title: 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.
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.
authors: Department of Psychiatry and Psychotherapy, University of Greifswald, Germany. grabeh@uni-greifswald.de
authors: Hans Jörgen
authors: HJ
authors: Grabe
authors: Christian
authors: C
authors: Schwahn
authors: Jessie
authors: J
authors: Mahler
authors: Katja
authors: K
authors: Appel
authors: Andrea
authors: A
authors: Schulz
authors: Carsten
authors: C
authors: Spitzer
authors: Kristin
authors: K
authors: Fenske
authors: Sven
authors: S
authors: Barnow
authors: Harald Jürgen
authors: HJ
authors: Freyberger
authors: Alexander
authors: A
authors: Teumer
authors: Astrid
authors: A
authors: Petersmann
authors: Reiner
authors: R
authors: Biffar
authors: Dieter
authors: D
authors: Rosskopf
authors: Ulrich
authors: U
authors: John
authors: Henry
authors: H
authors: Völzke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D003866:Depressive Disorder / Q000150:complications / Q000235:genetics* / Q000523:psychology; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012727:Sex Characteristics; D044465:White People / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins