Alliance for Research Progress — July 12, 2013 Meeting
Meeting Summary (Outreach): July 12, 2013
The National Institute of Mental Health (NIMH) convened the nineteenth meeting of the NIMH Alliance for Research Progress (Alliance) on Friday, July 12, 2013 in Bethesda, MD; this document provides an overview of the proceedings. At Alliance meetings, leaders from national organizations focused on mental illness hear about projects and activities at NIMH and the National Institutes of Health (NIH). They also hear about and discuss advances in mental health and mental illness research, network with colleagues, and interact directly with NIMH Director, Thomas Insel, M.D. and senior NIMH staff. At the July 12 meeting, participants heard an update on the State of the NIMH from Dr. Insel and listened to presentations about a behavioral weight loss intervention for persons with serious mental illness; patient empowerment; brain imaging as a potential biomarker for personalized medicine; and prospects for novel diagnostics and therapeutics.
For more information on the speakers, please see the attached agenda and participant list.
Welcome and State of the NIMH
Dr. Insel’s presentation focused on three topics: genetics, diagnostics, and the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, which was announced at a White House Conference on April 2. He noted a significant increase in news coverage of mental health-related topics over the last seven months. He also talked briefly about the White House National Conference on Mental Health on June 3, the MentalHealth.gov online resource and the National Dialogue on Mental Health, and the proposed National Research Action Plan for the continuing challenge of military suicide. Dr. Insel told participants that several mental illnesses are highly heritable (e.g., schizophrenia, bipolar disorder), but genetic research has not revealed specific causal genes; rather, some mental illnesses are likely the result of spontaneous mutations. Dr. Insel highlighted advances in other areas, such as cancer and cystic fibrosis—wherein researchers are able to develop precise medical interventions (precision medicine) based on an individual’s genetic profile—as examples of the direction in which research on mental disorders is headed. Regarding advances in diagnostics, Dr. Insel discussed the Research Domain Criteria (RDoC) project, which is still in the early stages. He noted that many disorders have similar symptoms and that, while diagnosis based on clinical symptoms is not always scientifically valid, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the International Classification of Diseases (ICD) are currently the best tools available for diagnosis and subsequent reimbursement by payers. Parenthetically, he noted that much work is needed to combat public distrust of mental health providers. He concluded with a description of the public-private BRAIN Initiative partnership, which will increase knowledge about the brain through the development and application of tools that will enable scientists to view dynamic images of individual cells and neural circuits in the brain.
Alliance members voiced their support for NIMH, saying that the patients they represent want cures. One participant asked if NIMH is funding the right mix of basic and translational science. Dr. Insel said that we could only know the answer to that question in retrospect, but NIMH works hard to achieve that balance. Another participant discussed the lack of comprehensive information on the MentalHealth.gov website, and asked how Alliance members could contribute to the information and review of the site. Dr. Insel asked every Alliance member to look over the website and encouraged them to submit feedback.
A Behavioral Weight Loss Intervention in Persons with Serious Mental Illness
Gail L. Daumit, M.D., M.H.S., Associate Professor of Medicine, Psychiatry, Epidemiology, Health Policy and Management and Mental Health at the Johns Hopkins Medical Institutions discussed the ACHIEVE trial, a modified lifestyle intervention for overweight or obese individuals with serious mental illnesses (SMI). Alliance members are well aware that people with SMI die prematurely at a higher rate than that of the general population. Despite many calls to action, there is insufficient data on the prevalence of several of the contributing cardiovascular risk factors among people with SMI, including obesity. Dr. Daumit noted that in her research, 85% of the SMI population was overweight or obese and taking an average of three psychotropic drugs. As every class of psychotropic drugs causes weight gain, the goal of the ACHIEVE trial was to develop behavioral interventions that promote weight loss. Dr. Daumit explained how researchers brought fitness instructors and experts in nutrition to places most frequented by patients with SMI, such as psychiatric rehabilitation outpatient programs. Participants were successful in weight loss and in maintaining their behavior changes. This study ushered in new weight loss interventions for people with SMI, as participants engaged Dr. Daumit and colleagues in conversations about eating disorders and related behaviors. On average, participants lost seven pounds, which decreased their risk for other health problems, including cardiovascular disease.
