<h3>Context</h3> 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. <h3>Objective</h3> 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 (<i>CRHR1</i>) gene. <h3>Design</h3> Association study examining gene × environment interactions between genetic polymorphisms at the<i>CRHR1</i>locus and measures of child abuse on adult depressive symptoms. <h3>Setting</h3> General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia. <h3>Participants</h3> 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). <h3>Main Outcome Measures</h3> Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for<i>DSM-IV</i>Axis I Disorders. <h3>Results</h3> Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the<i>CRHR1</i>gene were examined. We found significant gene × environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402,<i>P</i> = .008) as well as with a common haplotype spanning intron 1 (<i>P</i> &lt; .001). Specific<i>CRHR1</i>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). <h3>Conclusions</h3> 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<i>CRHR1</i>risk or protective alleles who have a history of child abuse.

Influence of Child Abuse on Adult Depression