Catechol-O-methyltransferase modulation of cortisol secretion in psychiatrically at-risk and healthy adolescents

• Type of Material: Article
• Authors: Deborah J. Walder, The City University of New York; Hanan Trotman, Emory University; Joseph Cubells, Emory University; Joy Brasfield, Emory University; Yilang Tang, Emory University; Elaine Walker, Emory University
• Language: English
• Date: 2010-08-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Lippincott Williams & Wilkins.; © 2010 Wolters Kluwer Health
• Final Published Version (URL): http://dx.doi.org/10.1097/YPG.0b013e32833a1ff3
• Title of Journal or Parent Work: Psychiatric Genetics
• ISSN: 0955-8829
• Volume: 20
• Issue: 4
• Start Page: 166
• End Page: 170
• Grant/Funding Information: This research was supported in part by grant # RO1 MH4062066 awarded to Dr. Walker by the National Institute of Mental Health.
• Keywords: genetic; STRESS; SALIVARY CORTISOL; Life Sciences & Biomedicine; psychosis; cortisol; DISORDER; Science & Technology; risk; Genetics & Heredity; SCHIZOPHRENIA; Neurosciences & Neurology; PSYCHOSIS; RESPONSES; catechol-o-methyltransferase; Neurosciences; schizophrenia; hypothalamic-pituitary-adrenal axis; stress; POLYMORPHISM; COMT
• Research Categories: Psychology, Behavioral; Biology, Genetics

Abstract

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.