Mutations Associated with Obsessive Compulsive Disorder

Their findings were reported in the October 23, 2003, issue of Molecular Psychiatry.

A second variant in the same gene of some patients with this mutation suggests a genetic "double hit,” which results in greater biochemical effects and more severe symptoms. Psychiatric interviews of the patients' families revealed that six of the seven individuals with the mutation had OCD and some also had anorexia nervosa, Asperger's syndrome, social phobia, tic disorder, and alcohol or other substance abuse dependence. After analyzing DNA from 170 unrelated individuals, including 80 healthy control subjects and 30 patients with OCD, eating disorders, and seasonal affective disorder, researchers detected gene variants by scanning the hSERT gene's coding sequence. They found a substitution of Val425 for lie425 in the sequence in two patients with OCD and their families but not in other patients or controls.

In addition, two original subjects and their siblings had a particular form of another hSERT variant, two long alleles of the 5-HTTLPR polymorphism. This variant suggests two changes within the same gene, both of which increase serotonin transport by themselves and may explain the unusual severity and treatment resistance of the illnesses in the subjects and their siblings.

"This is a new model for neuropsychiatric genetics, the concept of two or maybe more within-gene modifications being important in each affected individual. This is also probably the first report of a modification in a transporter gene resulting in a gain rather than a decrease in function,” noted Thomas Insel, M.D., director of the U.S. National Institute of Mental Health (Bethesda, MD, USA), which conducted the study.




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National Institute of Mental Health