Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia

472 

Abstract Submission 

Lukas Roell¹

¹Department of Psychiatry and Psychotherapy, LMU Hospital Munich, Munich, Bavaria

Lukas Roell  
Department of Psychiatry and Psychotherapy, LMU Hospital Munich
Munich, Bavaria

Aerobic exercise as an adjunct therapy for schizophrenia leads to additional improvements in psychiatric symptoms and cognitive performance. However, the neural mechanisms underlying these clinical improvements are not fully understood. Therefore, our aim was to identify exercise-induced structural and functional adaptations at the neural level that underlie the clinical rehabilitation processes of patients with schizophrenia. Insights into the neural mechanisms induced by aerobic exercise can contribute to a better understanding of the pathophysiology of schizophrenia and may provide a basis for optimizing current treatment approaches.

We analyzed comprehensive clinical and MRI data of 100 patients with schizophrenia from the ESPRIT C3 study (NCT03466112) and the BrainTrain study (NCT05956327). These large-scale randomized controlled trials investigate the effect of an aerobic exercise program on stationary bicycles compared to flexibility, strengthening, and balance training on various health outcomes in patients with schizophrenia. We acquired multimodal MRI at baseline and post-intervention, comprising T1- and T2-weighted structural MRI, resting-state functional MRI, diffusion-tensor imaging (DTI), arterial spin labeling (ASL) and magnetic resonance spectroscopy (MRS) of the hippocampus. At both timepoints, we computed global and regional brain volumes, cortical thickness, cortical gyrification, static and dynamic functional connectivity, structural connectivity, global and regional brain perfusion, and relevant neurotransmitter concentrations in the hippocampus, aiming to identify neural mechanisms that drive a clinical response after exercise in schizophrenia.

First, we identified compensatory relationships between aerobic fitness and functional connectivity within the default mode network and the cortical-striatal-thalamic-cerebellar network. Additionally, associations with symptom severity were present for the latter. Second, we found positive effects of aerobic exercise on the structural and functional organization of the default mode network, the cortical-striatal-thalamic-cerebellar network, and the cortical-striatal-pallidal-thalamic-cortical loop. Adaptations within the de-fault mode network were related to improvements in overall disorder severity. Third, we discovered positive associations between patients' aerobic fitness and the volume of the hippocampus, particularly prominent in the hippocampal subregions CA1-4 and DG. However, we did not find stable relationships with symptom severity and cognitive performance. Fourth, we observed exercise-induced increases in the hippocampal subfields CA1-4 and DG, but could not detect volume increases in the total hippocampus. However, these effects were not associated with relevant clinical parameters.

In summary, we identified four neural entities in schizophrenia – the hippocampus, the default-mode network, the cortical-striatal-thalamic-cerebellar network, and the cortical-striatal-pallidal-thalamic-cortical loop – that exhibit beneficial adaptations as a result of aerobic exercise. While we were able to demonstrate a few associations between these neural changes and clinical improvements, further large-scale randomized controlled exercise studies in patients with schizophrenia are warranted to elucidate the clinical relevance of these neural adaptations.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Neural Plasticity and Recovery of Function ²

Basal Ganglia

Cognition

FUNCTIONAL MRI

Psychiatric Disorders

Schizophrenia

STRUCTURAL MRI

Thalamus