A recently discovered genetic mutation that causes dysfunction in the synthesizing of serotonin might explain why some depressed patients are resistant to drug treatment, researchers say.
Xiaodong Zhang, M.D., and colleagues at Duke University, Durham, N.C., screened 87 adults with unipolar major depression, 60 adults with bipolar disorder, and 219 controls for a mutant allele known as 1463A in an enzyme that helps direct synthesis of serotonin known as human tryptophan hydroxylase 2 (hTPH2).
The gene mutation occurred in 10% of patients with major depression, compared with 1% of the controls. None of the individuals with bipolar disorder had the mutation (Neuron 2005;45:11-6).
Seven of the nine depression patients with the hTPH2 mutation had a family history of mental illness or drug and alcohol abuse, six had either attempted suicide or shown suicidal behavior, and four demonstrated generalized anxiety symptoms. In addition, seven of the patients with the mutation showed a lack of responsiveness to an SSRI, and the other two responded only to high doses.
Communication among neurons may stall if serotonin levels are low, as they often are in people with depression, anxiety, posttraumatic stress disorder, and even attention-deficit hyperactivity disorder. Additional larger studies are needed to confirm these findings and explore links between genetics and depression.