Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

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...

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Autores principales:	Dennis Hernaus, Ruud van Winkel, Ed Gronenschild, Petra Habets, Gunter Kenis, Machteld Marcelis, Jim van Os, Inez Myin-Germeys, Dina Collip, for Genetic Risk and Outcome in Psychosis (G.R.O.U.P.)
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6ebe141b3af841afac850883f1fe142d
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spelling	oai:doaj.org-article:6ebe141b3af841afac850883f1fe142d2021-11-18T08:26:44ZBrain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.1932-620310.1371/journal.pone.0092722https://doaj.org/article/6ebe141b3af841afac850883f1fe142d2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24658422/?tool=EBIhttps://doaj.org/toc/1932-6203In 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.Dennis HernausRuud van WinkelEd GronenschildPetra HabetsGunter KenisMachteld MarcelisJim van OsInez Myin-GermeysDina Collipfor Genetic Risk and Outcome in Psychosis (G.R.O.U.P.)Public Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92722 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dennis Hernaus Ruud van Winkel Ed Gronenschild Petra Habets Gunter Kenis Machteld Marcelis Jim van Os Inez Myin-Germeys Dina Collip for Genetic Risk and Outcome in Psychosis (G.R.O.U.P.) Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
description	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.
format	article
author	Dennis Hernaus Ruud van Winkel Ed Gronenschild Petra Habets Gunter Kenis Machteld Marcelis Jim van Os Inez Myin-Germeys Dina Collip for Genetic Risk and Outcome in Psychosis (G.R.O.U.P.)
author_facet	Dennis Hernaus Ruud van Winkel Ed Gronenschild Petra Habets Gunter Kenis Machteld Marcelis Jim van Os Inez Myin-Germeys Dina Collip for Genetic Risk and Outcome in Psychosis (G.R.O.U.P.)
author_sort	Dennis Hernaus
title	Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
title_short	Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
title_full	Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
title_fullStr	Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
title_full_unstemmed	Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
title_sort	brain-derived neurotrophic factor/fk506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6ebe141b3af841afac850883f1fe142d
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Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood trauma interactions do not impact on hippocampal volume and cognitive performance.

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