New Insights Into the Genetics and Treatment of OCD

Norman Sussman, MD, DFAPA

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, New York University School of Medicine

OCD is a highly distressing and frequently disabling psychiatric illness. Up to three percent of the population may suffer from OCD. Symptoms of OCD include checking, repeated questioning, indecisiveness, cleaning, washing, counting, hoarding, touching, tapping, ordering, arranging, rubbing, and procrastination. At the moment, the medications proven to have antiobsessional properties are the SSRIs and clomipramine. However, these agents, even when augmented with other medications or with cognitive therapy, usually produce limited or no improvement in many patients. This situation may soon change, as investigators come closer to elucidating the underlying neuropathology and genetic basis of the disorder.

It has long been recognized that OCD has a genetic basis, but research teams working independently of one another have found a link between the transmission of OCD in males and a genetic locus on a specific chromosome—9p24. These findings may not be generalizable to all patients with OCD, but appear to involve males with early-onset OCD. This locus codes for an amino acid transporter responsible for terminating the action and regulating concentrations of the excitatory amino acid glutamate. This gene is expressed in areas of the brain previously found to be implicated in the pathophysiology of OCD—the thalamus, striatum, and cortex.

The findings of these genetic studies fit neatly into pharmacological research that suggests glutamate dysfunction underlies some cases of OCD. For example, the anti-glutamate agent riluzole, a medication used to treat amyotrophic lateral sclerosis, has been shown in a pilot study to ease the symptoms of OCD. In that study, of 13 patients unresponsive to other medications and cognitive behavioral therapy, seven patients treated with riluzole experienced a 35 percent reduction in symptoms, with five categorized as responsive to the treatment. One patient did not complete the study. (Clinicians should know that riluzole is not yet used routinely as an antiobsessional agent, partly because its efficacy in that role remains to be established, but also because the drug is hepatotoxic.)

If, as these studies suggest, altered glutamatergic neurotransmission is indeed involved in the pathogenesis of OCD, pharmacology researchers may be able to develop safer and more effective interventions that target glutamate.

Disclosure: Dr. Sussman reports no affiliations with or financial interests in any organization that may pose a conflict of interest.