MiIus riJ( utgtnl1 ned r1r pu~h arioll

Cumn~tI~c E 111 amp Omiddotie_ P T (20 10 HlIIrd n mjlwrrl t dtdtlrll An ttrltNljrrlltll W(lrin lfrrffN ilf lew Yr]( Goti lfllrd fu~

D1n~ A CIpi A il h ~m B Amb- r A 5ufdcn K amp ~ ikr Jbull tl I eOl 1) [hooJllal e lTbltddll~ 01 )1nmiddot~~ Ihmugh inFln)rllJlo promiddot ce ~lt m Cb l lhoooJ Iur ltIr p bull~ huf 10 2-16

Danc-gte - McEuCll B S (lU 11 AJerc c~jooxI cJperi rIo~s bulltf 1~middot

1115 tl llgtsfalic t03d and ~ -emiddottrl l cd dr5ltllt rhJfCJo~ amp Bd r-n Jf 106 29-19

Drmiddot~ A Moffill T E PlIlncC ~L -nlbler A flu llHl R_ amp Ca~P A (2(()S EICiICd lfI1almauClrl tc~Jj 111 ~r~ltoed adul~ imt hisshyIm) oi dldh LX-j matrr-illTtCnt An nil lt oJ (inm Plt Irlun middot 65 409 415

Oan~A PrimltC L Cgtlfl1 A Tt~ k~A 1atoR (lOJ1) Cti i hood m~UeOIlmIOI prNict~ rduh IIlIam mlti(1l1 tn l IIC (lIgtC ltlUd) Pmmiddot c(r)i~lt~( nNGll()ndA (i1ommiddot~ SImiddotinlaquol I 11 9- 124

igtwes h J bull CoUIltJ R Appeby P amp Ptl R 11~8 vs-=I3Iioll Ji bri~ nltgtgen CmiddotreacUr protcin altgtntd ur JeUKo-VIt counl Ib C(II)IlfV h~an di lttle MC1ll an l1SeS of p1tI)((l l~ (Udmiddotle~ J Jlfflll (J fdlt Alllt Irln 11(di u Asolilitlll 279 11 77 1middotS2

Dl1110u4L U amp SruhlRliC1 (lOI2) Limo -S Lon C lum CU1 Guen or ~b dhQitd mI11~mrnl fCeahd by iu~tlinnill ~nd ~fUcWral magn~ lic lSltnace imag ltg Hw fWo PSlni(fT) 7J 2Sh-9J

DanU(T R OmiddotCoonOf Jc FreundG G J lln~on R W amp KeHey K W (ll l)8 Front inJhlllffiJ lion 10 ltidne~ nd dpres~1Un When lh~ m mune ~)SI(m ~t1bj1Jpes Ih~ brai ll Njr~ 1(~ i J vtUDJlmiddott middot 9 6 ~6

DlU~nmler J Lill Jbull Br- kc-um E Hlaquo In F M Kri_ltllkr J ManirJa N 13 (10 I l) CIl ~e in 51n-s (lf i ~szlig and n lmbolie rXI)f$ ill re ~cd f chut~e~)n h lllolc llS~ Cli iy 1Ir 111 111led nmJfu l~~S il lcr Venl1jII pill~ ~lUdy fS)~bIl r I7JntfJC rmaJultr_ Ji 917-98

Dri tlSltn R J amp Me-Ewcn B S ~O l 2) Su i1 i n iJ~lt Oll nturvplaltn citymiddot Slre~lt ttJ hler~Iill1lt 10 PlOJOlc II l1 middotholI Nlwr( ilmiddotu roscitna 15 689 695 bull

Ot~ks ~1 N bull Voll M bull IIJ ltle) R LUIIllgtn K Dixll A LoeSlort S bull t t aI (Q12) F Ull C110 l1l nnotliOltl uf the h umlm briln OJ( 1n~ Inc Iden

1631

I lic~ II ut ~pcllic (pi cl1~ UC VlllatlOl1 ~cro~ lIn 11111 hOoltl Ctllomr IJrJaf 11 R~ doi 1 0 II S61~b-~O I 2-t r~3

