title: Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
abstract: In the development of psychotic symptoms, environmental and genetic factors may both play a role. The reported association between childhood trauma and psychotic symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs) associated with the stress response, such as FK506-binding protein 5 (FKBP5) and brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood trauma by SNP interactions have inconsistently found the hippocampus to be a potential target underlying these interactions. Therefore, more detailed modelling of these effects, using appropriate covariates, is required. We examined whether BDNF/FKBP5 and childhood trauma interactions affected two proxies of hippocampal integrity: (i) hippocampal volume and (ii) cognitive performance on a block design (BD) and delayed auditory verbal task (AVLT). We also investigated whether the putative interaction was different for patients with a psychotic disorder (n = 89) compared to their non-psychotic siblings (n = 95), in order to elicit possible group-specific protective/vulnerability effects. SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5) and rs6265 (BDNF). In the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not different for patients and siblings. The omission of drug use and alcohol consumption sometimes yielded false positives, greatly affected explained error and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by childhood trauma interactions on assessments of hippocampal integrity suggests that the effect of these interactions on psychotic symptoms is not mediated by hippocampal integrity. The importance of appropriate statistical designs and inclusion of relevant covariates should be carefully considered.
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Hernaus
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands; University Psychiatric Centre Catholic University Leuven, Kortenberg, Belgium.
authors.forename: Ruud
authors.initials: R
authors.lastname: van Winkel
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: Gronenschild
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Habets
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Machteld
authors.initials: M
authors.lastname: Marcelis
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands; King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom.
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Inez
authors.initials: I
authors.lastname: Myin-Germeys
authors.affiliation: Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, School for Mental Health and NeuroScience MHeNS Maastricht University, Maastricht, The Netherlands.
authors.forename: Dina
authors.initials: D
authors.lastname: Collip
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003071:Cognition; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology*; D012307:Risk Factors; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5