Additive gene-environment effects on hippocampal structure in healthy humans
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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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Stressful life events interact with genotypes of 5-HT metabolism and BDNF on hippocampal structure.
“Strikingly, stressful life events interact with genotypes of 5-HT metabolism and BDNF on hippocampal structure (Rabl et al., 2014).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Rabl et al., 2014
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Flagged first, then by citations
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Sorted by citations
Kraus, C., Castrén, E., Kasper, S., & Lanzenberger, R. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.007 · Cited by 457 · see citing works
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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)
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-07-23
- Volume
- 34
- Issue
- 30
- Pages
- 9917-9926
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4107408
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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