De-l) I J llk mJ1 M c SItCT J M Whlle) L J 6 Imiddotox Ir C (z()()) The imp-I v( d tlldhooJ inerhgtn~ (In k~r Ji f~ full lMlng up Ih~ SCOItISh lnI1IUI ~u ltc~ ~ (1f 19~ OLnd 194 7 JUfmJ1oIp r wru ilil) Sod )1 JJCliolt1p ~ lO- Tmiddotli

De Bel i) M 0 amp Kcdll rJO 1 S 120021- Br~m muN~ iI pciJIUO mJltrtltlwmiddottnlmiddotnleJ Xhlllt11szlig1Jil s1r~ ooonic r ~oc -ldt 1lffr~ph imiddot

d l~ mdl-U rud-r B~lirr1 pSmiddotSlrIrmiddot 52 1OM-- I078 )c Bdls M 0 amp KII ~middoth ihh~~ f (~ Cerebclb Cll u~ in peJI ti~

ml~lremlc llLmiddotrgtela1d pu~lrunl3C S1[(gto d iltn rder IJIOffirt uf PS)hwnmiddot lt)0 691 iO~

Dt-b in~middot r E l hllllmnll A P Cn~cu] A 1 U11111 M K amp Sttltmiddot R - rlO I1) Trolun Imiddot(LVJ -J Clttliuc bch iorallh~r4py ru r Coll Jnn Im middot p~ If he tramn3 ~ Irrn ht aJ 1nmiddotiiiTTl~lt In~fh D~p~Hirm 4 1xmiddot Ul 67 75

DIz A amp Sam~lI N I (20 1m l1fed o f hctlthy lifo1~l c bchVIO bullbulln I r~ a~Slt( Idroa bel-tCl hukoc~l( rt lomcn letSI~ ~ld CUiln argt 1fIlt1)

(3ciull r II 1n Jormhl l nf Corltl flfII I U6 6io-OO3 Doli~r M so E Lelq bull E IaurenCC11 ] P amp Lel ~ S (1003) Ermiddot

fcr of an an ~h1l(lImiddot tgtloed m l(I ~mitm on rhelaquof l~oI rrltdurion d inmiddot i~m~II nddltlS m f(~~leTC~ Dlt Iil II II IIlId Pr 1middotlfnloy 20 8015- 89

DnJry S S ll-tII K Gwn M M Smylt T IX Vl~o 1 Wons] Y bull cI 1 (241 LI I- TdLlmere Jenglll amJ tJ1y (VM ~OCl l lk rn ali on

L1 Jl ng eJ ~ ~jWI-fl uno ~Ij ulr I f in Molt(ulr Pndl1lry 17 ~IY-727

EdmlftOA E c Wlllg F bull r-hzurc C M_ Guiney 1 SlOhli R Mle C cl d rlOl1 J Con Kmll middothmbi~ nlY m~rter Olorptolof j J jl~emiddot cen ts tr gtltlfrcpormiddotd cxpl~u rt tu dllJdbooJ lT)ilJUlmclll ll ~ llI tmiddots 1- Pedlw rC nnd d lrkeni M(ilnne 115 1ouml69-Hl71

El rlt~h~h S bull Wtlld t P KH~dtl S Willen J bull Reinll M Sch4ntla K cl tl (2(1OQ ) b nc1l Os 00 Lhc- mU I(J1 r re lwlle lel lmrn 101 h (I(r 10 ~Il in Ihe fIOrUlllli1il blaquoI Rrtnct1 SIUJ) hl txucriM of a I~ 10 1rojk-J b gIHMlUt101uI W II) Jrrrm igtlkl l h m nnJtgt Elflti IIIj(lonJ8172 - 11 )4

c~L E S szlig 1lCktgt lil1 E H 1111 J Do1t1rar F S bull AUJ(T N E MoltlVgt J D Il r 2fX141 Acc-lenued le l(m~ 1t htYlening in rt~ pcngtc 10 lir~ m tgtS

