Altered glutamate concentration in the subcortical nuclei and its correlation with resting-state functional connectivity in unmedicated obsessive-compulsive disorder.

The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) in the cortico-striatal-thalamo-cortical (CSTC) circuit is closely related to the onset of obsessive-compulsive disorder (OCD). The caudate nucleus and thalamus are the critical hubs of the CSTC circuit; however, few studies have explored the correlation between the neurochemical changes of subcortical nuclei and the resting-state functional connectivity (rsFC) within the CSTC circuit in OCD patients. In this study, 24 OCD patients and 17 healthy controls (HCs) underwent resting-state functional MRI (rs-fMRI) scans and proton magnetic resonance spectroscopy (H-MRS) acquisition. The bilateral caudate nucleus and thalamus were used as the regions of interest (ROIs) for ROI-to-ROI rsFC analysis within CSTC circuit and Glu/GABA calculation to explore altered metabolite concentration in the subcortical nuclei and its correlation with rsFC. A significant increase of Glu in the left thalamus (Thalamus_L), an increase of Glu/GABA in the right thalamus (Thalamus_R), and a decrease of GABA in Thalamus_R were observed in the OCD patients compared to HCs. The rsFC showed widespread reductions among CSTC core nodes (caudate-thalamus-orbitofrontal cortex (OFC)). Furthermore, correlation analysis revealed a significant positive correlation between left caudate Glu levels and left caudate-right OFC rsFC. These findings provided the new evidence of glutamatergic modulation in this pathway's functional integration.