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 Publications  Washington, D.C., March 30, 2008 Reports on PTSD and other war-related psychological problems; also new findings on bipolar disorder, schizophrenia and childhood psychiatric disorders The psychological toll of war, particularly post-traumatic stress disorder (PTSD), was discussed by public health experts from the military and scientific communities at NARSAD’s fifth annual “Mission Possible” Mental Health Research Symposium, held March 30th in Washington, D.C. The symposium also featured reports on bipolar disorder, schizophrenia and child and adolescent psychiatric disorders. The day-long event, which was free and open to the public, was presented by NARSAD of Greater Washington, D.C., with support from the Washington Psychiatric Society and the Uniformed Services Branch of the American Psychiatric Association (APA). The symposium moderator was Darrel A. Regier, M.D., M.P.H., executive director of APA’s Institute for Research and Education, which has primary responsibility for the Diagnostic and Statistical Manual (DSM). Among many contributions to public service, Dr. Regier was scientific coordinator and director for four National Advisory Mental Health Council reports to Congress on mental health insurance parity. He served for 25 years with the National Institute of Mental Health (NIMH), and was assistant surgeon general with the United State Public Health Service. Following is a summary of the symposium proceedings. Taking Care of Soldiers and Families: Past, Present and Future The first speaker, retired U.S. Army Lt. Gen. Theodore G. Stroup, Jr., presented a historical overview of war-related mental health problems, and how the military has dealt with them, from the days of what was called shell shock or combat fatigue to what is now referred to as post-traumatic stress disorder. Gen. Stroup is vice president for education of the Association of the United States Army and executive director of its Institute of Land Warfare. Before retiring from active service, he was the Army’s deputy chief of staff for personnel. He is the founding director of the Helping Our Heroes Foundation at Walter Reed Army Medical Center, among his many community-service positions. With each successive war Americans have fought, Gen. Stroup said, the lethality of weapons has increased, and military medicine has had to rise to the challenge. While acknowledging recent public and media concern over treatment of wounded and traumatized service personnel returning from Iraq, he said that his examination of the situation has revealed mainly failures of administrative processing. In contrast, he believes that military medicine is performing well. He cited, as example, the “remarkable” recoveries being made from loss of limbs. With regard to PTSD and other psychological consequences of battle, Gen. Stroup reported that a new program has been instituted in military hospitals across the country in which special units staffed by social workers, psychologists, psychiatrists, physical therapists and other health care personnel are working with the country’s “warriors in transition” to help them recover physically and mentally. Services also include job counseling and aid to families. PTSD: From Battlefield to Home Front The next speaker was Robert J. Ursano, M.D., professor of psychiatry and neurology and chairman of psychiatry at the Uniformed Services University of the Health Sciences and founding director of the Center for the Study of Traumatic Stress. The first chairman of the APA’s committee on the psychiatric dimensions of disaster, he chaired the association committee that developed treatment guidelines for PTSD and he edited the first text book on disaster psychiatry. Dr. Ursano began by stressing that war-related PTSD must be viewed as a national concern. Of 30,000 service personnel wounded to date in Iraq, an estimated 20 percent, or 6,000, have or will develop PTSD; and of the 1.6 million people deployed in Iraq and Afghanistan overall, the figure may reach as high as 80,000. (The VA’s number for veterans of all wars currently receiving some type of disability support for PTSD is 300,000.) The most significant finding in all studies of populations exposed to trauma, Dr. Ursano said -- whether Hurricane Katrina, Iraq, World Wars I and II, Vietnam or 9/11 -- is that the more severe the trauma the higher the rates of psychiatric casualties. Citing the current gap between needs and services, Dr. Ursano said that of the returnees from Iraq who screened positive for moderate or severe PTSD, only about 25 to 30 percent received help in the past 12 months. Among other barriers to care, a majority or near-majority of those screened worried they would be seen as weak or their unit leadership might view them differently, that it would hurt their career or it would be difficult to get time off from work for treatment. Nearly 40 percent expressed some distrust of mental health professionals. Appropriate care, Dr. Ursano stated, will require understanding of how to address these and other problems, such as how to detect PTSD initially and over time, how to determine optimum treatments and train people to provide them, how to determine and provide necessary administrative and data systems and how to respond to the needs of service families and communities.  View Dr. Ursano's powerpoint presentation:Part 1 Part 2 Part 3 The Mental Health Consequences of War The research reported by the third speaker, Yuval Neria, Ph.D., grew out of his own experience of combat and injury as an Israeli soldier in the 1973 Yom Kippur War, for which he received his country’s Medal of Valor. Formerly on the faculty of Tel Aviv University, he was recruited by Columbia University following the Sept. 11, 2001 terrorist attacks. He is an associate professor of clinical psychology in the departments of psychiatry and epidemiology at Columbia and director of the trauma and PTSD program at the New York State Psychiatric Institute. He has received a NARSAD Young Investigator Award and a NARSAD Klerman Award Honorable Mention for clinical research. Describing a study of Yom Kippur War veterans that he and his colleagues conducted some years after the war, Dr. Neria said the findings, consistent with Dr. Ursano’s, showed a strong correlation between