title: Association between genes, stressful childhood events and processing bias in depression vulnerable individuals.
abstract: The brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes are relevant candidates for depression. Variation in these genes is associated with stress sensitivity and depressotypic cognitive biases. The interaction between genes and stressful events is considered as an important mechanism in the development of depression. This study examined the effects of the BDNF and COMT genes on biased processing and the interaction with childhood stress in vulnerable individuals. A total of 198 remitted depressed individuals performed an n-back task with emotional facial stimuli (happy and sad). Childhood events were measured with a questionnaire. Genotype by childhood events interactions were analyzed for happy and sad expressions for BDNF (Val66Met; rs6265) and COMT (Val158Met; rs4680), individually and combined. BDNF and COMT both interacted significantly (P = 0.006 and P = 0.014, respectively) with childhood trauma on reaction time for happy faces. For both genes, Met-carriers with childhood trauma showed less positive bias for happy faces than those without childhood trauma. Val-carriers did not show a differential bias. Individuals with childhood trauma and 3 or 4 risk alleles (BDNF and COMT combined) showed less positive bias than those without childhood trauma (P = 0.011). The BDNF × COMT × childhood trauma interaction yielded a P = 0.055, but had limited power. A potential weakness is the measurement method of the childhood events, as negative bias might have affected participants' recall. Our findings endorse the association of BDNF and COMT with stress and depression and provide a possible intermediate, i.e. biased processing of positive information. Tailoring treatment to specific risk profiles based on genetic susceptibility and childhood stress could be promising.
authors.affiliation: Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: J N
authors.initials: JN
authors.lastname: Vrijsen
authors.affiliation: Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: van Oostrom
authors.affiliation: Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Arias-Vásquez
authors.affiliation: Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.affiliation: Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: E S
authors.initials: ES
authors.lastname: Becker
authors.affiliation: Department of Psychiatry, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Speckens
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002649:Child Abuse / Q000523:psychology; D003863:Depression / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D004644:Emotions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013315:Stress, Psychological / Q000150:complications / Q000235:genetics*; D014796:Visual Perception
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: BDNF; COMT; candidate gene; childhood trauma; cognitive bias; depression; life events; processing bias; stress; working memory