Cited by 68Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolMemory and Neural Mechanisms

Additive gene-environment effects on hippocampal structure in healthy humans

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Rabl, U., Meyer, B. M., Diers, K., Bartova, L., Berger, A., Mandorfer, D., Popovic, A., Scharinger, C. +15 more·2014·Journal of Neuroscience

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).

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Authors
Rabl, U., Meyer, B. M., Diers, K., Bartova, L., Berger, A., Mandorfer, D., Popovic, A., Scharinger, C., Huemer, J., Kalcher, K., Pail, G., Haslacher, H., Perkmann, T., Windischberger, C., Brocke, B., Sitte, H. H., Pollak, D. D., Dreher, J.-C., Kasper, S., Praschak-Rieder, N., Moser, E., Esterbauer, H., & Pezawas, L.
Affiliations
  • Medical University of Vienna (AT)
  • Technische Universität Dresden (DE)
  • Institute of Pharmacology (CZ)
  • Lyon 1 Université (FR)
Venue
Journal of Neuroscience
Published
2014-07-23
Volume
34
Issue
30
Pages
9917-9926
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1984233832
Cited by
68
References
98
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 12 · 2015: 13 · 2014: 1
FWCI
5.18
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Agence Nationale de la Recherche (LABEX ANR-11-LABEX-0042, ANR-11-IDEX-0007, ANR-11-LABEX-0042, ANR-11-IDEX, 11 IDEX - 0007)
  • Austrian Science Fund (F3506-B11, F3514-B11, F3506)
  • Technische Universität Dresden
  • Oesterreichische Nationalbank
  • Institute for the Study of Affective Neuroscience
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
gene-environment interaction, hippocampal volume, chronic stress, environmental adversity, COMT Val158Met, BDNF Val66Met polymorphism, 5-HTTLPR, life events, hippocampal subfields, subiculum, dentate gyrus, CA2/3, mood disorders, post-traumatic stress disorder
MeSH terms
Adolescent, Adult, Female, Health Status, Hippocampus, Humans, Life Change Events, Male, Organ Size, Young Adult, Gene-Environment Interaction

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