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Alliance for Research Progress - July 21, 2008 Meeting


Bethesda MD

Overview

The National Institute of Mental Health (NIMH) convened its ninth meeting of the Alliance for Research Progress (Alliance) on Monday, July 21, 2008 in Bethesda, Maryland. This document provides an overview of the proceedings. The meeting served as an opportunity for participants to hear about exciting new research and advances in the field, to network with colleagues, and to interact directly with the NIMH director, Dr. Thomas Insel, and senior NIMH staff. Invitees included representatives from national voluntary organizations representing patients and their families. Presentations focused on neurodevelopment research and included information on the recently released RAND report – Invisible Wounds of War and finally an update on the development of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V). For more information on the speakers, please see the attached agenda and roster of participants.

Major Themes

State of the NIMH
Dr. Thomas Insel provided brief updates on science of note, transitions in the intramural and extramural research programs, activities surrounding financial conflict of interests (FCOI), and the initiative to enhance peer review at NIH. He talked about the importance of genetic research and models of discovery for other disease areas and their potential for the mental health field. Specifically, he mentioned models used by cancer and juvenile diabetes researchers to identify genes, develop research models, discover the cellular pathology, identify targets, and develop therapeutics to address the disorder. He discussed recent schizophrenia and autism studies and the need for additional research to solve the mysteries of these developmental brain disorders. Dr. Insel noted the growing concern about FCOI among NIH grantees and how NIMH has encouraged grantee institutions to monitor and report conflicts. He stressed four points concerning FCOI – financial interest does not always result in a FCOI; investigators are responsible for disclosing FCOI to their institution; universities are responsible for managing and disclosing FCOI to NIH; and NIH will work closely with recipient institutions to resolve issues quickly and comprehensively. Dr. Insel briefly mentioned that there is a great deal happening with the peer review process at NIH. He noted that different approaches in peer review will begin in 2009; the new process should have a reduced burden on reviewers and different categories of scores on applications; and that public membership on review committees is encouraged.

Alliance members actively participated in the discussion periods throughout the day. They expressed their concern over FCOI and the fact that growing attention is being directed towards advocacy groups that fund research projects. Participants also discussed the President’s New Freedom Commission on Mental Health Report and said that the report shows that the cost of mental health care in the United States was greater than the revenue of many Fortune 500 companies. The status of the mental health parity bill was also discussed. Mr. Andrew Sperling of the National Alliance on Mental Illness provided an update on the legislation and explained the need for a budget offset to address the shortfall in the United States Treasury that would be caused due to the fact that medical healthcare premiums paid by employers are not treated as income and are not taxed.

Bipolar Disorder in Youth: Diagnosis and Brain Mechanisms
Ellen Leibenluft, M.D., Chief of the NIMH Section on Bipolar Spectrum Disorders, Emotion and Development Branch, Mood and Anxiety Program, presented information on diagnosis of bipolar disorder and associated brain mechanisms. She discussed a study to determine if children who have severe mood dysregulation (SMD) respond to frustration similarly to children who have bipolar disorder. She told Alliance members about NIMH-funded research that addresses the question as to whether or not SMD and attention deficit hyperactivity disorder (ADHD), without clear manic episodes, is a form of bipolar disorder in children. She noted that bipolar disorder in adults is often characterized by episodes of mania and depression; however it is unclear if bipolar disorder in children presents differently and is characterized by severe irritability and ADHD symptoms. Dr. Leibenluft said that children with SMD are often irritable and have symptoms that look like ADHD, but without the clear manic episodes observed in children with bipolar disorder. She also noted that irritability is a common indicator for many disorders described in the DSM-IV and is ubiquitous to many childhood-onset disorders.

Dr. Leibenluft discussed a study in which investigators analyzed event related potentials, during “frustration tests,” to measure changes in the brain as the children with either SMD, bipolar disorder, or those in the control group became progressively irritated. The researchers found that while both the children with bipolar disorder and those with SMD became more frustrated than did healthy children performing the same task, the brain mechanisms associated with their frustration differed. Children with bipolar disorder had an abnormality in the brain's P3 electrical signals, which measure ability to purposefully direct attention, but children with SMD had abnormalities in N1 signals, which occur when a stimulus grabs someone's attention. Both abnormalities suggest deficits in the brain's attention-related activity, but in different phases of that activity.

Dr. Leibenluft went on to note that there are treatment implications related to the question as to whether or not SMD is a form of bipolar disorder. For example, if SMD is a form of bipolar disorder, then, children with SMD could be treated with antipsychotics and mood stabilizing medication. However, Dr. Leibenluft also presented data indicating that youth with SMD might be at risk for major depression in early adulthood. If SMD is more closely related to depression and ADHD than to bipolar disorder, then treatment with antidepressants and stimulants would be a good option, but if SMD is more closely related to bipolar disorder, then such treatment might make children worse. Therefore, it is important to conduct additional research of brain mechanisms to establish linkages between SMD, on the one hand, and bipolar disorder or depression on the other. Dr. Leibenluft ended by stating that SMD is very common, and that the data thus far do not indicate that we should conclude that all (or even most) severely irritable children meet criteria for bipolar disorder.

