Enhancing Cognitive Training through Aerobic Exercise after a First Schizophrenia Episode: Theoretical Conception and Pilot Study Keith H. Nuechterlein, PhD1,2, Joseph Ventura, PhD1, Denise Gretchen-Doorly, PhD1, Sarah C. McEwen, PhD1, Sophia Vinogradov, MD3, and Kenneth L. Subotnik, PhD1 1 Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA; 2UCLA Department of Psychology; 3Department of Psychiatry, UC San Francisco ). Introduction Structured cognitive training and aerobic exercise have separately shown promise for improving cognitive deficits in schizophrenia (SZ) (Wykes et al., 2011; Pajonk et al., 2010). Regular aerobic exercise releases brain-derived neurotrophic factor (BDNF) which promotes synaptic plasticity and neurogenesis. Thus, aerobic exercise provides a neurotrophic platform to enhance the impact of neuroplasticity-based cognitive training. The combination of aerobic exercise and cognitive training in SZ may yield more robust effects than cognitive training alone. Furthermore, providing this combined intervention in the initial period of illness may lead to greater impact and broader generalization to functional outcomes compared to periods in which chronic illness factors are well established. Results Attendance for the in-clinic CT&E sessions was excellent for both the cognitive training (100%) and the exercise groups (95%). Adherence with the CT&E at-home exercise component was similar (92%). Cohen’s f of 0.40 is considered large Method 16 patients with a recent first episode of schizophrenia from the UCLA Aftercare Research Program were assigned to either Cognitive Training & Exercise (CT&E; n=7) or Cognitive Training alone (CT; n=9) for 10 weeks Both groups completed PositScience computer-based cognitive training for 2 days/week, 2 hrs/day, based on neuroplasticity enhancing principles. Programs focused on auditory processing and social cognitive training. The CT&E group also completed aerobic conditioning for 30-min sessions twice a week in clinic and twice a week at home. Groups were stratified demographically, but not randomly assigned. Assessments were completed at baseline and again after participants completed 10 weeks of either CT&E or CT. Measures: MATRICS Consensus Cognitive Battery (MCCB), Role Functioning Scale, and BDNF. Data Analysis: Cohen’s f effect sizes between groups calculated based on Group X Time interaction. BDNF: Initial analyses of a subgroup with neurotrophin data suggests that serum BDNF increases more in CT&E (mean change of 4220 vs. 1544 pg/mL) References Pajonk, F. G., et al …Falkai, P. (2010). Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry, 67(2), 133-143. Wykes, T., Huddy, V., Cellard, C., McGurk, S. R., & Czobor, P. (2011). A meta-analysis of cognitive remediation for schizophrenia: Methodology and effect sizes. Am J Psychiatry, 168(5), 472-485. Discussion Aerobic exercise produces neurotrophic factors that boost synaptic plasticity and learning potential, raising the possibility that it may increase the impact of neuroplastiticity-based cognitive training. Our initial feasibility data indicate that it is possible to achieve excellent treatment adherence with a combined cognitive training and aerobic exercise program. Initial data also suggest that several effect sizes for differential gains in CT&E compared to CT alone may be large. These encouraging preliminary findings support the promise of combining cognitive training and aerobic exercise to improve the early course of SZ. A randomized controlled trial is now ongoing at UCLA. Cognitive Training and Exercise: Program Details We used neuroplasticity-based programs from PositScience (Brain HQ Brain Fitness Program and SocialVille) in sequence for cognitive training. The auditory discrimination and verbal processing components of BrainHQ Brain Fitness focus on basic neurocognitive functions designed to tune neural circuits related to perceptual processing and verbal learning and memory. The social cognitive training in SocialVille builds on this base using the same learning principles but with social and affective stimuli more relevant to everyday social interactions. Aerobic exercise included heart rate monitoring to optimize time within target heart rate zone. A bridging group was used to increase program adherence and to discuss how cognitive skills might be generalized to daily living. Presented at the 2014 Schizophrenia International Research Society conference in Florence, Italy. Correspondence to Keith Nuechterlein, PhD, University of California, Los Angeles, 300 UCLA Medical Plaza, Room 2240, Los Angeles, CA 90095-6968, USA. E-mail: keithn@ucla.edu Research supported by NIMH research grants R34 MH102529 and P50 MH066286 (PI: K. H. Nuechterlein)