A mutant gene that starves the brain of serotonin, a mood-regulating chemical messenger, has been discovered and found to be 10 times more prevalent in depressed patients than in control subjects. Patients with the mutation failed to respond well to the most commonly prescribed class of antidepressant medications, which work via serotonin, suggesting that the mutation may underlie a treatment-resistant subtype of the illness. The mutant gene codes for the brain enzyme, tryptophan hydroxylase-2, that makes serotonin, and results in 80 percent less of the neurotransmitter. It was carried by nine of 87 depressed patients, three of 219 healthy controls and none of 60 bipolar disorder patients, report Drs. Marc Caron, Xiaodong Zhang and colleagues at Duke Unversity. "If confirmed, this discovery could lead to a genetic test for vulnerability to depression and a way to predict which patients might respond best to serotonin-selective antidepressants," noted NIMH Director Thomas Insel, M.D.

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