Brain Imaging and Attention Deficit Hyperactivity Disorder
Jay N. Giedd, M.D., Chief of the NIMH Unit on Brain Imaging, Child Psychiatry Branch, presented information on the historical perspective, diagnosis, and biology of ADHD. He referenced nursery rhymes from the late 1800’s that described attention problems and fidgetiness of children at home and in social settings and said that the authors may have been describing children with ADHD. He defined ADHD as a developmental disorder that can be characterized by the hyperactivity and inattentive behavior of those with the disorder. Dr. Giedd talked about concerns associated with a diagnosis of childhood ADHD as it relates to physician or rater bias and symptom cut-offs. He mentioned the difficulties of distinguishing between normal childhood behavior and ADHD. Dr. Giedd told Alliance members about the rate of thickening of white and gray matter in the brain as it relates to neurodevelopment and differences found in children with ADHD. He talked about twin studies that showed that the brain of the affected twin was different and often had lesions in the basal ganglia. He also noted unique differences in the cerebellum of twins with ADHD. In conclusion, Dr. Giedd stressed the importance of long term study of ADHD to monitor the neurodevelopmental changes that occur in the brain.

Prodrome of Schizophrenia: New Opportunities for Early Detection and Intervention
Robert Heinssen, Ph.D., ABPP, the Acting Deputy Director of the NIMH Division of Services and Intervention Research, provided an overview of what is known about the prodrome of schizophrenia – the period preceding the onset of the first psychotic episode, with increasing symptomatic presentation and functional deterioration – and current research on early detection and intervention. He told Alliance members that researchers are interested in studying the schizophrenia prodrome because it is believed that effective intervention during the prodromal stage might prevent or delay the onset of schizophrenia. He discussed how investigators have categorized the prodromal period into three at-risk mental states used to identify individuals at increased risk for schizophrenia. The at-risk states are characterized by attenuated psychotic symptoms; genetic risk and functional deterioration; and brief, limited, intermittent psychotic episodes. Dr. Heinssen described research using the Structured Interview for Prodromal Syndromes (SIPS) to assess an individual’s thoughts in response to specific questions to determine if they were in an at-risk mental state for schizophrenia.

Dr. Heinssen highlighted lessons learned through past studies and current NIMH-funded projects focusing on early detection of schizophrenia through research of the prodromal period. He noted that NIMH is supporting nine investigator-initiated projects to study prediction and prevention of psychosis onset. Dr Heinssen provided a detailed description of the North American Prodrome Longitudinal Study (NAPLS) – a consortium of eight studies with a common focus on the characterization and prediction of schizophrenia. He told Alliance members that researchers hope that data from NAPLS will set the stage for discovering predictive biomarkers and selective recruitment into preventive intervention studies. Dr. Heinssen also stated that treatments for the prodromal period are being vigorously researched, and include novel pharmacologic, psychotherapeutic, and rehabilitation approaches.

During the discussion period, Alliance members acknowledged the benefits of predictive research and voiced their concerns about how information about risk would be shared with at-risk individuals. Dr. Heinssen stated that predictive research and the use of targeted early interventions will help people. He also noted that the current research and data is encouraging for future treatments of individuals in the prodromal period.

Invisible Wounds of War
Lisa H. Jaycox, Ph.D., Senior Behavioral Scientist and Clinical Psychologist at the RAND Corporation presented information on the report entitled Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery (http://www.rand.org/multi/military/veterans). The study was done in response to rising concerns about returning service members deployed to operations in Afghanistan and Iraq and reported symptoms of psychological and cognitive injuries. The report focused on post traumatic stress disorder (PTSD), major depression, and traumatic brain injury (TBI) and examined the prevalence, social costs, and gaps in care services afforded to returning service members. Dr. Jaycox defined each of these terms and discussed progress made through scientific research in screening and treating mental illness.

Dr. Jaycox told Alliance members about the study approach and methods of collecting information, as well as the report’s recommendations. Researchers conducted telephone surveys with returned service members; completed a literature review; held interviews with stakeholders and program officials; constructed models to estimate costs; and conducted focus groups with service members and their spouses. She mentioned the long-term consequences of PTSD, TBI, and major depression on service members and their families and said that many service members who are eligible for care do not seek it due to concerns about side effects of treatment; military culture and values; lack of access to care; and the complexities of navigating the care systems. The report recommends that the government increase the supply of providers who deliver effective care; encourage active duty personnel and veterans to seek care; deliver effective care in all settings; and invest in research to close knowledge gaps, especially concerning TBI.

In response to questions, Dr. Jaycox mentioned that the Department of Defense (DOD) was receptive to the report recommendations and is encouraging health-seeking behaviors among commanders and upper level military officials. She also said that there is public concern about TBI and its treatment and a need for much more research in this area.

Update on DSM V
Darrel A. Regier, M.D., M.P.H., Director, Division of Research, American Psychiatric Association; and Executive Director, American Psychiatric Institute for Research and Education, provided an update on the development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Dr. Regier briefly discussed the importance of classifying medical disorders and the history surrounding the development of DSM. He talked about the perceived limitations of DSM-IV and new research developments that may impact the revision process, which started in 1999. Dr. Regier told Alliance members about the strategies and process of revising DSM, which include building diagnoses on a foundation of scientific findings from various disciplines; seeking assistance from the multidisciplinary international scientific community; and using input from scientists, clinicians, and consumers to refine revisions. DSM-V is scheduled to be completed and released in May 2012.

Photographs

NIMH Alliance for Research Progress - July 21, 2008
Alliance Speakers (L to R): Dr. Leibenluft, Dr. Giedd, Dr. Heinssen, Dr. Jaycox, Dr. Regier
Alliance Speakers (L to R): Dr. Leibenluft, Dr. Giedd, Dr. Heinssen, Dr. Jaycox, Dr. Regier
Dr. Insel addressing Alliance members
Dr. Insel addressing Alliance members
Alliance Members
Alliance Members