NAMHC Minutes of the 273rd Meeting

May 30 and May 31, 2024

Department of Health and Human Services
Public Health Service
National Institutes of Health
National Advisory Mental Health Council

Introduction

The National Advisory Mental Health Council (NAMHC) held its 273^rd meeting at 1:00 pm, May 30, 2024, in person and via Zoom and NIH videocast. In accordance with Public Law 92-463, the session was open to the public until approximately 5:00 pm and was followed by the closed session on May 31, 2024. Joshua Gordon, M.D., Ph.D., Director of the National Institute of Mental Health (NIMH), presided as Chair for both sessions. 

Council Members Present

• Edwin (Ted) Abel, III, Ph.D.
• Olusola Ajilore, M.D., Ph.D.
• Rinad Beidas, Ph.D.
• Pamela Collins, M.D., M.P.H.
• Marguerita Lightfoot, Ph.D.
• Angus MacDonald, III, Ph.D.
• Velma McBride Murry, Ph.D.
• Joel Nigg, Ph.D.
• Matthew Nock, Ph.D.
• Jyotishman Pathak, Ph.D.
• Bryan Roth, M.D., Ph.D.
• Laura Scott, Ph.D., M.P.H.

Council Members Absent

• Daniel  Gillison, Jr.
• Patricia Recupero, M.D., J.D.

Department of Veteran Affairs (Ex Officio Member)

• Amy Kilbourne, Ph.D., M.P.H.

Liaison Representative (Ex Officio Member)

• Anita Everett, M.D., DFAPA

Others present at Open Policy Session (Appendix B)

Others present at Closed Grant Review Session (Appendix C)

OPEN PORTION OF THE MEETING

1. Open Policy Session Call to Order & Opening Remarks, Joshua Gordon, M.D., Ph.D. (NIH Videocast  @00:06)

   NIMH Director Dr. Joshua Gordon opened the hybrid NAMHC meeting and welcomed Council members, NIMH staff, NIH staff, and members from various constituent communities. Following a review of in-person and virtual meeting etiquette, the Council unanimously passed a motion approving the final Summary Minutes of the January 2024 meeting. 

2. NIMH Director’s Report, Joshua Gordon, M.D., Ph.D. (NIH Videocast  @04:50)

   1. Congressional Interactions

      Dr. Gordon reviewed NIMH engagement with Congress, including participation in congressional briefings and responding to requests for information on topics such as general mental health research, the relationship between mental health and sleep, children’s mental health, suicide prevention, health disparities, transcranial magnetic stimulation, and focused ultrasound neuromodulation. NIMH leadership, along with representatives from other federal agencies, participated in a Staff Roundtable with the Senate and Congressional Mental Health Caucuses. NIMH staff also attended congressional events, including the Advancing Cures Today for NIH  and an NIMH 75^th Anniversary Celebration.

   2. Appropriations and Budget Updates

      In March 2024, President Joe Biden signed the Consolidated Appropriations Act of 2024 , as well as the Further Consolidated Appropriations Act of 2024 , which proposed a budget increase of $75 million for NIMH. Dr. Gordon discussed the recent decrease in the BRAIN Initiative budget  and highlighted how the additional NIMH allocation would help offset it. President Biden’s proposed fiscal year 2025 (FY25) budget requested $50.1 billion for NIH, which is an increase of $2.4 billion from FY23 enacted levels and includes a $200 million increase for mental health research. Both NIH Director Monica Bertagnolli, M.D., and HHS Secretary Xavier Becerra, J.D., testified before congressional appropriations committees regarding the FY25 budget requests. 

   3. HHS and NIH Updates

      On April 23, 2024, HHS released the 2024 National Strategy for Suicide Prevention  and an accompanying Federal Action Plan ; Dr. Gordon talked about the dramatic increase in both the amount of funding and quality of suicide prevention research across NIMH over the last decade. The Interagency Autism Coordinating Committee (IACC) held a full committee meeting  on April 17, 2024, and published its 2019-2020 IACC Autism Research Portfolio Analysis Report  on May 2, 2024. Dr. Gordon highlighted changes to the Simplified Review Framework (SRF) for NIH research project grants , which reframes the existing five criteria into three factors to focus application review on the quality of research and the likelihood of project success rather than investigator or institution reputational factors. NIH provided guidance  to help investigators understand how these changes impact their applications.

