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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Novel Molecular Targets for
Mood Disorders and Psychosis

PROCEEDINGS OF A WORKSHOP

Lisa Bain, Chanel Matney, and Clare Stroud, Rapporteurs

Forum on Neuroscience and Nervous System Disorders

Board on Health Sciences Policy

Health and Medicine Division

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

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This activity was supported by contracts between the National Academy of Sciences and Alzheimer’s Association; Cohen Veterans Bioscience; Department of Health and Human Services’ Food and Drug Administration (1R13FD005362-06) and National Institutes of Health (NIH) (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; Janssen Research & Development, LLC; 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; Sanofi; Simons Foundation Autism Research Initiative; Society for Neuroscience; Takeda Pharmaceuticals International, Inc.; 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: 978-0-309-68590-0
International Standard Book Number-10: 0-309-68590-7
Digital Object Identifier: https://doi.org/10.17226/26218

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2021. Novel molecular targets for mood disorders and psychosis: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26218.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

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The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.

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Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

Image

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.

Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.

For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

PLANNING COMMITTEE ON NOVEL MOLECULAR TARGETS IN MOOD DISORDERS AND PSYCHOSIS1

LINDA BRADY (Chair), National Institute of Mental Health

TIFFANY FARCHIONE, Food and Drug Administration

DAVID GRAY, Cerevel Therapeutics

MAGALI HAAS, Cohen Veterans Bioscience

STUART HOFFMAN, Department of Veterans Affairs

JOHN KRYSTAL, Yale University School of Medicine

CARLOS LARRAURI, National Alliance on Mental Illness

HUSSEINI MANJI, Johnson & Johnson

SHARON MATES, Intracellular Therapies

STEVE PAUL, Karuna Therapeutics

MORGAN SHENG, Broad Institute of the Massachusetts Institute of Technology and Harvard University

GREG SIMON, Kaiser Permanente Washington Health Research Institute

ILINA SINGH, University of Oxford

Health and Medicine Division Staff

CLARE STROUD, Director, Forum on Neuroscience and Nervous System Disorders

CHANEL MATNEY, Program Officer (from October 2020)

SHEENA M. POSEY NORRIS, Program Officer

KIMBERLY SUTTON, Senior Program Assistant (until March 2021)

ANDREW M. POPE, Senior Director, Board on Health Sciences Policy

___________________

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.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

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

ELINE APPELMANS, Foundation for the National Institutes of Health

RITA BALICE-GORDON, Muna Therapeutics

KATJA BROSE, Chan Zuckerberg Initiative

EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology

JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai

SARAH CADDICK, Gatsby Charitable Foundation

MARIA CARRILLO, Alzheimer’s Association

EDWARD CHANG, University of California, San Francisco

TIMOTHY COETZEE, National Multiple Sclerosis Society

JONATHAN COHEN, Princeton University

ROBERT CONLEY, Eli Lilly and Company (until May 2021)

BILLY DUNN, Food and Drug Administration

MICHAEL EGAN, Merck Research Laboratories

MICHELLE ELEKONICH, National Science Foundation

NITA FARAHANY, Duke University

JOSHUA GORDON, National Institute of Mental Health

MAGALI HAAS, Cohen Veterans Bioscience

RAMONA HICKS, One Mind (until May 2021)

RICHARD HODES, National Institute on Aging

STUART HOFFMAN, Department of Veterans Affairs

JONATHAN HORSFORD, National Institute of Dental and Craniofacial Research

YASMIN HURD, Icahn School of Medicine at Mount Sinai

STEVEN HYMAN, Broad Institute of the Massachusetts Institute of Technology and Harvard University

MICHAEL IRIZARRY, Eisai Inc.

PUSHKAR JOSHI, One Mind (from June 2021)

GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism

WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke

STORY LANDIS, National Institute of Neurological Disorders and Stroke (Emeritus)

___________________

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.

Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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ALAN LESHNER, American Association for the Advancement of Science (Emeritus)

HUSSEINI MANJI, Johnson & Johnson

JOHN NGAI, BRAIN Initiative

STEVEN PAUL, Karuna Therapeutics

SARAH SHEIKH, Takeda Pharmaceuticals International, Inc.

