Financial Disclosure Statement: There were no commercial sponsors or commercial relationships related to the current work. All additional past and present financial ties of the investigators are disclosed herein. Dr. Binder receives grant support or has received awards from NARSAD, the Doris Duke Foundation, and NIMH. Dr. Bradley receives grant support or has received awards from AFSP and the American Psychoanalytic Association Psychoanalytic Research Fund. Dr. Gillespie receives grant support or has received awards from APIRE, NARSAD, NIDA, and NIMH. Dr. Ressler has received awards and/or funding support related to other studies from Lundbeck, Burroughs Wellcome Foundation, Pfizer, NARSAD, NIMH, NIDA, and has a consulting agreement with Tikvah Therapeutics for NMDA-based therapeutics. In the past, Dr. Nemeroff consulted to, served on the Scientific Advisory Board and/or Board of Directors, has been a grant recipient, and/or owned equity in one or more of the following: Abbott Laboratories, Acadia Pharmaceuticals, American Foundation for Suicide Prevention (AFSP), American Psychiatric Institute for Research and Educations (APIRE), AstraZeneca, BMC-JR LLC, Bristol-Myers-Squibb, CeNeRx, Corcept, Cypress Biosciences, Cyberonics, Eli Lilly, Forest Laboratories, George West Mental Health Foundation, GlaxoSmithKline, i3 DLN, Janssen Pharmaceutica, Lundbeck, National Alliance for Research on Schizophrenia and Depression (NARSAD), Neuronetics, NIMH, NFMH, NovaDel Pharma, Otsuka, Pfizer Pharmaceuticals, Quintiles, Reevax, UCB Pharma, Wyeth-Ayerst. Currently, Dr. Nemeroff serves on the Scientific Advisory Board for Astra-Zeneca, Johnson & Johnson, Pharma Neuroboost, and NARSAD. He serves on the Board of Directors of AFSP, NovaDel Pharmaceuticals, Mt. Cook Pharma, Inc., and the George West Mental Health Foundation. He owns equity in CeNeRx and Reevax. He owns stock or stock options in Corcept and NovaDel. Dr. Smith has received an award from AFSP and grant support from Schering-Plough Pharmaceuticals. Dr. Ressler and Dr. Binder had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. None of the above funding agencies had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
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Research Article
Polymorphisms in CRHR1 and the serotonin transporter loci: Gene × Gene × Environment interactions on depressive symptoms†‡
Article first published online: 22 DEC 2009
DOI: 10.1002/ajmg.b.31052
Copyright © 2009 Wiley-Liss, Inc.
Issue
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 153B, Issue 3, pages 812–824, April 2010
Additional Information
How to Cite
Ressler, K. J., Bradley, B., Mercer, K. B., Deveau, T. C., Smith, A. K., Gillespie, C. F., Nemeroff, C. B., Cubells, J. F. and Binder, E. B. (2010), Polymorphisms in CRHR1 and the serotonin transporter loci: Gene × Gene × Environment interactions on depressive symptoms. Am. J. Med. Genet., 153B: 812–824. doi: 10.1002/ajmg.b.31052
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How to Cite this Article: Ressler KJ, Bradley B, Mercer KB, Deveau TC, Smith AK, Gillespie CF, Nemeroff CB, Cubells JF, Binder EB. 2010. Polymorphisms in CRHR1 and the Serotonin Transporter Loci: Gene × Gene × Environment Interactions on Depressive Symptoms. Am J Med Genet Part B 153B:812–824.
Publication History
- Issue published online: 19 MAR 2010
- Article first published online: 22 DEC 2009
- Manuscript Accepted: 21 OCT 2009
- Manuscript Received: 18 AUG 2009
Funded by
- National Institutes of Mental Health. Grant Numbers: MH071537, MH069884, MH082256
- National Institute of Drug Abuse. Grant Number: DA015766
- Emory and Grady Memorial Hospital General Clinical Research Center
- NIH National Centers for Research Resources. Grant Number: M01 RR00039
- Doris Duke Foundation
- Burroughs Wellcome Fund
- Abstract
- Article
- References
- Cited By
Keywords:
- child abuse;
- childhood maltreatment;
- trauma;
- depression;
- PTSD;
- genetic;
- risk factor
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. © 2009 Wiley-Liss, Inc.