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. Drs. Marc Caron, Xiaodong Zhang and colleagues at Duke Unversity announced their findings in the January 2005 Neuron, published online in mid-December.
"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.
The Duke researchers had previously reported in the July 9, 2004 Science that some mice have a tiny, one-letter variation in the sequence of their tryptophan hydroxylase gene (Tph2) that results in 50-70 percent less serotonin. This suggested that such a variant gene might also exist in humans and might be involved in mood and anxiety disorders, which often respond to serotonin selective reuptake inhibitors (SSRIs) antidepressants that block the re-absorption of serotonin, enhancing its availability to neurons.
In the current study, a similar variant culled from human subjects produced 80 percent less serotonin in cell cultures than the common version of the enzyme. More than 10 percent of the 87 patients
Contact: Jules Asher
NIH/National Institute of Mental Health