Critical slowing down as an early warning of transitions in episodes of bipolar disorder: A simulation study based on a computational model of circadian activity rhythms

Bipolar disorder is characterized by repeated episodes of mania and depression, and can be understood as pathological complex system behaviour involving cognitive, affective and psychomotor disturbance. Accurate prediction of episode transitions in the long-term pattern of mood changes in bipolar disorder could improve the management of the disorder by providing an objective early warning of relapse. In particular, circadian activity changes measured via actigraphy may contain clinically relevant signals of imminent systemic dysregulation. In this study, we propose a mathematical index to investigate the correlation between apparently irregular circadian activity rhythms and critical transitions in episodes of bipolar disorder. Not only does the proposed index illuminate the effects of pharmacological and psychological therapies in control over the state, but it also provides a framework to understand the dynamic (or state-dependent) control strategies. Modelling analyses using our new approach suggest that key clinical goals are minimizing side effects of mood stabilizers as well as increasing the efficiency of other therapeutic strategies.