The candidate's long-term goal is to develop an independent research program investigating the role of circadian rhythm disturbance and impaired reward function as mechanisms of vulnerability to substance use disorders (SUDs). Evidence suggests that circadian rhythms may play a key role in substance use (SU), specifically via interactions with the reward system. However, human studies have not yet examined the precise underlying mechanisms of these relationships. Thus, two priorities are (1) investigating the neurobehavioral underpinnings of circadian-reward interactions, and (2) clarifying how these circadian-reward mechanisms may contribute to SUD risk. Adolescence is a key developmental stage in which to investigate these mechanisms, as it is a period of marked changes in circadian rhythms, reward function, and initiation of SU. Studying the neurobehavioral mechanisms by which circadian rhythms modulate reward functioning may lead to a better understanding of the etiology of adolescent SU and inform prevention and treatment efforts. The candidate has a strong background in circadian and sleep research, and needs additional training to develop mastery in SU research and neuroimaging methods. The proposed K01 Mentored Research Scientist Development Award would ensure the candidate's successful transition to an independent investigator by providing conceptual and methodological training in three key areas: (1) expertise in adolescent SU from a developmental perspective, (2) expertise in the neurobiology of SU with particular focus on models of altered reward function, and (3) expertise in fMRI methodology, analysis, and interpretation. These training aims are well-matched to the proposed research plan, which aims to investigate the neurobehavioral underpinnings of circadian-reward interactions, and to explore whether circadian-reward mechanisms contribute to risk for SUDs. These goals align with NIDA's 2010 Prevention Objectives of elucidating the neural circuitry underlying addiction, and clarifying how environment and development influence risk and protective factors for SUDs. The proposed research will investigate an adolescent sample in cross-sectional and experimental studies, using a novel within-person design and fMRI to probe the role of circadian rhythms in reward-related brain function.
The aims are: (1) to assess cross-sectional associations between SU, SUD risk, and self-reported circadian-sleep timing;(2) to assess diurnal variation in reward-related brain activation;(3) to examine the effects of experimentally-induced, ecologically-valid circadian misalignment on reward-related brain activation;and (4) to gather preliminary data on whether misalignment-associated changes in reward-related brain activation are related to SUD vulnerability. The proposed K01 award will integrate the candidate's previous experience and new skill areas, thus providing him with a solid foundation to launch an innovative, independent research program aimed at investigating the neurobehavioral mechanisms linking SU, reward function, and circadian rhythms, with the ultimate goal of translating identified mechanisms into novel interventions.

Public Health Relevance

Adolescence is a time of particular vulnerability to substance use disorders;initiation of substance use often occurs during this developmental period, and the progression from first use to substance dependence occurs more rapidly in adolescents than in adults. This project will study whether substance-related vulnerabilities may be explained by adolescent changes in circadian rhythms, sleep, and reward function. Findings may have important implications for developing more effective preventive programs to delay substance use initiation and reduce risks for adolescent substance use disorders.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Development Award - Research & Training (K01)
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Special Emphasis Panel (ZDA1-NXR-B (14))
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Sirocco, Karen
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University of Pittsburgh
Schools of Medicine
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Hasler, Brant P; Soehner, Adriane M; Clark, Duncan B (2015) Sleep and circadian contributions to adolescent alcohol use disorder. Alcohol 49:377-87
Hasler, Brant P; Soehner, Adriane M; Clark, Duncan B (2014) Circadian rhythms and risk for substance use disorders in adolescence. Curr Opin Psychiatry 27:460-6
Hasler, Brant P; Forbes, Erika E; Franzen, Peter L (2014) Time-of-day differences and short-term stability of the neural response to monetary reward: a pilot study. Psychiatry Res 224:22-7
Hasler, Brant P; Martin, Christopher S; Wood, D Scott et al. (2014) A longitudinal study of insomnia and other sleep complaints in adolescents with and without alcohol use disorders. Alcohol Clin Exp Res 38:2225-33
Hasler, Brant P; Sitnick, Stephanie L; Shaw, Daniel S et al. (2013) An altered neural response to reward may contribute to alcohol problems among late adolescents with an evening chronotype. Psychiatry Res 214:357-64
Clark, D B; Chung, T; Pajtek, S et al. (2013) Neuroimaging methods for adolescent substance use disorder prevention science. Prev Sci 14:300-9
Hasler, Brant P; Clark, Duncan B (2013) Circadian misalignment, reward-related brain function, and adolescent alcohol involvement. Alcohol Clin Exp Res 37:558-65