Exercise Intervention in Individuals at Clinical High Risk for Psychosis: Benefits to Fitness, Symptoms, Hippocampal Volumes, and Functional Connectivity

Background and Hypothesis Individuals at clinical high risk for psychosis (CHR-p) are less fit than nonclinical peers and show hippocampal abnormalities that relate to clinical symptoms. Exercise generates hippocampal neurogenesis that may ameliorate these hippocampal abnormalities and related cognitive/clinical symptoms. This study examines the impact of exercise on deficits in fitness, cognitive deficits, attenuated psychotic symptoms, hippocampal volumes, and hippocampal connectivity in individuals at CHR-p. Study Design In a randomized controlled trial, 32 individuals at CHR-p participated in either an exercise (n = 17) or waitlist (no exercise) (n = 15) condition. All participants were sedentary at use and absent of current antipsychotic medication, psychosis diagnoses, or a substance use disorder. The participants completed a series of fitness, cognitive tasks, clinical assessments, and an MRI session preintervention and postintervention. The exercise intervention included a high-intensity interval exercise (80% of VO(2)max) with 1-minute high-intensity intervals (95% of VO(2)max) every 10 minutes) protocol twice a week over 3 months. Study Results The exercise intervention was well tolerated (83.78% retention; 81.25% completion). The exercising CHR-p group showed that improved fitness (pre/post-d = 0.53), increased in cognitive performance (pre/post-d = 0.49), decrease in positive symptoms (pre/post-d = 1.12) compared with the waitlist group. Exercising individuals showed stable hippocampal volumes; waitlist CHR-p individuals showed 3.57% decreased hippocampal subfield volume. Exercising individuals showed that increased exercise-related hippocampal connectivity compared to the waitlist individuals. Conclusions The exercise intervention had excellent adherence, and there were clear signs of mechanism engagement. Taken together, evidence suggests that high-intensity exercise can be a beneficial therapeutic tool in the psychosis risk period.