Project Details
Projekt
Understanding Hippocampal Neuroplasticity in Schizophrenia by Targeting Molecular Pathways Through Physical Exercise Training (PsychTrain)
Subject Area
Biological Psychiatry
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 515976200
Aerobic exercise has been shown to improve cognition, hippocampal volume, and functional outcomes in individuals with schizophrenia. Research indicates that improvements may be mediated by neuroplastic brain regeneration moderated by genetic risk factors. However, a limitation of prior research is that it did not identify the molecular pathways linking exercise with genes and specific neuroplastic mechanisms. We will address this research gap by investigating the impact of genetics-related moderators of aerobic exercise. The primary outcome of our study will be the correlation of a schizophrenia polygenic risk score (PRS), assessed by genome-wide association studies, with the change in volume of the hippocampal subfield cornu ammonis 4 (CA4)/dentate gyrus (DG) after a 3-month aerobic exercise intervention compared with balance and tone training, the control condition. Previously, we found preliminary evidence for effects of PRS on volume change in the CA4/DG subregion after aerobic exercise training. Secondary outcomes will be synapse-related pathways, brain structural and resting-state functional alterations, symptoms, cognition, and epigenetic parameters. We will investigate a sample of 142 patients with schizophrenia. A total of 65 patients with schizophrenia have already completed the 3-month training in our aerobic exercise study of the BMBF-funded “Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments” (ESPRIT) consortium. Of these patients, 34 underwent 3-Tesla multimodal magnetic resonance imaging (MRI) scans and provided blood for genetic and molecular biomarker investigations and will be included in this study. In addition, for additional assessment of secondary outcomes, blood has been collected from 31 patients of the ESPRIT study with only clinical phenotyping. According to our power calculation, assuming a drop-out rate of 30% we additionally need to enroll a further 156 patients in the planned study. We will construct PRSs and include molecular pathways that mediate synaptic plasticity, as indicated by our recent aerobic exercise studies, including Synapse Part (GO: 0045202) and Chemical Synaptic Transmission (GO: 0007268), and compare them with pathways not related to synaptic processes. We will use machine learning to stratify patients according to CA4/DG volume and thus approach the complex construct of neuroplasticity. Furthermore, we will determine the influence of PRS on structural MRI, diffusion tensor imaging, resting-state functional MRI, and electroencephalography parameters. Rich, multimodal longitudinal imaging data will be analyzed by multivariate techniques, including independent component analyses and advanced longitudinal modeling techniques. We will harness genetic, epigenetic, neuroimaging, clinical, and cognitive data acquired before and after the intervention to identify predictive multimodal signatures.
DFG Programme
Research Grants
Co-Investigators
Professor Dr. André Fischer; Professor Dr. Nikolaos Koutsouleris
