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Understanding Circadian Physiology in Early Childhood: the Role of Napping and Light at Night PDF

178 Pages·2017·1.61 MB·English
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University of Colorado, Boulder CU Scholar Integrative Physiology Graduate Teses & Integrative Physiology Dissertations Spring 1-1-2016 Understanding Circadian Physiology in Early Childhood: the Role of Napping and Light at Night Lameese Dana Akacem University of Colorado at Boulder, UNDERSTANDING CIRCADIAN PHYSIOLOGY IN EARLY CHILDHOOD: THE ROLE OF NAPPING AND LIGHT AT NIGHT by LAMEESE D. AKACEM, M.S. B.A., University of Colorado Boulder, 2013 M.S., University of Colorado Boulder, 2013 A thesis submitted to the Faculty of the Graduate School of the University of Colorado in partial fulfillment of the requirement for the degree of Doctor of Philosophy Department of Integrative Physiology 2016 This thesis entitled: Understanding Circadian Physiology in Early Childhood: The Role of Napping and Light at Night written by Lameese D. Akacem has been approved for the Department of Integrative Physiology Monique K. LeBourgeois, Ph.D Kenneth P. Wright Jr., Ph.D. Monika R. Fleshner, Ph.D. Robert L. Spencer, Ph.D. Ann C. Halbower, MD Date The final copy of this thesis has been examined by the signatories, and we find that both the content and the form meet acceptable presentation standards of scholarly work in the above mentioned discipline. IRB protocol # FWA00004460 (Brown University); 10-0115 and 15-0080 (University of Colorado Boulder) ii ABSTRACT Akacem, Lameese D. (Department of Integrative Physiology) Understanding Circadian Physiology in Early Childhood: The Role of Napping and Light at Night Thesis directed by Assistant Professor Monique K. LeBourgeois The circadian clock, localized to the suprachiasmatic nucleus of the anterior hypothalamus, is responsible for regulating rhythms in behavior and physiology including the timing and secretion of the hormone melatonin. Light is the strongest environmental input to the circadian system. Specifically, light at night can delay the timing of the melatonin rhythm and suppress secretion of this sleep -promoting hormone. Although data on factors that influence the biological clock of adolescents and adults is expanding, very little is known about circadian physiology in the early childhood years. The collective aim of this dissertation was to assess the influence of several modifiable factors on the circadian physiology of young children. In study 1, sleep and circadian timing were compared between napping and non-napping toddlers. Napping toddlers had significantly later bedtimes, sleep onset times and circadian phases than non-napping toddlers. These differences in circadian timing are likely mediated by the later bedtimes of nappers, which facilitate light exposure later in the evening thereby delaying the clock. The purpose of study 2 was to quantify the magnitude of light-induced melatonin suppression in response to evening light exposure in preschoolers. Children experienced ~90% melatonin suppression in response to a 1 hour long bright light stimulus before bedtime, an effect that persisted up to 50 minutes iii after the light stimulus was terminated. In study 3, we examined children’s evening light exposure in association with circadian timing. The amount of light children were exposed to during the 2 hours before bedtime predicted variance in circadian timing over and above bedtime alone in our sample of young children. The findings of this dissertation demonstrate the robust sensitivity of the circadian system of young children to light at night and represent important first steps in understanding fundamental aspects of circadian physiology during the early years of life. iv DEDICATION I would like to dedicate this dissertation to my family and friends who have supported me throughout my graduate career. Specifically, I would like to dedicate this to my parents who both made many sacrifices to allow me to get the education that I received and for their continuous encouragement as I pursued my doctorate. I wouldn’t have been able to get to this far without them. v ACKNOWLEDGEMENTS Firstly, I would like to thank my advisor Dr. Monique K. LeBourgeois for mentoring and supporting me over the past 5 years. I would also like to thank my committee members Dr. Kenneth P. Wright, Jr., Dr. Monika R. Fleshner, Dr. Robert L. Spencer, and Dr. Ann C. Halbower. I would like to especially thank Dr. Kenneth P. Wright Jr. for his advice and support throughout the progress of my dissertation and Dr. Ann C. Halbower for her help with one of my dissertation studies. I would like to thank the research participants and their families as well as the staff and students of the Sleep and Development Laboratory at Brown University and at the University of Colorado Boulder. I would also like to acknowledge our support: K01- MH074643 and R01-MH08556 were awarded to Dr. Monique K. LeBourgeois from the National Institutes of Health, the Summer Graduate School Fellowship, Sleep Research Society Travel Awards, as well as Travel Awards from the Department of Integrative Physiology, the Graduate School and the Society for Research on Biological Rhythms Fellowship Award. Data from the study presented in Chapter 3 of this dissertation, “Bright Light Exposure Before Bedtime Suppresses Melatonin in Preschool-Age Children”, was crowd-funded through the University of Colorado. I would like to acknowledge the following individuals for their generous contributions to my crowdfunding campaign that made the study possible: Mia Fill, Corey Theiss, Evan Chinoy, Raymond Najjar, Brian Brady, Jessica vi Calihan, Tsegereda Teklewold, Laura Maguire, Tracy Mott, Matthew Mizer, Kent Lindquist, Tresdon Jones, Byron Ellis, Dennis Miller, Alex Berger, Kati Pederson, Leonardo Bermudez, Josiane Broussard, Tim Mickiewicz, Colleen Gribbin, Stephen Lassonde, Lisa Korte, Roman Mitz, Jayne Bellando, Alexander Jones, Laurie Maguire, Jim Crossin, Tami Meier, Cristin Bazzanella, Felix Castanar, Karen Schneider, Rebekah Tribble, Steven Hobbs, Margaret Doucette, Katherine Sharkey, Hannah Craven, Jakob Sedig, April Schmidt, Becky Crossin, Jennifer Doucette and the company Lumie. vii TABLE OF CONTENTS Chapter 1. 1 Circadian Phase in Humans: Age-Related Differences and the Influence of Light Lameese D. Akacem Introduction 2 Two-Process Model of Sleep Regulation 4 The Circadian System 5 Age-Related Changes in Circadian Phase 14 Light and Circadian Phase 19 Summary 30 References 32 Chapter 2. 55 The Timing of the Circadian Clock and Sleep Differ between Napping and Non- Napping Toddlers Lameese D. Akacem, Charles T. Simpkin, Mary A. Carskadon, Kenneth P. Wright Jr., Oskar G. Jenni, Peter Achermann, Monique K. LeBourgeois Abstract 56 Introduction 58 Methods 61 viii Results 65 Conclusion 69 Acknowledgements 78 References 79 Chapter 3. 85 Light-Induced Melatonin Suppression in Preschool-Age Children Lameese D. Akacem, Kenneth P. Wright Jr., Monique K. LeBourgeois Abstract 86 Introduction 87 Materials and Methods 88 Results 94 Discussion 96 Acknowledgements 101 References 102 Chapter 4. 107 Evening Light Exposure Influences Circadian Timing in Preschool-Age Children: A Field Study Lameese D. Akacem, Kenneth P. Wright Jr., Monique K. LeBourgeois Abstract 108 ix

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