DESCRIPTION (provided by applicant): Geriatric depression is associated with poor treatment response and compliance and polypharmacy. Only about 30% of elderly depressed patients achieve remission and functional recovery in response to first-line antidepressant pharmacotherapy. Complementary mind-body interventions used in older adults with depressive symptoms may be important in treatment and prevention of relapse and recurrence of major depressive disorders via stress-reduction, improved physical functioning, increased socialization, and reduced risks of polypharmacy. Our pilot study of 112 older adults with major depression demonstrated that the addition of 10-week Tai-Chi-Chih (TCC) to the standard antidepressant treatment in 73 partial responders improved the overall response to an antidepressant but also resulted in the improved quality of life and cognitive function, and reduced levels of C-reactive protein when compared to the Health Education. The proposed randomized trial aims to investigate neural mechanisms of brain connectivity when comparing response to TCC to stretching exercise or to health and wellness education classes using fMRI biomarkers of emotional regulation and cognition. Control groups will include stretch exercise and health wellness education programs (STRETCH and HEW) that will help to control for the effect of non-chi generating exercise and non-specific social support factors. Primary outcomes include measures of depressive symptom severity and fMRI correlates of emotional processing and connectivity in related functional networks. Secondary outcomes include cognition, resilience, health functioning, quality of life, neural correlates of working memory, and brain structure. Maintenance of response and relapse of major depression will be determined during 6 month follow-up. We will investigate whether variations in emotional regulation will moderate or predict emotional and functional improvement linked to TCC. We will recruit 330 un-medicated older adults with depressive symptoms who will be randomly assigned to 12 weeks of: 1.Ta-Chi-Chih (TCC) class; or 2. Health/Wellness Education Program (HEW); or 3. Stretching exercise (STRETCH) class - all for 120 minutes per week. All subjects will receive comprehensive evaluations of mood, mental and physical health, and cognition at baseline, 12 weeks, and 6 months. Changes over time in measures of depressive symptoms, resilience, quality of life, and cognition will be assessed in random regression models. We anticipate that clinical improvement in mood and cognition will occur in association with change in the activation in the right ventro-lateral prefrontal cortex (VLPFC) and amygdala in an affect labeling task, and working memory-related activation of dorso-lateral prefrontal cortex (DLPFC), and change in functional connectivity in brain network activity. This is the first randomized trial investigating neural mechanisms of response to TCC that integrates the use of fMRI biomarkers of response to guide the development of treatment and preventive approaches to geriatric depression.

PUBLIC HEALTH RELEVANCE: We will examine the neural mechanisms of brain connectivity in response to Tai Chi Chih compared to stretching exercise and health and wellness education seminar using fMRI biomarkers of emotional regulation and working memory in 330 older un-medicated participants with depressive symptoms. Overall, we will establish whether variations in emotional regulation and brain connectivity moderate or predict mood and functional improvement linked with TCC using markers of fMRI brain emotional processing over the course of the 12 week interventions with either TCC or Health and Wellness Education or Stretching exercise controls, and will follow maintenance of response in a 6-month follow-up. We anticipate that clinical and cognitive benefits will be accompanied by the changes in brain connectivity using fMRI measures of emotional processing and memory.