When questioned whether the average weight loss of seven pounds was significant enough to benefit participants, and Dr. Daumit said that even just five to ten pounds of weight loss can improve health and decrease heart disease risk. In closing, she emphasized the significance of the trial by highlighting the fact that all of “the large clinical trials that have looked at weight loss for the overall U.S. population systematically exclude most mental health consumers;” thus, the ACHIEVE trial uniquely targeted a population that is susceptible to weight gain and has additional challenges losing weight due to the nature of SMI. Dr. Daumit hopes to see additional research on the long-term benefits of the trial and other lifestyle interventions targeted to this population.
Empowered Patients Live Longer: The Bonnie J. Addario Lung Cancer Foundation
Scott Santarella, President and CEO of the Bonnie J. Addario Lung Cancer Foundation (BJALCF) talked with Alliance members about issues that are common to both lung cancer and mental illnesses, such as stigma, inadequate research funding, and disparity in treatments. He discussed the high mortality rates associated with lung cancer and the “shame” often associated with the disease. The BJALCF was created to increase survivability of lung cancer and is working to categorize it as a chronically managed disease by 2023. He insisted that a lot can be learned from patients and caregivers, and noted that the BJALCF advocates for treating people on a personalized basis and for improving treatment at the community level where most receive care—often sub-optimally. The Foundation developed ALCMI (Addario Lung Cancer Medical Institute and pronounced “al-ka-me” ), an international consortium of leading medical institutions and community hospitals dedicated to working together to catalyze and accelerate discovery, development, and delivery of new and more effective treatment options. Mr. Santarella discussed how the BJALCF has developed patient-focused tools and resources to educate and empower patients and families, such as the Guide to Navigating Lung Cancer, which will soon be available as a mobile application. He also described how a 21-year-old patient inspired the creation of a young adult advisory board focused on social media, education, stigma reduction, and motivating advocates and researchers. Mr. Santarella said the BJAFCF is a model that can be adapted to mental illnesses.
Alliance participants were very interested in the presentation, and engaged in significant dialogue with Mr. Santarella about smoking cessation and other comorbid conditions shared between mental illness and lung cancer. Mr. Santarella talked about the Patient 360 Community Hospital Program, a unique multidisciplinary approach that coordinates the standard of care for patients individually. In closing, he suggested partnerships with the multiple myeloma and cystic fibrosis communities as resources to learn how to “harness the outrage” to overcome denial and blame. Mr. Santarella also noted that the high morbidity in mental illness needs wider appreciation.
Predictive Medicine for Psychiatry: Optimizing Treatment for Depression Using Brain Imaging
Helen S. Mayberg, M.D., Professor of Psychiatry, Neurology and Radiology and Dorothy C. Fuqua Chair in Psychiatric Neuroimaging and Therapeutics at Emory University School of Medicine told Alliance members that it is the suffering associated with depression that brings people to treatment. She opened her talk by asking: What does it mean to have psychic pain? What does it mean to be “paralyzed” when you don’t have a spinal cord injury? What is brain illness and where is it in the brain? These are the questions that she is tasked with answering as a neuroscientist when evaluating which treatments work, developing metrics and biomarkers, and constructing treatment interventions. She explained that current treatments for depression are inadequate, and that over time, depression can undergo a malignant transformation causing treatments that once worked to become ineffective. She noted that there are real consequences if patients get the wrong treatment, including harmful side effects and the risk of suicide. Dr. Mayberg explained that when treating patients she focuses on two goals: addressing the episode as fast as possible; and matching the patient to his/her optimal treatment while avoiding those interventions that are likely to be unhelpful. She discussed her work to develop brain-based biomarkers to guide treatment for depression based on a “brain-type.” Her research demonstrated how pre-treatment scans of brain activity were used to predict whether depressed patients would best achieve remission with an antidepressant medication (escitalopram) or psychotherapy (cognitive behavioral therapy, CBT). Among several sites of brain activity related to outcome, activity in the anterior insula best predicted response and non-response to both treatments. If a patient’s pre-treatment resting brain activity was low in the front part of the insula, on the right side of the brain, this signaled a significantly higher likelihood of remission with CBT and a poor response to escitalopram. Conversely, high activity in the insula predicted remission with escitalopram and a poor response to CBT.
Dr. Mayberg also discussed her work involving deep brain stimulation for treatment-resistant depression. In a proof-of-principle pilot safety study, she found that 4 out of 6 patients improved after their first treatment. Dr. Mayberg responded to concerns about the size of the test group and discussed other studies with more participants that yielded a positive long-term response rate to treatment. She noted that not all of the study participants got well. In an effort to understand why patients did and did not respond favorably, she searched for the sources of variability, and discovered that small differences in surgical location of electrodes implanted in the brain benefited non-responsive patients. She concluded her presentation by discussing the importance of helping people to get “unstuck” from their depression, and strengthening their ability to keep aberrant behaviors like eating disorders or OCD in check when the depression is lifted.