      Dr. Gordon announced NIH’s plans to establish the Communities Advancing Research Equity for Health  (CARE for Health™), an initiative to integrate clinical research into primary care settings—particularly among communities that are historically underrepresented in clinical research or underserved in health care. CARE for Health would allow NIMH to reach these underrepresented communities without the need to provide additional funding or infrastructure to develop a separate clinical research network.

      Dr. Gordon announced NIH leadership changes, including the appointments of Kathleen Neuzil, M.D., as Director of the Fogarty International Center (FIC) and Sean Mooney, Ph.D., as Director of the NIH Center for Information Technology (CIT). Dr. Gordon also highlighted the NIH Climate Change and Health Initiative’s first annual CAFÉ Climate and Health Conference  on February 5-7, 2024, and promoted the 10^th Annual BRAIN Initiative Conference  on June 17-18, 2024.

   4. NIMH News to Know

      Dr. Gordon announced that he would step down  as NIMH Director effective June 14, 2024. NIMH Deputy Director Shelli Avenevoli, Ph.D., will serve as Acting NIMH Director. Dr. Gordon expressed his gratitude for his time serving NIMH over the last eight years. NIMH continues to celebrate its 75^th anniversary with events, such as the symposium Amplifying Voices and Building Bridges: Toward a More Inclusive Future on March 18, 2024 and a final symposium to celebrate NIMH research to be held on September 20, 2024, in Washington, D.C. Dr. Gordon encouraged Council members to review other 75^th Anniversary events and resources.

      NIMH completed its annual update to the Strategic Plan for Research, which included an emphasis on research to meet the needs of underserved communities, an update to the NIMH global mental health program, and an expansion of the use of data and digital health technologies to identify clinical symptoms and provide personalized treatments. Dr. Gordon invited attendees and the public to provide feedback  for the next iteration of the Strategic Plan for Research and to review and share its 2023 Progress Report. Dr. Gordon also announced two Requests for Information (RFIs) for research gaps on the impacts of racism  on brain and behavioral health across the lifespan and strategies to advances the relevance and impact of mental health services . Additionally, NIMH published a Notice for Applications Supporting Exceptionally Well-Funded Investigators , which clarifies the multiple-Program Directors(PDs)/Principal Investigators (PIs) requirement for Special Council Review of exceptionally well-funded investigators procedures for managing the concentration of funding.

      Dr. Gordon highlighted some recently funded NIMH initiatives, including the Individually Measured Phenotypes to Advance Computational Translation in Mental Health (IMPACT-MH), which is supporting research to develop data-driven clinical signatures and improve clinical prediction and decision-making. He also reviewed a collection of recent publications from the PsychENCODE  initiative, in which researchers provide the largest and most advanced multidimensional maps of gene regulation networks in the brains of people with and without mental disorders. 

      Dr. Gordon announced staff news, including the passing of Herbert Pardes, M.D. , who served as the  NIMH Director from 1978 to 1984. In March 2024, Susan Azrin, Ph.D., retired from her position as Chief of the Early Psychosis Prediction and Prevention Unit. In July 2023, Ellen Leibenluft, M.D., retired from her position as Chief of the Section on Mood Dysregulation and Neuroscience in the NIMH Intramural Research Program (IRP). In May 2024, Sarah Morris, Ph.D., Branch Chief of the Adult Psychopathology and Psychosocial Interventions Research Branch within the NIMH Division of Translational Research, was appointed as the Head of the NIMH Research Domain Criteria (RDoC) Unit. Janet Clark, Ph.D., Director of the NIMH IRP Office of Fellowship Training, was named Fellow of the American Society for Pharmacology and Experimental Therapeutics and Fellow of the American College of Neuropsychopharmacology. Armin Raznahan, M.D., Ph.D., Chief of the Section on Developmental Neurogenomics in the NIMH IRP, was elected to the American Society for Clinical Investigation.

