Panic disorder is associated with the serotonin transporter gene (SLC6A4) but not the promoter region (5-HTTLPR)
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Panic disorder (PD) and social anxiety disorder (SAD) are moderately heritable anxiety disorders. We analyzed five genes, derived from pharmacological or translational mouse models, in a new case-control study of PD and SAD in European Americans: (1) the serotonin transporter (SLC6A4), (2) the serotonin receptor 1A, (3) catechol-O-methyltransferase, (4) a regulator of g-protein signaling and (5) the gastrin-releasing peptide receptor. Cases were interviewed using the schedule for affective disorders and schizophrenia and were required to have a probable or definite lifetime diagnosis of PD (N=179), SAD (161) or both (140), with first onset by age 31 and a family history of anxiety. Final diagnoses were determined using the best estimate procedure, blind to genotyping data. Controls were obtained from the National Institute of Mental Health Human Genetics Initiative; only subjects above 25 years of age who screened negative for all psychiatric symptoms were included (N=470). A total of 45 single nucleotide polymorphisms were successfully genotyped over the five selected genes using Applied Biosystems SNPlex protocol. SLC6A4 provided strong and consistent evidence of association with the PD and PD+SAD groups, with the most significant association in both groups being at rs140701 (chi(2)=10.72, P=0.001 with PD and chi(2)=8.59, P=0.003 in the PD+SAD group). This association remained significant after multiple test correction. Those carrying at least one copy of the haplotype A-A-G constructed from rs3794808, rs140701 and rs4583306 have 1.7 times the odds of PD than those without the haplotype (95% confidence interval: 1.2-2.3). The SAD only group did not provide evidence of association, suggesting a PD-driven association. The findings remained after adjustment for age and sex, and there was no evidence that the association was due to population stratification. The promoter region of the gene, 5-HTTLPR, did not provide any evidence of association, regardless of whether analyzed as a triallelic or biallelic locus, nor did any of the other four candidate genes tested. Our findings suggest that the serotonin transporter gene may play a role in PD; however, the findings require replication. Future studies should attend to the entire genetic region rather than the promoter.
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The serotonin transporter gene is connected with both PD and OCD pathologies.
“Another interesting association is referring to connection between the serotonin transporter gene and both PD [213] and OCD [214] pathologies.”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [214]
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“In the same way, it seems that mitochondrial dysfunction could be an important mechanism for the pathology of OCD [45].”
BackgroundInfluentialThe Genetic Basis of Panic Disorder
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- Authors
- Strug, L. J., Suresh, R., Fyer, A. J., Talati, A., Adams, P. B., Li, W., Hodge, S. E., Gilliam, T. C., & Weissman, M. M.
- Affiliations
- Hospital for Sick Children (CA)
- Columbia University (US)
- New York State Psychiatric Institute (US)
- University of Chicago (US)
- Corresponding author
- Weissman, M M
- Venue
- Molecular Psychiatry
- Published
- 2008-07-29
- Volume
- 15
- Issue
- 2
- Pages
- 166-176
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2811233
- OpenAlex
- W1966239200
- Cited by
- 87
- References
- 59
- Citations by year
- 2024: 1 · 2023: 4 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 6 · 2015: 12 · 2014: 1 · 2013: 5 · 2012: 9
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Columbia Academic Commons (Columbia University)
- Funders
- University of Pennsylvania
- Emory University
- Northwestern University
- Louisiana State University
- School of Medicine, Emory University
- National Institute of Mental Health (R01MH059566, R01MH059571, R01MH060879, R01MH059565, P01MH060970, R01MH060870, R01MH061675, R01MH059586, P01 MH60970-04, R01MH059588, R01MH048858, R01MH067257, R01MH059587, MH 48858)
- National Human Genome Research Institute (R03HG004314, HG-004314)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- panic disorder, social anxiety disorder, serotonin transporter gene, serotonin transporter, 5-HTTLPR, promoter polymorphism, genetic association, single nucleotide polymorphisms, haplotypes, anxiety disorders, European Americans, candidate genes, catechol-O-methyltransferase, gastrin-releasing peptide receptor, G protein-coupled receptors
- MeSH terms
- Adolescent, Adult, Aged, Female, Genotype, Humans, Male, Middle Aged, Phobic Disorders, Promoter Regions, Genetic, Panic Disorder, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptor, Serotonin, 5-HT1A, Serotonin Plasma Membrane Transport Proteins, Genome-Wide Association Study, Young Adult
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