Effects of exercise on hippocampal formation volume and connectivity in patients with schizophrenia - a multicenter randomized-controlled trial

Aerobic exercise is a promising add-on treatment to counteract structural and functional impairments of the hippocampal formation and associated clinical outcome in schizophrenia. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is still limited and inconclusive. Therefore, we aim to assess the impact of aerobic exercise on the volume and functional connectivity of the hippocampal formation and explore the clinical relevance of potential exercise-induced adaptations in people with schizophrenia. In this multicenter randomized-controlled clinical trial, a total of 92 patients with schizophrenia underwent serial 3T-MRIs and were randomly assigned to either an aerobic exercise intervention or a flexibility, strengthening and balance training as a control group. Both groups exercised for six months and completed approximately one training session per week on average. Clinical assessments and structural and functional MRI scans were conducted at three consecutive timepoints. Linear mixed models, linear and logistic regressions and mediation analyses were computed to examine the effects of exercise on the volume and connectivity of the hippocampal formation and their potential clinical relevance. In the aerobic exercise group, but not in the control group, volumes within the hippocampal formation increased, especially in CA3. No effects of exercise on functional connectivity of the hippocampal formation were observed. The present study indicates that aerobic exercise in people with schizophrenia can lead to volumetric increases within the hippocampal formation with most robust effects on CA3. Hence, the current findings support previous evidence that aerobic exercise can prevent neurodegenerative processes in this key region.