   5. Science Highlights

      Dr. Gordon shared three science highlights. The first study used a pioneering approach to study the development of small assemblies of brain tissue that had been grown from human stem cells from individuals with and without Timothy syndrome and were implanted into a mouse brain to further mature. Investigators found that the brain tissue from individuals with Timothy syndrome had a less elaborate dendritic arbor than the brain tissue from individuals without Timothy syndrome. The investigators then explored a potential treatment using antisense oligonucleotides to suppress CACNA1C exon 8a. They found that that the treatment not only reduced the calcium channel protein mutation and restored dendritic growth, but also reversed the key phenotypes involved in the neurodevelopmental challenges associated with Timothy syndrome.

      The second study² was a clinical trial of dialectical behavioral therapy (DBT) for adolescents with bipolar disorder. Investigators found that while both DBT and Standard of Care improved mood symptoms, only DBT reduced the number of suicide attempts over a year. To date, no other psychosocial intervention had specifically targeted suicide behaviors among people with bipolar disorder, who are at high risk for suicide.

      The third study³ sought to establish a causal relationship between the neurons involved in encoding faces and the experience of perceiving a face using non-human primates (NHPs). The researchers used muscimol to inhibit face-selective neurons in the inferior temporal (IT) cortex and found that it impaired NHPs’ ability to focus their eyes on faces. These findings confirmed there is a causal relationship between the activity of these neurons and higher order visual processing, which could inform the development of treatment for individuals with prosopagnosia (i.e., face blindness).

      Discussion

      Following Dr. Gordon’s update, Council members thanked Dr. Gordon for his service to NIMH, particularly the commitment to diversify the workforce; increase funding for mental health services, behavioral research, and implementation science; and promotion of research excellence. Council members expressed interest in further expanding mental health services research and collaboration with other organizations. They also commented on the NIMH budget and asked how the $75 million increase was to be allocated and how future budgets might impact science. They also asked about the CARE for Health™  initiative and strategies needed to ensure the program reaches underserved communities.

      Dr. Gordon thanked Council for their kind words. He noted that the Substance Abuse and Mental Health Services Administration (SAMHSA) had seen dramatic increases in their budget over the last several years, part of which had led to the expansion of Certified Community Behavioral Health Centers (CCBHCs) and the ability for NIMH investigators to leverage community-based research in those settings. He said that the increased budget allowed NIMH to provide a modest increase for postdoctoral salaries (with the aim of reaching a minimum salary of $70,000 within the next few years), as well as modest increases for graduate students and training grants. If the budget remains static in future years, it could affect funding for postdoctoral and training programs. He added that the CARE for Health™ initiative would first focus on established community-based clinical networks before seeking to invest in clinical networks in communities that were still underrepresented. 

3. NIH Director Presentation, Monica M. Bertagnolli, M.D., Director, National Institutes of Health, (NIH Videocast  @01:19:39)

   Dr. Gordon introduced a video recording from Dr. Bertagnolli, who expressed concern about the declining life expectancy among Americans, largely due to deaths of despair related to substance abuse, suicide, drug poisoning, and cardiometabolic diseases. She talked about two major challenges that NIH should prioritize: the need to ensure representation in research and the need to translate science into evidence-based clinical practices. Dr. Bertagnolli emphasized that NIH’s work was not done when it delivered scientific discovery, but rather when those discoveries were connected to everyday life and clinical practices so that people could live long, healthy lives. She commended Dr. Gordon for his leadership at NIMH and highlighted his accomplishments in expanding research in suicide prevention, neural circuitry, computational psychiatry, novel interventions, and telemedicine.

