Rhythm and Blues: Changing the Clock to Breakthrough in Bipolar Disorder

Circadian rhythm disruption, as marked by circadian rhythm variability, eveningness (i.e., preference for later sleep timing), and delayed sleep-wake phase disorder (DSPD, characterized by eveningness) are common among adults with bipolar disorder. Importantly, DSPD, eveningness, and circadian rhythm variability are the most robust predictors of a poorer clinical course in bipolar disorder, including greater functional impairment and relapse to mood episodes across 1-5 years. Efficacious therapies such as Interpersonal and Social Rhythms Therapy (IPSRT) seek to improve outcomes in BD by indirectly targeting the circadian system through stabilization of social rhythms. In this project, we build vertically upon IPSRT by testing the mechanisms of a strategic intervention that directly targets the circadian system disruptions observed in BD—low-dose afternoon supplemental melatonin plus time in bed scheduling. With demonstrated efficacy for DSPD, this strategic intervention is low-burden to person, stabilizes dysregulated sleep patterns, improves sleep, increases morningness, and normalizes circadian timing. We will complete a randomized controlled trial of low-dose afternoon melatonin plus time in bed scheduling relative to control (sleep hygiene education plus placebo pill) for DSPD in adults with bipolar disorder and clinically significant depressive symptoms to determine its engagement of the novel mechanistic target of circadian timing. Specific aims are as follows: AIM 1: Determine the effect of low-dose afternoon melatonin plus time in bed scheduling vs. sleep hygiene education plus placebo pill on the primary mechanistic probe of circadian timing as measured by the gold-standard biomarker, dim light melatonin onset (DLMO); AIM 2: Evaluate DLMO advance as a predictor of change in depression symptoms (self-reported and Ecological Momentary Assessment, EMA); Evaluate exploratory mechanisms (increase in morningness and reduction in sleep variability) as predictors of reduction in depression symptoms (self-reported and EMA); AIM 3. Evaluate DLMO advance as a predictor of exploratory outcomes (total sleep time, sleep-related impairment, mania symptoms). This study is led by Dr. Sarah Sperry with collaborating researchers Dr. Leslie Swanson and Dr. Helen Burgess