Journal
ARCHIVES OF GENERAL PSYCHIATRY
Volume 65, Issue 2, Pages 190-200Publisher
AMER MEDICAL ASSOC
DOI: 10.1001/archgenpsychiatry.2007.26
Keywords
-
Categories
Funding
- NCATS NIH HHS [UL1 TR000454] Funding Source: Medline
- NCRR NIH HHS [M01 RR000039, M01 RR00039] Funding Source: Medline
- NIDA NIH HHS [K02 DA015766, DA015766] Funding Source: Medline
- NIMH NIH HHS [MH-42088, P50-MH 68036, MH071537, MH-58922, R01 MH071537-01A1, R01 MH071537, K01 MH069884, R56 MH071537, R01 MH071537-02, P50 MH058922, P50 MH068036, MH069884, R01 MH042088] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available