Mapping Brain Circuits Provides Clues to Schizophrenia, Earlier Detection of Psychosis

Two regions in the brain have been linked to schizophrenia and psychosis, which may lead to earlier detection of this disorder and symptom, reported an imaging study funded by the National Institute of Mental Health (NIMH) that was published online last month in Biological Psychiatry. Background Patients with schizophrenia experience decreased activity in the prefrontal cortex ( blue, top figure) and excess activity in the basal ganglia (red, bottom figure). The greater the disconnect between these two regions, the higher the level of psychosis seen in these patients. Psychosis is a loss of contact with reality that usually includes false beliefs about what is taking place or who one is (delusions) and seeing or hearing things that aren’t there (hallucinations). Numerous medical problems can cause psychosis such as substance abuse, brain tumors, and certain mental disorders such as schizophrenia and bipolar disorder. Treatment approaches include hospitalization, antipsychotic drugs, and various psychosocial treatments. Too often, psychosis is not diagnosed or treated early enough. The longer this duration of untreated psychosis, the poorer the patient’s long-term functioning and response to treatment. In the United States, the average time between the first onset of psychotic symptoms and the initiation of treatment is about 110 weeks, or over 2 years. Disordered thinking and psychosis often go hand-in-hand in patients with the chronic brain disorder schizophrenia. A popular and long-standing theory in the field implicates the prefrontal cortex, the brain area just behind the forehead that normally supports higher-order capabilities such as prioritizing, categorizing, and strategizing. Damage to this area causes not only disordered thinking but also leads to psychosis from the excess release of the neurotransmitter dopamine into regions deep inside the brain. While this theory offers a compelling explanation for the co-occurrence of these two symptoms in schizophrenia, there have been only a small handful of studies that have directly supported this theory. Identification of the exact circuit(s) involved has so far remained elusive Professional Counselor Continuing Education “Schizophrenia is a very complex condition, involving a constellation of diverse symptoms. This diversity presents both a challenge and a constraint for figuring out the neurobiological root causes of schizophrenia. There is likely not just one lesion but a number of lesions that are present across different brain regions that are the proximal causes for these symptoms.” explained Jong H. Yoon, M.D., at the University of California, Davis, and lead author of the study. Yoon’s study focused on the prefrontal cortex and the basal ganglia. The basal ganglia is a subcortical collection of neuron clusters, including the ventral tegmental area and substantia nigra, which produce the majority of the brain’s dopamine, and the striatum, an important site of action of dopamine. Using functional magnetic resonance imaging (fMRI), the researchers examined the brain activity within the prefrontal cortex and basal ganglia of 18 individuals with schizophrenia and 19 healthy controls. The subjects completed a memory task in which they had to remember images of faces across a brief delay period to determine if subsequently presented faces were the same faces; it was hypothesized that patients with schizophrenia would have more difficulty performing this task. Results of the Study Patients with schizophrenia experienced excess activity in the substantia nigra, decreased activity in the prefrontal cortex, and diminished functional connectivity between these regions, suggesting that communication among these regions was out of sync. Additionally, the higher the level of connectivity between the substantia nigra and the striatum, the higher the level of psychosis seen in the patients with schizophrenia. Significance These findings suggest that the prefrontal cortex-basal ganglia circuit may be a common pathway linking cognitive deficits and psychosis in schizophrenia. It also points to a more widespread use of fMRI in diagnosis and treatment. Compared to other neuroimaging techniques such as positron emission tomography (PET), fMRI yields more detailed images, does not use radiation, and is relatively widely available since most university-based brain imaging centers have this technology. These findings could also lead to the creation of a better animal model of psychosis, of which there currently are few. Biomedical research has shown that early detection and intervention could preempt later stages of diseases. This concept of “treatment as prevention” is seen in the NIMH-supported North American Prodrome Longitudinal Study (NAPLS), which is using biological assessments, such as neuroimaging, to predict who will convert to psychosis and to develop new treatment and prevention approaches. Another NIMH study, Recovery After an Initial Schizophrenia Episode (RAISE), supports the development and testing of two complementary models for early intervention in schizophrenia. Research is also underway to identify genes and environmental elements associated with schizophrenia. What’s Next Because the study involved patients with established illness who are already on antipsychotic medications, it needs replication in patients with schizophrenia who are not medicated and/or in the early phases of illness. The study should also be performed in individuals at high risk of developing psychosis to see if these findings could help identify individuals in the earliest stages of illness when interventions to prevent or significantly ameliorate schizophrenia can be instituted. To obtain greater precision in localizing brain regions, the study also warrants replication with high-resolution fMRI. Furthermore, the techniques in this study could also be applied to other disorders that can have psychosis as one of its symptoms, such as mood disorders, and post-traumatic stress disorder. Reference Yoon JH, Minzenberg MJ, Raouf S, D’Esposito M, Carter CS. Impaired Prefrontal-Basal Ganglia Functional Connectivity and Substantia Nigra Hyperactivity in Schizophrenia. Biological Psychiatry, published online January 14, 2013.

