title: Additive gene-environment effects on hippocampal structure in healthy humans.
abstract: Hippocampal volume loss has been related to chronic stress as well as genetic factors. Although genetic and environmental variables affecting hippocampal volume have extensively been studied and related to mental illness, limited evidence is available with respect to G × E interactions on hippocampal volume. The present MRI study investigated interaction effects on hippocampal volume between three well-studied functional genetic variants (COMT Val158Met, BDNF Val66Met, 5-HTTLPR) associated with hippocampal volume and a measure of environmental adversity (life events questionnaire) in a large sample of healthy humans (n = 153). All three variants showed significant interactions with environmental adversity with respect to hippocampal volume. Observed effects were additive by nature and driven by both recent as well as early life events. A consecutive analysis of hippocampal subfields revealed a spatially distinct profile for each genetic variant suggesting a specific role of 5-HTTLPR for the subiculum, BDNF Val66Met for CA4/dentate gyrus, and COMT Val158Met for CA2/3 volume changes. The present study underscores the importance of G × E interactions as determinants of hippocampal volume, which is crucial for the neurobiological understanding of stress-related conditions, such as mood disorders or post-traumatic stress disorder (PTSD).
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Ulrich
authors: U
authors: Rabl
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Bernhard M
authors: BM
authors: Meyer
authors: Department of Psychology, Dresden University of Technology, 01069 Dresden, Germany.
authors: Kersten
authors: K
authors: Diers
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Lucie
authors: L
authors: Bartova
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Andreas
authors: A
authors: Berger
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Dominik
authors: D
authors: Mandorfer
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Ana
authors: A
authors: Popovic
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Christian
authors: C
authors: Scharinger
authors: Department of Child and Adolescent Psychiatry.
authors: Julia
authors: J
authors: Huemer
authors: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering.
authors: Klaudius
authors: K
authors: Kalcher
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Gerald
authors: G
authors: Pail
authors: Department of Laboratory Medicine.
authors: Helmuth
authors: http://orcid.org/0000-0003-4605-2503
authors: H
authors: Haslacher
authors: Department of Laboratory Medicine.
authors: Thomas
authors: T
authors: Perkmann
authors: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering.
authors: Christian
authors: http://orcid.org/0000-0002-9944-0190
authors: C
authors: Windischberger
authors: Department of Psychology, Dresden University of Technology, 01069 Dresden, Germany.
authors: Burkhard
authors: B
authors: Brocke
authors: Center of Physiology and Pharmacology, Institute of Pharmacology, and.
authors: Harald H
authors: http://orcid.org/0000-0002-1339-7444
authors: HH
authors: Sitte
authors: Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Daniela D
authors: DD
authors: Pollak
authors: Neuroeconomics Laboratory: Reward and Decision-Making, Centre de Neurosciences Cognitives, Centre National de la Recherche Scientifique/Unité Mixte de Recherche 5229, 69500 Bron, France, and Université Claude Bernard Lyon 1, 69100 Villeurbanne, France.
authors: Jean-Claude
authors: http://orcid.org/0000-0002-2157-1529
authors: JC
authors: Dreher
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Siegfried
authors: S
authors: Kasper
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria.
authors: Nicole
authors: N
authors: Praschak-Rieder
authors: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering.
authors: Ewald
authors: E
authors: Moser
authors: Department of Laboratory Medicine.
authors: Harald
authors: H
authors: Esterbauer
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna, Austria, lukas.pezawas@meduniwien.ac.at.
authors: Lukas
authors: http://orcid.org/0000-0002-1329-6352
authors: L
authors: Pezawas
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D059647:Gene-Environment Interaction; D006304:Health Status; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008016:Life Change Events; D008297:Male; D009929:Organ Size / Q000502:physiology; D055815:Young Adult
keywords: BDNF; COMT; MRI; SLC6A4; hippocampus; stress