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

Walder, Deborah J.a; Trotman, Hanan D.b; Cubells, Joseph F.c d; Brasfield, Joyb; Tang, Yi-Langc; Walker, Elaine F.b

doi: 10.1097/YPG.0b013e32833a1ff3
Original Articles

Objective Recent research implicates the catechol-O-methyltransferase (COMT) Val 108/158 Met 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.

aDepartment of Psychology, Brooklyn College and The Graduate Center of The City University of New York, New York

Departments of bPsychology

cHuman Genetics

dPsychiatry and Behavioral Sciences, School of Medicine, Emory University, Georgia, USA

Correspondence to Deborah J. Walder, PhD, Department of Psychology, Room 5315 James Hall, Brooklyn College of the City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA

Tel: +1 718 951 5000 x6013; fax: +1 718 951 4814;


Received 6 January 2009 Revised 11 November 2009 Accepted 7 December 2009

© 2010 Lippincott Williams & Wilkins, Inc.