Protective Effect of CRHR1 Gene Variants on the Development of Adult Depression Following Childhood Maltreatment: Replication and Extension | Child Abuse | JAMA Psychiatry | JAMA Network
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Moussavi  SChatterji  SVerdes  ETandon  APatel  VUstun  B Depression, chronic diseases, and decrements in health: results from the World Health Surveys.  Lancet 2007;370 (9590) 851- 858PubMedGoogle ScholarCrossref
Sullivan  PFNeale  MCKendler  KS Genetic epidemiology of major depression: review and meta-analysis.  Am J Psychiatry 2000;157 (10) 1552- 1562PubMedGoogle ScholarCrossref
McCauley  JKern  DEKolodner  KDill  LSchroeder  AFDeChant  HKRyden  JDerogatis  LRBass  EB Clinical characteristics of women with a history of childhood abuse: unhealed wounds.  JAMA 1997;277 (17) 1362- 1368PubMedGoogle ScholarCrossref
Teicher  MHSamson  JAPolcari  A McGreenery  CE Sticks, stones, and hurtful words: relative effects of various forms of childhood maltreatment.  Am J Psychiatry 2006;163 (6) 993- 1000PubMedGoogle ScholarCrossref
López-León  SJanssens  ACGonzalez-Zuloeta Ladd  AMDel-Favero  JClaes  SJOostra  BAvan Duijn  CM Meta-analyses of genetic studies on major depressive disorder.  Mol Psychiatry 2008;13 (8) 772- 785PubMedGoogle ScholarCrossref
Rutter  M Genetic Effects on Environmental Vulnerability to Disease.  Chichester, England John Wiley & Sons2008;
Heim  CPlotsky  PMNemeroff  CB Importance of studying the contributions of early adverse experience to neurobiological findings in depression.  Neuropsychopharmacology 2004;29 (4) 641- 648PubMedGoogle ScholarCrossref
Kessler  RCMagee  WJ Childhood adversities and adult depression: basic patterns of association in a US national survey.  Psychol Med 1993;23 (3) 679- 690PubMedGoogle ScholarCrossref
Gunnar  MQuevedo  K The neurobiology of stress and development.  Annu Rev Psychol 2007;58145- 173PubMedGoogle ScholarCrossref
Cicchetti  DRogosch  FASturge-Apple  ML Interactions of child maltreatment and serotonin transporter and monoamine oxidase A polymorphisms: depressive symptomatology among adolescents from low socioeconomic status backgrounds.  Dev Psychopathol 2007;19 (4) 1161- 1180PubMedGoogle Scholar
Kaufman  JYang  BZDouglas-Palumberi  HHoushyar  SLipschitz  DKrystal  JHGelernter  J Social supports and serotonin transporter gene moderate depression in maltreated children.  Proc Natl Acad Sci U S A 2004;101 (49) 17316- 17321PubMedGoogle ScholarCrossref
Widom  CSBrzustowicz  LM MAOA and the “cycle of violence”: childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior.  Biol Psychiatry 2006;60 (7) 684- 689PubMedGoogle ScholarCrossref
Moffitt  TECaspi  ARutter  M Strategy for investigating interactions between measured genes and measured environments.  Arch Gen Psychiatry 2005;62 (5) 473- 481PubMedGoogle ScholarCrossref
Mello  AFJuruena  MFPariante  CMTyrka  ARPrice  LHCarpenter  LLDel Porto  JA Depression and stress: is there an endophenotype? [in Portuguese].  Rev Bras Psiquiatr 2007;29 ((suppl 1)) S13- S18PubMedGoogle ScholarCrossref
Bradley  RGBinder  EBEpstein  MPTang  YNair  HPLiu  WGillespie  CFBerg  TEvces  MNewport  DJStowe  ZNHeim  CMNemeroff  CBSchwartz  ACubells  JFRessler  KJ Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene.  Arch Gen Psychiatry 2008;65 (2) 190- 200PubMedGoogle ScholarCrossref
Steckler  THolsboer  F Corticotropin-releasing hormone receptor subtypes and emotion.  Biol Psychiatry 1999;46 (11) 1480- 1508PubMedGoogle ScholarCrossref
Owens  MJNemeroff  CB Physiology and pharmacology of corticotropin-releasing factor.  Pharmacol Rev 1991;43 (4) 425- 473PubMedGoogle Scholar
McGaugh  JL The amygdala modulates the consolidation of memories of emotionally arousing experiences.  Annu Rev Neurosci 2004;271- 28PubMedGoogle ScholarCrossref
Merikangas  KRRisch  N Will the genomics revolution revolutionize psychiatry?  Am J Psychiatry 2003;160 (4) 625- 635PubMedGoogle ScholarCrossref
Moffitt  TEE-Risk Study Team, Teen-aged mothers in contemporary Britain.  J Child Psychol Psychiatry 2002;43 (6) 727- 742PubMedGoogle ScholarCrossref
Moffitt  TECaspi  ARutter  MSilva  PA Sex Differences in Antisocial Behaviour: Conduct Disorder, Delinquency, and Violence in the Dunedin Longitudinal Study.  Cambridge, England Cambridge University Press2008;
Bernstein  DFink  L Childhood Trauma Questionnaire Manual.  San Antonio, TX The Psychological Corp1998;
Caspi  A McClay  JMoffitt  TEMill  JMartin  JCraig  IWTaylor  APoulton  R Role of genotype in the cycle of violence in maltreated children.  Science 2002;297 (5582) 851- 854PubMedGoogle ScholarCrossref
Danese  AMoffitt  TEPariante  CMAmbler  APoulton  RCaspi  A Elevated inflammation levels in depressed adults with a history of childhood maltreatment.  Arch Gen Psychiatry 2008;65 (4) 409- 415PubMedGoogle ScholarCrossref
Caspi  ASugden  KMoffitt  TETaylor  ACraig  IWHarrington  H McClay  JMill  JMartin  JBraithwaite  APoulton  R Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene.  Science 2003;301 (5631) 386- 389PubMedGoogle ScholarCrossref
Robins  LNCottler  LBucholz  KKCompton  W Diagnostic Interview Schedule for DSM-IV.  St Louis, Mo Washington University School of Medicine1995;
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC American Psychiatric Association1994;
Robins  LNHelzer  JECottler  LGoldring  E Diagnostic Interview Schedule, Version III-R.  St Louis, MO Washington University School of Medicine1989;
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 3rd ed revised. Washington, DC American Psychiatric Association1987;
Lake  SLLyon  HTantisira  KSilverman  EKWeiss  STLaird  NMSchaid  DJ Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous.  Hum Hered 2003;55 (1) 56- 65PubMedGoogle ScholarCrossref
Satten  GAEpstein  MP Comparison of prospective and retrospective methods for haplotype inference in case-control studies.  Genet Epidemiol 2004;27 (3) 192- 201PubMedGoogle ScholarCrossref
McGaugh  JL Memory—a century of consolidation.  Science 2000;287 (5451) 248- 251PubMedGoogle ScholarCrossref
Chen  YBrunson  KLMuller  MBCariaga  WBaram  TZ Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF(1))-like immunoreactivity in the mouse brain: light microscopy analysis using an antibody directed against the C-terminus.  J Comp Neurol 2000;420 (3) 305- 323PubMedGoogle ScholarCrossref
Hubbard  DTNakashima  BRLee  ITakahashi  LK Activation of basolateral amygdala corticotropin-releasing factor 1 receptors modulates the consolidation of contextual fear.  Neuroscience 2007;150 (4) 818- 828PubMedGoogle ScholarCrossref
Roozendaal  BBrunson  KLHolloway  BL McGaugh  JLBaram  TZ Involvement of stress-released corticotropin-releasing hormone in the basolateral amygdala in regulating memory consolidation.  Proc Natl Acad Sci U S A 2002;99 (21) 13908- 13913PubMedGoogle ScholarCrossref
Bradley  BPMogg  KWilliams  R Implicit and explicit memory for emotion-congruent information in clinical depression and anxiety.  Behav Res Ther 1995;33 (7) 755- 770PubMedGoogle ScholarCrossref
Watkins  PCMathews  AWilliamson  DAFuller  RD Mood-congruent memory in depression: emotional priming or elaboration?  J Abnorm Psychol 1992;101 (3) 581- 586PubMedGoogle ScholarCrossref
Ramel  WGoldin  PREyler  LTBrown  GGGotlib  IH McQuaid  JR Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse.  Biol Psychiatry 2007;61 (2) 231- 239PubMedGoogle ScholarCrossref
Hamilton  JPGotlib  IH Neural substrates of increased memory sensitivity for negative stimuli in major depression.  Biol Psychiatry 2008;63 (12) 1155- 1162PubMedGoogle ScholarCrossref
Burmeister  M McInnis  MGZollner  S Psychiatric genetics: progress amid controversy.  Nat Rev Genet 2008;9 (7) 527- 540PubMedGoogle ScholarCrossref
 An unnecessary battle.  Nature 2008;454 (7201) 137- 138PubMedGoogle Scholar
Caspi  AMoffitt  TE Gene-environment interactions in psychiatry: joining forces with neuroscience.  Nat Rev Neurosci 2006;7 (7) 583- 590PubMedGoogle ScholarCrossref
Original Article
September 2009