Prgtlt t dmX5 l~f I 110111 Atrd( tllmiddot tljSdtncr$ 101 17311 - 7315 Epd E 5 Mcrk tn S S ( 3wll(gtn R BlolCkbur1 l H Adler 1 b

Pltlchcr M 1 ~I al (10091 Tb~ rJte of lculocytc ldttmcX $h l cnil~ prcd ~ t Ol1t ir ffQ[l nJiWb ulLlt dlSClSlt in c hti) mlI h ng I SI --SX

FClOher~ A P I1J JO) EpihtIlIInk rcnab fll n rinn)] gclKtl1 l ljlOlllY

an a ItW ~rrnlJdl (0 comnlOli di cMe mlnr 8Of(middotclIwJq8Y 18 1149-1052

Feimingham K K~mp WiihtJm D~~ P HIIlbe~ G amp PeJUln A iOO7_ Clges rn llJtcnor (fa JIG~ ltl ltl am) gJlII aflU ro riJe bemiddot h i r Ih~rapy tgt( p~nrltu mlltic ~trelts 1l5C1 rUe r Pfyd middotgtlIItgtJ SltI-r 11 117-1 9

Finlclhor D ([ 99i1 Zur blcmmmI1en EpiltJeml k~lC Oll e llelcm ~hszligmiddot lHludl 1 ~mJrr In G wann amp R lppli1cr(Hngr SltX~~ft ~middotsmiddot $brrwl-h UM-D lirl JI r lJ f5chllng 8tmfi~ IIl1d Thn or it [J Hmj 11( ( pp 1 2- i Rt lw Ull rtsearth Clut~li~g 111 US) [Sexua aOIlgtC lleltlflymiddot middot- cmpenUlumJ lubioCl Dpmiddotmiddoterlag

hnkelhor D Om-rod R K_ amp Th n tr H A (2 7) RemiddotIC1imi7lfion prumiddot ltl1lS b 1I n3olJlIJU iO~ll1dinampl -ampt o i childrtszligailll OClh CIlM limu amp N~ltf 31 middot119-~H

hnkelhor D UumlTlt lOJ K K amp middotImltr H A fOO9) liftim IIgt-csOleill nf p1) itlimilalil1n 1 a 11it ()nlJ ~p~lt of (hikren a ~J )ltgtulk el1 dd lbJ tsr amp- f bull gllta JJ -t01-tJ I

FinltllL D lm~r H Ormrod R H~nlh~ S L (20nlJ ViokllC obl~ and crim~ ~PIlSure ina nru ln lt1 sampc ~i chl1drell aJ youumllh Pt dirIM 114 1-1I - 113

Jihtr ~ L o hlii n T F HOUf~ R bull Rd~ky O Wbull Ar$(~II 1 L amp UumlL~PI 3 (101 2t 3nll) log JenmiSdlon iln cl Ihk or ~c i holIil in eilv ado~nt- tlIL]IIUdroal cob ~rudy IJrtmli -IrJ(n1JUJlnlot )44 e16r]

Fisher H L Sdrticr A ZUTImil S MII~hHfl B bull MunI) M R Ltwi G_ amp ullot D 10 1 1 PhWJ~ OClIel chldhnvd iU mll3ClJ 1d pSth~IS lil~ )mpIOm il l~ ~ ALSP-C binh cClhon SJlm0thrrlfia 8ulltU Advune O1 ir ~ rlhh~tllon uoi O I U9)J~hboJAlgtltfl 18

fh~f P r GJ~w M R Chunbt r1tUl P amp R(id J B (lj)()h fu cn wmiddot lt II1 ((ncnnOIl for mL(((iCd pre-chool hil(~rel Impecl 00 eii ldrer ~

