Longitudinal alterations of modular functional-metabolic coupling in first-episode schizophrenia

Altered network organization and aberrant neurometabolic levels have been associated with schizophrenia. However, modular alterations of functional-neurometabolic coupling in various stages of schizophrenia remain unclear. This longitudinal study enrolled 34 drug-naïve first-episode schizophrenia (FES) patients and 30 healthy controls (HC). The FES patients underwent resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy (¹H-MRS) at baseline, 2 months, and 6 months of treatment. For ¹H-MRS, the concentrations of γ-aminobutyric acid (GABA), N-acetylaspartate (NAA) and glutamate + glutamine in the ventromedial prefrontal cortex region were measured. A graph theoretical approach was applied for functional connectivity-based modular parcellation. We found that intra-default mode network (DMN) connectivity, inter-modular connectivity between the DMN and the hippocampus, and inter-modular connectivity between the DMN and the frontoparietal module were significantly different across 6-month treatment in the FES patients. The inter-module connectivity of the DMN and hippocampus correlated positively with NAA concentration in the HC group, while this correlation was absent in FES patients. This exploratory study suggests an altered modular connectivity in association with neurometabolite concentrations in FES patients and provides insights into multimodal neuroimaging biomarkers in schizophrenia. Future studies with larger sample sizes are needed to consolidate our findings.