Exploring Sleep
Disturbance in Central
Nervous System
Disorders

______

Lisa Bain, Eva Childers, and
Sheena M. Posey Norris, Rapporteurs

Forum on Neuroscience and
Nervous System Disorders

Board on Health Sciences Policy

Health and Medicine Division

Proceedings of a Workshop

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by contracts between the National Academy of Sciences and Acadia Pharmaceuticals, Alzheimer’s Association; American Brain Coalition; American Neurological Association; Boehringer Ingelheim; California Institute for Regenerative Medicine; Cerevel Therapeutics; Cohen Veterans Bioscience; Department of Health and Human Services’ Food and Drug Administration (R13FD005362) and National Institutes of Health (75N98019F00769 [Under Master Base HHSN263201800029I]) through the National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Environmental Health Sciences, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, NIH Blueprint for Neuroscience Research, and NIH BRAIN Initiative; Department of Veterans Affairs (36C24E20C0009); Eisai Inc.; Eli Lilly and Company; Foundation for the National Institutes of Health; Gatsby Charitable Foundation; Harmony Biosciences, Janssen Research & Development, LLC; Karuna Therapeutics; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; National Multiple Sclerosis Society; National Science Foundation (DBI-1839674); One Mind; The Paul G. Allen Frontiers Group; Sanofi; Simons Foundation Autism Research Initiative; Society for Neuroscience; Takeda; and Wellcome Trust. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-70186-0
International Standard Book Number-10: 0-309-70186-4
Digital Object Identifier: https://doi.org/10.17226/26938

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. Exploring sleep disturbance in central nervous system disorders: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26938.

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PLANNING COMMITTEE ON SLEEP DISTURBANCE IN CENTRAL NERVOUS SYSTEM DISORDERS¹

LOUIS PTÁČEK (Co-Chair), University of California, San Francisco

HEATHER SNYDER (Co-Chair), Alzheimer’s Association

BRIAN FISKE, The Michael J. Fox Foundation for Parkinson’s Research

PERCY GRIFFIN, Alzheimer’s Association

FRANCES JENSEN, University of Pennsylvania

KATHLEEN MERIKANGAS, National Institute of Mental Health

JUKKA-PEKKA (“JP”) ONNELA, Harvard University

UMA RAO, University of California, Irvine

AMITA SEHGAL, University of Pennsylvania

JOHN SPIRO, Simons Foundation

HAO WANG, Takeda

JERRY YAKEL, National Institute of Environmental Health Sciences

Health and Medicine Division Staff

EVA CHILDERS, Associate Program Officer (starting August 2022)

EDEN NELEMAN, Senior Program Assistant

SHEENA M. POSEY NORRIS, Director, Forum on Neuroscience and Nervous System Disorders

CHRISTIE BELL, Senior Finance Business Partner

CLARE STROUD, Senior Director, Board on Health Sciences Policy

Consultant

LISA BAIN, Science Writer

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS¹

FRANCES JENSEN (Co-Chair), University of Pennsylvania

JOHN KRYSTAL (Co-Chair), Yale University

SUSAN AMARA, National Institute of Mental Health (until December 2022)

RITA BALICE-GORDON, Muna Therapeutics

KATJA BROSE, The Chan Zuckerberg Initiative

EMERY BROWN, Massachusetts General Hospital

TERESA BURACCHIO, Food and Drug Administration (starting April 2023)

JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai

SARAH CADDICK, The Gatsby Charitable Foundation

ROSA CANET-AVILÉS, California Institute for Regenerative Medicine

MARIA CARRILO, Alzheimer’s Association

MICHAEL CHIANG, National Eye Institute

TIMOTHY COETZEE, National Multiple Sclerosis Society

JONATHAN COHEN, Princeton University

BEVERLY DAVIDSON, University of Pennsylvania

BILLY DUNN, Food and Drug Administration (until March 2023)

MICHAEL EGAN, Merck Research Laboratories (until December 2022)

MICHELLE ELEKONICH, National Science Foundation

NITA FARAHANY, Duke University

EVA FELDMAN, University of Michigan

BRIAN FISKE, The Michael J. Fox Foundation for Parkinson’s Research

JOSHUA GORDON, National Institute of Mental Health

MORTEN GRUNNET, Lundbeck (starting March 2023)

MAGALI HAAS, Cohen Veterans Bioscience

RICHARD HODES, National Institute of Aging

STUART HOFFMAN, Department of Veterans Affairs

YASMIN HURD, Icahn School of Medicine at Mount Sinai

STEVEN HYMAN, The Broad Institute of MIT and Harvard

MICHAEL IRIZARRY, Eisai Inc.

