Alteration of state-transition dynamics and its clinical significance in schizophrenia and bipolar disorder

Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric disorders characterized by cognitive impairment. Evidence suggests that humans execute various cognitive functions through transitioning between different brain states. However, whether these state transitions are abnormal in SZ and BD patients remains unclear. We hypothesized that their state-transition dynamics are altered, and these alterations may relate to symptom severity.

This study proposes two state transition indicators, Hetero-state Transition Energy (HeTE) and Homo-state Maintenance Energy (HoME), by integrating structural and functional information. For comprehensive comparison, we also considered traditional controllability indicators based only on structural information, including average controllability and modal controllability. Subsequently, we performed intergroup comparisons, correlation analysis with node degree, participant classification and clinical scales prediction to investigate alteration in state-transition dynamics and its clinical significance in SZ and BD.

Patients with SZ and BD showed significantly increased HeTE and decreased HoME, both of which were negatively correlated with node degree. Crucially, the combination of HeTE and HoME was superior to traditional controllability indicators, achieving higher accuracy in participant classification (97.76 % for SZ vs. HC), and stably predicting BPRS and SANS clinical scales (all p < .05).

Our results indicate that abnormalities of HeTE and HoME in SZ and BD reflect impaired efficiency in state transition, and have a tendency to maintain the current pathological states, potentially resulting in cognitive flexibility impairment. Compared with traditional controllability indicators, the proposed HeTE and HoME may serve as sensitive quantitative markers to guide functional recovery in psychiatric disorders.