Implicit social animations lead to distinct changes of dopaminergic, corticostriatal and thalamocortical functional connectivity in schizophrenia and bipolar disorder

OBJECTIVE: Theory of mind (ToM) is a central pillar of social cognition and crucial for effective social interactions. Impairment in ToM is a major predictor of global functioning in schizophrenia (SCZ) and bipolar disorder (BPD). Based on the hypothesis that subcortical and reward circuit functional connectivity is distinct in SCZ and BPD and can be better revealed using ToM task-based approaches, we tested whether functional connectivity patterns of cortico-subcortical networks are a discriminative feature of these disorders. METHODS: We conducted a cross-sectional study (n = 60) to investigate the modulation of task-induced functional connectivity in SCZ (n = 20), BPD (n = 20), and healthy controls (n = 20) during implicit ToM processing with a visual paradigm leading to the interpretation of social meaning based on simple geometric figures with implied social content. Functional connectivity was estimated using generalized psychophysiological analysis of functional magnetic resonance imaging data. RESULTS: We found unique connectivity patterns in SCZ and BPD within subcortical loops. The SCZ group exhibited specifically disrupted connectivity in corticostriatal and thalamocortical pathways involving ToM and the mesolimbic pathways. A single common pattern of aberrant connectivity in BPD and SCZ occurred between the VTA and dorsal striatum, suggesting increased midbrain-striatal (actor-critic) connectivity in both disorders. CONCLUSIONS: The unique patterns of altered connectivity in SCZ (imbalance between striatothalamic and thalamocortical connectivity), and BPD, while sharing a common pattern of increase between VTA and dorsal striatum, may represent candidate biomarkers of pathophysiological significance, or as biological targets for validating differential therapeutic neuromodulation.