SAN DIEGO, CALIFORNIA--Variants in two genes may explain why psychotherapy helps only some people with depression, according to a preliminary study presented here Friday at the annual meeting of the American Society of Human Genetics.
Researchers are uncovering more and more evidence that genetics play a role in how people respond to psychotropic drugs. In 2006, for example, scientists identified a gene variant that seems to explain why some patients respond better to antidepressants than others (ScienceNOW, 20 March 2006). And just last month, researchers found that variants in two genes could account for the increased suicide risk associated with antidepressants (ScienceNOW, 28 September).
Psychiatrist John Kelsoe and colleagues at the University of California (UC), San Diego, wanted to know if genetic variants could also account for why some people respond better to psychotherapy. Graduate student Amelia Kotte gathered therapy records and blood samples for 65 volunteers who had completed 16 weeks of psychotherapy, some of whom were also taking antidepressants. Kelsoe's team then analyzed DNA in the patients' blood for five genes thought to be involved in responses to antidepressants, because some brain-imaging studies have suggested biological similarities in responses to both antidepressants and psychotherapy.
Two of these genes seem to affect responses to psychotherapy, Kotte reported at the meeting. Patients with two copies of a particular variant of a gene called NTRK2 showed more improvement from psychotherapy than did those with one or no copy of the variant, dropping eight points on a 63-point assessment called the Beck Depression Inventory compared with a five-point drop for those with one or no copy of the variant. People who lacked these variants but who had two copies of a certain variant of the HTR2A gene were also more responsive to psychotherapy, improving six points compared with a three-point improvement for those without the beneficial HTR2A variants. NTRK2 has been linked previously to how well patients respond to the psychotropic drug lithium, whereas HTR2A variants appear to affect response to serotonin-based antidepressants such as Prozac.
Kelsoe has started a company called Psynomics Inc. to develop diagnostic tests for such variants. Psychiatrist James Kennedy of the University of Toronto in Canada says such tests "may be very useful to clinicians in the future in that they may be able to determine the best treatment for a given individual." First, however, the UC San Diego researchers need to repeat their study with a larger sample, he says.