期刊
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
卷 36, 期 2, 页码 264-270出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2011.09.010
关键词
Brain-derived neurotrophic factor; Childhood abuse; Depression; Gene-environment interaction; Serotonin transporter promoter polymorphism
资金
- German Research Foundation
- Federal Ministry of Education and Research Germany
- Janssen-Cilag
- AstraZeneca
- SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health
- Federal Ministry of Health Germany
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Family Ministry of the Federal Republic of Germany
- German Cancer Aid
- European Union
- Social Ministry of the Federal State of Mecklenburg-West Pomerania of Germany
- Ivoclar
- Sirona
- Dentsply
- Kavo
- Wieland Ceramics
- GC
- Heraeus
- Dentaurum
- Merz-Dental
- Krupp-Foundation
- German Society of Dentistry (DGZMK)
- German Society of Prosthetic Dentistry and Dental Materials (DGZPW)
- Alfried Krupp von Bohlen und Halbach Foundation
- Sanofi-Aventis
- Biotronik
- Humboldt Foundation
- Federal Ministry of Education and Research (Germany)
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03Z1K012]
- Ministry of Cultural Affairs
- Siemens Healthcare
- Erlangen
- German Research Foundation (DFG) [GR 1912/5-1]
- Eli Lilly
- Novartis
Background: Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene-gene-environment interaction moderating the interaction between the s/l- promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms. Methods: 2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms. Results: Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p = 0.02). Emotional abuse carried the main effect of the interaction (p = 0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles. Conclusions: Our results point to a gene-gene-environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms. (C) 2011 Elsevier Inc. All rights reserved.
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