Genotype Determining Low Catechol-O-methyltransferase
Activity as a Risk Factor for Obsessive-Compulsive Disorder
Maria Karayiorgou(1), Margaret Altemus(1,2),
Brandi L. Galke (1), David Goldman (3), Dennis L. Murphy (4),
Jurg Ott(1), and Joseph A. Gogos(1,5)
(1) The Rockefeller University, New York, NY 10021;
(2) Cornell University Medical College, Department of
Psychiatry, New York, NY 10021;
(3) Laboratory of Neurogenetics, National Institute of Alcohol Abuse and
Alcoholism, Rockville, MD 20852;
(4) Laboratory of Clinical Science, National Institute of Mental Health,
Bethesda, MD 20892; and
(5) Columbia University, College of Physicians and Surgeons, Center for
Neurobiology and Behavior, New York, NY 10032
Communicated by Donald W. Pfaff, Rockefeller University, New York, NY, February 24, 1997 (received for
review January 14, 1997)
Proc. Natl. Acad. Sci. USA , Vol. 94, pp. 4572-4575, April 1997
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.
