NIMH Alliance for Research Progress Meeting
On Friday, September 15, 2017, the National Institute of Mental Health (NIMH) convened the twenty-fourth meeting of the Alliance for Research Progress (Alliance) in Bethesda, Maryland. The purpose of Alliance meetings is to foster dialogue, so that participants can directly hear about NIMH activities, including science advances, exciting new and ongoing research projects, and a variety of ongoing and new initiatives of the Institute. Alliance meetings also provide opportunities for attendees to network with their colleagues in the advocacy community in person and to interact directly with senior NIMH staff. The NIMH Director, Joshua Gordon, M.D., Ph.D., presided. Invitees included leaders from national mental health-related organizations representing and advocating for patients and their families. The September meeting included discussions about scientific solutions to the opioid crisis, treatments for obsessive compulsive disorder (OCD) and depression, and new family-centered approaches to partner with consumers to improve child mental health services. For more information, please see the meeting agenda and participant list.
Welcome and State of the NIMH
Joshua Gordon, M.D., Ph.D., Director, NIMH
Dr. Gordon welcomed participants and updated them on news and priorities, noting that, Dr. Francis Collins and Dr. Shelli Avenevoli have retained their roles as Director of NIH and Deputy Director of NIMH, respectively; and that Dr. Elinore McCance-Katz was confirmed as the Assistant Secretary for Mental Health and Substance Use – providing leadership to the Substance Abuse and Mental Health Services Administration (SAMHSA). In his first year as Director, Dr. Gordon identified three research priorities: (1) suicide prevention (short-term), (2) neural circuits (medium-term), and (3) computational psychiatry (long-term). He briefly discussed these priority areas and the importance of funding excellent science across all timescales. Regarding the budget, the proposed House and Senate FY18 Appropriations bills suggest a $1 – $2 billion increase for NIH above the FY 2017 level. He noted that the 21st Century Cures Act was passed in December 2016 and will increase NIH collaboration with SAMSHA and includes funding for the BRAIN Initiative and All of Us Research Program. In June, NIH launched the Next Generation Researchers Initiative to encourage early and mid-career investigators with novel research programs to gain earlier independence. Dr. Gordon stated that effective January 2018, all NIH funded research involving human subjects must be pre-registered and outcomes must be reported to encourage public data-sharing. Dr. Gordon also shared the results of two recently published studies on post-traumatic stress disorder (PTSD) and maternal depression, as well as new findings from Suicide Prevention in an Emergency Department Population (ED-SAFE) study.
During the dialogue period, Dr. Gordon discussed a recently funded convergent neuroscience initiative which aims to bring physicists, engineers, computational scientists, neuroscientists, and psychiatrists together to develop approaches to modeling the multi-gene problem. A question was raised as to how universities might build their workforces to prepare for future changes in the field resulting from current research. Dr. Gordon stated that NIMH supports curriculum development for neuroscience residents through educational grants and training programs, so they can develop the skills they’ll need to do their jobs in the future.
Scientific Solutions to the Opioid Crisis
Nora Volkow, M.D., Director, National Institute on Drug Abuse (NIDA)
Dr. Nora Volkow began her presentation with a personal story and by noting that besides marijuana, opioids are the most frequent substance of abuse in the United States. She described the challenges of the epidemic and a recent study1 that estimated that adults with a mental health disorder account for over 50% of the opioid prescriptions. NIDA has been funding research on alternative, non-addictive pain medications and opioid addiction treatments and interventions. NIH is also partnering with pharmaceutical companies to develop extended release formulations to prevent the likelihood of relapse. She mentioned that emergency department administration of the opioid agonist buprenorphine significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services. Dr. Volkow concluded by stressing the importance of education and training for healthcare providers on the screening and management of pain and substance abuse disorders.
In response to questions from Alliance members, Dr. Volkow stated that recognizing the overlap of basic neurocircuitry in the brain’s response to physical and emotional pain will lead to better opioid addiction treatments. Participants also asked for additional information on NIH research on non-addictive treatments for chronic pain. Dr. Volkow noted that non-drug interventions demonstrate good or better efficacy, but are more expensive, and take additional time and patient commitment. She supports the CDC’s guidelines recommending a combination of drug and non-drug treatment strategies.