4. Progress in Disparities Research and Workforce Diversity at NIMH, Christina Borba, Ph.D., M.P.H., Director, Office for Disparities Research and Workforce Diversity (NIH Videocast  @01:27:40)

   Dr. Borba introduced the Office for Disparities Research and Workforce Diversity (ODWD) team and reviewed the different activities that ODWD had embarked on to promote research to reduce mental health disparities and advance mental health equity. Dr. Borba highlighted the recent NIH designation  of people with a disability as a population with health disparities; in response, ODWD established a Task Force to define research priorities on the intersection of disability and mental illness. Another key highlight was a RFI  on moving beyond individual-level determinants of mental health toward a better understanding of the social and structural levels. On June 6, 2024, ODWD supported a workshop focused on discrimination as a social determinant of health, which garnered substantial interest from the community.

   ODWD also contributed to several funding opportunities, including research on the impact of social disconnection and suicide risk in late life, the intersection of stigma and discrimination in HIV prevention and treatment, and the impact of COVID-19 on underserved and vulnerable populations. Additionally, ODWD collaborated with other NIH institutes on funding opportunities related to social determinants of health, community-engaged research, structural racism and discrimination, and sexual and gender minority populations.

   Dr. Borba reviewed ODWD’s accomplishments in promoting workforce diversity and equity, including the development of a special interest group within NIMH to broaden participation among investigators from historically underrepresented communities. ODWD also manages a Diversity Supplement program and staff have provided technical assistance to support applicants to this program, which helped dramatically increase the number of successful applicants. Additionally, NIMH ranked fourth in the number of awards in the NIH-wide career continuity initiative, which aimed to supplement investigators’ absences due to critical life events.

   Dr. Borba spoke about other efforts to support underrepresented populations. For instance, NIH released a Notice of Special Interest  focused on the diseases and health conditions that predominantly impact women. NIMH plans to host a women’s roundtable in 2024 to spotlight research related to mental health during pregnancy and the postpartum period. NIMH has also increased its portfolio for rural mental health and supported the development of Rural Mental Health in the United States: 2006-2022 , a publication that describes the state of research on rural mental health. In addition, NIMH funded research efforts focused on American Indian/Alaska Native (AI/AN) populations, including research centers, intervention development, and a special effort within the Helping to End Addiction Long Term (HEAL) Initiative  to address opioid misuse and pain management. 

   Dr. Borba posed three questions for Council members to consider: 1) how NIMH can aspire to center equity in its science, 2) NIMH’s priorities for mental health disparities, and 3) the current challenges within their organizations in supporting health disparities research.

   Discussion
   Council members commended ODWD and the Disparities Team for their work. They addressed the three questions that were posed, specifically referencing the need to reduce inherent biases in data collection processes, build research infrastructure and capacity, explore the ODWD portfolio at NIMH, train the workforce on developing structural interventions, and continue informing Congress on mental health disparities

   Dr. Borba agreed with these suggestions and talked about their current efforts to address them. For example, there had been discussions about how to mitigate bias in data collection by ensuring that people with lived experience were at the table, efforts to develop structural interventions through Community Partnerships to Advance Science for Society (ComPASS) , and in-depth conversations to define the terms community engagement and lived experience. She also highlighted efforts by ODWD’s Juliette McClendon, Ph.D., and her team to audit the NIMH portfolio and disparities research. 

5. Council Workgroup on High Dimensional Data: Presentation of Recommendations, Laura A. Almasy, Ph.D., Co-Chair, University of Pennsylvania and Damien Fair, PA-C, Ph.D., Co-Chair, University of Minnesota (NIH Videocast  @02:07:22)

   Dr. Fair reviewed the rationale for the Council Workgroup on High Dimensional Data. Over the last few decades, data in mental health research had become bigger, more complex, and multidimensional—using multiple data sources to study many different relationships. Research standards that had previously been adopted for scientific rigor and reproducibility were often insufficient for studies using multidimensional data. Therefore, the Workgroup aimed to identify both broad best practices and recommendations for specific study types across four specific areas: 1) ensuring statistic rigor and enhancing reproducibility, 2) understanding the role of hypotheses and conceptual frameworks, 3) guiding studies involving high dimensional data, and 4) assessing the clinical utility of studies.

