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
United States
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Hasler, Brant P; Franzen, Peter L; de Zambotti, Massimiliano et al. (2017) Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol and Marijuana Use in Adolescence: Initial Findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence Study. Alcohol Clin Exp Res 41:1154-1165
Hasler, Brant P; Casement, Melynda D; Sitnick, Stephanie L et al. (2017) Eveningness among late adolescent males predicts neural reactivity to reward and alcohol dependence 2 years later. Behav Brain Res 327:112-120
Hasler, Brant P; Buysse, Daniel J; Germain, Anne (2016) Shifts Toward Morningness During Behavioral Sleep Interventions Are Associated With Improvements in Depression, Positive Affect, and Sleep Quality. Behav Sleep Med 14:624-35
Wilckens, Kristine A; Aizenstein, Howard J; Nofzinger, Eric A et al. (2016) The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults. J Sleep Res 25:296-306
Mike, Thomas B; Shaw, Daniel S; Forbes, Erika E et al. (2016) The hazards of bad sleep-Sleep duration and quality as predictors of adolescent alcohol and cannabis use. Drug Alcohol Depend 168:335-339
Taylor, Briana J; Matthews, Karen A; Hasler, Brant P et al. (2016) Bedtime Variability and Metabolic Health in Midlife Women: The SWAN Sleep Study. Sleep 39:457-65
Wong, Patricia M; Hasler, Brant P; Kamarck, Thomas W et al. (2015) Social Jetlag, Chronotype, and Cardiometabolic Risk. J Clin Endocrinol Metab 100:4612-20
Brown, Sandra A; Brumback, Ty; Tomlinson, Kristin et al. (2015) The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use. J Stud Alcohol Drugs 76:895-908
Hasler, Brant P; Soehner, Adriane M; Clark, Duncan B (2015) Sleep and circadian contributions to adolescent alcohol use disorder. Alcohol 49:377-87
Gunn, Heather E; Buysse, Daniel J; Hasler, Brant P et al. (2015) Sleep Concordance in Couples is Associated with Relationship Characteristics. Sleep 38:933-9

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