Reducing functional dysconnectivity in people with schizophrenia spectrum disorders

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Schizophrenia spectrum disorders (SSD) are characterized by the dysconnection hypothesis, suggesting impaired brain connectivity contributes to symptoms.
• Physical exercise shows promise in ameliorating these connectivity issues and clinical impairments in SSD.

Purpose of the Study:

• To determine if exercise-induced reductions in functional dysconnectivity correlate with clinical improvements in SSD patients.
• To explore the genetic factors, specifically using imaging transcriptomics, underlying these exercise-related brain changes.

Main Methods:

• Analysis of 23 SSD patients from the ESPRIT C3 trial undergoing 6-month exercise interventions.
• Assessment of functional dysconnectivity at baseline and post-intervention using whole-brain, network, and regional analyses.
• Statistical modeling (linear mixed effects, voxel-wise correlations) to link exercise effects with clinical outcomes and gene expression.

Main Results:

• Significant decrease in functional dysconnectivity post-exercise, primarily associated with increased oligodendrocyte-related gene expression.
• Reduced default-mode network dysconnectivity correlated with better global functioning.
• Changes in insular, somatomotor, frontoparietal, and language networks (e.g., Broca's area) linked to symptom severity, functioning, and cognitive improvements.

Conclusions:

• Findings support oligodendrocyte pathology's role in SSD.
• Targeting dysconnectivity in specific brain networks (default-mode, salience, language) via exercise may improve functioning, reduce symptoms, and enhance cognition in SSD.