Mechanisms of Risky Alcohol Use in Young Adults: Linking Sleep to Reward- and Stress-Related Brain Function

This research will use biobehavioral approaches to generate understanding about the linkages between stressful life events, sleep duration and timing, and alcohol use in young adults, with a long-term aim of developing effective preventative interventions for alcohol use disorders.

High-risk drinking (consuming ≥ 4 drinks/day or ≥ 8/week for women, ≥ 5 drinks/day or ≥ 15/week for men) is reported by one in four young adults within the past month and predicts the development and progression of alcohol use disorder (AUD). High-risk drinking can also have terrible costs beyond developing AUD, including death and disability from unintended injuries and suicide attempts, physical and sexual assault, and a wide range of acute and chronic health problems. The high degree of morbidity and mortality associated with high- risk drinking in young adulthood makes this a key developmental period for AUD research and intervention.

High-risk drinking in young adults is related to high exposure to stressors, insufficient sleep duration, and late sleep timing. Alarmingly, almost half of young adults report at least moderate exposure to stressors, only 30% regularly obtain the recommended hours of sleep, and sleep timing is at its latest around age 20. Stressors and short/late sleep may also cause disruptions in reward- and stress-related brain function (e.g., medial prefrontal cortex response to monetary reward, autonomic and neuroendocrine function during stressors), which are key biobehavioral mechanisms of AUD. Short and late sleep habits are a prime target for AUD prevention in young adults; however, there is insufficient causal evidence that improving sleep opportunity and/or timing will alter the biobehavioral mechanisms of AUD or decrease high-risk drinking, particularly in at-risk young adults.

The overall objective of this R01 is to evaluate a biobehavioral model whereby sufficient sleep duration and/or early sleep timing can reduce high-risk drinking by promoting reward- and stress-related brain function in young adults with high lifetime stress load. The long-term goal of this research is to leverage sleep and circadian function to promote mental health. A series of studies by the PI and Co-I Hasler demonstrate that stressful life events, short sleep, and late sleep independently predict future reward- and stress-related brain function and alcohol use and dependence symptoms in adolescents and young adults. However, these studies do not evaluate the additive and interactive effects of stressful life events and sleep/circadian function and do not include experimental designs. More recent research by the PI and Co-I Hasler uses sleep and circadian manipulation to target reward- and stress-related brain function and improve mental health in adolescents and young adults. Building from this research, this R01 will test the central hypothesis that extending and advancing sleep will alter reward- and stress-related brain function in young adults with a history of high-risk drinking and elevated lifetime exposure to stressors. This proposal is consistent with the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Strategic Objective to identify mechanisms underlying AUD and comorbid disorders.

Eligibility Criteria:
Inclusion Criteria:

1. 18-24 years of age;
2. NIAAA criteria for past-month high-risk drinking (i.e., ≥ 4 drinks/day or ≥ 8/week for women, ≥ 5 drinks/day or ≥ 15/week for men);
3. short and late sleep (weekday sleep duration ≤ 7 hours and bedtime ≥ 24:00 (midnight); n=60) or long and early sleep (weekday sleep duration ≥ 7 hours and bedtime ≤ 24:00 (midnight); n=30), which will be determined with the Munich Chronotype Questionnaire;
4. at least moderate lifetime exposure to stressors (≥ 2 events on the 20-item Adult Stress and Adversity Inventory-Screener);
5. not currently in high school; and
6. English language fluency.

Exclusion Criteria:

1. Severe alcohol use disorder (AUD) and/or substance use disorder (SUD), defined as ≥6 AUD/SUD criteria in the Diagnostic and Statistical Manual-5;
2. acute alcohol intoxication on the days of the laboratory post-intensive visits, operationalized as a blood alcohol concentration of .02 or higher during Breathalyzer saliva screen;
3. current sleep disorders other than insomnia, delayed sleep phase disorder, or hypersomnia;
4. lifetime diagnosis of bipolar or schizophrenia spectrum disorder;
5. urgent suicide risk, defined by moderate/severe risk as per Columbia Suicide Severity Rating (CSSR) Community Card, and clinician determination that current risk requires immediate action, precluding engagement in study;
6. certain medical conditions (e.g., serious neurological disorder, heart failure or serious trouble, history of head injury with unconsciousness \> 5 minutes);
7. conditions that are contraindicated for MRI (e.g., ferrous metal in the body);
8. positive screen for participant-reported eye disease, epilepsy, or photosensitizing medications that are contraindicated during the manipulation condition when bright light is administered (e.g., psychiatric neuroleptic drugs \[e.g., phenothiazine\], psoralen drugs, antiarrhythmic drugs \[e.g., amiodarone\], antimalarial and antirheumatic drugs, porphyrin drugs used in photodynamic treatment of skin diseases);
9. use of melatonin if participant is not willing to discontinue use for the duration of the study.

We will schedule around (i.e., delay appointments as needed) to avoid the timeframe of the following events:

1. travel across two or more time zones within the month prior to the overnight study visits.
2. begin/end a prescribed medication within 2 months of the observational study;
3. medication dose changes within the timeframe calculated as 5x the drug's half-life \[the time to reach pharmacokinetic steady-state\] before the initiation of the observational or experimental studies;
4. participant-anticipated changes in prescribed medications or medication dosing during the observational or experimental studies.

Participants with positive breathalyzer screen (blood alcohol level \> .02) will be rescheduled for an alternative overnight visit date. Participants excluded for suicide risk may become eligible for the study when the risk has dissipated. We will reschedule participants who have current symptoms of an airborne infectious illness (e.g., COVID).