Sheena M. Posey Norris – författare

Accumulating evidence gathered over the past three decades has demonstrated a biological basis for differences between men and women with respect to clinical features and treatment responses to several neuropsychiatric, neurodevelopmental, and neurodegenerative disorders. Dramatic sex differences have also been identified in the brain transcriptomes of individuals with multiple brain disorders, including depression, posttraumatic stress disorder, and autism. The brain transcriptome includes all of the messenger RNA as well as the non-protein-coding RNA molecules expressed in brain tissue and thus represents gene activity. To explore these sex-based transcriptomic differences further, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders hosted a workshop on September 23, 2020, titled Sex Differences in Brain Disorders: Emerging Transcriptomic Evidence and Implications for Therapeutic Development. The workshop brought together a broad spectrum of stakeholders to share cutting-edge emerging evidence, discuss challenges, and identify future opportunities and potential directions. This publication summarizes the presentation and discussion of the workshop.

While significant progress has been seen in fields such as cardiovascular medicine and cancer in improving patient stratification and developing targeted drugs based on genetic findings, progress continues to lag for neuropsychiatric disorders. To address this issue, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders convened a workshop in October 2021.

The workshop brought together government, philanthropic foundations, and disease-focused non--profit organizations to discuss new genetic and neuroscience technologies and explore how they can be used to elucidate disease mechanisms and to advance the development of biomarkers and targeted therapies for people with neurological and psychiatric disorders. This Proceedings of a Workshop summarizes the presentations and discussions of the workshop.

In 2011 the Grand Challenges in Global Mental Health initiative identified priorities that have the potential to make a significant impact on the lives of people with mental, neurological, and substance use disorders. Reduction of the cost and improvement of the supply of effective medicines was highlighted as one of the top five challenges. For low- and middle-income countries, improving access to appropriate essential medicines can be a tremendous challenge and a critical barrier to scaling up quality care for mental, neurological, and substance use disorders. Reduction of cost and improvement of the supply of effective medicines has the potential to significantly impact the lives of patients with these disorders.

Improving Access to Essential Medicines for Mental, Neurological, and Substance Use Disorders in Sub-Saharan Africa is the summary of a workshop convened by the Institute of Medicine Neuroscience Forum in January 2014 in Addis Ababa, Ethiopia to discuss opportunities for achieving long-term affordable access to medicines for these disorders. This report examines challenges and opportunities for improving access to essential medicines in four critical areas: demand, selection, supply chains, and financing and pricing. The report also discusses successful activities that increase access to essential medicines both within Sub-Saharan Africa and in other developing countries, and considers the role of governments, nongovernmental organizations, and private groups in procurement of essential medicines for mental, neurological, and substance use disorders.

Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline.

There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

The BioWatch program, funded and overseen by the Department of Homeland Security (DHS), has three main elements—sampling, analysis, and response—each coordinated by different agencies. The Environmental Protection Agency maintains the sampling component, the sensors that collect airborne particles. The Centers for Disease Control and Prevention coordinates analysis and laboratory testing of the samples, though testing is actually carried out in state and local public health laboratories. Local jurisdictions are responsible for the public health response to positive findings. The Federal Bureau of Investigation is designated as the lead agency for the law enforcement response if a bioterrorism event is detected. In 2003 DHS deployed the first generation of BioWatch air samplers. The current version of this technology, referred to as Generation 2.0, requires daily manual collection and testing of air filters from each monitor. DHS has also considered newer automated technologies (Generation 2.5 and Generation 3.0) which have the potential to produce results more quickly, at a lower cost, and for a greater number of threat agents.

Technologies to Enable Autonomous Detection for BioWatch is the summary of a workshop hosted jointly by the Institute of Medicine and the National Research Council in June 2013 to explore alternative cost-effective systems that would meet the requirements for a BioWatch Generation 3.0 autonomous detection system, or autonomous detector, for aerosolized agents . The workshop discussions and presentations focused on examination of the use of four classes of technologies—nucleic acid signatures, protein signatures, genomic sequencing, and mass spectrometry—that could reach Technology Readiness Level (TRL) 6-plus in which the technology has been validated and is ready to be tested in a relevant environment over three different tiers of temporal timeframes: those technologies that could be TRL 6-plus ready as part of an integrated system by 2016, those that are likely to be ready in the period 2016 to 2020, and those are not likely to be ready until after 2020. Technologies to Enable Autonomous Detection for BioWatch discusses the history of the BioWatch program, the role of public health officials and laboratorians in the interpretation of BioWatch data and the information that is needed from a system for effective decision making, and the current state of the art of four families of technology for the BioWatch program. This report explores how the technologies discussed might be strategically combined or deployed to optimize their contributions to an effective environmental detection capability.