Protective Effect of CRHR1 Gene Variants on the Development of Adult Depression Following Childhood Maltreatment: Replication and Extension

Author Affiliations

Author Affiliations: Departments of Psychology and Neuroscience and Psychiatry and Behavioral Sciences and Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina (Drs Polanczyk, Caspi, Sugden, and Moffitt and Mr Williams); Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, England (Drs Polanczyk, Caspi, Price, Danese, Sugden, Uher, and Moffitt and Mr Williams); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (Dr Polanczyk); and Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Dunedin, New Zealand (Dr Poulton).

Arch Gen Psychiatry. 2009;66(9):978-985. doi:10.1001/archgenpsychiatry.2009.114

Context  A previous study reported a gene × environment interaction in which a haplotype in the corticotropin-releasing hormone receptor 1 gene (CRHR1) was associated with protection against adult depressive symptoms in individuals who were maltreated as children (as assessed by the Childhood Trauma Questionnaire [CTQ]).

Objective  To replicate the interaction between childhood maltreatment and a TAT haplotype formed by rs7209436, rs110402, and rs242924 in CRHR1, predicting adult depression.

Design  Two prospective longitudinal cohort studies.

Setting  England and New Zealand.

Participants  Participants in the first sample were women in the E-Risk Study (N = 1116), followed up to age 40 years with 96% retention. Participants in the second sample were men and women in the Dunedin Study (N = 1037), followed up to age 32 years with 96% retention.

Main Outcome Measure  Research diagnoses of past-year and recurrent major depressive disorder.

Results  In the E-Risk Study, the TAT haplotype was associated with a significant protective effect. In this effect, women who reported childhood maltreatment on the CTQ were protected against depression. In the Dunedin Study, which used a different type of measure of maltreatment, this finding was not replicated.

Conclusions  A haplotype in CRHR1 has been suggested to exert a protective effect against adult depression among research participants who reported maltreatment on the CTQ, a measure that elicits emotional memories. This suggests the hypothesis that CRHR1's protective effect may relate to its function in the consolidation of memories of emotionally arousing experiences.