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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents



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ID: 475612.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
Polymorphisms in CRHR1 and the Serotonin Transporter Loci: Gene x Gene x Environment Interactions on Depressive Symptoms
Authors:Ressler, K. J.; Bradley, B.; Mercer, K. B.; Deveau, T. C.; Smith, A. K.; Gillespie, C. F.; Nemeroff, C. B.; Cubells, J. F.; Binder, E. B.
Language:English
Date of Publication (YYYY-MM-DD):2010-04
Title of Journal:American Journal of Medical Genetics Part B-Neuropsychiatric Genetics
Volume:153B
Issue / Number:3
Start Page:812
End Page:824
Review Status:not specified
Audience:Not Specified
Abstract / Description:Gene x environment (G x 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 x gene gene (G x G) interactions between CRHR1 and 5-HTTLPR polymorphisms. We used an association study examining G x G x 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 x 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 x G interaction. (C) 2009 Wiley-Liss, Inc.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
Identifiers:ISI:000276574300011 [ID No:1]
ISSN:1552-4841 [ID No:2]
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