Pitt Psychiatry Awarded $14M NIH Center for Adolescent Reward, Rhythms, and Sleep

CARRS Investigators

The National Institute on Drug Abuse (NIDA) has awarded Pitt Psychiatry a Center of Excellence (P50) grant renewal for the Center for Adolescent Reward, Rhythms and Sleep (CARRS), led by Colleen McClung, PhD (Professor of Psychiatry and Clinical and Translational Science), and Daniel Buysse, MD (UPMC Endowed Chair in Sleep Medicine and Distinguished Professor of Psychiatry, Clinical and Translational Science, and Medicine). CARRS focuses on risk factors for substance use disorders that emerge from the interaction of reward, cognitive control, circadian rhythms, and sleep, which show marked developmental changes during adolescence. 

Adolescence is a time of heightened reward sensitivity, increased impulsivity, risk taking, and increased risk for substance use. According to NIDA’s Monitoring the Future survey in 2023, 11% of 8th graders and 31% of 12th graders reported some substance use, with the most common being cannabis, alcohol, and nicotine. In addition, rates of cannabis use are growing as the public perception of harm decreases and cannabis products become more widely available. Early onset of drug use is strongly related to the development of substance use disorder. 

During its first five years, the CARRS team identified specific sleep and circadian phenotypes that associate with impulsivity and risk-taking in rodent studies. They also discovered important addiction-related behavioral consequences of sleep restriction and circadian misalignment during adolescence, and important molecular and cellular differences that may underlie these behavioral changes. CARRS additionally completed the largest studies to date of circadian rhythms and sleep in human adolescents. These studies showed robust rhythms of multiple physiological characteristics, mood, and reward-related task function, which differed for early and late sleepers. CARRS investigators also showed that the timing of these rhythms can be changed with a brief behavioral and light intervention. 

Over the next five years, CARRS rodent projects will delve more deeply into specific cellular mechanisms and testing of causal relationships between circadian rhythms, sleep, and addiction. They will also add new measures from human blood and saliva samples to create a translational bridge to rodent findings. CARRS investigators will expand their human laboratory studies to a larger age range and a broader spectrum of substance use risk. They will also apply novel statistical approaches to “big data” from local and national cohort studies, such as the Adolescent Brain and Cognitive Development (ABCD) study (Pittsburgh principal investigator: Duncan Clark, MD, PhD). New markers derived from these studies will be mapped onto the more intensive laboratory measures of CARRS to identify markers and biosignatures of substance use risk.  

Below are the CARRS cores and projects:

  • Dr. McClung and Dr. Buysse lead the Center and Core A, which serves as the hub for Center activities, including educational and outreach efforts. Co-investigator: Jessica Levenson, PhD. Sarah Aerni, MLIS, serves as the Center Administrator. Ronette Blake serves as Lead Research Project Coordinator, contributing to Core B, Project 1, and Project 2.
  • Core B Phenotyping & Biobanking - Multiple Principal Investigators (MPI): Duncan Clark, MD, PhD (Professor of Psychiatry and Pharmaceutical Sciences), and Mary Torregrossa, PhD (Associate Professor of Psychiatry). 
  • Core C Data Management & Statistics - PI: Meredith Wallace, PhD (Associate Professor of Psychiatry and Biostatistics). Co-investigators: Adriane Soehner, PhD; George Tseng, PhD.
  • Project 1 Circadian rhythms and homeostatic sleep regulation during adolescence: Implications for reward, cognitive control and substance use risk - PI: Peter Franzen, PhD (Associate Professor of Psychiatry, Psychology, and Clinical and Translational Science). Co-investigators: Dr. Buysse; Brant Hasler, PhD; Greg Siegle, PhD; Brian Coffman, PhD.
  • Project 2 Circadian rhythms, sleep, and substance use risk during adolescence: observational, experimental, and longitudinal studies - MPI: Adriane Soehner, PhD (Associate Professor of Psychiatry), and Dr. Wallace. Co-investigators: Brant Hasler, PhD; Duncan Clark, MD, PhD.
  • Project 3: Molecular rhythms and substance abuse vulnerability in adolescents - PI: Dr. McClung. Co-investigators: Brant Hasler, PhD; Marianne Seney, PhD; Matthew MacDonald, PhD.
  • Project 4 Determining the role of adolescent sleep and circadian factors on risk for substance use in a rat model - PI: Dr. Torregrossa. Co-investigators: Sierra Stringfield, PhD; Sara Morrison, PhD. 
  • Project 5 Regulation of nucleus accumbens neurons by sleep and circadian rhythm - PI: Yanhua Huang, PhD (Associate Professor of Psychiatry). Co-investigator: Yan Dong, PhD.