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b-hJmiddotior llt URCfldcxri nlt i~lill y a1J fchlef P3tnt fu~dil n i il g ()firn(

cJfrr rII1NIltm t l cnd ml ClIlId t Adncrlll P himrymiddot 39 135bshyDl

nUl~ln J M Popendlky(e V fbzd-L tmiddotOi]c N Sobole M lgtfiJliJshydh A SCiJmaclJa 1 e l llJ llfAumlltIl hnJ- and illtrinoJi idual lplJeshynet ii n ujcl ll ill hllmln gClm ~middotcb rlm rX ~I ) omoJaf HlIlJwJ (jrr~middot

In 7Y 61-szligS FrlE3 M F B3lestr 1 bull Pu M f Ro~rl S Stoiien F B [ e~LT M L

l1 al (2005-) Epiglt lldlC iliffcrellltes anse dUMlle lhc llfdililt of HlillOl)shy

ou l wh~ rdillg oj 11 a il~ fli cnJ m 1 Stln i 102 I 06(l1- 1 06(A

Gibcrt R fcmp 1 Thollurn J S i~oolhm p Radfil rJ L amp Glar D el a (2()Qo1l ReClliil~i ilgt ~lIj Ib-pJluing 10 hlfd fT1lreaur-nl hilf a l 373 167 - 180

G llLlt I1 R WlJ n1C 5 Browll( K rt tfl~1 D Wcbtgt E amp Joll1sonS (2009) Burjen 111 clm~nll C I i ( oild muumlnmiddotl lmcrl 11 tHflmiddotlnCHme L JU Mtne UI(ltI J7J 63-ti

Gilt-ltnsol M W Pulu~ L A middotillJstln S K GUI Il T v La~ lo t B Pimm R K et ru C0Q6) NCUlo(opoiuumlC fu)~tio~ in mo-ozyOlC l lloU1~ J Igto(lf dult i lf c Clmtl olpoiu rr middot Rthtiontup 10 IX uJ l I1ltti C

Q5 illt$$ di$OlJei JlJUfltlJ l rJf AhruMl l SJI hrl()(I J I 5 I~1-11)5 Glb$ 0 Part~ L Knilll lrs D 11 A amp SpcctCgtr T D (1010) No c-or

11I In btrvttn chiltlloId 1lI1l11ftlll rnn ll md tdorrtlt elgthJluhtilILjIJ PS) lt hiorry 6~ e2 1 c22

Gluok ma1 P D Hlrwll Mgt szlig rw lt A S (2007J E1rly I f~ ltICIIS JU thelr hltucnos r1 lwet d~ lif lJ~r~ am] clflIUlmJ11f) ~rltJC ctimiddott AIIrlnlll )oruri11 (IrHIIJrcJ 8rolmiddot 19 1- 19

GO~Wl L S (2(XH ln l lllge l) I- il IItC c-ptdCniolo L-ls elu5i1( furuLmlCrLal cac-e- I cltoCi a In( i n~qu~i tiC ltl I~lh-l lcfmllli of Pfllfll~I1I J Sm I PJ I -hIQ amp6 1 7-+- 1 9~

Green J G ~fcLaU~Jl iil Kmiddot A Bcrglen1 P gt GtJ~r M J Sampsor N A amp Z3sb S ly A M (20 101 Chldhnod 3JIcf~ iri ~ gt lnu ldol p()chishyiI riC di~unf~ in Iht HaJ iol ~oI(gtt-bdi l) jU rle~ r~ph HUl I A oLIl

tnm~ nh iill Ol ~C I of D$MmiddotJV d lonfe~ Arc il V nfGtJrol f~ ( 11 ~f1 ry67 l t-1 23

Gunnar M amp QIleedo K [ZW1 Th C lcurobology of SlJess and deldorshyme- nt vlwal Re llt of Pr- r htJy 5fijmiddot 145 73

Hilhlwcg K Bamom D H Grlw~ middotGedlCf M amp Snyder D K IOlol Stnni-Lhrninf lIUP~c l lld j 1lllk~ Di ~s~m i nIlaquo1 0 Imellenl IUl ior Ihc IrcatmCm a1l1 peemioo c f CVUrc dl ~rt- In K HUlfwcg M GrlwtmiddotGerler amp D H RuJlIl l h h l lrirmnmiddot CtlJl I~s Th Ikillt I~r pl iTtrJI) tQ amt (PP -Oi GlIlIl 1gen GermulIY HoSrck