   The Workgroup first developed a framework for recommendations based on five research design categories: 1) exploratory or descriptive, 2) inferential or predictive, 3) causal intervention, 4) mechanistic or exploratory, and 5) methods or tool development. The Workgroup then identified 10 topic areas for their recommendations. These topic areas spanned the research process from goals, aims, and hypotheses through publication planning and early investigator training. Dr. Fair highlighted a number of recommendations across each of the 10 topic areas. 

   Discussion
   Council and Workgroup member Laura Scott, M.P.H., Ph.D., talked about the different audiences for the report of recommendations, which included NIMH program officers, mental health investigators applying for NIMH funding, and the broader research community. She added that it would be important for NIMH to track and document its progress along these recommendations. For example, NIMH could track how often the report was being accessed, how it was used, what happened as a result, and what other public feedback would be important to capture. Dr. Gordon agreed that tracking these outcomes was important. Additionally, NIMH would not only publish the report on its website, but it would also review the recommendations to determine whether any merited a policy change.

   Dr. Gordon called for a vote to accept the recommendations without edits. The Council unanimously passed a motion accepting the Workgroup on High Dimensional Data report of recommendations in its current form. 

6. Concept Clearances (NIH Videocast  @02:48:58)

   1. Neuromodulation/Neurostimulation Device Development for Mental Health Applications, Lizzy Ankudowich, Ph.D., Division of Translational Research

      Dr. Ankudowich said that the goal of this concept is to encourage the development of novel brain stimulation devices to enable the improved delivery of invasive and noninvasive brain stimulation approaches towards optimized effectiveness. The concept would aim to overcome some of the challenges in application across the spectrum of serious mental illness, as well as current limitations toward regulatory approval and wider adoption.

       Discussion
      Discussants: Dr. Olusola Ajilore and Dr. Matthew Nock 
      Drs. Ajilore and Nock expressed support for this concept and offered two suggestions: 1) that the concept include real time neurofeedback as one of the technologies and 2) that there be a focus on the most difficult to treat conditions.

   2. Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders, Lizzy Ankudowich, Ph.D., Division of Translational Research

      The goal of this concept is to encourage research using invasive neural recording opportunities in humans to study neural circuitry, as well as underlying complex moods, emotions, cognitive functions, and behaviors, with high precision. The concept also aims to translate findings from animal studies into normal treatment courses for different clinical conditions. Research under this concept could advance the understanding of the circuitry related to mental health conditions and inform the design of future intervention studies. 

   3. Genetic Architecture of Mental Disorders in Ancestrally Diverse Populations II, Miri Gitik, Ph.D., Division of Neuroscience and Basic Behavioral Science

      Dr. Gitik described the NIMH Ancestral Populations Network (APN), which aims to accelerate research on genetic contributions to mental illnesses by including more cohorts with non-European ancestry, who have historically been underrepresented in genetics research. This concept represents the second phase of the APN and expands on previous efforts by collecting larger samples that can help advance genetic discovery to diversify mental health phenotypes and genotypes, identify ethical best practices with vulnerable populations, and develop practices for studies of social determinants of health and genetic studies at a large scale. 

      Discussion
      Discussants: Dr. Laura Scott and Dr. Pamela Collins
      Drs. Scott and Collins expressed support for this concept and asked a number of questions about strategies for ensuring geographic diversity, as well as investigator diversity across both career stage and ancestry. Dr. Gitik talked about the need to further diversify their samples. Dr. Waldeck said that NIMH does not have access to information about investigator race, ethnicity, or gender in funding decisions. 

   4. National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders or Alcohol Use Disorder, Yael Mandelblat-Cerf, Ph.D., Division of Neuroscience and Basic Behavioral Science, National Cooperative Drug/Device Discovery/Development

      Dr. Mandelblat-Cerf said that, despite the high cost and number of years needed to develop safe, effective therapeutics, 90 percent fail between phases 1 and 3 of clinical trials. Therefore, the aim of this concept is to accelerate the development of innovative drug and device therapeutics to treat mental disorders. This could be accomplished by fostering collaborative partnerships between academic and industry researchers and multidisciplinary teams to generate novel therapeutics and to identify or validate drug targets, clinical measures, and biomarkers. 