Imaging Biomarker Predicts Response to Rapid Antidepressant

Signals Dysfunction in Brain System Targeted by Scopolamine – NIH Study A telltale boost of activity at the back of the brain while processing emotional information predicted whether depressed patients would respond to an experimental rapid-acting antidepressant, a National Institutes of Health study has found. NIMH’s Dr. Maura Furey talks about scopolamine research “We have discovered a potential neuroimaging biomarker that may eventually help to personalize treatment selection by revealing brain-based differences between patients,” explained Maura Furey, Ph.D., of NIH’s National Institute of Mental Health (NIMH). Furey, NIMH’s Carlos Zarate, M.D., and colleagues, reported on their functional magnetic resonance imaging (fMRI) study of a pre-treatment biomarker for the antidepressant response to scopolamine, Jan. 30, 2013, online in JAMA Psychiatry. Scopolamine, better known as a treatment for motion sickness, has been under study since Furey and colleagues discovered its fast-acting antidepressant properties in 2006. Unlike ketamine, scopolamine works through the brain’s acetylcholine chemical messenger system. The NIMH team’s research has demonstrated that by blocking receptors for acetylcholine on neurons, scopolamine can lift depression in many patients within a few days; conventional antidepressants typically take weeks to work. But not all patients respond, spurring interest in a predictive biomarker Alcoholism and Drug Abuse Counselors Continuing Education The acetylcholine system plays a pivotal role in working memory, holding information in mind temporarily, but appears to act by influencing the processing of information rather than through memory. Imaging studies suggest that visual working memory performance can be enhanced by modulating acetylcholine-induced activity in the brain’s visual processing area, called the visual cortex, when processing information that is important to the task. Since working memory performance can predict response to conventional antidepressants and ketamine, Furey and colleagues turned to a working memory task and imaging visual cortex activity as potential tools to identify a biomarker for scopolamine response. Depressed patients have a well-known tendency to process and remember negative emotional information. The researchers propose that this bias stems from dysregulated acetylcholine systems in some patients. They reasoned that such patients would show aberrant visual cortex activity in response to negative emotional features of a working memory task. They also expected to find that patients with more dysfunctional acetylcholine systems would respond better to scopolamine treatment. Before receiving scopolamine, participants performed a working memory task while their brain activity was monitored via fMRI. For some trials, it required that they pay attention to, and remember, the emotional expression (sad, happy, etc.) of faces flashing on a computer monitor. For other trials, they had to pay attention to only the identity, or non-emotional feature, of the faces. After scanning, and over the following several weeks, 15 patients with depression and 21 healthy participants randomly received infusions of a placebo (salt solution) and/or scopolamine. Mood changes were monitored with depression rating scales. Overall, scopolamine treatment reduced depression symptoms by 63 percent, with 11 of the patients showing a significant clinical response. The strength of this response correlated significantly with visual cortex activity during key phases of the working memory task – while participants were paying attention to the emotional content of the faces. There was no such correlation for trials when they attended to the identity of the faces. The findings suggest that acetylcholine system activity drives visual cortex activity that predicts treatment response – and that differences seen between depressed patients and controls may be traceable to acetylcholine dysfunction. Overall, patients showed lower visual cortex activity than controls during the emotion phase of the task. Patients showing activity levels most dissimilar to controls experienced the greatest antidepressant response to scopolamine treatment. Visual cortex activity in patients who didn’t respond to scopolamine more closely resembled that of controls. As hypothesized, the pretreatment level of visual cortex activity appears to reflect the extent of patients’ acetylcholine system dysfunction and to predict their response to the experimental medication, say the researchers. Preliminary evidence suggests that such visual cortex activity in response to emotional stimuli may also apply to other treatments and may prove to be a shared biomarker of rapid antidepressant response, according to Furey. The level of increased activity in left and right visual cortex (blue), while attending to emotional faces in a working memory task, predicted depressed patients’ responsiveness to the experimental antidepressant scopolamine. View from the back of the brain shows fMRI data superimposed on anatomical MRI scan data. Source: Maura Furey, Ph.D., NIMH Experimental Therapeutics and Pathophysiology Branch Working memory task: Over several trials, participants were required to attend to either the identity (non-emotional feature) or the emotion of a face, remember it during a 9 second delay, and match the feature to a subsequent face. Neural activity in the visual cortex elicited by the emotion trials predicted a patient’s subsequent responsiveness to scopolamine treatment. Source: Maura Furey, Ph.D., NIMH Experimental Therapeutics and Pathophysiology Branch References Potential of Pretreatment Neural Activity in the Visual Cortex During Emotional Processing to Predict Treatment Response to Scopolamine in Major Depressive Disorder. Furey ML, Drevets WC, Hoffman EM, Frankel E, Speer AM, Zarate CA. JAMA Psychiatry. 