Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions. Symptoms of the disorder include excessive washing or cleaning; repeated checking; extreme hoarding; preoccupation with sexual, violent or religious thoughts; aversion to particular numbers; and nervous rituals, such as opening and closing a door a certain number of times before entering or leaving a room.
Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder 1997
Obsessive-compulsive disorder (OCD) is a common and severe psychiatric illness that affects 1–3% of the population (1, 2) and is characterized by anxiety-producing intrusive thoughts and performance of anxiety-reducing rituals. Very little is known about the pathogenesis of the disorder. Several studies suggest a genetic component in the etiology of OCD (3, 4). In addition, the selective response of the illness to treatment with serotonin reuptake inhibiting agents has led to the hypothesis that OCD may be associated with dysregulation of serotonergic neurotransmission (5, 6). Although serotonin reuptake inhibitors are clearly the first-line pharmacotherapy for OCD, complete relief of symptoms is rare during treatment with these medications, and 30–40% of patients remain clinically unchanged (7). Augmentation of serotonin reuptake inhibitor treatment with dopamine antagonists appears to be useful for a subset of OCD patients (8), thus implicating involvement of dopaminergic pathways as well in the illness.
It has been previously described that patients with 22q11 microdeletions manifest a number of psychiatric phenotypes, including schizophrenia and OCD (9, 10). A more recent follow-up study (11) on behavioral phenotypes observed in patients with the 22q11 deletion reported OC symptoms in the majority of these patients, thus providing even stronger evidence that the 22q11 locus harbors gene(s) predisposing to OCD. The gene for catechol-O-methyltransferase (COMT), which is involved in the inactivation of catecholamines including the neurotransmitter dopamine , maps to the 22q11 region (15), and is frequently deleted in patients with 22q11 microdeletions (9). comt therefore represents an attractive candidate gene for OCD.