Center for Adolescent Reward, Rhythms and Sleep (CARRS)

OVERALL SUMMARY Adolescence marked by increased reward sensitivity, impulsivity, risk taking, and increased substance use (SU). At the same time, genetic and environmental factors lead to changes in sleep patterns and circadian rhythms, leading to chronic sleep deprivation and circadian misalignment similar to jet lag (i.e. “social jet lag”). In fact, the American Academy of Pediatrics has labeled insufficient sleep in teens as a public health epidemic that increases risk for substance use disorders (SUD) and other health problems. Over the last 4+ years, the Center for Adolescent Reward, Rhythms and Sleep (CARRS) has performed comprehensive clinical studies paired with innovative mechanistic experiments to understand the impact of adolescent sleep and circadian rhythm changes (both biologically and environmentally induced) on reward circuitry and substance use (SU)-relevant outcomes. We use a translational approach including human and rodent studies that inform each other using similar constructs and methods. We have identified specific circadian and sleep phenotypes that strongly associate with SU-behavior and determined the impact of sleep and circadian disruptions during adolescence on a range of molecular, synaptic and behavioral phenotypes. In addition to the mechanistic understandings gained through research in CARRS-1, our data continues to influence societal debates regarding school start times and the use of electronic devices at night. This proposal outlines the plans for CARRS-2, which will build on studies from CARRS-1 to better understand cell type specific mechanisms, sex and other biological differences across populations, and conduct more thorough testing of causal mechanisms. We also enhance our interactions with other NIDA funded centers and have expanded our SU community outreach, including several new partners and organizations. Thus, the continuation of CARRS will have real, tangible impact on the health of teens. The projects and cores will focus on our central hypothesis which is that changes in sleep and circadian rhythms associated with adolescent development impact cortico-limbic functions critical to substance use risk (e.g., reward and cognitive control). We further hypothesize that: 1) Sex and other biological, social, and environmental factors influence these relationships; and 2) Screening algorithms and biomarkers reflecting sleep-circadian function can identify adolescents at risk for SU and SUD. Our findings will ultimately inform novel SUD prevention and intervention strategies based on sleep and circadian function.