severity of exposure to trauma and outcomes. The research also pointed to the significant role played by an individual’s personality in resilience to trauma; i.e., those who performed heroically in combat, and suffered fewer PTSD symptoms, tended to have personalities that sought novel, risky experiences. Among other influencing factors, Dr. Neria said, childhood experiences with caregivers may shape later functioning in extreme conditions, as well as attitudes toward combat. He stated that in a study of Vietnam veterans, 70 percent of those who saw the war as negatively impacting their lives developed PTSD as opposed to 18 percent among those who viewed the experience as positive. Based on his studies, Dr. Neria stressed that for those with persistent PTSD, treatment is essential. Untreated, such individuals will likely have severe difficulties in functioning and could develop substance abuse or depression or become suicidal or homicidal. For those who have recovered from early symptoms, he suggested routine follow-up, especially for those slated for subsequent combat. In terms of continuing research, he said that there is now broad interest in further exploring the determinants of psychological resilience. View Dr. Neria's powerpoint presentationPsychological Health and Traumatic Brain Injury Next on the program, Loree Sutton, M.D., special assistant to the Assistant Secretary of Defense for Health Affairs, described the work of a new Department of Defense (DOD) Center of Excellence for psychological health and traumatic brain injury, of which she is the director. A highly decorated medical officer whose posts have included combat zones, she recently served as commander of the Carl R. Darnall Army Community Hospital, in Fort Hood, Texas. She holds the rank of Colonel (P), designating a pending promotion to brigadier general. Col. Sutton explained that the Center of Excellence was established as a clearinghouse to make the resources and programs within the armed services, DOD, and VA more readily available to military personnel and their families. It serves as a “center of centers,” coordinating with other centers. These include: Dr. Ursano’s Center for the Study of Traumatic Stress; the Defense and Veterans Brain Injury Center, a network of 16 sites that includes four VA polytrauma centers, eight military treatment facilities and several civilian institutions; the Center for Deployment Psychology, recently instituted to train psychologists and other health specialists in PTSD; the Deployment Health Clinical Center, which works at the intersection of primary care and behavioral health for those who have not responded to other treatment; and the Intrepid Fallen Heroes Fund, which is building a National Intrepid Center of Excellence devoted to psychological health and traumatic brain injury. Col. Sutton’s center is also collaborating with the NIMH to launch a national public health awareness campaign relating to service personnel and their families, which also involves a VA-DOD working group on reintegration for service members, drawing on resources of the department of labor, education, small business and others. UPDATE ON BIPOLAR DISORDER The second part of the Washington, DC symposium opened with a report on new findings about bipolar disorder by Andrew A. Nierenberg, M.D., who served as one of the leaders of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and the Sequential Treatment Alternatives to Relieve Depression (STAR*D), which Dr. Regier called two of the most important clinical trials ever supported by NIMH. The recipient of two NARSAD Independent Investigator Awards, Dr. Nierenberg is professor of psychiatry at Harvard Medical School and associate director of the Depression Clinical and Research Program and medical director of the Bipolar Clinic and Research Program at Massachusetts General Hospital. Currently, he is principal investigator and director of the NIMH Bipolar Trials Network. The multi-site STEP program, which involved 4,300 people, was based on an unusual approach, Dr. Nierenberg explained, in which doctors and patients collaborated in monitoring, evaluating and negotiating treatment based on shared observations and measurements of symptoms, side effects and overall functioning. Among the program’s findings were some that contradicted commonly held assumptions about bipolar disorder and how best to treat it. Careful initial screening revealed that half of those enrolled in the program suffered from comorbid (co-existing) anxiety disorder, which Dr. Nierenberg said has generally gone unrecognized by physicians. These patients recovered more slowly and at a lower rate than those without anxiety, and fewer remained well after recovery. It was also observed that people with bipolar disorder while in a depressive episode can still have manic symptoms, and that if the mania was not addressed, relapse into depression was more frequent and antidepressants did not help speed their recovery. These and other unexpected findings, Dr. Nierenberg said, suggested differences affecting bipolar depression as opposed to unipolar depression. In another study with people who had not responded to antidepressants, Dr. Neirenberg said, treatment with lamotrigine, a drug used originally for epilepsy, added to a mood stabilizer, appeared to ease depression. It was further observed that those given psychotherapy in addition to drug therapy recovered from major depressive episodes much earlier than the other trial participants. Dr. Nierenberg said that in a major STEP achievement reported just two weeks earlier, specific genetic differences were identified between bipolar patients and normal controls. An important research area still in its infancy is the quest for genetic and other biomarkers that can lead to individualized treatment. Lithium, the best known treatment, has been in use for decades, often combined with other medications, but never systematically studied. In closing, Dr. Nierenberg announced that the Bipolar Trials Network, under his direction, was about to launch a new study, which he has named LiTMUS, to examine strategies of lithium use so as to determine optimal treatment modalities. View Dr. Nierenberg's powerpoint presentationHow Do Genes Cause Mental Illness? To set the stage for his talk, Daniel Weinberger, M.D., one of the