Using biomarkers to identify and treat schizophrenia

Researchers say lab-based tests may be boon to both clinicians and researchers In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder. "A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes," said Gregory A. Light, PhD, associate professor of psychiatry and the study's first author. "Diagnoses are currently based on a clinician's ability to make inferences about patients' inner experiences." continuing education for counselors Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors. "Schizophrenia is among the most severe and disabling conditions across all categories of medicine," said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System. The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families. Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient's inner experiences. That is, their ability to describe what's happening inside their minds. "But even the best clinicians struggle with diagnostic complexities based on sometimes fuzzy clinical phenomenology," said Light. The clinical challenge is compounded by the fact that "many schizophrenia patients have cognitive and functional impairments," said Light. They may not be able to reasonably explain how or what they think. Light and colleagues investigated whether a select battery of neurophysiological and neurocognitive biomarkers could provide clinicians with reliable, accurate, long-term indicators of brain dysfunction, even when overt symptoms of the disorder were not apparent. These markers ranged from tests of attention and memory to physiological assessments of basic perceptual processes using scalp sensors to measure brain responses to simple sounds. The researchers measured the biomarkers in 550 schizophrenia patients, and then re-tested 200 of the patients one year later. They found that most of the markers were significantly abnormal in schizophrenia patients, were relatively stable between the assessments and were not affected by modest fluctuations in clinical status of the patient. Light said further research is required, including whether the endophenotypes can differentiate other psychiatric disorders, be used to anticipate patient response to different kinds of drugs or non-pharmacological interventions or even be used to predict which subjects are at high risk of developing a psychotic illness. "We believe this paper is an important step towards validating laboratory-based biomarkers for use in future genomic and clinical treatment studies of schizophrenia," Light said. ### Co-authors are Neal R. Swerdlow, Anthony J. Rissling and Marlena Pela, Department of Psychiatry, UCSD; Allen Radant, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; Catherine A. Sugar, Departments of Psychiatry and Biostatistics, UCLA; Joyce Sprock, Mark A. Geyer and David L. Braff, Mental Illness, Research, Education and Clinical Center, San Diego VA Healthcare System and Department of Psychiatry, UCSD. Funding for this research came, in part, from National Institute of Mental Health grants MH042228, MH079777 and MH065571 and the Department of Veterans Affairs.

Research at UH finds cognitive-behavioral therapy effective in combatting anxiety disorders

