How Can Sleep Disruption Trigger Mood Episodes?

Colleen McClung, PhD, discussed the role of sleep and circadian rhythm disruption in psychiatric illness, with particular focus on bipolar disorder. She described her laboratory's use of postmortem human brain tissue to characterize molecular circadian rhythms in psychiatric disease.

McClung noted that nearly every psychiatric disorder has a sleep or circadian component embedded in its diagnostic criteria. In major depressive disorder, patients may experience hypersomnia or insomnia; in bipolar disorder, sleep need and pattern fluctuate markedly between mood states. She emphasized that disruption to the sleep-wake cycle, such as that caused by shift work or travel, is among the most potent precipitants of mood, psychotic, and anxiety episodes. McClung noted that this relationship also carries therapeutic implications, citing bright light therapy, dark therapy, and interpersonal and social rhythm therapy as interventions that work by stabilizing and amplifying circadian rhythms.¹ She stated more broadly that the underlying biology "really points to the circadian system and sleep as having a major contribution to the regulation of mood and reward."

McClung identified bipolar disorder as an area of particular interest for her group, noting that patients with bipolar disorder exhibit substantial day-to-day and within-day variability in circadian rhythms. During manic episodes, patients require minimal sleep and demonstrate a phase-advanced circadian rhythm, whereas depressive episodes are associated with a phase-delayed rhythm. She emphasized that rhythm stabilization is a key treatment target in bipolar disorder management.

To investigate the molecular underpinnings of these phenomena, McClung's group uses human postmortem brain tissue obtained through a collaboration between the University of Pittsburgh brain bank and the Pittsburgh Coroner's Office. Because both the time and date of death are documented for each donor, McClung's team can computationally align subjects along a 24-hour cycle referenced to sunrise on the day of death. This approach enables RNA sequencing-based gene expression analysis to determine whether specific genes exhibit rhythmic expression patterns, allowing direct comparison between healthy comparison subjects and individuals with psychiatric disorders.² McClung noted there have been substantial differences identified in rhythmic gene expression between these groups.

Dr McClung is professor of psychiatry and clinical and translational science at the University of Pittsburgh School of Medicine.

References

1. McCarthy MJ, Gottlieb JF, Gonzalez R, et al. Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: a critical multidisciplinary literature review and agenda for future research from the ISBD task force on chronobiology. Bipolar Disord. 2022;24(3):232–263.

2. Seney ML, Cahill K, Enwright JF 3rd, et al. Diurnal rhythms in gene expression in the prefrontal cortex in schizophrenia. Nat Commun. 2019;10(1):3355.