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

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

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1
Atlanta VA Medical Center, Georgia, USA.

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.

PMID:
18250257
PMCID:
PMC2443704
DOI:
10.1001/archgenpsychiatry.2007.26
[Indexed for MEDLINE]
Free PMC Article

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