Polymorphisms in CRHR1 and the Serotonin Transporter Loci: Gene × Gene × Environment Interactions on Depressive Symptoms

• Type of Material: Article
• Authors: Kerry Ressler, Emory University; Bekh Bradley-Davino, Emory University; Kristina B. Mercer, Emory University; Todd C. Deveau, Emory University; Alicia K Smith, Emory University; Charles Gillespie, Emory University; Charles B. Nemeroff, Emory University; Joseph F Cubells, Emory University; Elisabeth B. Binder, Emory University
• Language: English
• Date: 2009-12-22
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2009 Wiley-Liss, Inc.
• License: Creative Commons Attribution 2.5 Generic
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.31052/abstract
• Title of Journal or Parent Work: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
• ISSN: 1552-4841
• Volume: 153B
• Issue: 3
• Start Page: 812
• End Page: 824
• Grant/Funding Information: Grant sponsor: National Institutes of Mental Health; Grant numbers: MH071537, MH069884, MH082256; Grant sponsor: National Institute of Drug Abuse; Grant number: DA015766; Grant sponsor: Emory and Grady Memorial Hospital General Clinical Research Center; Grant sponsor: NIH National Centers for Research Resources; Grant number: M01 RR00039; Grant sponsor: Doris Duke Foundation; Grant sponsor: Burroughs Wellcome Fund.
• Keywords: PTSD; depression; trauma; child abuse; childhood maltreatment; risk factor; genetic
• Research Categories: Psychology, General; Biology, Genetics

Abstract

Gene × environment (G × E) interactions mediating depressive symptoms have been separately identified in the stress-sensitive serotonergic (5-HTTLPR) and corticotropin-releasing hormone (CRHR1) systems. Our objective was to examine whether the effects of child abuse are moderated by gene × gene (G × G) interactions between CRHR1 and 5-HTTLPR polymorphisms. We used an association study examining G × G × E interactions of CRHR1 and 5-HTTLPR polymorphisms and measures of child abuse on adult depressive symptomatology. The participant population (N = 1,392) was African-American, of low socioeconomic status (60% with <$1,000/month family income), and with high rates of childhood and lifetime trauma. Depressive symptoms were measured with Beck Depression Inventory (BDI) and history of Major Depression by Structure Clinical Interview based on DSM-IV (SCID). We first replicated an interaction of child abuse and 5-HTTLPR on lifetime SCID diagnosis of major depression in a subsample (N = 236) of the study population—the largest African-American 5-HTTLPR cohort reported to date. We then extended our previously reported interaction with both a CRHR1 SNP (rs110402) and TCA haplotype interacting with child abuse to predict current symptoms (N = 1,059; P = 0.0089). We found that the 5-HTTLPR S allele interacted with CRHR1 haplotypes and child abuse to predict current depressive symptoms (N = 856, P = 0.016). These data suggest that G × E interactions predictive of depressive symptoms may be differentially sensitive to levels of childhood trauma, and the effects of child abuse are moderated by genetic variation at both the CRHR1 and 5-HTTLPR loci and by their G × G interaction.