world’s leading authorities on the subject of genes in mental illness, began by stressing that genes are not about “fate.” Rather, he said, they are about risk -- liability to mental illness. Indeed, they are the only absolutely objective means by which risk status can be identified. And they provide the first real clues to the causes of neuropsychiatric illnesses and to the identification of drugs that may be developed based on these clues. Dr. Weinberger directs the Genes, Cognition, and Psychosis Program of the Intramural Research Program at NIMH. His studies defined dysfunctional neural brain systems in schizophrenia and his lab identified the first specific genetic mechanism of schizophrenia risk. A member of the NARSAD Scientific Council, he has received NARSAD’s Lieber Prize for Outstanding Achievement in Schizophrenia Research and a NARSAD Distinguished Investigator Award, among many other honors including the NIH Directors Award, awards from the APA and election to the Institute of Medicine of the National Academies. While many candidate genes for psychiatric disorders are emerging, Dr. Weinberger emphasized the complexity of these disorders in general and of schizophrenia in particular. Among the list of possible schizophrenia susceptibility genes, there is no single, outstanding “schizophrenia gene,” just as there is no single “cancer gene.” Each gene, in his view, contributes only a small effect, and none of the genes so far identified appears to be specific only to schizophrenia. Further, psychiatric disorders like schizophrenia are genetically heterogeneous: individual patients have different complements of risk factors. Risk genes for mental illness can be significantly influenced by interaction with a person’s environment, Dr. Weinberger said. A variation of a gene called COMT is associated with psychosis. A long-term study in New Zealand, since confirmed by other studies, showed that early adolescent marijuana use increased the risk of psychosis two- or three-fold in those with the risk-factor COMT gene variation. Serotonin is a neurotransmitter, an actor in cell communication in the brain. A particular variant of the gene that codes for the serotonin transporter protein, interacting with adverse life events, becomes a risk factor for depression. Genes also interact with one another. Serotonin is involved in fearfulness. The brain system that reacts to danger is the amygdala. People with the variant form of the serotonin transporter gene have more reactive amygdalas, Dr. Weinberger explained, but one form of another gene, BDNF, protects against the impact of the serotonin risk gene for depression. In the search for susceptibility genes for psychiatric disorders, Dr. Weinberger said, current evidence is converging on subtle molecular “bottlenecks” in brain processing and development related to the neurocircuitry of cognition and emotion. Therapeutic advances will emerge from a thorough understanding of the molecular biology of susceptibility genes and the neurocircuitries they influence. View Dr. Weinberger's powerpoint presentation:Part 1 Part 2 What Is the Brain Teaching Us about Child and Adolescent Psychiatric Disorders? The final speaker at the symposium, Francisco Xavier Castellanos, M.D., presented recent research on childhood bipolar disorder and attention-deficit hyperactivity disorder (ADHD). The Brooke and Daniel Neidich Professor of Child and Adolescent Psychiatry at the New York University School of Medicine, where he established the Institute for Pediatric Neuroscience, Dr. Castellanos is also professor of radiology, underlining, as Dr. Regier pointed out, the critical link between new technologies of neuroimaging and recent research advances. Dr. Castellanos received a NARSAD Distinguished Investigator Award and an APA award for his ADHD studies. Childhood bipolar disorder is a field that has generated controversy, Dr. Castellanos stated, because most children described as bipolar do not display the classic episodic pattern of the disorder. A number of long term studies have been trying to resolve this question. One study found that these children later appeared to be at greater risk for unipolar depression. Studies have pointed to episodicity of symptoms and the presence of euphoria, less common in these children than depression, as the best marker of future bipolarity. Among drug trials, children had good responses to valproic acid (Depakote) combined with lithium. But all these results, Dr. Castellanos cautioned, are still incomplete. As with other psychiatric disorders, an important step forward in studying childhood mental illness has been the development of advanced methods of brain visualization. Currently in the planning stage, Dr. Castellanos reported, is a large-scale, long-term collaborative project that will combine imaging, genetics and other research tools to study a hoped-for base of up to 50,000 people. Turning to ADHD, the most studied of childhood psychiatric disorders, Dr. Castellanos said that imaging studies of the cortical area of the brain have revealed people with ADHD to have slightly thinner cortices. (Their cortices, furthermore, reach their maximum thickness three or more years later than normal controls.) Other studies have shown differences in how brain areas communicate in ADHD. These findings have led researchers to look at the precuneus, an area of the brain that is still little understood. Dr. Castellanos said that the precuneus is thought to help steer the back of the brain and connect it to the frontal regions, which are important for regulating large brain circuits. What is not known is whether these findings point to cause or effect, a puzzle that it is hoped genetic studies will help to elucidate. Citing NIMH statistics that 75 percent of mental health problems begin before the age of 24, the good news, Dr. Castellanos said, is that studies of child and adolescence psychiatric illnesses are growing and improving. The hope is that the ability to diagnose and intervene earlier will improve, which he believes is beginning to happen with ADHD. There is also the hope that methods being worked out with ADHD will have application to other, more intractable problems. View Dr. Castellanos's powerpoint presentation:Part 1 Part 2 Part 3 |
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