Alterations in static and dynamic intrinsic brain local connectivity and associated molecular analysis in drug-naïve first-episode schizophrenia: Insights from resting-state functional magnetic resonance imaging.

Abstract

Schizophrenia is a severe psychiatric disorder marked by widespread brain abnormalities. Recent studies suggest that pathological changes may originate from focal 'epicenter' regions and subsequently spread to other brain areas strongly connected to them. Investigating drug-naïve first-episode schizophrenia (dn-FES) patients may help characterize early-stage regional functional abnormalities and their potential neurochemical underpinnings. Resting-state functional magnetic resonance imaging data were acquired from 50 dn-FES patients and 50 age- and sex-matched healthy controls (HCs). Static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were compared between groups, and correlations with psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). We further used the JuSpace toolbox to test whether spatial patterns of ReHo alterations were associated with specific neurotransmitter receptor/transporter densities. Compared with HCs, dn-FES patients showed reduced sReHo in the bilateral postcentral/precentral gyri, bilateral paracentral lobules and right supplementary motor area, and increased dReHo in the left lingual gyrus. sReHo in the right postcentral gyrus was inversely correlated with PANSS positive scores, whereas dReHo in the left lingual gyrus was negatively correlated with PANSS general scores. Schizophrenia-related sReHo alterations showed significant spatial associations with serotonergic, dopaminergic, noradrenergic and cholinergic systems, whereas dReHo alterations were associated with serotonergic, dopaminergic, cannabinoid and opioid systems. Taken together, this study identifies abnormal static and dynamic local functional connectivity in sensorimotor and visual regions in drug-naïve first-episode schizophrenia, and the spatial correspondence between these alterations and receptor/transporter distributions may offer insight into the molecular substrates associated with these functional abnormalities.