On the basis of impaired functional connectivity in psychosis: the role of structural substrate and neurometabolites contribution

Abstract

Psychotic disorders are characterized by the presence of symptoms related to a distortion of one’s perception of reality. In its early stages (First Episode of Psychosis, FEP), patients may show diffuse symptomatology that lays in a spectrum delimited by bipolarity and schizophrenia on both ends. Some studies point to a disconnection of the brain as a network as the most likely cause of the symptoms of the disease. Functional connectivity (FC) arises from the interaction of neurometabolites and a structural substrate, and inferring the contribution of each of these elements is not possible using traditional approaches. Accordingly, we aimed to explore the structural connectivity and use of simulations to infer the synaptic contribution of the emerging FC in FEP patients. First, structural connectivity from diffusion-weighted images was obtained and compared between Healthy Controls (HC), Affective Psychoses (AF), and Schizophrenia Spectrum Disorders. Second, synaptic-level properties, such as global connectivity, were inferred per subject based on Hopf-Bifurcation by selecting the parameters that produce the closest FC simulated to the experimental FC. Finally, a comparison of the extracted measures between the three groups was performed. The obtained results showed differences in the substrate of the three groups, with AF being the one with larger disparities from HC. As for the simulations, there were no differences for the global connectivities that generated the most accurate representation; however, for AF the similarity of the simulated static FC was lower to experimental static FC, which could suggest a higher neurometabolic contribution for this group.