Catechol-O-methyltransferase modulation of cortisol secretion in psychiatrically at-risk and healthy adolescents
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OBJECTIVE: Recent research implicates the catechol-O-methyltransferase (COMT) ValMet polymorphism in stress sensitivity, through modulation of hypothalamic-pituitary-adrenal (HPA) function. In healthy samples, Met homozygosity has been associated with greater HPA activity (i.e., cortisol) and stress sensitivity, though findings are mixed among clinical samples. To date, there are no reports examining baseline or longitudinal changes in HPA activity as a function of COMT genotype in youth. This study tested the hypothesis that COMT genotype would be associated with cortisol secretion in normal and at-risk adolescents; specifically, that COMT genotype would be linked in a dose-response manner such that Met homozygotes would have the highest salivary cortisol levels, followed by heterozygotes, then Val homozygotes. In addition, this study examined the relation of COMT genotype with longitudinal changes in cortisol. METHODS: This study examined the association of COMT with salivary cortisol across a 1-year period in healthy and at-risk adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision Axis II diagnoses. RESULTS: Results indicated higher cortisol levels for Met homozygotes (compared with heterozygotes and Val homozygotes) at the 1-year follow-up, and increased mean cortisol levels across a 1-year period among Met carriers, suggesting that COMT associates with differences in cortisol secretion during adolescence. CONCLUSION: Findings are discussed with respect to COMT genotype as a potential genetic indicator of psychiatric risk that modulates developmental changes in HPA activity.
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The COMT genotype is associated with an altered cortisol response.
“The COMT genotype, which influences the enzyme’s stability and hence dopaminergic activity [17], is also associated with an altered cortisol response [26,27].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [27]
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- Authors
- Walder, D. J., Trotman, H. D., Cubells, J. F., Brasfield, J., Tang, Y.-L., & Walker, E. F.
- Affiliations
- The Graduate Center, CUNY (US)
- Emory University (US)
- Corresponding author
- Walder, Deborah J.
- Venue
- Psychiatric Genetics
- Published
- 2010-08
- Volume
- 20
- Issue
- 4
- Pages
- 166-170
- ISSN
- 0955-8829 (ISSN-L)
- PMC
- PMC3522124
- OpenAlex
- W2146759661
- Cited by
- 34
- References
- 27
- Citations by year
- 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 2
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (R01MH4062066, R01MH062066, U01MH081988)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- catechol-O-methyltransferase, COMT Val158Met polymorphism, salivary cortisol, hypothalamic-pituitary-adrenal axis, stress sensitivity, adolescents, psychiatric risk, genetic risk markers, dose-response relationship
- MeSH terms
- Adolescent, Mental Disorders, Catechol O-Methyltransferase, Child, Health, Humans, Hydrocortisone, Risk Factors, Saliva, Genetic Predisposition to Disease
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