Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene

Arch Gen Psychiatry. 2008 Feb;65(2):190-200. doi: 10.1001/archgenpsychiatry.2007.26.

Abstract

Context: 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.

Design: Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms.

Setting: General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia.

Participants: 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).

Main outcome measures: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Continental Ancestry Group / genetics
  • African Continental Ancestry Group / psychology
  • Aged
  • Aged, 80 and over
  • Alleles
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology
  • Child
  • Child Abuse / diagnosis
  • Child Abuse / psychology*
  • Chromosomes, Human, Pair 16
  • Cross-Cultural Comparison
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / psychology
  • European Continental Ancestry Group / genetics
  • European Continental Ancestry Group / psychology
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetics, Population
  • Genotype*
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Mental Disorders / diagnosis
  • Mental Disorders / genetics
  • Mental Disorders / psychology
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Risk Factors
  • Social Environment*
  • Socioeconomic Factors

Substances

  • Receptors, Corticotropin-Releasing Hormone
  • CRF receptor type 1