Physio-genomics? Genes may modulate exercise benefits in depression

Exercise has long been known to be beneficial to people with depression, but a new study suggests that the dividends may vary according to an individual’s genetic makeup. The findings could spawn a new form of personalized medicine—call it physio-genomics—by helping to identify those people with depression who would benefit the most from hitting the gym.

“I’d like to better understand who could benefit most from physical activity,” said lead author Dr. Vonetta Dotson of the University of Florida College of Public Health and Health Professions. “I’d like to take the same approach to exercise that we take to medication, which is to have a personalized medicine approach.”

The study, which was published recently in The Journal of Frailty and Aging, discovered that men who were carriers of two specific gene types had the most significant response to exercise, based on the results of a screening test for depression and depressive disorders. The project was designed to investigate the effect of physical activity on changes in depressive symptoms relative to variations in three genes thought to be associated with susceptibility to depression: a gene called BDNF (brain-derived neurotrophic factor), a serotonin transporter gene (5- HTT), and apolipoprotein E (APOE).

The Lifestyle Interventions and Independence for Elders Pilot study (LIFE-P) Contently 1 enrolled 396 sedentary adults aged 70-89, who were randomly assigned to two different groups. One group, serving as the experimental control, received a year of health education classes, while the other seniors were given moderate physical activity classes for the same period. At the beginning and end of the year-long interventions, the participants were given a validated screening test for depression and depressive disorder, the Center for Epidemiologic Studies Depression Scale. The scale, which is one of the most widely used instruments in psychiatric epidemiology, looks at four factors—symptoms of sadness and fearfulness, symptoms like loss of appetite and concentration difficulties, and reduced capacity to experience pleasure or perceived difficulties in social relationships.

Digging deeper

Initial analysis seemed to indicate that exercise had not significantly affected symptoms of depression, but when the researchers examined the data more closely, they discovered something else entirely.

“When we looked at subgroups, we ended up finding significant response to exercise in men who were carriers of a specific gene,” Dotson explained. Men in the exercise group who carried the BDNF genetic variation that predisposed them to depression had the largest decrease in symptoms such as loss of appetite and concentration difficulties. Also, men with specific versions of the 5-HTT gene who had exercised regularly increased their capacity to experience pleasure.

Future directions?

Those intriguing results raise a series of important questions, with more research in this area clearly called for. For example, why did the benefits of exercise only show up in men? And what might be the impact of medications such as antidepressants and the many other prescription drugs taken by many seniors? Would the same benefits be seen in a more general population with a wider age range? Are other genetic variations possibly at play? Also, it should be noted that the study was conducted in people whose symptoms were not severe enough to be officially diagnosed with clinical depression. Would the association become more or less pronounced in clinically depressed patients?

Although the study’s results certainly add to the case for the potential benefits of exercise in people genetically susceptible to depression, more data may have a Contently 2 simple, positive effect. “If we show through systematic research that exercise has a good chance of helping a patient because of their particular characteristics, I think that might help with patients’ motivation to exercise,” Dotson said.