Chronobiology of Mood Disorders: The Role of the Biological Clock in Depression and Bipolar Disorder.

Mood disorders, including major depressive disorder, bipolar disorder, and seasonal affective disorder, exhibit significant heterogeneity, with disturbances in biological rhythms playing a central role. These disturbances not only contribute to the onset and progression of mood disorders but also serve as important predictors of relapse ("Chronos syndrome") and treatment response. Circadian disruptions, which are influenced by factors such as seasonality, jet lag, shift work, and childbirth, are hallmarks of mood episodes and are pivotal in transitions between mood states. Longitudinal studies have revealed a bidirectional relationship between circadian dysregulation and mood disorders, suggesting that biological clock abnormalities may both signal and predispose individuals to mood episodes. Despite their significance, no single circadian biomarker has demonstrated sufficient specificity or sensitivity for diagnostic precision. This underscores the urgent need for multimodal approaches that integrate circadian markers with other physiological and behavioral dimensions. Advancing mood disorder care requires biomarkers that capture individualized biological signatures, revealing circadian dysregulation and its interactions with multiple other physiological systems to enable precise subtyping and improved interventions. In this review, we emphasize the potential of integrating biological rhythms into a dimensional framework, leveraging advanced digital tools and mathematical models to provide ecologically-valid insights into mood disorder mechanisms. Such approaches aim to bridge the gap between clinical observations and biological underpinnings, paving the way for biologically informed classifications and personalized treatment strategies. By addressing the complexity of circadian disruptions and their interplay with other systems, this paradigm shift offers a promising path to enhancing mood disorder diagnostics and therapeutics.