3/2/19 Circadian rhythms (very brief) intro Rhythms and reward: Do - PDF document

3/2/19 Circadian rhythms – (very brief) intro Rhythms and reward: Do circadian factors contribute to risk for adolescent substance use? Brant P Hasler, PhD, CBSM º Organize physiological and behavioral processes for optimal interaction with Johns Hopkins Bloomberg School of Public Health the environment Department of Mental Health Noon Seminar Series February 27, 2019 º “Temporal order is essential for health” - Anna Wirz-Justice (2003) Reward and circadian modulation (briefly) Clocks everywhere Wanting Liking Pursuing Consuming rewards rewards Circadian control of reward http://naef-lab.epfl.ch/page-34743-en.html circuitry (e.g., Logan et al, 2014, 2017; McClung, 2007; Webb et al, 2015) October 2, 2017 Arble & Sandoval (2013) Front. Neurosci Mechanisms? A good overview… Review Biological Sleep and/or Mood and Psychiatry circadian substance use disturbance disorders Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents • Appetitive motivation and reward processes are Ryan W. Logan, Brant P. Hasler, Erika E. Forbes, Peter L. Franzen, Mary M. Torregrossa, Yanhua H. Huang, Daniel J. Buysse, Duncan B. Clark, and Colleen A. McClung modulated by the circadian system • Circadian disturbance can dysregulate appetitive ABSTRACT ª 2017 Society of Biological Psychiatry. 987 ISSN: 0006-3223 Biological Psychiatry June 15, 2018; 83:987 – 996 www.sobp.org/journal motivation and reward function 1

3/2/19 “Two process model” of Research Strategies positive affect and reward 1. Documenting circadian rhythmicity in affect, behavior, and brain function 2. Examining associations between circadian alignment (or proxies thereof), affect/motivation, and symptoms 3. Examining associations between circadian alignment and brain function (observational Murray et al. (2009) Emotion and experimental) Boivin et al. (1997) Arch Gen Psychiatry Diurnal rhythms in Time of day changes in neural response reward-related processes to monetary reward Positive Affect Negative Affect SOCIALIZING Reward activation High reward activation – High VS Low reward activation – Low VS 4 8 12 16 20 24 4 Clock time Hours since wake • Pilot fMRI study ALCOHOL USE ‘WANTING’ on BART • 11 healthy young adults • Morning and afternoon fMRI scans • Card guessing task (block design) • Counterbalanced order PM>AM in right • Within-person comparison Ventral Striatum • ROI: Ventral Striatum Hasler, et al (2014) Psychiatry Res: Neuroimaging Arfken (2008); Byrne et al (2017); Hasler et al (2008; unpublished) Time of day changes in neural response For a deeper dive… to monetary reward: Take 2 • 16 right-handed males (M+/-SD 22.7 +/- 2.9 years) • Card guessing task (Delgado et al, 2000) from Human Connectome Project • Repeated-measures ANOVA model with factor Time of Day (10.00, 14.00, and 19.00 h) • mPFC, VTA, anterior cingulate cortex, caudate, NAc, and putamen Byrne, et al (2017) J Neurosci 2

3/2/19 Circadian misalignment Research Strategies (working definition) 1. Documenting circadian rhythmicity in affect, behavior, and brain function A mismatch between the timing of the 2. Examining associations between circadian behavioral sleep-wake schedule and that of alignment (or proxies thereof), the internal circadian clock affect/motivation, and symptoms 3. Examining associations between circadian alignment and brain function (observational and experimental) Circadian alignment and “Normal” Circadian Alignment adolescent substance abuse Dim Light Endogenous Melatonin Onset melatonin (DLMO) profile ž Sample of 21 sleep- disturbed adolescents with Sleep Sleep history of substance abuse onset Midsleep offset ž Shorter phase angles 10 hr associated with greater Phase 6 hr substance abuse and angles dependence 2 hr r 2 = .38, p < .01 • WAKE SLEEP WAKE 20 21 22 23 0 1 2 3 4 5 6 7 8 9 10 Hasler, Bootzin, et al. 2008 Clock time (hours) “Normal” Circadian Alignment Circadian Misalignment due to Delayed Phase Dim Light Dim Light Endogenous Endogenous Melatonin Onset Melatonin Onset melatonin melatonin (DLMO) (DLMO) profile profile Sleep Sleep Sleep Sleep onset Midsleep offset onset Midsleep offset 10 hr Phase Phase 6 hr angles angles 2 hr WAKE SLEEP WAKE WAKE SLEEP WAKE 20 21 22 23 0 1 2 3 4 5 6 7 8 9 10 20 21 22 23 0 1 2 3 4 5 6 7 8 9 10 Clock time (hours) Clock time (hours) 3

3/2/19 Adolescents are subject to chronic circadian Proxies for circadian misalignment: Evening chronotype misalignment (aka social jet lag) • Circadian and preferred sleep timing shift later (delay) post-puberty • Chronotype (sleep timing preference) on a continuum • Shift towards evening chronotype • Morning-types (larks) and evening-types (owls) • Mismatch with early school start times • Chronotype correlates with (physiological) circadian phase Preferred s/w timing – Morning- and evening-types have different phase alignment Monday Circadian Tuesday misalignment; • Evening types tend to exhibit more disrupted insomnia and Wednesday sleep, depression, and substance involvement sleep loss Thursday • Evening types tend to report more Better Friday impulsivity, risk-taking, and sensation and/or alignment; Saturday make up sleep novelty seeking Sunday 12 14 16 18 20 22 0 2 4 6 8 10 12 Clock Time Proxies for circadian misalignment: Evening-types exhibit delayed and blunted Social jet lag rhythms in positive affect • SJL = difference in sleep timing on school/work days and free days* Healthy young adults Healthy middle-aged adults Adults with primary insomnia (n=62) (n=100) (n=408) • Tends to be worse for evening-types/late chronotypes 21 20 19 18 Mean DLMO delay of 45 min 17 0 5 10 15 20 Clock Time (hours) 10 teens (15-16 y/o) from Crowley & Carskadon (2010) Hasler (unpublished) Hasler et al (2012) J Sleep Res Miller et al (2015 ) Chrono Int Wittman et al (2006) In 1,456 11-17 y/o’s from the NSF 2006 Sleep in America poll, teens went to bed ~90 minutes later and slept ~75 minutes more on non-school days (137 and 93 min for 17 y/os) Childhood and adolescent sleep characteristics Eveningness, late sleep timing, and short sleep, but predict later substance involvement not social jet lag, predict heavy alcohol use @ 1-year 729 adolescents 12-21 y/o’s from NCANDA study, baseline and 1-year follow-up SLEEP DISTURBANCE Alcohol use Insomnia Binge drinking Binge alcohol use @ 1-year Poor sleep quality Alcohol intoxication Restless sleep Alcohol-related problems AUD diagnosis or symptoms SLEEP LOSS Onset of alcohol involvement Daytime sleepiness Marijuana use Short sleep duration Marijuana-related problems “CIRCADIAN” CHARACTERISTICS Other illicit drug use Evening chronotype SUD diagnosis or symptoms Weekend delays (SJL) Covariates: age, sex, race, ethnicity, SES, and baseline substance use Onset of marijuana involvement Variable sleep timing Nicotine/tobacco use N-CANDA Hasler et al, 2014; 2016, 2017; Haynie et al, 2018, Mike et al, 2016; Miller et al, 2017; Pasch et al, 2015; Pieters Hasler et al (2017) ACER et al 2015; Roane and Taylor 2008 ; Tavernier et al, 2015; Warren et al , 2017; Wong et al, 2004; 2010; 2016 4