Pioneering Fast-Acting Treatments for Obsessive-Compulsive Disorder
Carolyn Rodriguez, M.D., Ph.D., Assistant Professor, Department of Psychiatry and Behavioral Science, Stanford University
Dr. Carolyn Rodriguez spoke about innovations in OCD research. She mentioned that the only FDA approved pharmacological interventions for OCD are selective serotonin reuptake inhibitors (SSRIs), which can take months to take effect and may not work for all patients. Dr. Rodriguez’s laboratory applies a neuroscience-focused approach to OCD research, investigating abnormalities in OCD brain circuits and associated chemical messengers (e.g., serotonin, glutamate, and gamma-aminobutyric acid [GABA]) involved in communication between brain cells. There is increasing evidence that glutamate plays a significant role in OCD symptoms, and ketamine is a drug suspected to change levels of glutamate in the brain. Administration of ketamine was found in a 2013 NIH funded study to provide relief of OCD symptoms for up to one week post-treatment in half of study participants. In another study, the ketamine combined with a brief course of cognitive behavioral therapy (CBT) sustained effects for over two weeks in over half of study participants. However, she noted that ketamine has transient side effects including feeling dissociated (e.g., feeling of floating). Ketamine also has abuse potential as demonstrated by its use as a club drug called “Special K.” Less is known about its long-term side effects. Taken together, Dr. Rodriguez notes that these issues urge all of us to find out more, scientifically, about ketamine before we routinely use it for treatment of OCD. Dr. Rodriguez also described research to understand the mechanism of OCD using a non-invasive neuroimaging technique, called magnetic resonance spectroscopy, which revealed that GABA increased one hour post-infusion while glutamate levels did not change. This is in contrast to a partner study on major depression showing that glutamate and GABA increased in the same region of the brain in the same time course. The results suggest that ketamine may have a unique neurochemical signature in OCD in relation to depression. Dr. Rodriguez partnered with Dr. Joseph Moskal of Northwestern University and colleagues to study the drug GLYX-13 (now called raspastinel) that also acts on the glutamate system and had previously been shown to have rapid antidepressant activity with minimal risk for ketamine-like side effects. To test whether rapastinel had similar effects in OCD, Dr. Rodriguez conducted a small pilot study. Rapastinel decreased symptoms of OCD, anxiety, and depression within hours, and was well-tolerated (e.g. no dissociative or other ketamine-like side effects). The effects of a single dose of rapastinel did not persist to one week, suggesting next steps for development include repeated dosing and testing new formulations within a therapeutic class. Alliance members expressed concern regarding the historical stigma surrounding ketamine as a street drug with addictive properties. Dr. Rodriguez noted that her goal is to use ketamine as a probe to understand the underlying brain mechanisms of ketamine’s rapid action and use that knowledge to ultimately develop rapid acting drugs that do not have ketamine’s side effects.
Mechanisms and Treatment of Adolescent Depression
Argyris Stringaris, M.D., Ph.D., MRCPsych, Chief, Mood and Brain Development Unit, Division of Intramural Research Programs, NIMH
Dr. Stringaris discussed the origins, lethality, and societal implications of depression which often starts in adolescence and increases in incidence with increasing age. He noted that there has been no single new drug discovery for adolescent depression for several years and little progress has been made in terms of understanding the genetics behind it. Dr. Stringaris’ laboratory has demonstrated that adolescents with low activity in the ventral striatum, an area of the brain involved in motivation and reward processing, are at increased risk for developing depressive disorders. They are conducting a study using computational models of reward pathways in the brain and effects on mood from administration of the drug lurasidone to patients with depression. Dr. Stringaris is also due to conduct a trial on growth mindset interventions (GMIs), an interactive 30-minute computer-based interventions based on the core idea that personality traits are malleable. When administered prior to CBT, GMIs may influence top-down motivation networks for long-lasting effects that increase adherence to CBT treatment. Dr. Stringaris concluded by stressing the importance of further research on how to safely and rigorously evaluate the neural mechanisms of depression and suicide to provide high-end effective treatments.
Family-Centered Research: New Approaches to Partner with Consumers to Improve Child Mental Health Services
Gloria Reeves, M.D., Associate Professor, Department of Psychiatry, University of Maryland School of Medicine;
Tammy Clough, Family Navigator, University of Maryland School of Medicine
Parents face many barriers to utilizing child mental health services, and children may receive medication-only treatment instead of comprehensive care because of challenges accessing behavioral services. Dr. Gloria Reeves discussed the shift in clinical care to better engage parents in their child’s recovery. Dr. Reeves presented information on the Family VOICE study, funded by the Patient-Centered Outcomes Research Institute under the Affordable Care Act, which enrolled 350 parents of Medicaid-insured youth approved for antipsychotic medication across Maryland. The study introduced an ad hoc peer support program connecting parents to Family Navigators by telephone for 90 days. Family Navigators are parents who themselves have raised a child with special mental health needs. The goals of Family VOICE are to evaluate the effects of a peer support program on parental empowerment, social support, and satisfaction with child services, as well as how it may improve therapy service utilization, behavior functioning, and medication dose in children. Parents could also utilize the Family Navigator service to address resource needs for other family members and to address basic household needs. Parents frequently identified food and housing needs for their families, which the Family Navigators were able to assist with resource/referral information. The Family Navigator services did not result in improved use of therapy services or parent reported outcomes, but children whose parents received navigation were less likely to have an antipsychotic dose increase at 90 days. Dr. Reeves emphasized the value of telephone services to reach families in rural communities and how the convenience of ad hoc availability of Family Navigators enabled families to incorporate this intervention into their busy schedules. Family Navigator, Ms. Tammy Clough discussed her participation in the Family VOICE study and personal stories of families she has assisted through the study.
Final Discussion and Wrap Up
During the final discussion, Alliance members asked questions about continued collaborations between NIMH and SAMHSA as a result of the 21st Century Cures Act; updates on the Research Domain Criteria (RDoC) initiative; the future of data-driven and computational approaches to mental health research; and the use of large data sets to enhance the granularity of risk adjustment. Dr. Gordon and senior staff responded to questions and encouraged continued feedback and dialogue moving forward. In closing, Dr. Gordon thanked the Alliance members for their participation and looks forward to future collaborations and meetings.
1Davis MA et al., JABFM July–August 2017; 30(4).