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PreI ~n1l1 nlmt d i ~trn~ lhnulb Uuml gtl IltLJllClllli (1 alJ COnJll m~l~eshyrr cnl trlill ng A 4- anJ 5middot) ~lf foUo -up JOI7UiI oConJllllillg amp CIIIshyi11 Pn -coolo 61 70-77

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1Xrullll V Uher R S Da~~ A (OJl Child hInJ szlig1tremnenl predCL~ un r1~rJb e OUSot nf Wne 3ld u~amen l Ufllc n~ in crrts~lUn middot A fTl~ iS l~ii 5 Alrlnrrn iounral vf 1 rIu10 M9 J) Imiddot 151

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Shonoii J P Gam et A Sbull amp tte U llmnillei on P~yc ocl luuml DeIetOpshyffiI 1 tal lL1t1 S~h oral Pnllatnc (10 [21 TI~ hfgtll1ij1 -ift1S Pchildmiddot hood )h lcsity ltItJ too c ~ut~ ldllm- 11lt 201 1 2663

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T~ Il( C A GJ[tTT1an K szlig Let S H amp Ib nlUl P J I ~IXN) Irt rmgtl t pslkl ~t rre-ma Sire nxl ll y Jlnd n sk for mol ~m~ I middot UeIl

rr~1 oi lllolli childO I1 AmniC JJgtlI1tr1l (1Prthli( HI ilh 9 175- 18] TaytCf S E Wa) B M amp Scern an T E 20 11) iarl) ~J -nlt j l) l r1 j1J1

hhh OUlcomco D ffUIt111 und p~middoth(llfJrholoiY 23 939-95- Teiche r M H TOllod a A amp A Ij er ~ S L IOO6 Neumlgto~ Kd ~ 1

5C-q ll lItltS If euly ~rrt_ auJ c1I1I 1no)d m~I1tlmtnt Are rcsull- fmm human and animA tudi~ t comp1lh)e~ AJirHlls oj Jj N rJ A11 )I

(1 5middot]r bull 107I l l 3-323 110~ K amp Donepu l E 2l I ) T~tll 1eJ eCf(((l ~ inu=- ntl ant-shy

rior(~gulIle roneo ti middot1)11 JllIIng dQ~ic lllll el1lio J[ Smlgtp m tcrmiddot fClcllGC in chilI abulaquomiddot reluCd c llp lc~ po S Imiddotlr~unlilic lt reraquo Jl ltlllk r Ps-middotoloiru 4f dld l( 22 l - I ~

Thunlluer F EngL J amp Hah Lg K 19)91 Elcptid uf Dauer- ~-Ielh Mi 1ntJ le und Efr~I~middot i l i t ~in es prn en imiddot~ n P~lrl(llmmlli1j wonmiddot

ltItlmill~~ EtgebaigtSe noh 5 JoJIfI~n ot ti lal qtlM~li ll f~n MClbgtd CltoilftllL M d cifltc tivcJltH o f precmiOl lllc l mion $ year rt ~ u J51 7- ilu lmj jiir Klmi fdl ~ P$)middot(middotholt ~k 8 6-lt 62

T lh S L PICregu Srronllh E Rcgosch f Capla1 R amp Ck IO1i D (201 I) m OpGlt thi 1king allJ hliJlJit d iltonkrb rr It otllcd dllldren JmnJal rj lII o 1W I ACltl(fimyoCIlt AdOIJJ clII PJyclul ft jO 659--668

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T E M offill (m d ilt Klall$middotGra ( 2012 TlIIlk Tmv

T~ rk~ A R Priee L H Kau H T Ioo J S MtN~l i S amp Corpenmiddot tcr L L (20 10) Childtwod lT ltl~~nt alld tt ~omcre ~ tl middot~ci1 l ~

llJnLu~~ l1jlpor1 fOfl cfigtX1tJ ltat ly Sln 01 rel ullit agilI Brooriral IJ )Churnmiddot 67 531-534