Neural Circuits: The New Frontier of Neuropsychiatric Diagnostics and Therapeutics
Kafui Dzirasa, M.D., Ph.D., Assistant Professor, Department of Psychiatry and Behavioral Sciences at the Center for Neuroengineering at Duke University Medical Center began his presentation by recounting the story of a family whose son was experiencing a psychotic break. Dr. Dzirasa explained how their confusion, denial, and search for answers served as a backdrop for the data and findings in his talk. He described the challenges he’s encountered as a young scientist and clinician. He connected with Alliance members by noting his personal experiences with family members and friends who have neuropsychiatric disorders, described his fascination with neurocircuitry, and said that we must do better to understand how the brain functions and translate research into treatment and treatment into cures. He compared current methods for understanding brain function to the approaches Aristotle, Socrates, and Plato might try to understand a computer. They would take it apart to see the underlying mechanics, but doing so couldn’t inform them about software, or the Internet, or the bigger picture of computer functionality and use.
Dr. Dzirasa broadly described our current understanding of mental disorders and how one of the challenges faced by clinicians when trying to cure people is to understand what is “normal,” while another is explaining the labels used for diagnosis. For example, two people may exhibit completely different sets of symptoms, but have the same disorder. He noted that RDoC is a framework for reclassifying mental illnesses that will allow clinicians and scientists to investigate the roles played by brain circuits and genetics. He described his research using animal models to create an animal analog of human post-traumatic stress disorder (PTSD). In his research, mice were implanted with electrodes and exposed to a version of the fearful faces test—i.e., exposing and stressing smaller mice by introducing them into an environment with larger, aggressive mice. The stressed mice went on to develop an aggravated fear response, which is an analog of PTSD behaviors and symptoms. He explained that they were able to extinguish the fear behavior by using viruses to target a specific receptor that was introduced into the mouse brain, turning off the fear response. Dr. Dzirasa discussed the possible implications of this research on the field and potential benefits to individuals with PTSD. His laboratory is now looking for the common circuits to treat “disorders of synchrony.” To do this, his research team has built a prototype “external brain pacemaker” to encourage different parts of the brain to work together, thereby restoring behavioral function. While additional research is necessary, this neural circuit research could lead to the development of new models and new frameworks for study.
During the discussion periods, Alliance members shared their views on the presentations and asked questions of speakers. Alliance members applauded the exciting research developments presented, especially the opportunity to reverse behaviors by understanding and modifying circuits. They noted that the idea of going to a doctor to have him/her tell you what is wrong with you is antiquated. Instead, patients today often figure out what is wrong and link with others to determine what will work best for them. However, with mental illnesses, many patients may not know, may be too impaired, or may actively deny that they have a disorder, and may therefore not be able to advocate for themselves. Alliance members expressed concern about what psychiatrists are being taught today. Members said that many mental health providers with professional degrees have no knowledge of neurobiology or evidence-based treatments. There is a disconnection between what is being taught and what research is teaching us. Many mental health specialists feel that “the new science” won’t help in their clinics. Alliance members stated that many institutions use an apprenticeship model of teaching; therefore, if teachers are not proficient in the scientific model, it will not be taught. The burden is on the scientific community to move the field forward. Clinicians and advocates must work to together on the critical need to get better diagnostics and treatments to patients. They stated that the need for better science and better data does not end with new treatments only, as understanding why some high risk people recover from or avoid mental illness is critical. However, the discussion continued to note that studying resilience is difficult, because well and recovered people are not volunteering, and the science must be concise and complex enough to tease out the subtle differences in people.
Alliance members commented that language is a big problem for the field, as there are many different ways to talk about brain disorders: mental health, mental disorders, mental illness, schizophrenia, bipolar disorder, neuropsychiatric disorder—yet none of these words address the earliest symptoms such as the isolation, which can help to identify people in need of help long before a clinical diagnosis. Alliance members discussed the recent White House Conference and language used by President Obama when describing “Mental Health Disorders,” and noted that without agreement on something as small as language, progress will be difficult.
View additional images from the 2013 Alliance for Research Progress Summer Meeting on the NIMH Flickr photo stream at http://www.flickr.com/photos/nimhgov/sets/72157635459576066/