Background: Aberrant resting-state functional connectivity is a neuropathological feature of schizophrenia (SCZ). Prior investigations into functional connectivity abnormalities have primarily employed seed-based connectivity analysis, necessitating predefined seed locations. To address this limitation, a data-driven multivariate method known as connectome-wide association study (CWAS) has been proposed for exploring whole-brain functional connectivity.
Methods: We conducted a CWAS analysis involving 46 patients with SCZ and 40 age- and sex-matched healthy controls. Multivariate distance matrix regression (MDMR) was utilized to identify key nodes in the brain. Subsequently, we conducted a follow-up seed-based connectivity analysis to elucidate specific connectivity patterns between regions of interest (ROIs). Additionally, we explored the spatial correlation between changes in functional connectivity and underlying molecular architectures by examining correlations between neurotransmitter/transporter distribution densities and functional connectivity.
Results: MDMR revealed the right medial frontal gyrus and the left calcarine sulcus as two key nodes. Follow-up analysis unveiled hypoconnectivity between the right medial frontal superior gyrus and the right fusiform gyrus, as well as hypoconnectivity between the left calcarine sulcus and the right lingual gyrus in SCZ. Notably, a significant association between functional connectivity strength and positive symptom severity was identified. Furthermore, altered functional connectivity patterns suggested potential dysfunctions in the dopamine, serotonin, and gamma-aminobutyric acid systems.
Conclusions: This study elucidated reduced functional connectivity both within and between the medial frontal regions and the occipital cortex in patients with SCZ. Moreover, it indicated potential alterations in molecular architecture, thereby expanding current knowledge regarding neurobiological changes associated with SCZ.
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| http://dx.doi.org/10.1016/j.schres.2024.06.031 | DOI Listing |
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