Combination of treatments provides improvement for disorders such as fear of flying, public speaking or spiders Whether it is a phobia like a fear of flying, public speaking or spiders, or a diagnosis such as obsessive compulsive disorder, new research finds patients suffering from anxiety disorders showed the most improvement when treated with cognitive-behavioral therapy (CBT) in conjunction with a "transdiagnostic" approach – a model that allows therapists to apply one set of principles across anxiety disorders Anxiety Disorders CE Course The combination was more effective than CBT combined with other types of anxiety disorder treatments, like relaxation training according to Peter Norton, associate professor in clinical psychology and director of the Anxiety Disorder Clinic at the University of Houston (UH) CADC I & II Continuing Education Norton concludes that therapists treating people with anxiety disorders may effectively use a treatment that applies one set of principals across all types of anxiety disorders. The findings are the result of a decade of research, four separate clinical trials and the completion of a five-year grant funded by the National Institute of Mental Health. Norton defines anxiety disorders as when anxiety and fear are so overwhelming that it can start to negatively impact a person's day-to-day life. He notes anxiety disorders include: panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social anxiety disorder, specific phobias and generalized anxiety disorder. Often anxiety disorders occur with a secondary illness, such as depression, substance or alcohol abuse. Norton says there are targeted treatments for each diagnosis, but there has been little recognition that the treatments don't differ much, and they only differ in very specific ways. IMAGE:This is Peter Norton, associate professor in clinical psychology and director of the Anxiety Disorder Clinic at the University of Houston. Click here for more information. "The Diagnostic and Statistical Manual of Mental Disorders (DSM) has been an important breakthrough in understanding mental health, but people are dissatisfied with its fine level of differentiation," said Norton. "Panic disorders are considered something different from social phobia, which is considered something different from PTSD. The hope was that by getting refined in the diagnosis we could target interventions for each of these diagnoses, but in reality that just hasn't played out." As a graduate student in Nebraska, Norton couldn't get enough people together on the same night to run a group treatment for social phobia, and that marked the beginning 10 years of work on the transdiagnostic treatment approach. "What I realized is that I could open a group to people with anxiety disorders in general and develop a treatment program regardless of the artificial distinctions between social phobia and panic disorder, or obsessive-compulsive disorder, and focus on the core underlying things that are going wrong," said Norton. Norton finds cognitive-behavioral therapy (CBT), a type of treatment with a specific time frame and goals, helps patients understand the thoughts and feelings that influence behaviors to be the most effective treatment. The twist for him was using CBT in conjunction with the transdiagnostic approach. The patients receiving the transdiagnostic treatment showed considerable improvement, especially with treating comorbid diagnoses, a disease or IMAGE:This is the cover of "Group Cognitive-Behavioral Therapy of Anxiety. A Transdiagnostic Treatment Manual, " by Peter J. Norton. Click here for more information. condition that co-exists with a primary disease and can stand on its own as a specific disease, like depression. "What I have learned from my past research is that if you treat your principal diagnosis, such as social phobia and you hate public speaking, you are going to show improvement on some of your secondary diagnosis. Your mood is going to get a little better, your fear of heights might dissipate. So there is some effect there, but what we find is when we approach things with a transdiagnostic approach, we see a much bigger impact on comorbid diagnoses," said Norton. "In my research study, over two-thirds of comorbid diagnoses went away, versus what we typically we find when I'm treating a specific diagnosis such as a panic disorder, where only about 40 percent of people will show that sort of remission in their secondary diagnosis. The transdiagnostic treatment approach is more efficient in treating the whole person rather than just treating the diagnosis, then treating the next diagnoses." Norton notes the larger contributions of the studies are to guide further development and interventions for how clinical psychologists, therapists and social workers treat people with anxiety disorders. The data collected will be useful for people out on the front lines to effectively and efficiently treat people to reduce anxiety disorders. ### Norton is the author of the book, "Group Cognitive-Behavioral Therapy of Anxiety. A Transdiagnostic Treatment Manual," and co-author of "The Anti-Anxiety Workbook: Proven Strategies to Overcome Worry, Phobias, Panic and Obsessions." He has authored more than 90 research papers on such topics as anxiety disorders, CBT and chronic pain, and he serves on the editorial boards of two scientific journals. He has received early career awards and research grants for his work on studying and treating anxiety from the National Institute of Mental Health, the University of Nebraska – Lincoln, UH, the Anxiety Disorders Association of America and the American Psychological Association. About the Anxiety Disorder Clinic The Anxiety Disorder Clinic (ADC) is a specialty treatment and research clinic at the University of Houston. The goal of the ADC is to help clients overcome their problems with anxiety without medication by using the most effective psychological therapies available. Both research opportunities and low-cost clinical services based on the latest scientific evidence are offered to individuals. For more information about research opportunities and clinical services at ADC, please call 713-743-8600 or visit the ADC website www.uh.edu/anxiety About the University of Houston The University of Houston is a Carnegie-designated Tier One public research university recognized by The Princeton Review as one of the nation's best colleges for undergraduate education. UH serves the globally competitive Houston and Gulf Coast Region by providing world-class faculty, experiential learning and strategic industry partnerships. Located in the nation's fourth-largest city, UH serves more than 39,500 students in the most ethnically and culturally diverse region in the country.

