Customize your JAMA Network experience by selecting one or more topics from the list below.
Bradley RG, Binder EB, Epstein MP, et al. Influence of Child Abuse on Adult Depression: Moderation by the Corticotropin-Releasing Hormone Receptor Gene. Arch Gen Psychiatry. 2008;65(2):190–200. doi:10.1001/archgenpsychiatry.2007.26
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 × environment interaction at this locus may be important in depression.
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.
Association study examining gene × environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms.
General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia.
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.
Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene × 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).
These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene × 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.
Create a personal account or sign in to: