Background Converging evidence suggests that physical activity is an Salinomycin (Procoxacin) Salinomycin (Procoxacin) effective treatment for both clinical major depression and sub-threshold depressive symptoms; however findings are not constantly consistent. Institute Stanford Salinomycin (Procoxacin) University or college University or college of Pittsburgh and Wake Forest University or college). Participants Salinomycin (Procoxacin) 396 EGR1 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). Treatment 12 PA treatment compared to an education control. Measurements Polymorphisms in the serotonin transporter (5-HTT) brain-derived neurotrophic element (Met allele. Symptoms of lack of positive affect decreased more in males compared to ladies particularly in those possessing the 5-HTT L allele but the effect did not differ by treatment arm. status did not affect switch in depressive symptoms. Conclusions Results of this study suggest that the effect of PA on depressive symptoms varies by genotype and sex and that PA may mitigate somatic symptoms of major depression more than additional symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of major depression is viable. ε4 allele the Met allele and the 5-HTT long (L) allele are associated with higher probability of positive response and remission after antidepressant treatment. It is unclear whether genetic differences also effect the effectiveness of PA in treating major depression or depressive symptoms as the evidence is limited and results are combined. One study reported that young adults with at least one 5-HTT L allele showed higher reductions in depressive symptoms after a 5-week exercise treatment [10]. In contrast a recent cross-sectional study in middle-aged adults found that the Val66Met polymorphism did not moderate the relationship between self-reported physical activity and depressive symptoms [11]. This query has not been investigated in older adults. Also unclear is definitely whether PA effects particular symptom sizes of major depression more than others. Major depression is a clinically heterogeneous disorder that comprises a variety of different symptoms (e.g. stressed out affect reduced positive affect and somatic symptoms). Growing evidence suggests that specific sizes of depressive symptoms are related to specific brain changes and domains of cognitive dysfunction [12 13 Corroborating the variation of symptom sizes of major depression there is evidence of unique vascular degenerative and inflammatory contributors to different depressive sign clusters [14] and genetic work has shown significant positive familial correlations for different sign dimensions [15]. As such it is possible that PA would improve particular types of depressive symptoms but not others. Moreover the effect of PA on depressive symptoms may vary by sex. Numerous studies have shown that men and women not only differ in their risk for major depression and vulnerability to depression-related bad sequelae but also in the associations of genotype with major depression risk and response to major depression treatment [16 17 Some studies possess reported a sex difference on the relationship between PA and depressive symptoms with the effect being found specifically or to a greater degree in either males [e.g. 18 or ladies [e.g. 11 A recent meta-analysis of randomized tests showed Salinomycin (Procoxacin) a stronger effect of exercise in males [19]. The goal of the present investigation was to increase upon earlier work in the LIFE-P cohort [6] by analyzing the part of variants in the genes in the antidepressant response to a physical activity treatment and by separately analyzing different symptom sizes of major depression. Based on earlier studies documenting a better treatment response in stressed out carriers of the ε4 allele the Met allele and the 5-HTT L allele we expected LIFE-P participants possessing these genetic markers to show the greatest reduction in depressive symptoms after a 12-month PA treatment compared to an educational control treatment. METHODS Participants Data for the present investigation came from the Lifestyle Treatment and Independence for Elders Pilot (LIFE-P) Study a randomized controlled trial evaluating the effect of physical activity on physical overall performance measures linked with mobility disability. Details of the study design for LIFE-P have been explained elsewhere [20]. Briefly community-dwelling adults aged 70-89 years were recruited from four field centers (Cooper Institute Stanford University or college University or college of Pittsburgh and Wake Forest.