The Neuronal Transporter Gene SLC6A15 Confers Risk to Major Depression
Open accessAbstract
Major depression (MD) is one of the most prevalent psychiatric disorders and a leading cause of loss in work productivity. A combination of genetic and environmental risk factors probably contributes to MD. We present data from a genome-wide association study revealing a neuron-specific neutral amino acid transporter (SLC6A15) as a susceptibility gene for MD. Risk allele carrier status in humans and chronic stress in mice were associated with a downregulation of the expression of this gene in the hippocampus, a brain region implicated in the pathophysiology of MD. The same polymorphisms also showed associations with alterations in hippocampal volume and neuronal integrity. Thus, decreased SLC6A15 expression, due to genetic or environmental factors, might alter neuronal circuits related to the susceptibility for MD. Our convergent data from human genetics, expression studies, brain imaging, and animal models suggest a pathophysiological mechanism for MD that may be accessible to drug targeting.
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The MDD risk gene SLC6A15 is decreased in postmortem MDD NAc.
“For example, the MDD risk gene SLC6A15 [135] is decreased in postmortem MDD NAc.”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [135]
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- Authors
- Kohli, M. A., Lucae, S., Saemann, P. G., Schmidt, M. V., Demirkan, A., Hek, K., Czamara, D., Alexander, M., Salyakina, D., Ripke, S., Hoehn, D., Specht, M., Menke, A., Hennings, J., Heck, A., Wolf, C., Ising, M., Schreiber, S., Czisch, M., Müller, M. B., Uhr, M., Bettecken, T., Becker, A., Schramm, J., Rietschel, M., Maier, W., Bradley, B., Ressler, K. J., Nöthen, M. M., Cichon, S., Craig, I. W., Breen, G., Lewis, C. M., Hofman, A., Tiemeier, H., van Duijn, C. M., Holsboer, F., Müller-Myhsok, B., & Binder, E. B.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Erasmus MC (NL)
- University of Bonn (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- University Hospital Bonn (DE)
- Heidelberg University (DE)
- Howard Hughes Medical Institute (US)
- Emory University (US)
- King's College London (GB)
- Corresponding author
- Kohli, Martin A.
- Binder, Elisabeth B.
- ORCID
- Lucae, Susanne
- Schmidt, Mathias V.
- Hek, Karin
- Czamara, Darina
- Salyakina, Daria
- Ripke, Stephan
- Hoehn, David
- Menke, Andreas
- Hennings, Johannes
- Heck, Angela
- Wolf, Christiane
- Ising, Marcus
- Schreiber, Stefan
- Czisch, Michael
- Müller, Marianne B.
- Becker, Albert
- Rietschel, Marcella
- Bradley, Bekh
- Ressler, Kerry J.
- Nöthen, Markus M.
- Cichon, Sven
- Craig, Ian W.
- Breen, Gerome
- Lewis, Cathryn M.
- Tiemeier, Henning
- Binder, Elisabeth B.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 70
- Issue
- 2
- Pages
- 252-265
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3112053
- OpenAlex
- W2003551015
- Cited by
- 228
- References
- 70
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 13 · 2023: 9 · 2022: 9 · 2021: 12 · 2020: 8 · 2019: 16 · 2018: 16 · 2017: 13 · 2016: 14 · 2015: 23 · 2014: 22 · 2013: 27 · 2012: 26
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Burroughs Wellcome Fund
- Centre for Medical Systems Biology (RO1 MH071537-01A1)
- Wellcome Trust (085475)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (050-060-810, 175.010.2005.011, 911- 03-012)
- National Alliance for Research on Schizophrenia and Depression
- Bundesministerium für Bildung und Forschung (01GS08145, FKZ 01GS0481)
- Max-Planck-Gesellschaft
- National Institute on Drug Abuse
- H. Lundbeck A/S
- National Institute of Mental Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, SLC6A15, neutral amino acid transporter, genetic susceptibility, hippocampus, chronic stress, hippocampal volume, neuronal integrity, gene downregulation, risk alleles, neural circuits
- MeSH terms
- Adult, Analysis of Variance, Animals, Aspartic Acid, Chromosomes, Human, Pair 12, Depressive Disorder, Major, Major Depressive Disorder, Disease Models, Animal, Female, Gene Expression Regulation, Gene Frequency, Genotype, Germany, United Kingdom, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Tissue Proteins, Magnetic Resonance Spectroscopy, Risk Factors, RNA, Messenger, Stress, Psychological, Tritium, Meta-Analysis as Topic, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Amino Acid Transport Systems, Neutral, Mice, Genome-Wide Association Study
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