      Discussion
      Discussants: Dr. Ted Abel and Dr. Angus MacDonald
      Drs. Abel and MacDonald expressed support for this concept and offered several suggestions, including working with the Food and Drug Administration to identify lessons learned and successes in streamlining projects and reducing redundant efforts, as well as working with the BRAIN Initiative Neuroethics Working Group. Dr. MacDonald asked what the overlap was between this and the first concept on neuromodulation devices. Dr. Mandelblat-Cerf answered that the first concept is focused on optimizing existing devices, whereas this concept focuses on early development. A Council member suggested requiring an implementation scientist on the team to ensure that clinician and patient perspectives are included early in the process. 

7. Public Comment (NIH Videocast  @03:31:50)

   Dr. Gordon opened the meeting to the registered public commenter, James Cromwell, an advocate from the People for the Ethical Treatment of Animals (PETA). He expressed concerns about the animals in research studies and asked the Council to redirect resources from animal studies to human research. 

   Written public comment submitted to Council (Appendix D) 

8. Adjournment

   Dr. Gordon adjourned the open session of the meeting at 5:00 pm.

CLOSED PORTION OF THE MEETING

This portion of the meeting was closed to the public in accordance with the determination that it was concerned with matters exempt from mandatory disclosure under sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., and section 1009(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. §§ 1001-1014).

Tracy Waldeck, Ph.D., Executive Secretary of the Council, explained policies and procedures regarding confidentiality and conflict of interest to the members of the Council. 

Members absented themselves from the meeting during the discussion of and voting on applications from their own institutions, or other applications in which there was a potential conflict of interest, real or apparent. Members were asked to sign a statement to this effect.

1. Review of Applications

   Refer to Appendix C

2. Adjournment

   Dr. Gordon adjourned the open session of the meeting at 1:00 pm.

   APPENDIX A
   DEPARTMENT OF HEALTH AND HUMAN SERVICES
   NATIONAL INSTITUTES OF HEALTH
   NATIONAL INSTITUTE OF MENTAL HEALTH
   NATIONAL ADVISORY MENTAL HEALTH COUNCIL 
   (Terms end 9/30 of designated year)

   CHAIRPERSON	EXECUTIVE SECRETARY
   Joshua A. Gordon, M.D., Ph.D. Director National Institute of Mental Health Bethesda, MD	Tracy Waldeck, Ph.D. Director Division of Extramural Activities National Institute of Mental Health Bethesda, MD

   NATIONAL ADVISORY MENTAL HEALTH COUNCIL BOARD

   MEMBERS
   Edwin G. Abel, III, Ph.D. (24) Chair and Departmental Executive Officer Department of Neuroscience and Pharmacology Carver College of Medicine University of Iowa Iowa City, IA	Daniel H. Gillison, Jr. (25) Chief Executive Officer National Alliance on Mental Illness Arlington, VA
   Olusola Ajilore, M.D., Ph.D. (25) Associate Professor Director, Mood, and Anxiety Disorders Program Department of Psychiatry University of Illinois Chicago Chicago, IL	Marguerita A. Lightfoot, Ph.D. (24) Professor Associate Dean for Research OHSU-PSU School of Public Health Portland, OR
   Rinad S. Beidas, Ph.D. (26) Ralph Seal Paffenberg Professor Chair, Department of Medical Social Sciences Feinberg School of Medicine Northwestern University Chicago, IL	Angus W. MacDonald, III, Ph.D. (26)  Professor and Director of Clinical Training  Department of Psychology  University of Minnesota  Minneapolis, MN
   Pamela Y. Collins, M.D., M.P.H, (24) Professor of Psychiatry and Behavioral Sciences Professor of Global Health Schools of Medicine and Public Health University of Washington Seattle, WA	Velma McBride Murry, Ph.D. (25) Lois Autrey Betts Endowed Chair Associate Provost, Office of Research and Innovation University Distinguished Professor Departments of Health Policy & Human and Organizational Development Vanderbilt University Nashville, TN
   Joel T. Nigg, Ph.D. (24) Professor and Vice Chair for Psychology Director, Center for ADHD Research Department of Psychiatry Oregon Health and Science University Portland, OR	Patricia R. Recupero, M.D., J.D. (24) Senior Vice President of Education and Training Care New England Butler Hospital Providence, RI
   Matthew K. Nock, Ph.D. (24) Edgar Pierce Professor of Psychology Harvard College Professor Chair, Department of Psychology Harvard University Cambridge, MA	Bryan L. Roth, M.D., Ph.D. (24) Michael Hooker Distinguished Professor Department of Pharmacology School of Medicine University of North Carolina at Chapel Hill Chapel Hill, NC
   Jyotishman Pathak, Ph.D. (26) Frances & John L. Loeb Professor of Medical Informatics Department of Population Health Sciences Weill Cornell Medicine Cornell University New York City, NY	Laura Scott, M.P.H., Ph.D. (25) Research Professor Department of Biostatics University of Michigan Ann Arbor, MI

