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

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• 作者：Hans Jö ; rgen Grabe^a ; ^{grabeh@uni-greifswald.de} ; Christian Schwahn^b ; Jessie Mahler^a ; Katja Appel^a ; Andrea Schulz^a ; Carsten Spitzer^c ; Kristin Fenske^d ; Sven Barnow^e ; Harald Jü ; rgen Freyberger^a ; Alexander Teumer^f ; Astrid Petersmann^g ; Reiner Biffar^b ; Dieter Rosskopf^h ; Ulrich Johnⁱ ; Henry Vö ; lzke^j
• 关键词：BDNF ; brain-derived neurotrophic factor ; 5-HTTLPR ; promoter polymorphism of the serotonin transporter ; 5-HT ; 5-hydroxytryptophan (serotonin) ; SHIP ; Study of Health in Pomerania ; BDI-II ; Beck Depression Inventory (II) ; CTQ ; Childhood Trauma Questionnaire
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2012
• 出版时间：30 March 2012
• 年：2012
• 卷：36
• 期：2
• 页码：264-270
• 全文大小：296 K

文摘

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.