Trr Rmiddot Price L H middotanh C Wttc f5 Q C amp C upellc r L L (2012) Ctn ld~1II uHmiddotriC) epi~ rte C nlllJ ul ~J kl l ofthr eu tOC)1t ~h coorti coitl ~t~plUr Pn=(irnlMal) find go In hllb ~ ndl lt~ PfAS mmiddotlE 7 tJ(1 1 4~

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11 A M~ruL- T Ou-Jncr J P_ KinUfL 1 Oe ~ner E_ Chth~ L f ~I n (2005l OOcil) (I ~VCI1e ltmoling and Idrgtlnere kn~lh I ~

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Wifg1l1S T L Sofw1off K 6 Sardr~ 111 R (2009 fgtJthI~ ~ Tripc p plth-e ~ning PmgtJffi_ [a~b un plInlmiddot ehl rU ~i ill iOllhi p 3ml ct bd a or pn bllVlt Fli r-uh P1Yllt r H 4$ 51 7-530

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1620

is illhal chHngeS Here we look a po tential changes in oflenshysrud ied indicators o f th e hellrh of the bady (inflammatory Teshy

actions telomere eros ion epigenetic melhylaLion and gene expression) and brain (mental disorders neuroimaging and neuro psy(hological (e so ng)

Wh) is il importallt ro know that suess ful experiences durshylng childhood mighl Slart 0 child on the lang roJd 10 hean di sshyease or dememia Tltis infonnruion is lOlPOrtaszligt far developshymental sciemis ls because ir opens he door (Q earl) prevention which is imperalivc today because ur currem

demographie shifls Life expeclanc) is growing lange r and langer Demographie trends suggest the possibiJiry mar Ihe

euerent generalion oF c hildren will li ve an average of nearl)

100 years (Vaupel 20 10) Policymakers and cilizens are conshyce med that mese man y extrJ years of life should be health y productive and enjoYlble not ex tra years of disease d iS abi 1shyiry and depe ndence on ot hers Past medical research has shown thm u-eatlng adult palienlS afler lhey have conrracled illnesses such as cardiovascular disease diabetes or demenshytia genernlly does not fully res(ore Iheir guai() o f life (Jansshyson 2005 McG ill amp MeMahon 2003 Wellcome Trust 2006) There fore the hope of increasing children s lifelong productiviry health and well-being calls for research to idenshybull dfy prevenuumlol1 targe ts that can be lackled success fully in early life well be fore disease takes hold

At the same time hat life expee[ancy is growing Ion ger for todays c hUdren worldwide birth rates are dropping There

are fewer young people even in developing nauumlons Simulshytaneously baby boomers are beconting senior citize ns The ruio of young tO old is shifting heavily (oward older people The math is compelling soon each young persoD who is able 10 work will be depended on 10 support Ihe heathcare and soshycial securil) eosls of older people This is called the SlIPpOIl

ratio and it has beee changing aloegside the young 10 old demographie balance and I1 is expecled to cominue changing woridwide (hrrp Hen wikipediaorgwikiIPulenlOl_supporshy_muo) Thi s rJtio mCJns Ihm c hildre n are an increasin gy vashy

bull -J luable economic conunodity lnsuring the lifeloog health ltIOd proouctivi ry of each childmiddotcitilen is beeorrung more imporshy(aOt for the world economy than ever before We want todays

chi1dren co ha e life long good health because we love (hem hul we alsu Want lhem to be able [0 kee p (he economy going and suppon us in our ow n old age