From its very beginning, neuroscience has been fundamentally interdisciplinary. As a result of rapid technological advances and the advent of large collaborative projects, however, neuroscience is expanding well beyond traditional subdisciplines and intellectual boundaries to rely on expertise from many other fields, such as engineering, computer science, and applied mathematics. This raises important questions about to how to develop and train the next generation of neuroscientists to ensure innovation in research and technology in the neurosciences. In addition, the advent of new types of data and the growing importance of large datasets raise additional questions about how to train students in approaches to data analysis and sharing. These concerns dovetail with the need to teach improved scientific practices ranging from experimental design (e.g., powering of studies and appropriate blinding) to improved sophistication in statistics. Of equal importance is the increasing need not only for basic researchers and teams that will develop the next generation of tools, but also for investigators who are able to bridge the translational gap between basic and clinical neuroscience.

Developing a 21st Century Neuroscience Workforce is the summary of a workshop convened by the Institute of Medicine''s Forum on Neuroscience and Nervous System Disorders on October 28 and 29,2014, in Washington, DC, to explore future workforce needs and how these needs should inform training programs. Workshop participants considered what new subdisciplines and collaborations might be needed, including an examination of opportunities for cross-training of neuroscience research programs with other areas. In addition, current and new components of training programs were discussed to identify methods for enhancing data handling and analysis capabilities, increasing scientific accuracy, and improving research practices. This report highlights the presentation and discussion of the workshop.

The Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders, in collaboration with the IOM Forum on Drug Discovery, Development, and Translation, convened a workshop on January 20-21, 2015, to explore policy changes that might increase private sector investment in research and development innovation that fills unmet medical needs for central nervous system (CNS) disorders. Workshop participants strategized about how to incentivize companies to fortify their CNS drug development programs, shrinking obstacles that currently deter ventures. Representatives from academia,government agencies, patient groups, and industry gathered to share information and viewpoints, and to brainstorm about budget-neutral policy changes that could help widen the pipeline toward drugs that address unmet needs for CNS disorders. This report summarizes the presentations and discussion of the workshop.

On March 3-4, 2016, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders held a workshop in Washington, DC, bringing together key stakeholders to discuss opportunities for improving the integrity, efficiency, and validity of clinical trials for nervous system disorders. Participants in the workshop represented a range of diverse perspectives, including individuals not normally associated with traditional clinical trials. The purpose of this workshop was to generate discussion about not only what is feasible now, but what may be possible with the implementation of cutting-edge technologies in the future.

Compared with other disease areas, central nervous system (CNS) disorders have had the highest failure rate for new compounds in advanced clinical trials. Most CNS drugs fail because of efficacy, and the core issue underlying these problems is a poor understanding of disease biology. Concern about the poor productivity in neuroscience drug development has gained intensity over the past decade, amplified by a retraction in investment from the pharmaceutical industry. This retreat by industry has been fueled by the high failure rate of compounds in advanced clinical trials for nervous system disorders.

In response to the de-emphasis of CNS disorders in therapeutic development relative to other disease areas such as cancer, metabolism, and autoimmunity, the National Academies of Sciences, Engineering, and Medicine initiated a series of workshops in 2012 to address the challenges that have slowed drug development for nervous system disorders. Motivated by the notion that advances in genetics and other new technologies are beginning to bring forth new molecular targets and identify new biomarkers, the Academies hosted the third workshop in this series in September 2016. Participants discussed opportunities to accelerate early stages of drug development for nervous system disorders in the absence of animal models that reflect disease and predict efficacy. This publication summarizes the presentations and discussions from the workshop.

Neuroinflammation is a burgeoning area of interest in academia and biopharma, with a broadly acknowledged role in many central nervous system (CNS) disorders. However, there is little agreement on the pathophysiological mechanisms that underlie the manifestations of neuroinflammation in the CNS compartment and how neuroinflammation operates as a driver and also as a consequence of disease in the brain. Moreover, another unclear area is how to translate increased understanding of the mechanisms that underlie neuroinflammation and its manifestations in the CNS to therapeutics.

To address these gaps in understanding mechanisms and how to translate that understanding into therapeutics, the Forum on Neuroscience and Nervous System Disorders of the National Academies of Sciences, Engineering, and Medicine convened a workshop on March 20-21, 2017, bringing together key leaders in the field from industry, academia, and governmental agencies to explore the role and mechanisms of neuroinflammation in a variety of CNS diseases. The workshop also considered strategies to advance the identification and validation of biomarkers of neuroinflammation that could accelerate development of therapies, bringing much-needed treatments to patients with disorders ranging from neuroinflammatory diseases such as multiple sclerosis (MS) to neuropsychiatric disorders such as depression. This publication summarizes the presentations and discussions from the workshop.