DAVID SHURTLEFF, National Center for Complementary and Integrative Health

JOHN SIMS, Eli Lilly and Company (from June 2021)

JOHN SPIRO, Simons Foundation Autism Research Initiative (from May 2021)

SANTA TUMMINIA, National Eye Institute

NORA VOLKOW, National Institute on Drug Abuse

ANDREW WELCHMAN, Wellcome Trust

DOUG WILLIAMSON, Lundbeck

RICHARD WOYCHIK, National Institute of Environmental Health Sciences

STEVIN ZORN, MindImmune Therapeutics, Inc.

Health and Medicine Division Staff

CLARE STROUD, Director, Forum on Neuroscience and Nervous System Disorders

CHANEL MATNEY, Program Officer (from October 2020)

SHEENA M. POSEY NORRIS, Program Officer

EDEN NELEMAN, Senior Program Assistant (from July 2021)

KIMBERLY SUTTON, Senior Program Assistant (until March 2021)

PHOENIX WILSON, Senior Program Assistant (until October 2020)

CHRISTIE BELL, Finance Business Partner (from October 2020)

ANDREW M. POPE, Senior Director, Board on Health Sciences Policy

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

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 LESLIE Z. BENET, University of California, San Francisco. 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.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×

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Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Acronyms and Abbreviations

5-HT 5-hydroxytryptamine (also known as serotonin)
ABC-CT Autism Biomarkers Consortium for Clinical Trials
AD antidepressant
AMP-Schizophrenia Accelerating Medical Partnerships–Schizophrenia
AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
BDNF brain-derived trophic factor
BNSS Brief Negative Symptom Scale
BRAIN Brain Research Through Advancing Innovative Neurotechnologies
CDC Centers for Disease Control and Prevention
CGI-S Clinical Global Impressions Severity
D dopamine receptor
DEA Drug Enforcement Administration
ECT electroconvulsive therapy
FDA Food and Drug Administration
FNIH Foundation for the National Institutes of Health
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×
GABA gamma-aminobutyric acid
GABR gamma-aminobutyric acid receptor
HDRS Hamilton Depression Rating Scale
LSD lysergic acid diethylamide
M muscarinic receptor
mAChR muscarinic acetylcholine receptor
MADRS Montgomery-Asberg Depression Rating Scale
MAO monoamine oxidase
MIT Massachusetts Institute of Technology
mPFC medial prefrontal corex
mTOR mechanistic target of rapamycin
NAMI National Alliance on Mental Illness
NHS National Health Service
NIDA National Institute on Drug Abuse
NIMH National Institute of Mental Health
NMDA N-methyl-D-aspartate
PAM positive allosteric modulator
PANSS Positive and Negative Syndrome Scale
PET positron emission tomography
PPD postpartum depression
PTSD posttraumatic stress disorder
PV parvalbumin
REMS risk evaluation and mitigation strategy
SNRI serotonin and norepinephrine reuptake inhibitor
SSRI selective serotonin reuptake inhibitor
TAAR1 trace amine-associated receptor 1
TBI traumatic brain injury
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Page R12
Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
×
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2021. Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: 10.17226/26218.
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Next: 1 Introduction and Background »
Novel Molecular Targets for Mood Disorders and Psychosis: Proceedings of a Workshop Get This Book
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Mood disorders - including depression and bipolar disorder - are common, disabling, and potentially lethal disorders, characterized by a shortened lifespan from comorbid medical illness and rising suicide rates. Medications for these conditions have been shown to be insufficiently effective in the majority of people who take them, and there remains a tremendous unmet medical need. Recent advances towards understanding the mechanisms of action for psychiatric medicines have led to the identification of potential novel molecular targets and agents for treating mood disorders. While these promising avenues for further investigation have re-energized scientific research in this area, many open questions remain. In response to this interest, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders convened a workshop in March 2021, Novel Molecular Targets for Mood Disorders and Psychosis.

The goal of this workshop was to explore the landscape of novel pharmacologic treatments for psychiatric disorders, review the challenges and opportunities that have been highlighted by the development of recently approved drugs, and reflect on how to apply those lessons learned towards current and future efforts to identify and validate additional novel molecular targets. With a grounding in the personal experiences of patients living with depression and schizophrenia, workshop participants discussed the scientific, clinical, technological, regulatory, and ethical considerations of this topic. Examples of drug classes discussed in the workshop include antagonists for NMDA (N-methyl-D-aspartate) receptors and GABA (gamma-aminobutyric acid) receptors, as well as modulators for muscarinic and serotonergic receptors. This publication summarizes the presentations and discussions from the workshop.

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