TY - JOUR
T1 - Influence of child abuse on adult depression
T2 - Moderation by the corticotropin-releasing hormone receptor gene
AU - Bradley, Rebekah G.
AU - Binder, Elisabeth B.
AU - Epstein, Michael P.
AU - Tang, Yilang
AU - Nair, Hemu P.
AU - Liu, Wei
AU - Gillespie, Charles F.
AU - Berg, Tiina
AU - Evces, Mark
AU - Newport, D. Jeffrey
AU - Stowe, Zachary N.
AU - Heim, Christine M.
AU - Nemeroff, Charles B.
AU - Schwartz, Ann
AU - Cubells, Joseph F.
AU - Ressler, Kerry J.
PY - 2008/2/1
Y1 - 2008/2/1
N2 - 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.
AB - 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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U2 - 10.1001/archgenpsychiatry.2007.26
DO - 10.1001/archgenpsychiatry.2007.26
M3 - Article
C2 - 18250257
AN - SCOPUS:38949159163
VL - 65
SP - 190
EP - 200
JO - JAMA Psychiatry
JF - JAMA Psychiatry
SN - 2168-622X
IS - 2
ER -