Effects of aerobic exercise on hippocampal formation volume in people with schizophrenia – a systematic review and meta-analysis with original data from a randomized-controlled trial

Abstract

Background: 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 patients with schizophrenia is still limited and inconclusive. Therefore, we aim to assess the impact of aerobic exercise on the volume and connectivity of the hippocampal formation and explore the clinical relevance of potential exercise-induced adaptations.Methods: In this multicenter randomized-controlled clinical trial, a total of 92 patients with schizophrenia (31 female, 61 male) underwent serial 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 three times per week for six months. 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.Results: In the aerobic exercise group, but not in the control group, volumes within the hippocampal formation increased, especially in the cornu ammonis. No effects of exercise on hippocampal formation connectivity were observed.Conclusions: The present study supports the evidence in favor of beneficial effects of aerobic exercise on hippocampal volume in patients with schizophrenia with most robust effects on CA3 and therefore underlines the potential of aerobic exercise to prevent neurodegenerative processes in this key region involved in memory processes.

The Effect of Physical Exercise on People with Psychosis: A Qualitative Critical Review of Neuroimaging Findings

“…Therefore, the utmost investigated brain region is the hippocampus, together with its subfields and the parahippocampal areas. Volumetric studies reported mixed results consequent to aerobic fitness, with evidences for either an increased cortical volume of the hippocampus in schizophrenic patients [ 25 , 27 , 30 , 35 , 39 ] or stable hippocampal grey matter both in clinical high-risk subjects [ 23 , 24 ] and later stages of psychosis [ 31 , 36 , 37 ]. The same pattern is found also while looking at the hippocampal subfields, with Damme et al [ 23 ] reporting a negative correlation of its volume in the absence of aerobic activity and Maurus et al [ 25 ] reporting an increased volume associated with physical activity; whereas Malchow et al [ 31 ] describe no structural changes.…”

“…Indeed, the vast majority of functional studies based their hypotheses on previous structural findings and aimed at shining new light on hippocampal changes consequent to exercise training by looking at its functional connectivity [ 23 , 24 , 27 , 32 ]. Functional connectivity of the hippocampus seemed to increase with the occipital lobe after physical exercise both in ultra-high risks subjects for psychosis [ 24 ] and in attenuated forms of psychosis [ 23 ] compared to control conditions.…”

“…Functional connectivity of the hippocampus seemed to increase with the occipital lobe after physical exercise both in ultra-high risks subjects for psychosis [ 24 ] and in attenuated forms of psychosis [ 23 ] compared to control conditions. However, while looking at patients with schizophrenia, no changes were found in hippocampal functional connections to more neighboring structures (e.g., subfields, parahippocampal regions, amygdala, thalamus, middle/frontal and cingulate gyrus) after physical activity [ 27 , 32 ].…”

“…Therefore, the utmost investigated brain region is the hippocampus, together with its subfields and the parahippocampal areas. Volumetric studies reported mixed results consequent to aerobic fitness, with evidences for either an increased cortical volume of the hippocampus in schizophrenic patients [25,27,30,35,39] or stable hippocampal grey matter both in clinical high-risk subjects [23,24] and later stages of psychosis [31,36,37]. The same Therefore, the utmost investigated brain region is the hippocampus, together with its subfields and the parahippocampal areas.…”

“…Functional MRI Looking at the total number of studies included in this narrative review, a smaller portion of the studies (N = 8) investigated the effect of exercise on functional connections in psychotic patients compared to those dedicated to structural plasticity (Table 2, Figure 2C). Indeed, the vast majority of functional studies based their hypotheses on previous structural findings and aimed at shining new light on hippocampal changes consequent to exercise training by looking at its functional connectivity [23,24,27,32]. Functional connectivity of the hippocampus seemed to increase with the occipital lobe after physical exercise both in ultra-high risks subjects for psychosis [24] and in attenuated forms of psychosis [23] compared to control conditions.…”