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Genetic epistasis between the brain-derived neurotrophic factor Val66Met polymorphism and the 5-HTT promoter polymorphism moderates the susceptibility to depressive disorders after childhood abuse
- Source :
-
Progress in Neuro-Psychopharmacology & Biological Psychiatry . Mar2012, Vol. 36 Issue 2, p264-270. 7p. - Publication Year :
- 2012
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Abstract
- Abstract: 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 02785846
- Volume :
- 36
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Progress in Neuro-Psychopharmacology & Biological Psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 70262193
- Full Text :
- https://doi.org/10.1016/j.pnpbp.2011.09.010