Uncontrollable anger prevalent among US youth

Intermittent Explosive Disorder affects up to 6 million US adolescents Nearly two-thirds of U.S. adolescents have experienced an anger attack that involved threatening violence, destroying property or engaging in violence toward others at some point in their lives. These severe attacks of uncontrollable anger are much more common among adolescents than previously recognized, a new study led by researchers from Harvard Medical School finds. The study, based on the National Comorbidity Survey Replication Adolescent Supplement, a national face-to-face household survey of 10,148 U.S. adolescents, found that nearly two-thirds of adolescents in the U.S. have a history of anger attacks. It also found that one in 12 young people—close to six million adolescents—meet criteria for a diagnosis of Intermittent Explosive Disorder (IED), a syndrome characterized by persistent uncontrollable anger attacks not accounted for by other mental disorders. The results will be published July 2 in Archives of General Psychiatry. IED has an average onset in late childhood and tends to be quite persistent through the middle years of life. It is associated with the later onset of numerous other problems, including depression and substance abuse, according to senior author Ronald Kessler, McNeil Family Professor of Health Care Policy at HMS and leader of the team that carried out the study. Yet only 6.5 percent of adolescents with IED received professional treatment for their anger attacks. Study findings indicate that IED is a severe, chronic, commonly occurring disorder among adolescents, one that begins early in life. Yet the study also shows that IED is under-treated: although 37.8 percent of youths with IED obtained treatment for emotional problems in the 12 months prior to the study interview, only 6.5 percent received treatment specifically for anger. The researchers argue for the importance of identifying and treating IED early, perhaps through school-based violence prevention programs. "If we can detect IED early and intervene with effective treatment right away, we can prevent a substantial amount of future violence perpetration and associated psychopathology," Kessler said. To be diagnosed with IED, an individual must have had three episodes of impulsive aggressiveness "grossly out of proportion to any precipitating psychosocial stressor," at any time in their life, according to the Diagnostic and Statistical Manual of Mental Disorders. The investigators used an even more stringent definition of IED, requiring that adolescents not meet criteria for other mental disorders associated with aggression, including bipolar disorder, attention-deficit/hyperactivity disorder, oppositional defiant disorder and conduct disorder. As a result, researchers found that 1 in 12 adolescents met criteria for IED Anger Management CE Course ### Collaboraters included Katie McLaughlin, an HMS assistant professor of pediatrics and psychology at Boston Children's Hospital, Jennifer Greif Green at Boston University School of Education, Alan Zaslavsky, an HMS professor of health care policy, as well as statistical programmer and data analyst Irving Hwang and Nancy Sampson, a project director at HMS. This research was funded by the National Institute of Mental Health (U01-MH60220 and R01-MH66627), the National Institute on Drug Abuse, the Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation and the John W. Alden Trust. Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School's Boston campus or in one of 47 hospital-based clinical departments at 16 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Cambridge Health Alliance, Children's Hospital Boston, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Exposure to violence has long-term stress effects among adolescents

UNIVERSITY PARK, Pa. -- Children who are exposed to community violence continue to exhibit a physical stress response up to a year after the exposure, suggesting that exposure to violence may have long-term negative health consequences, according researchers at Penn State and University College London. "We know that exposure to violence is linked with aggression, depression, post-traumatic stress symptoms and academic and cognitive difficulties in the short term, but little is known about the long-term effects of such exposure," said Elizabeth Susman, Jean Phillips Shibley Professor of Biobehavioral Health, Penn State. "Our data show that the stress reaction to violence exposure is not just immediate. There's an effect that endures." The scientists recruited 124 adolescents, ranging in age from 8 to 13 and living in small city and rural communities, to participate in the study social worker continuing education "Most studies of the effects of exposure to violence look at children who live in inner cities and urban communities," said Melissa Peckins, biobehavioral health graduate student, Penn State. "Our study is unique because we focused on children who live in small towns, so they are not children you would normally expect to be exposed to a lot of violence. Also, these were healthy children without a history of reported maltreatment." The researchers gave each of the adolescents a questionnaire, which identified their lifetime exposure to violence and exposure within the past 12 months. They then gave the adolescents the beginning of a story and asked them to complete it in front of two mock judges, whom they were told were evaluating their responses and performances for later comparison to those of other children the same age. Following the story-completion task, adolescents were also given a serial subtraction task. "The story completion task and mental arithmetic task are commonly used to elicit a stress response in laboratory settings," Peckins said. "Our hypothesis was that children who have been exposed to more violent events in the past year will have an attenuated response to the laboratory stressor -- even 12 months after the incidence -- compared with children who experienced fewer violent events." The team measured the children's stress responses by comparing the cortisol levels present in samples of their saliva collected before and after the stress test was administered. "In males, we found that as exposure to violence increased, cortisol reactivity decreased, so cortisol reactivity was attenuated; it was a habituation effect," Peckins said. The finding was not present in females. The results were published online in a recent issue of the Journal of Adolescent Health. "In enduring stressful conditions, we may have adapted evolutionarily to suppress our cortisol levels because higher and more prolonged levels of cortisol in the bloodstream can lead to negative health consequences, such as autoimmune disorders, lowered immunity, arthritis and atypical depression. This may explain why cortisol reactivity was lower for males," Susman said. "However, there is a theory that females may react to stressful situations by talking about it, which may be their way of reducing the negative effects of cortisol in the bloodstream. If parents and other adults are available to discuss episodes of violence with children, it might help the children, especially females, to reduce their cortisol levels." In the future, the team hopes to examine the role of duration of exposure to violence and time elapsed after exposure to violence on cortisol reactivity. ### Other researchers on this project were Samantha Dockray, research fellow, University College London, and Jacey Eckenrode, graduate student in biobehavioral health and Jodi Heaton, administrative assistant, biobehavioral health, both at Penn State. The National Institute of Mental Health, the General Clinical Research Center of the National Institutes of Health and Penn State supported this work.