Chronic pain is one of the most prevalent, costly, and disabling health conditions in the United States. Estimates show that more than 11 percent of the American population suffer from chronic pain, yet the federal pain research investment has been minimal. In parallel with a gradual increased recognition of the problems of treating chronic pain, the opioid epidemic has emerged as a growing public health emergency. The intersection of these two crises lies in the fact that an unintended consequence of treating pain has been an increasing number of opioid prescriptions and diversion of drugs for illicit purposes.

In May 2017, the National Institutes of Health (NIH), and the National Institute on Drug Abuse announced a public–private partnership to develop solutions to the opioid crisis and cut in half the time it takes to develop non-addictive analgesics. To advance the planning of NIH''s anticipated public–private partnerships, the National Academies'' Forum on Neuroscience and Nervous Systems Disorders hosted a public workshop that brought together a diverse group of stakeholders from academia, federal agencies, advocacy organizations and companies developing therapeutics for pain and opioid use disorders. Participants discussed potential strategies to accelerate development of non-addictive pain medications and treatments for opioid use disorders. This publication summarizes the presentations and discussions from the workshop.

Technological advances in noninvasive neuroimaging, neurophysiology, genome sequencing, and other methods together with rapid progress in computational and statistical methods and data storage have facilitated large-scale collection of human genomic, cognitive, behavioral, and brain-based data. The rapid development of neurotechnologies and associated databases has been mirrored by an increase in attempts to introduce neuroscience and behavioral genetic evidence into legal proceedings.

In March 2018, the National Academies of Science, Engineering and Medicine organized a workshop in order to explore the current uses of neuroscience and bring stakeholders from neuroscience and legal societies together in both the United Kingdom and the United States. Participants worked together to advance an understanding of neurotechnologies that could impact the legal system and the state of readiness to consider these technologies and where appropriate, to integrate them into the legal system. This publication summarizes the presentations and discussions from the workshop.

To examine the promise, concerns, and challenges related to neuroscience research using genetically modified nonhuman primates, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop on October 4, 2018, bringing together an international group of experts and stakeholders representing academia, industry, laboratory animal management, disease-focused foundations, and federal agencies. The workshop was designed to explore the current state and future promise of research using genetically modified nonhuman primate models of disease to understand the complex functions of the brain that control behavior, movement, and cognition in both health and disease states. This publication summarizes the presentations and discussions from the workshop.

Pain is a leading cause of disability globally. The dramatic increase in opioid prescriptions within the past decade in the United States has contributed to the opioid epidemic the country currently faces, magnifying the need for longer term solutions to treat pain. The substantial burden of pain and the ongoing opioid crisis have attracted increased attention in medical and public policy communities, resulting in a revolution in thinking about how pain is managed. This new thinking acknowledges the complexity and biopsychosocial nature of the pain experience and the need for multifaceted pain management approaches with both pharmacological and nonpharmacological therapies.

The magnitude and urgency of the twin problems of chronic pain and opioid addiction, combined with the changing landscape of pain management, prompted the National Academies of Sciences, Engineering, and Medicine to convene a workshop on December 4-5, 2018, in Washington, DC. The workshop brought together a diverse group of stakeholders to discuss the current status of nonpharmacological approaches to pain management, gaps, and future directions. This publication summarizes the presentations and discussions from the workshop.

Humans are potentially exposed to more than 80,000 toxic chemicals in the environment, yet their impacts on brain health and disease are not well understood. The sheer number of these chemicals has overwhelmed the ability to determine their individual toxicity, much less potential interactive effects. Early life exposures to chemicals can have permanent consequences for neurodevelopment and for neurodegeneration in later life. Toxic effects resulting from chemical exposure can interact with other risk factors such as prenatal stress, and persistence of some chemicals in the brain over time may result in cumulative toxicity. Because neurodevelopmental and neurodegenerative disorders - such as attention-deficit hyperactivity disorder and Parkinson''s disease - cannot be fully explained by genetic risk factors alone, understanding the role of individual environmental chemical exposures is critical.

On June 25, 2020, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders hosted a workshop to lay the foundation for future advances in environmental neuroscience. The workshop was designed to explore new opportunities to bridge the gap between what is known about the genetic contribution to brain disorders and what is known, and not known, about the contribution of environmental influences, as well as to discuss what is known about how genetic and environmental factors interact. This publication summarizes the presentation and discussion of the workshop.