PUSHKAR JOSHI, One Mind

GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism

WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke

GEORGINA MACKENZIE, Wellcome Trust

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

HUSSEINI MANJI, Oxford University; Duke University (starting April 2023)

HUGH MARSTON, Boehringer Ingelheim (starting June 2023)

BILL MARTIN, The Janssen Pharmaceutical Companies of Johnson & Johnson

JOHN NGAI, BRAIN Initiative

STEVE MARC PAUL, Karuna Therapeutics, Inc.

KATHRYN RICHMOND, Allen Institute (starting June 2023)

MARGARET ELIZABETH ROSS, Weill Cornell Medical College (starting June 2023)

MARSIE ROSS, Harmony Biosciences (starting February 2023)

KATIE SALE, American Brain Coalition

RAYMOND SANCHEZ, Cerevel Therapeutics

SARAH SHEIKH, Takeda

DAVID SHURTLEFF, National Institutes of Health

JOHN SIMS, Eli Lilly and Company (until December 2022)

JOHN SPIRO, Simons Foundation

ALESSIO TRAVAGLIA, Foundation for the National Institutes of Health

NORA VOLKOW, National Institute on Drug Abuse

DOUG WILLIAMSON, Acadia Pharmaceuticals (starting March 2023)

RICHARD WOYCHIK, National Institute of Environmental Health Sciences

STEVIN ZORN, MindImmune Therapeutics, Inc.

Health and Medicine Division Staff

EVA CHILDERS, Associate Program Officer (starting August 2022)

MAYA THIRKILL, Associate Program Officer (starting May 2023)

EDEN NELEMAN, Senior Program Assistant

SHEENA M. POSEY NORRIS, Director, Forum on Neuroscience and Nervous System Disorders

CHRISTIE BELL, Senior Finance Business Partner

CLARE STROUD, Senior Director, Board on Health Sciences Policy

Reviewers

This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by ERIC B. LARSON, University of Washington. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.

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Contents

BOX, FIGURES, AND TABLE

ACRONYMS AND ABBREVIATIONS

1 INTRODUCTION AND BACKGROUND

Current State of Knowledge

Workshop Objectives

Organization of Proceedings

2 SLEEP DISORDERS AND TOOLS FOR ASSESSMENT

Sleep Health and Adverse Health Outcomes from Sleep Disturbances

Disparities in Sleep Disorders and Their Underlying Determinants

Tools for Assessing Sleep and Sleep Disturbances

3 UNDERLYING MECHANISMS AND MODEL SYSTEMS OF SLEEP

Highlights

Circadian Timing

Genetics

Neural Circuitry and Cortical Activity

Model Systems

4 SLEEP DISORDERS AND DISRUPTION IN CENTRAL NERVOUS SYSTEM DISORDERS

Highlights

Influence of Light on Sleep and Health

Central Nervous System Hypersomnias and Narcolepsy

Neurodevelopmental Disorders

Schizophrenia

Mood Disorders

Neurodegenerative Disorders

5 THERAPEUTIC DEVELOPMENT AND BIOMARKERS FOR SLEEP DISORDERS

Highlights

Pharmacotherapy for Insomnia

Pharmacotherapy for Narcolepsy

Non-Pharmacological Strategies

Biomarkers of Sleep and Sleep Disturbances

6 ADVANCING SLEEP AND CIRCADIAN RESEARCH, EDUCATION, AND CLINICAL CARE

Highlights

Research Opportunities

Understanding Current Research Gaps

Potential Opportunities to Advance Sleep Research and Treatment

Final Thoughts

APPENDIXES

A References

B Agenda

Box, Figures, and Table

BOX

1-1 Statement of Task

FIGURES

1-1 Sleep and other physiological processes regulated by circadian clocks

1-2 The synapsis homeostasis model

2-1 Sleep loss in the U.S. military

2-2 Brain aging index as a measure of brain health

3-1 Comparisons among model systems for sleep research

4-1 24-hour sleep recordings in narcolepsy

4-2 Forging links in causal chains: Genes to diagnosis to treatment

TABLE

5-1 Abuse Potential of Drugs for Insomnia

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Acronyms and Abbreviations