Neurometabolic and functional changes of default-mode network relate to clinical recovery in first-episode psychosis patients: A longitudinal (1)H-MRS and fMRI study

BACKGROUND: Antipsychotic treatment has improved the disrupted functional connectivity (FC) and neurometabolites levels of the default mode network (DMN) in schizophrenia patients, but a direct relationship between FC change, neurometabolic level alteration, and symptom improvement has not been built. This study examined the association between the alterations in DMN FC, the changes of neurometabolites levels in the medial prefrontal cortex (MPFC), and the improvements in psychopathology in a longitudinal study of drug-naïve first-episode psychosis (FEP) patients. METHODS: Thirty-two drug-naïve FEP patients and 30 matched healthy controls underwent repeated assessments with the Positive and Negative Syndrome Scale (PANSS) and 3T proton magnetic resonance spectroscopy as well as resting-state functional magnetic resonance imaging. The levels of γ-aminobutyric acid, glutamate, N-acetyl-aspartate in MPFC, and the FC of DMN were measured. After 8-week antipsychotic treatment, 24 patients were re-examined. RESULTS: After treatment, the changes in γ-aminobutyric acid were correlated with the alterations of FC between the MPFC and DMN, while the changes in N-acetyl-aspartate were associated with the alterations of FC between the posterior cingulate cortex/precuneus and DMN. The FC changes of both regions were correlated with patients PANSS positive score reductions. The structural equation modeling analyses revealed that the changes of DMN FC mediated the relationship between the changes of neurometabolites and the symptom improvements of the patients. CONCLUSIONS: The derived neurometabolic-functional changes underlying the clinical recovery provide insights into the prognosis of FEP patients. It is noteworthy that this is an exploratory study, and future work with larger sample size is needed to validate our findings.