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

被引:465
作者
Bradley, Rebekah G. [1 ,2 ]
Binder, Elisabeth B. [1 ,3 ]
Epstein, Michael P. [3 ]
Tang, Yilang [3 ]
Nair, Hemu P. [1 ]
Liu, Wei [3 ,5 ]
Gillespie, Charles F. [1 ]
Berg, Tiina [1 ]
Evces, Mark [1 ]
Newport, D. Jeffrey [1 ]
Stowe, Zachary N. [1 ]
Heim, Christine M. [1 ]
Nemeroff, Charles B. [1 ]
Schwartz, Ann [1 ]
Cubells, Joseph F. [1 ,3 ]
Ressler, Kerry J. [1 ,4 ]
机构
[1] Emory Univ, Dept Psychiat & Behav Sci, Yerkes Res Ctr, Atlanta, GA 30329 USA
[2] Emory Univ, Sch Med, Atlanta VA Med Ctr, Atlanta, GA USA
[3] Emory Univ, Sch Med, Dept Genet, Atlanta, GA USA
[4] Emory Univ, Sch Med, Yerkes Natl Primate Res Ctr, Atlanta, GA USA
[5] Beijing Inst Microbiol & Epidemiol, Beijing, Peoples R China
关键词
D O I
10.1001/archgenpsychiatry.2007.26
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
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收藏
页码:190 / 200
页数:11
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