Wednesday, May 14, 2025
5/14/2025
The Mind After Midnight: Mechanistic Examination of Nocturnal Wakefulness as aSuicide Risk Factor - ABSTRACT: Patients with wakefulness during the biological nigh frequently experience emotional dysregulation (e.g., negative affect, hopelessness) and cognitive dysregulation (e.g., impaired decision-making, impulsivity) that increase the likelihood of engaging in unhealthy behaviors. Consistent with this observation, meta-analyses indicate that sleep disruption triples suicide risk. Our group discovered that suicides are 3-4x more likely to occur between 2-4am than would be expected by chance. We have replicated this finding multiple times using both experimental and epidemiological data, demonstrating a relationship between nocturnal wakefulness and suicide ideation within individuals and across demographics, seasons, comorbidities, and depression status. This phenomenon may be explained by the “Mind After Midnight” hypothesis: Wakefulness during the biological night exposes the individual to enhanced negative affect, a reduced ability to make healthy decisions, and a level of disinhibition that enhances impulsivity. This occurs due to a confluence of factors related to the normal regulation of sleep, wakefulness, and circadian rhythms. If correct, this phenomenon would represent a transdiagnostic process applicable across the behavioral spectrum and partially explain why aberrant behaviors are more likely to occur at night or after sleep loss. Although we have ample cross-sectional data from the community, and laboratory-based feasibility data, our hypothesized model requires an experimental study to support mechanistically-informed treatments that reduce this modifiable suicide risk. The proposed experiment will be the first study of mood, neuropsychological function, and suicidality that probes both chronobiologic and homeostatic factors. This project will utilize an approach that can be used with subsequent neurophysiologic studies across a wide variety of conditions with similar features of impulse dysregulation, especially those occurring at night. To successfully execute this transdiagnostic, translational, and RDoC-responsive proposal, we will recruit n=90 adults with a history of suicide ideation in the past 6 months to complete a protocol that involves both in-lab and at-home components. This study includes a laboratory-based assessment (AIM 1) of whether suicide-associated cognitive processes (irrational and risky decision making, delay discounting) and affect (negative mood, hopelessness, suicide ideation) are greater at 2-4am, compared to other times of the day, within individuals. To examine the role of homeostatic sleep pressure on cognitive performance and dysregulated mood (AIM 2), we will examine individuals in two conditions at 2-4am: under high sleep pressure (kept awake until 2am) and low sleep pressure (allowed to sleep and awakened at 2am). To examine the role of circadian rhythms (AIM 3) in the model, we will capture ecologically-valid circadian (behavioral: amplitude, chronotype, regularity; and physiologic: melatonin) phenotyping data. The results from this experiment will advance the fields of circadian science and suicide prevention though an improved understanding of the physiologic mechanisms driving elevated suicide risk during the biological night.
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