Therapists phone it in and keep more patients

Telephone therapy retains more patients than face-to-face sessions and improves depression CHICAGO --- Phoning it in is more effective than the therapist's couch when it comes to keeping patients in psychotherapy. New Northwestern Medicine research shows patients who had therapy sessions provided over the phone were more likely to complete 18 weeks of treatment than those who had face-to-face sessions. The study, published in the June 6 issue of the Journal of the American Medical Association, is the first large trial to compare the benefits of face-to-face and telephone therapy. Phone therapy is a rapidly growing trend among therapists. About 85 percent of psychologists now deliver some of their services over the phone because competing demands, transportation time and other problems make it difficult for many patients to get to their offices social worker continuing education "Now therapists can make house calls," said David Mohr, the lead author and a professor of preventive medicine at Northwestern University Feinberg School of Medicine. "Our study found psychotherapy conveniently provided by telephone to patients wherever they are is effective and reduces dropout. This suggests these services now should be covered by insurance." While telephone therapy was as effective as face-to-face sessions in reducing depression during treatment, the improvement ebbed slightly six months after treatment ended compared to face-to-face therapy. The randomized control trial included 325 primary care patients with major depressive disorder. The results showed 20.9 percent of patients who had cognitive behavioral therapy over the phone dropped out compared to 32.7 percent for face-to-face therapy. Patients in both therapies showed equally good improvement in their depression when treatment ended. Six months after treatment ended, all patients remained much improved. However, patients who had the telephone therapy scored three points higher on a depression scale than those who had face-to-face sessions. "The three point difference is of questionable clinical significance but it raises the question whether some individuals are at risk of worsening after treatment with telephone therapy compared to face-to-face," Mohr said. It may be that the slight worsening seen in the telephone therapy after the end of treatment was because patients who had more mental health difficulties and who would have dropped out of face-to-face sessions were retained in telephone therapy, Mohr noted. Thus, this may not be a real finding. "But we can't rule out the possibility that it may be true and there is something about face-to-face treatment that creates better results for some people," Mohr said. "The physical presence of the therapist may be therapeutic in a way that helps some patients maintain their improvement in mood. There may be a unique quality about the human contact that increases resilience and maintains the skills learned to manage depression after treatment has ended." Mohr said he hopes the study results will encourage insurance providers including Medicare to reimburse telephone therapy sessions, which many companies currently don't cover. "There is good reason to reimburse these sessions," Mohr said. "Many people can't get to a therapist's office, but they want to talk to someone. Telephone therapy is highly effective and offers a solution to people with depression who otherwise would be left out." This is particularly true for disabled people or those who live where care is unavailable, such as in rural areas, he noted. Research shows people prefer talk therapy to antidepressant medication, but many quickly drop out of treatment or don't follow up on a referral from their primary care physicians, likely the result of obstacles that prevent them from getting to the therapist's office. ### Other Northwestern authors include: Joyce Ho, Jenna Duffecy, Michelle Nicole Burns, Ling Jin and Juned Siddique. This study was funded by the National Institute of Mental Health of the National Institutes of Health research grant NIMH R01-MH059708.

