Acute conceptual disorganization in untreated first-episode psychosis: A combined magnetic resonance spectroscopy and diffusion imaging study of the cingulum

Abstract

Background: Disorganized thinking is a core feature of acute psychotic episodes that is linked to social and vocational functioning. Based on the close association between cingulum and disorganized thinking, we examine three candidate mechanistic markers in relation to acute conceptual disorganization (CD) in first episode psychosis: glutamate excess; cortical antioxidant (glutathione) status and the integrity of the cingulum bundle. Methods: We used fractional anisotropy (FA) maps from 7T diffusion-weighted imaging to investigate bilateral cingulum based on a probabilistic white-matter atlas. We compared the high-CD, low-CD and healthy control groups and performed probabilistic fiber tracking from the identified clusters (ROI within cingulum) to the rest of the brain. We quantified glutamate and glutathione with magnetic-resonance-spectroscopy (MRS) in the dorsal anterior cingulate cortex.Results: There was a significant FA reduction (F=9.04; p=0.036) in a cluster in left cingulum in high-CD compared to low-CD (Cohen’s d=1.39; p=0.003) and controls (Cohen’s d=0.86; p=0.009). Glutamate levels did not vary among the groups, but glutathione levels were higher in high-CD compared to the low-CD group. Higher glutathione related to lower FA in the high-CD group in the cingulum cluster.Discussion: Acute CD relates to indicators of oxidative stress as well as reduced white matter integrity of the cingulum but not to MRI-based glutamatergic excess. We propose that both oxidative imbalance and structural dysconnectivity underlie acute disorganization.Limitation: MRS measures of glutamine were highly uncertain and MRs was acquired from a single voxel only.