NIH/NIAAA – Mechanistic studies on chronic alcohol use and sleep homeostasis (R01 Clinical Trial Optional)

A substantial body of evidence demonstrates many potential reciprocal interactions between alcohol use disorder (AUD) and sleep, some of which may have profound impacts on health. For example, findings from studies in humans and animal models suggest that AUD contributes to sleep disturbances and other changes that lead to disrupted sleep patterns. For individuals in recovery from AUD, these changes may persist for months or even after years of abstinence, suggesting that AUD may have enduring effects on homeostatic sleep processes. Such persistent sleep problems may lead to relapse, especially in individuals who may self-medicate with alcohol to induce sleep. Research also indicates a relationship between changes in brain structure and function and dysregulated sleep. This includes human brain imaging studies demonstrating an association between gray and/or white matter loss and sleep deficits in people with AUD, as well as studies showing that alcohol-induced changes in GABAergic and adenosinergic neurotransmission may play a role in sleep disruptions. Not only can alcohol contribute to disordered sleep, but disordered sleep, particularly in adolescence, may be a factor in the development of AUD.

Despite these findings, the relationships between alcohol-related sleep dysregulation and alterations in brain structure and neurochemistry are poorly understood. Furthermore, it is unclear how much abstinence will lead to a full normalization of sleep patterns, if ever.

Many alcohol-sleep interactions and their underlying mechanisms remain unclear, especially those involving AUD and chronic sleep problems. Studies on the cellular, molecular, and network-based mechanisms underlying reciprocal effects between AUD and sleep dysregulation are critically needed to guide therapeutic interventions aimed at correcting sleep problems associated with AUD.

Objective

The objective of this FOA is to promote research in animal models and human subjects on the reciprocal relationships between AUD and sleep disruptions. The major goal is to understand the underlying mechanisms that will lead to improved treatments for AUD. NIAAA strongly encourages collaborative efforts between experts in sleep research and established alcohol investigators to facilitate the development of applications incorporating both areas of research.

Appropriate topics include but are not limited to:

  • Understanding dose-related effects of chronic alcohol misuse on sleep homeostasis;
  • Studies of dysregulated sleep and its contribution to AUD and relapse;
  • Investigations on the mechanisms of persistent sleep problems in abstinence from AUD;
  • Studies on sex/gender, genetic, and epigenetic factors that regulate sleep problems in AUD;
  • Mechanistic proof-of-concept studies to remediate sleep dysregulation associated with AUD and the resulting benefits of recovery.

Applications that focus on topics listed below will be considered non-responsive and will not be reviewed.

  • Acute effects of alcohol on sleep in human or animal models;
  • Studies on chronobiology and circadian rhythm changes;
  • Observational and parametric human studies;
  • Studies the involve HIV/AIDS.

Deadline:  March 17, 2019 (letters of intent); April 17, 2019 (full proposals)

URL:  https://grants.nih.gov/grants/guide/rfa-files/RFA-AA-19-006.html