Constrained brain-state dynamics underlying suicide risk in bipolar disorder: An energy landscape analysis

Suicide is a major cause of mortality in bipolar disorder (BD), yet its neural underpinnings remain insufficiently understood. Suicide risk is thought to involve impaired cognitive-emotional flexibility arising from fundamental disturbances in brain dynamics. This study aimed to test this hypothesis by characterizing the energetic and dynamical constraints underlying suicide vulnerability in BD.

We applied energy landscape modeling to resting-state fMRI data from 123 individuals with BD (61 suicide attempters, 62 non-attempters) and 68 healthy controls. Brain activity was modeled as transitions between functional states, enabling quantification of neural rigidity. Group-level comparisons and correlation analyses were conducted to identify attractor stability, transition patterns, and their associations with clinical and cognitive measures.

Four dominant attractor basins were identified. Basins A and D showed progressively reduced appearance frequency and stability from healthy controls to non-attempters and suicide attempters. Increasing suicide risk was associated with greater neural rigidity, reflected in a more constrained transition architecture with shorter and more repetitive transition paths in suicide attempters. Lower stability of basin A was associated with higher suicide risk, with cognitive impairment statistically accounting for part of this association in mediation analyses.

Suicide vulnerability in BD is associated with entrenched functional brain states, reduced transition diversity, and elevated energetic constraints that may limit adaptive brain-state reconfiguration. These findings provide a mechanistic account of neural rigidity and suggest that altered brain-state dynamics may serve as a potential biomarker of suicide risk in BD.