Project Summary DESCRIPTION (provided by applicant): The goal of the proposed study is to examine the impact of aerobic exercise (AE) training on cognitive functioning in people with schizophrenia (SZ). People with SZ display a broad range of cognitive impairments that have been identified as major determinants of poor functional outcome and disability, thus representing an important public health concern and a target for interventions. At present, available treatments offer only minimal to limited benefits to ameliorate these deficits. Extensive animal and human research literatures converge in supporting the positive influence of AE training on cognitive functioning. Preliminary data indicate that AE training is effective in improving cognitive functioning in people with SZ. However, previous studies employed small samples, making it difficult to ascertain the potential impact of relevant biological variables. Additional limitations include focus on a single or limited range of cognitive domains and insufficient information on daily functioning or putative biomarkers underlying cognitive change. Finally, previous studies tended to view AE as a uniform intervention, with limited attention given to intervention characteristics, an issue critical to reproducibility. Thus, we lack fully powered studies to provide information to inform decisions regarding the effectiveness of AE training to ameliorate cognitive deficits in SZ. Altogether, these limitations hinder our ability to make informed decisions regarding the efficacy of AE to address cognitive deficits in people with SZ. To tackle this very specific need, the proposed research focuses on three major aims - AIM 1: confirm the efficacy of AE training to improve cognition in people with SZ; AIM 2: examine the impact of AE on daily functioning; and AIM 3: examine brain-derived neurotrophic factor (BDNF) as an AE-related biomarker of cognitive-change. Employing a single-blind, randomized clinical trial design, we will randomly assign 200 individuals with SZ from 4 U.S. sites to one of two 12-week, 3x-week, 1-hour treatment programs: 1) AE or 2) A stretching and toning (ST) control condition. All participants will undergo assessments of aerobic fitness, cognition, daily functioning, BDNF, and other putative biomarkers of cognitive change before the training and after 6- and 12-weeks of interventions.