Experimental Manipulation of Sleep and Circadian Rhythms and the Role Played on Reward Function in Teens

Substance use (SU) and substance use disorders (SUD) pose devastating health, financial, and societal costs. The incidence of SU and SUDs increases across adolescence, making this sensitive developmental period one of both heightened risk-and heightened opportunity for prevention and intervention. However, to develop effective interventions investigators need to identify novel and modifiable risk factors and mechanisms for SUD. Sleep and circadian rhythm disturbances are such risk factors, and the reward system, with its increasing sensitivity during adolescence, provides a plausible mechanistic substrate. The focus on sleep, circadian rhythms, and reward system function is particularly salient given the extensive, parallel development of these systems during adolescence, and the plausible linkages between sleep and circadian rhythms, reward function, and SUD risk.

Late sleep timing, short sleep duration and circadian misalignment are associated with increased substance use in teenagers and young adults. The central hypothesis of the Center for Adolescent Reward, Rhythms and Sleep (CARRS) is that adolescent development acts on underlying sleep and circadian traits to modify homeostatic sleep drive, circadian phase, and circadian alignment, which in turn impact cortico-limbic functions critical to SU risk (e.g., reward and cognitive control). Investigators further hypothesize that specific manipulations of sleep and circadian rhythms during adolescence will affect reward responsivity and cognitive control in either positive or negative directions. These manipulations will provide experimental support for our model, and proof of concept for novel clinical interventions to reduce the risk of SU and SUDs.

Most previous studies have examined individual components of circadian rhythms, sleep, and reward function in adolescence. Project 2 (P2) of CARRS will test an innovative and mechanistic model of brain circuitry that uses multi-method approaches, takes a developmental perspective, and incorporates key sleep and reward constructs. Most notably, P2 improves upon past observational work by testing an experimental intervention that manipulates sleep and circadian rhythms to directly examine its impact on reward function and cognitive control.

P2 will study 150 adolescents (age 13-15, 50% female) across two key sleep phenotypes: early sleep timing (low risk, n=50) and late sleep timing (high risk, n=100). All participants will complete the observational study: 2 weeks of home sleep monitoring (actigraphy & sleep diary), followed by an overnight laboratory visit to assess self-report, behavioral, and neuroimaging (fMRI) tasks tapping cognitive control and reward function, as well as circadian phase via salivary melatonin and molecular rhythms via hair follicles. The Late group will continue to the experimental study, each participant randomized to manipulation or attentional control conditions (n=50 each). Investigators will probe whether advancing sleep/circadian timing and extending sleep duration via sleep scheduling and chronotherapeutic approaches (reducing PM light exposure; administering AM bright light) improves sleep, circadian, and neurobehavioral function relevant to SUD risk. Finally, repeated 6-month follow-up assessments of sleep and SU for all participants are included to examine longitudinal associations.

Inclusion criteria

• Typically enrolled in a traditional high-school with synchronous learning (in-person or online synchronous learning, but not cyber- or home-schooling) [school closures during the COVID-19 pandemic are an exception to this]
• Physically and psychiatrically healthy
• Provision of written informed consent and assent
• Additional inclusion criterion for Experimental protocol: Meets operational definition of late sleep timing (>10:50PM habitual bedtime)

Exclusion criteria

• History of alcohol, cannabis, or illicit drug use in the past month, or greater than monthly use in the past year
• Significant or unstable acute or chronic medical conditions
• Frequent headaches or migraines
• History of seizures
• Current serious psychiatric disorder (e.g., depressive disorder, bipolar disorder, eating disorder, psychotic disorder diagnosis, alcohol use disorder or substance use disorder) that would interfere with completion of study procedures
• Current syndromal sleep disorders other than insomnia and delayed sleep phase disorder
• MRI contraindications (i.e., absence of metal in the body, claustrophobia)
• Medications that increase sensitivity to blue light/photosensitizing medications, including psychiatric neuroleptic drugs, psoralen drugs, antiarrhythmic drugs, etc.
• Changes to psychotropic medication regimen in the 2 weeks prior to enrollment, and/or major changes to medications during the study protocol
• If participants have an average bedtime that is later than 3:00AM or an average wake time later than 11:00AM they may be excluded from the study
• Participants should be EXCLUDED for other sleep disorders that require ongoing treatment
• Participants should be EXCLUDED for other sleep disorders that cause significant distress or impairment, per DSM 5 criteria in the Sleep SCID.