Childhood stress, serotonin transporter gene and brain structures in major depression
Open accessAbstract
The underlying neurobiology of major depression (MD) is likely to represent an interaction between genetic susceptibility and environmental factors such as stress. We investigated, in a multimodal high-resolution magnetic resonance imaging (MRI) genetic study, whether reduced hippocampal volumes and other brain alterations are associated with the tri-allelic polymorphism of the serotonin transporter and childhood stress in patients with MD and healthy subjects. Patients with MD and healthy participants were investigated using high-resolution MRI and genotyping for serotonin transporter polymorphism in the promoter region of the serotonin transporter gene (SLC6A4, 5-HTTLPR). Region of interest analysis of the hippocampus, whole-brain voxel-based morphometry (VBM), and assessment of childhood stress were carried out. Patients carrying the risk S-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared with patients who only had one risk factor (environmental or genetic). In patients, childhood stress also predicted further hippocampal white matter alterations independently from the genotype. Moreover, the left prefrontal cortex was smaller in patients, whereby childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele, suggesting preventive effects. The findings indicate that subjects with both environmental and genetic risk factors are susceptible to stress-related hippocampal changes. Structural brain changes due to stress represent part of the mechanism by which the illness risk and outcome might be genetically mediated.
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Imaging studies indicate that early life stress history is associated with volume loss in the hippocampus and medial prefrontal cortex.
“Imaging studies have also demonstrated that an ELS history was associated with hippocampal and mPFC volumetric decline (57–65).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [59]
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- Authors
- Frodl, T., Reinhold, E., Koutsouleris, N., Donohoe, G., Bondy, B., Reiser, M., Möller, H.-J., & Meisenzahl, E. M.
- Affiliations
- Trinity College Dublin (IE)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Frodl, Thomas
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2010-02-10
- Volume
- 35
- Issue
- 6
- Pages
- 1383-1390
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055341
- OpenAlex
- W2017181469
- Cited by
- 200
- References
- 57
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 4 · 2021: 26 · 2020: 8 · 2019: 10 · 2018: 14 · 2017: 12 · 2016: 17 · 2015: 16 · 2014: 15 · 2013: 12 · 2012: 14
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- major depressive disorder, childhood stress, serotonin transporter gene, 5-HTTLPR, serotonin transporter, hippocampal volume, emotional neglect, white matter changes, prefrontal cortex, genetic susceptibility, gene-environment interaction, brain structure
- MeSH terms
- Adolescent, Adult, Aged, Brain, Brain Chemistry, Child, Major Depressive Disorder, DNA Mutational Analysis, Female, Gene Frequency, Genetic Testing, Genotype, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Polymorphism, Genetic, Stress, Psychological, Prefrontal Cortex, Genetic Predisposition to Disease, Serotonin Plasma Membrane Transport Proteins, Young Adult
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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