Towards sleep and circadian diagnostic biomarkers for unipolar and bipolar depression

Altered sleep and circadian rhythms are common clinical features of both unipolar depression (major depressive disorder, MDD) and bipolar disorder (BD). Nonetheless, major knowledge gaps around predictive utility, specificity, heterogeneity and mechanism hamper the development of diagnostically useful, objective sleep and circadian biomarkers. Building on our work in schizophrenia (SCZ), we will collect a cohort (N = 200) of young adults with BD or MDD, their unaffected relatives (i.e. asymptomatic, high- risk individuals) and healthy controls, to identify electrophysiological signatures, shared across or unique to BD and MDD, integrating genetic risk and clinical moderators. Second, we will frame these sleep data within the broader context of ultradian and circadian rhythms, alterations of which are also linked to mood disorders, to generate more informative metrics. Finally, we will investigate the chronic and proximal functional consequences of altered sleep neurophysiology, via changes in cognition, emotion regulation and well-being. This proposed project aims to generate an invaluable resource linking sleep, circadian, genomic, cognitive and mood data. In particular, it will address two clinically relevant issues: 1) heterogeneous patient outcomes in BD and 2) the prediction of bipolarity in patients first presenting with depressive symptoms, an important clinical decision-point with potential for iatrogenic harm.