Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

^*The Rockefeller University, New York, NY 10021; ^‡Cornell University Medical College, Department of Psychiatry, New York, NY 10021; ^§Laboratory of Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, Rockville, MD 20852; ^¶Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892; and ^‖Columbia University, College of Physicians and Surgeons, Center for Neurobiology and Behavior, New York, NY 10032

Abstract

In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3- to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.

Footnotes

↵ † To whom reprint requests should be addressed at: The Rockefeller University, 1230 York Avenue, Box 313, New York, NY 10021. e-mail: karayim{at}rockvax.rockefeller.edu.
Donald W. Pfaff, Rockefeller University, New York, NY
ABBREVIATIONS:

OCD,

obsessive-compulsive disorder;

COMT,

catechol-O-methyltransferase