Methadone is a Food and Drug Administration- (FDA-) approved medication for treating opioid use disorder (OUD), a chronic brain disease that affects more than 2.7 million people in the United States aged 12 and older. Despite its effectiveness in saving lives, many barriers impede access to, initiation of, and retention in methadone treatment for OUD. To address these barriers, on March 3 and 4, 2022, the National Academies of Sciences, Engineering, and Medicine hosted a workshop on "Methadone Treatment for Opioid Use Disorder: Examining Federal Regulations and Laws," at the request of the Office of National Drug Control Policy in the Executive Office of the President. This publication summarizes the presentation and discussion of the workshop.

Psychiatric illnesses - such as major depressive disorder, anxiety disorder, substance use disorder, and posttraumatic stress disorder (PTSD) - are widely prevalent and represent a substantial health burden worldwide. Yet, conventional medications for mental illnesses often fail to provide relief to patients'' disruptive and disabling symptoms. Existing and emerging evidence that psychedelics (e.g., LSD and psilocybin) and entactogens (e.g., MDMA) may be useful as tools to alleviate mental illness has sparked a renaissance of interest by investigators, clinicians, drug developers, and patient advocates in recent years. While promising data on therapeutic efficacy has energized research and development, resolving the mechanisms of action will be important for optimizing the efficacy and safety of these medicines. Further, evaluating the effect of psychedelics and entactogens on mood and behavior comes with unique challenges still in need of resolution. These include unresolved questions relating to blinding, placebo and nocebo effects, and the impact of psychosocial contexts.

In response to this renewed interest, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders convened a workshop on March 29-30, 2022. The workshop brought together a diverse group of stakeholders to explore the use of psychedelics and entactogens as treatments for psychiatric disorders. This Proceedings of a Workshop summarizes the presentations and discussions of the workshop.

Chronic sleep disorders affect one in five Americans, and sleep deprivation costs significant U.S. GDP loss annually. Despite the indisputable biological importance of sleep, much remains unknown about underlying mechanisms.

The National Academies Forum on Neuroscience and Nervous System Disorders convened a public workshop in November 2022. Experts and leaders from academia, industry, government, philanthropic foundations, and disease-focused non-profit organizations gathered to review current sleep science, examine the relationships between central nervous system disorders and sleep, identify potential cross-disciplinary collaborations, and discuss opportunities to better understand and mitigate sleep disturbances commonly associated with CNS disorders. This proceedings document summarizes workshop discussions.

A key step towards reducing the burden of central nervous system (CNS) disorders is the identification of disease-specific biomarkers that can help predict, monitor, and guide treatment development. Recent technological advances have led to an increased number of biomarkers for different CNS disorders, providing the opportunity to generate multimodal biomarkers. While multimodal biomarkers can serve as promising tools to better diagnose and make accurate disease assessments, there remain challenges in current data collection, standardization, and validation practices that impede in their development. Recognizing the need for increased CNS biomarker integration, the National Academies Forum on Neuroscience and Nervous System Disorders hosted a public workshop in March 2023 to explore steps toward this goal, including data collection for biomarker discovery, development, validation, and assessment of clinical utility. This Proceedings of a Workshop summarizes the discussions held during the workshop.

Implantable brain stimulation has had a profound impact on neuroscience research and the treatment of central nervous system disorders by allowing physicians to directly intervene in the pathological neural circuits of their patients. To explore the logistical, educational, and economic barriers to adopting this technology into regular use in clinical care, the National Academies Forum on Neuroscience and Nervous System Disorders hosted a public workshop in October 2023.

Since artificial intelligence''s (AI) inception, AI and neuroscience have influenced each other to advance models of neural circuitry, analyze large and complex datasets, and inform the development of AI algorithms. This bidirectional relationship also has implications for health care as researchers and clinicians begin to explore the role of AI in clinical diagnosis, disease monitoring, and predicting treatment outcomes of central nervous system disorders. The National Academies Forum on Neuroscience and Nervous System Disorders hosted a public workshop in March 2024 to explore safe, responsible, and equitable use of AI in neuroscience and identify collaborative strategies for increasing AI literacy, building public trust, and creating accessible user interfaces.

Attention deficit/hyperactivity disorder (ADHD) diagnosis and treatment among adults has increased over the past decade in the U.S. and globally. Evidence suggests adults with ADHD may be more likely to develop a substance use disorder, and there are concerns that nonmedical use of prescription stimulants could lead to misuse, overdose, or toxicity. In December 2023, The National Academies Forum on Drug Discovery, Development, and Translation and Forum on Neuroscience and Nervous System Disorders held a public workshop to examine the diagnosis and treatment of adults with ADHD and explore the challenges and opportunities for the development of new therapeutics. The workshop was supported, in part, through a grant (PAR-23-072) from the Center for Drug Evaluation and Research at the FDA.