title: Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene.
abstract: BACKGROUND
  Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression.
  
  
  OBJECTIVE
  To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene.
  
  
  METHODS
  Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms.
  
  
  METHODS
  General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia.
  
  
  METHODS
  The primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished).
  
  
  METHODS
  Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders.
  
  
  RESULTS
  Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199).
  
  
  CONCLUSIONS
  These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.
authors.affiliation: Atlanta VA Medical Center, Georgia, USA.
authors.forename: Rebekah G
authors.initials: RG
authors.lastname: Bradley
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
authors.forename: Michael P
authors.initials: MP
authors.lastname: Epstein
authors.forename: Yilang
authors.initials: Y
authors.lastname: Tang
authors.forename: Hemu P
authors.initials: HP
authors.lastname: Nair
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Charles F
authors.initials: CF
authors.lastname: Gillespie
authors.forename: Tiina
authors.initials: T
authors.lastname: Berg
authors.forename: Mark
authors.initials: M
authors.lastname: Evces
authors.forename: D Jeffrey
authors.initials: DJ
authors.lastname: Newport
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Stowe
authors.forename: Christine M
authors.initials: CM
authors.lastname: Heim
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Ann
authors.initials: A
authors.lastname: Schwartz
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D044383:Black People / Q000235:genetics / Q000523:psychology; D002648:Child; D002649:Child Abuse / Q000175:diagnosis / Q000523:psychology*; D002885:Chromosomes, Human, Pair 16; D003431:Cross-Cultural Comparison; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012307:Risk Factors; D012931:Social Environment; D012959:Socioeconomic Factors; D044465:White People / Q000235:genetics / Q000523:psychology; D001741:Black or African American; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1