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A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders
Abstract
The different 5-HT (serotonin) receptors including the serotonin transporter (5-HTT) are candidate genes for affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). They have been investigated in a number of allelic association studies where the individual results have been inconsistent, and therefore, definite conclusions are difficult to make. Systematic reviews using meta-analytical techniques are a reliable method for objectively and reproducibly assessing individual studies and generating combined result. This study aimed at reviewing published studies investigating the association between affective disorders (MDD and BD) and variation at genes coding for serotonin receptors and the serotonin transporter. We performed National Library of Medicine database searches to identify potential studies. More than 430 articles were reviewed and 86 studies met the inclusion criteria for participation in our review. Of these, 41 studies investigated 45 different 5-HT receptor variants and 45 studies investigated at least one of two commonly studied 5-HTT polymorphisms in MDD. Many studies investigated the association between MDD and BD with the 5-HT2A 102 T/C, the 5-HTT promoter 44 bp insertion/deletion and the intron 2 VNTR polymorphisms, and thus, these could be pooled using meta-analytic techniques. The overall odds ratio (OR) for the combined individual results was significant for BD and the two 5-HTT polymorphisms: Mantel-Haenszel weighted OR=1.14, CI: 1.03-1.26, P=0.015 for the promoter locus (N=3467) and Mantel-Haenszel Weighted odds ratio OR=1.18, CI: 1.05-1.32, P=0.004 for the VNTR locus (N=3620). However, sensitivity analysis indicated that, in each case, the overall positive association could be mostly attributed to the large effect of one individual study. Therefore, these results suggest that, although promising, further studies are required to assess appropriately the evidence suggesting an association between BD and 5-HTT.
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Metadata
- Authors
- Anguelova, M., Benkelfat, C., & Turecki, G.
- Affiliations
- Douglas Mental Health University Institute (CA)
- McGill University Health Centre (CA)
- Corresponding author
- Turecki, G
- ORCID
- Turecki, G
- Venue
- Molecular Psychiatry
- Published
- 2003-06-01
- Volume
- 8
- Issue
- 6
- Pages
- 574-591
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W1997688244
- Cited by
- 276
- References
- 77
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 14 · 2015: 16 · 2014: 12 · 2013: 13 · 2012: 19
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Foundation for Suicide Prevention
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- serotonin receptors, serotonin transporter, 5-HTT polymorphism, 5-HT2A receptor, promoter polymorphism, major depressive disorder, bipolar disorder, mood disorders, candidate genes, genetic association
- MeSH terms
- Carrier Proteins, Humans, Membrane Glycoproteins, Nerve Tissue Proteins, Receptors, Serotonin, Mood Disorders, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
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