GreaJ suides hJ middote beeo made loward design ing trealmen ts thru work for children and Jdolescenlo who have leaming cmccional and behavioral problems as weH as prognuns to premiddot ven( such problems among culdren at risk However loday only a small fraction of young people have acct=Ss to the se ershyfcclive rreatmenlS and preventions (Mihalupuulos Vos Pirkis amp Carter 20 11 National Reseanh CouDcil and lnstiwte of Medicine 2009) 1f preserving and promoLing the psychologshyical health of duuml ld ren were undejlcod (0 be essential for worldwide economic securiry ebild mental-health intervention might wc Ubecome a key weapon in lhe fight 10 improve qualmiddot iry of life over the emire life course Publi c awareness of lhe comlecuon be(Ween chi ldhood su-ess and adult physical healrh

T 1 Mofjitl tlnd he KlallsmiddotGr]fle 2012 Thillk TOllk

and age-related disease has the pOIential ro galvanize polioCJI wiH (Oward prevention and trealmeIl( (eg see Tuugh 20 11 ) In eontrast we have noneed mal uumliteners who see m inured 10

news o f maltrea1ed c hildren s emotional problems are surmiddot prised and faseinlled whe n told thal malrreated children have eleva[ed blood proteins that convey risk for heart disease

On the 25th annlversary of Development alld Psychopa lho(ogy there is an upponuniry for Ihe fietd uf developmenml psychopatholog y to bring together (Wo of irs strOngest sc ienshy lilie themes sLrCss-biology research and eLinical intervention sc ie nce If the hypothesis is true (hat su-e ssors sueh as vioshylenee thaI preci pitale psyeho lugieal problems fo r you ng peoshypie also undermine theu lifelong ph ysical health this would imply thaI the burde n of adult and lale-life di seases could be red uced by successfuHy improving the psychologieal health of children First first examine the evidence that violenee ex middot posure eJuses alteraxions in su-e ss biomarkers Ho gocd is il This is DOI an exhausuumlve technical review but_ ralher an overview o f evidence for causation Seeond we envisage w~ys thaI clinical intervention researchers co uld incorporale

suess biomarkers into their c1inical trials to discover if in vimiddot dious effecls of eh I ildhood su-ess can be prevenred o r even re ersed by psyehosocial rreatmems We nOle a handful of srudies lhal have reported pre- versus posttfearmenl o r trealshymem versus comrol group differences in suess-sensiLi ve bioshy

logical measures and make reeommendations for more sucb research Readers can frnd briefing papers with more in-deplh coverage of he seetions of this artice at hnpIwwwmoffinshycaspi comieonlentlklaus-grawe-think -[ltlnk-2012

Childhood Viole nce Exposure

Trus aniele focuses on viulenee exposure for four reasons First viulenee eposure is ooe of the moSt common and severe sou~esof human suess Seeond (he hypo thesis is thaI su-ess in genernl affects health and studying vio lenee exposuse in parshylicu lar prov ides a slrong test of iL Third violenee ex posure can he measured with fairly good reliabiliry and validit) which ~ is an ad vantage over many other adversi ties and srressors Founh violence victimizauon is already a dcar targel of pubshylicmiddothealth tnd law-e nfoCement prevention effons as weU as -

many clinical psychosoc ial interve noon progrnms providing opporrunities for research ioto reversibility of putative effects of violen ce on stress biology r o r mi s artiele we defmed vioshylenee exposure as personJ1 exposure (0 physical acts of intenshytional harm in the f1fS 18 years of life We coosideted physical o r sexual malcrearment by parenlS ur other eang ivers physical or sexual assIUII by other adults exposure tO parenlS or careshygivers dumeotic violence bullying by peers o r si bting s and violence wiltun the comexl of an adolescent roman uc relationshystU p These form s of vic timi zation can be defined according to recent comprehensive reviews (Gitben er al 2009) and guidemiddot lines (Leeb Paulolai Melanson Simon amp Alias 2008) Q2 Other (nonviole nt) adversines and forms of trnuma undoub(shydly have health implicmions bUI were omined (Boyce Sokoshyluwski amp Robinson 2012)











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Childhood exposure to violence and lifelong health ... · today's chUdren. worldwide birth rates...

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Transcript of Childhood exposure to violence and lifelong health ... · today's chUdren. worldwide birth rates...