   EX OFFICIO MEMBERS

   Office of the Secretary, DHHS
   Xavier Becerra, J.D.
   Secretary
   Department of Health and Human Services
   Washington, DC

   National Institutes of Health
   Monica M. Bertagnolli, M.D.
   Director
   National Institutes of Health
   Bethesda, MD

   Department of Veterans Affairs
   Amy M. Kilbourne, Ph.D., M.P.H.
   Director, Quality Enhancement Research Initiative (QUERI)
   U.S. Department of Veterans Affairs
   Professor of Learning Health Sciences
   University of Michigan Medical School
   Ann Arbor, MI

   Liaison Representative
   Anita Everett, M.D., DFAPA
   Director
   Center for Mental Health Services
   US, HHS Substance Abuse and Mental Health Services
   Rockville, MD

   APPENDIX B
   Department of Health and Human Services
   Public Health Service
   National Institutes of Health
   National Advisory Mental Health Council
   Summary of 273^rd Meeting, May 30, 2024

   Federal Staff Present in Person for Open Policy:
   Paige Anderson Lizzy Ankudowich Shelli Avenevoli Rebecca Berman Christina Borba Susan Borja Linda Brady Marcy Burstein Holly Campbell-Rosen Sharon Chang Zieta Charles Leonardo Cubillos Debra Dabney Mannan Dasti Beshaun Davis Michele Ferrante Fernando Fernandez Meredith Fox Miri Gitik Joshua Gordon Margaret Grabb	Gregory Greenwood Brittany Haynes Lauren Hill Mi Hillefors Cathleen Hsu Monica Jacquet Terri Jarosik Brittany Johnson Jeymohan Joseph Erin King Su Koester Arina Knowlton Charisee Lamar Tamara Lewis Johnson Kelly Linthicum Christina Liu Allen Lo Rachel McConnaughhay Yael Mandelblat-Cerf Nicole Martino Tatiana Meza-Cervera	Dawn Morales Sarah Morris Eric Murphy Nikki North Nicolette O’Reilly Anna Ordóñez Christina Page Jenni Pacheco Jonathan Pevsner Dianne Rausch Emily Rolfes Laura Rowland Pamela Shell Joel Sherrill Rachel Smith Abigail Soyombo Natasha Sefcovic Julie Thai Leo Tonelli Tracy Waldeck Abera Wouhib

Others Present In-Person for Open Session:

Julian Baron, Federation of Associations in Behavioral and Brain Sciences

Alka Chandra, People for the Ethical Treatment of Animals

Carly Cooper, People for the Ethical Treatment of Animals

James Cromwell, People for the Ethical Treatment of Animals

Catherine Pak, George Washington University

Others Present Virtually for Open Session:

Appendix D

Written Public Comment Submitted to Council 

May 22, 2024

Re: Prohibition of the Forced Swim and Tail Suspension Tests; May 30, 2024 National Advisory Mental Health Council (NAMHC) Open Policy Session Public Comment

Sent via email to NAMHCPublicComment@mail.nih.gov

Dear Director Gordon and members of the NAMHC:

On behalf of the Physicians Committee for Responsible Medicine (PCRM), a nonprofit health advocacy organization supported by nearly one million members and supporters worldwide, thank you for the opportunity to comment on this meeting.

