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

Overview

Adolescence is a time of heightened reward sensitivity and greater impulsivity. On top of this, many teenagers experience chronic sleep deprivation and misalignment of their circadian rhythms due to biological shifts in their sleep/wake patterns paired with early school start times. Many studies find that this increases the risk for substance use (SU). However, what impact circadian rhythm and sleep disruption either together or independently have on the neuronal circuitry that controls reward and cognition, or if there are interventions that might help to modify these disruptions is unknown. Project 2 (P2) of the CARRS center 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.

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.