Obsessive Compulsive Gene

The Story: A gene has been found that may cause obsessive compulsive disorder. The story of this remarkable discovery is well told (below) in an article we have adapted from a news release from the NIH (National Institutes of Health) so we see no reason to recap the research.

Comments: One of the extraordinary aspects of the research on the gene for obsessive compulsive disorder is the discovery of two mutations in the same gene in some of the patients. In medical genetics, we are well acquainted with recessive diseases in which a person has two copies of a gene for the disease, one copy inherited from each parent. This phenomenon is called homozygosity. The presence of two different mutations within one gene essentially provides a new mechanism for this phenomenon -- called in within-gene homozygosity.

We remember the day, not too many years ago, when a friend of ours reported finding a gene for depressive disease in an eminent medical journal. He was roundly and severely criticized for his hubris in thinking that a form of major mental illness could possibly be due to the effects of a gene. That day has fortunately passed and now we can all benefit from a more open acceptance of both genetic and environmental factors in mental illness.

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Barbara K. Hecht, Ph.D.
Frederick Hecht, M.D.
Medical Editors, MedicineNet.com

Mutant Gene Linked to Obsessive Compulsive Disorder

Analysis of DNA samples from patients with obsessive compulsive disorder (OCD) and related illnesses suggests that these neuropsychiatric disorders affecting mood and behavior are associated with an uncommon mutant, malfunctioning gene that leads to faulty transporter function and regulation. Norio Ozaki, M.D., Ph.D., and colleagues in the collaborative study explain their findings in the October 23 Molecular Psychiatry.

Researchers have found a mutation in the human serotonin transporter gene, hSERT, in unrelated families with OCD. A second variant in the same gene of some patients with this mutation suggests a genetic "double hit," resulting in greater biochemical effects and more severe symptoms. Among the 10 leading causes of disability worldwide, OCD is a mental illness characterized by repetitive unwanted thoughts and behaviors that impair daily life.

"In all of molecular medicine, there are few known instances where two variants within one gene have been found to alter the expression and regulation of the gene in a way that appears associated with symptoms of a disorder," said co-author Dennis Murphy, M.D. of the National Institutes of Health (NIH). "This step forward gives us a glimpse of the complications ahead in studying the genetic complexity of neuropsychiatric disorders."

Psychiatric interviews of the patients' families revealed that 6 of the 7 individuals with the mutation had OCD or OC personality disorder and some also had anorexia nervosa (AN), Asperger's syndrome (AS), social phobia, tic disorder, and alcohol or other substance abuse/dependence. Researchers found an unusual cluster of OCD, AN, and AS/autism, disorders together with the mutation in approximately one percent of individuals with OCD.

The scientists analyzed DNA from 170 unrelated individuals, including 30 patients each with OCD, eating disorders, and seasonal affective disorder, plus 80 healthy control subjects. They detected gene variants by scanning the hSERT gene's coding sequence. A substitution of Val425 for Ile425 in the sequence occurred in two patients with OCD and their families, but not in additional patients or controls. Although rare, with the I425V mutation found in two unrelated families, the researchers propose it is likely to exist in other families with OCD and related disorders.