We commend the progress made through the National Institute of Mental Health’s (NIMH) Rapidly-Acting Treatments for Treatment-Resistant Depression (RAPID) initiative, including the pioneering work on ketamine and other N-methyl-D-aspartate receptor (NMDAR) antagonists, which have provided important improvements in the treatment of depression.

We are concerned, however, about two animal behavioral assays—the forced swim test and tail suspension test—and urge the NIMH to prohibit future funding of projects employing these procedures. The forced swim and tail suspension tests continue to receive NIMH funding despite their failures to reliably predict the clinical efficacy of non-monoaminergic classes of antidepressants, including NMDAR antagonists. As concluded in a 2022 meta-analysis by Viktorov and colleagues, “rodent models of behavioural despair are not predictive of clinical efficacy of drugs acting via NMDARs,” and the utility of these methods for the investigation of the mechanisms underlying ketamine’s effects is limited.1

Agencies in the United Kingdom and Australia have already taken steps to prohibit the forced swim test:

• The Animals in Science Committee concluded in its advice to the UK government that “the forced swim test should not be used as a model of depression or to study depression-like behaviour (including in the phenotyping of genetically altered mice) or for studies of anxiety disorders and their treatment.” The Home Office has acted on this advice by prohibiting the forced swim test for these purposes and has stated that it intends to pursue a full ban of the forced swim test in the UK.2
• The National Health and Medical Research Council, the Australian government’s primary authority on medical research and the country’s largest funder of medical research, has prohibited any new funding of the forced swim test as a model of depression or anxiety disorders and their treatments, concluding that “the scientific validity of the forced swim test for these purposes is not supported by evidence.”3
• Following expert testimonies and an inquiry committee conclusion that “the harm to animals occasioned [by the forced swim test] is greater than the human health benefits gained,” the New South Wales Parliament passed a bill in March 2024 to prohibit the forced swim test.4
• In a project initiated by the Animals in Science Regulation Unit (ASRU) at the UK Home Office, the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research collaborated with regulators and experts in the field to clarify the use and need for the forced swim and equivalent tests, concluding that researchers should “turn their efforts to tests which are unambiguously more refined than the forced swim test,” a statement that is supported by the ASRU.5

The Physicians Committee encourages the NAMHC to issue advice to the NIMH in support of such a prohibition. We appreciate your time and attention to this comment and welcome the opportunity for further dialogue

Sincerely,

Stephen Farghali, MSc 
Research Advocacy Coordinator 
Physicians Committee for Responsible Medicine

References

¹Viktorov, M., Wilkinson, M. P., Elston, V. C., Stone, M., & Robinson, E. S. (2022). A systematic review of studies investigating the acute effects of N-methyl-D-aspartate receptor antagonists on behavioural despair in normal animals suggests poor predictive validity. Brain and Neuroscience Advances, 6, 23982128221081645.

²Animals in Science Committee. ASC response to commission on forced swim test. Gov.uk. Published June 2023. Accessed March 4, 2024. https://www.gov.uk/government/publications/asc-response-to-commission-on-forced-swim-test . 

³National Health and Medical Research Council. Statement on the Forced Swim Test in Rodent Models. Published December 2023. Accessed March 4, 2024. https://www.nhmrc.gov.au/research-policy/ethics/statement-forced-swim-test-rodent-models 

⁴Hurst E. Animal Research Amendment (Prohibition of Forced Swim Tests and Forced Smoke Inhalation Experiments) Bill 2023. Accessed March 4, 2024. https://www.parliament.nsw.gov.au/bills/Pages/bill-details.aspx?pk=18431 

⁵Sewell F, Waterson I, Jones D, Tricklebank MD, Ragan I. Preclinical screening for antidepressant activity - shifting focus away from the Forced Swim Test to the use of translational biomarkers. Regul Toxicol Pharmacol. 2021;125:105002.