When being scared twice is enough to remember

One of the brain's jobs is to help us figure out what's important enough to be remembered. Scientists at Yerkes National Primate Research Center, Emory University have achieved some insight into how fleeting experiences become memories in the brain. Their experimental system could be a way to test or refine treatments aimed at enhancing learning and memory, or interfering with troubling memories. The results were published recently in the Journal of Neuroscience. The researchers set up a system where rats were exposed to a light followed by a mild shock. A single light-shock event isn't enough to make the rat afraid of the light, but a repeat of the pairing of the light and shock is, even a few days later. "I describe this effect as 'priming'," says the first author of the paper, postdoctoral fellow Ryan Parsons. "The animal experiences all sorts of things, and has to sort out what's important. If something happens just once, it doesn't register. But twice, and the animal remembers." Parsons was working with Michael Davis, PhD, Robert W. Woodruff professor of psychiatry and behavioral sciences at Emory University School of Medicine, who has been studying the molecular basis for fear memory for several years. Even though a robust fear memory was not formed after the first priming event, at that point Parsons could already detect chemical changes in the amygdala, part of the brain critical for fear responses. Long term memory formation could be blocked by infusing a drug into the amygdala. The drug inhibits protein kinase A, which is involved in the chemical changes Parsons observed. It is possible to train rats to become afraid of something like a sound or a smell after one event, Parsons says. However, rats are less sensitive to light compared with sounds or smells, and a relatively mild shock was used. Fear memories only formed when shocks were paired with light, instead of noise or nothing at all, for both the priming and the confirmation event. Parsons measured how afraid the rats were by gauging their "acoustic startle response" (how jittery they were in response to a loud noise) in the presence of the light, compared to before training began. Scientists have been able to study the chemical changes connected with the priming process extensively in neurons in culture dishes, but not as much in live animals. The process is referred to as "metaplasticity," or how the history of the brain's experiences affects its readiness to change and learn. "This could be a good model for dissecting the mechanisms involved in learning and memory," Parsons says. "We're going to be able to look at what's going on in that first priming event, as well as when the long-term memory is triggered." "We believe our findings might help explain how events are selected out for long-term storage from what is essentially a torrent of information encountered during conscious experience," Parsons and Davis write in their paper social worker ceus ### The research was supported by the National Institute of Mental Health (R37 MH047840 and F32 MH090700). Reference: R.G. Parsons and M. Davis. A metaplasticity-like mechanism supports the selection of fear memories: role of protein kinase A in the amygdala. J. Neurosci 32: 7843-7851 (2012).

Study identifies factors related to violence in veterans

CHAPEL HILL, N.C. – A national survey identifies which U.S. military veterans may be at most risk of aggression after deployment and what strategies could potentially help reduce likelihood of violence when service members return home counselor ceus The study examined protective factors that are important in preventing violence, including employment, meeting basic needs, living stability, social support, spiritual faith, ability to care for oneself, perceived self-determination, and resilience (ability to adapt to stress). Veterans with these factors in place were 92 percent less likely to report severe violence than veterans who did not endorse these factors. The majority of veterans (over three-quarters of those studied) did endorse most of these protective factors and thus posed a low threat of violence. These findings are reported in an article published June 25, 2012 in the Journal of Clinical Psychiatry of a National Institute of Mental Health-funded study led by Eric B. Elbogen, PhD, Research Director of the Forensic Psychiatry Program in the University of North Carolina School of Medicine and Psychologist in the U.S. Department of Veterans Affairs. "When you hear about veterans committing acts of violence, many people assume that post-traumatic stress disorder (PTSD) or combat exposure are to blame," Elbogen said. "But our study shows that is not necessarily true." The national survey revealed that other factors are just as important to understanding violence in veterans, including alcohol misuse, criminal background, as well as veterans' living, work, social, and financial circumstances. In fact, the survey found that veterans who didn't have enough money to cover basic needs were more likely to report aggressive behavior than veterans with PTSD. "Our study suggests the incidence of violence could be reduced by helping veterans develop and maintain protective factors in their lives back home," Elbogen said. The survey was conducted between July 2009 and April 2010. Responses were collected from 1,388 veterans who served in the Iraq and Afghanistan War era and theater after Sept. 11, 2001. The sample included veterans from all branches of the U.S. military and all 50 states. One-third of survey respondents self-identified committing an act of aggression towards others in the past year, most of which involved relatively minor aggressive behavior. Eleven percent of the sample reported more severe violence. Elbogen noted, "Although the majority of study participants did not report aggression, the potential for violence does remain a significant concern among a subset of returning veterans." Dr. Sally Johnson, co-author and Professor in the UNC Forensic Psychiatry Program, points out "Some veterans do not cope well with the loss of the structure, social, and financial support available in the military environment. Attention to helping veterans establish psychosocial stability in the civilian environment can help reduce post-deployment adjustment problems including aggression." ### The other co-authors H. Ryan Wagner, PhD, Virginia M. Newton, PhD Christine Timko, PhD, Jennifer J. Vasterling, PhD, and Jean C. Beckham, PhD are affiliated with the Department of Veterans Affairs.