2013 Jan 30:1-11. doi: 10.1001/2013.jamapsychiatry.60. [Epub ahead of print] PMID:23364679 Cholinergic Modulation of Cognition and Emotion in Mood Disorders ### The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website. About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Astrocytes identified as target for new depression therapy

Tufts neuroscientists find that starry brain cells can be used to mimic sleep deprivation BOSTON (January 23, 2013) — Neuroscience researchers from Tufts University have found that our star-shaped brain cells, called astrocytes, may be responsible for the rapid improvement in mood in depressed patients after acute sleep deprivation. This in vivo study, published in the current issue of Translational Psychiatry, identified how astrocytes regulate a neurotransmitter involved in sleep. The researchers report that the findings may help lead to the development of effective and fast-acting drugs to treat depression, particularly in psychiatric emergencies. Drugs are widely used to treat depression, but often take weeks to work effectively. Sleep deprivation, however, has been shown to be effective immediately in approximately 60% of patients with major depressive disorders. Although widely-recognized as helpful, it is not always ideal because it can be uncomfortable for patients, and the effects are not long-lasting Marriage and Family Therapist Continuing Education During the 1970s, research verified the effectiveness of acute sleep deprivation for treating depression, particularly deprivation of rapid eye movement sleep, but the underlying brain mechanisms were not known. Most of what we understand of the brain has come from research on neurons, but another type of largely-ignored cell, called glia, are their partners. Although historically thought of as a support cell for neurons, the Phil Haydon group at Tufts University School of Medicine has shown in animal models that a type of glia, called astrocytes, affect behavior. Haydon's team had established previously that astrocytes regulate responses to sleep deprivation by releasing neurotransmitters that regulate neurons. This regulation of neuronal activity affects the sleep-wake cycle. Specifically, astrocytes act on adenosine receptors on neurons. Adenosine is a chemical known to have sleep-inducing effects. During our waking hours, adenosine accumulates and increases the urge to sleep, known as sleep pressure. Chemicals, such as caffeine, are adenosine receptor antagonists and promote wakefulness. In contrast, an adenosine receptor agonist creates sleepiness. "In this study, we administered three doses of an adenosine receptor agonist to mice over the course of a night that caused the equivalent of sleep deprivation. The mice slept as normal, but the sleep did not reduce adenosine levels sufficiently, mimicking the effects of sleep deprivation. After only 12 hours, we observed that mice had decreased depressive-like symptoms and increased levels of adenosine in the brain, and these results were sustained for 48 hours," said first author Dustin Hines, Ph.D., a post-doctoral fellow in the department of neuroscience at Tufts University School of Medicine (TUSM). "By manipulating astrocytes we were able to mimic the effects of sleep deprivation on depressive-like symptoms, causing a rapid and sustained improvement in behavior," continued Hines. "Further understanding of astrocytic signaling and the role of adenosine is important for research and development of anti-depressant drugs. Potentially, new drugs that target this mechanism may provide rapid relief for psychiatric emergencies, as well as long-term alleviation of chronic depressive symptoms," said Naomi Rosenberg, Ph.D., dean of the Sackler School of Graduate Biomedical Sciences and vice dean for research at Tufts University School of Medicine. "The team's next step is to further understand the other receptors in this system and see if they, too, can be affected." ### Senior author, Phillip G. Haydon, Ph.D., is the Annetta and Gustav Grisard professor and chair of the department of neuroscience at Tufts University School of Medicine (TUSM). Haydon is also a member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts. Additional authors are Luke I. Schmitt, B.S., a Ph.D. candidate in neuroscience at the Sackler School; Rochelle M. Hines, Ph.D., a post-doctoral fellow in the department of neuroscience at TUSM; and Stephen J. Moss, Ph.D., a professor of neuroscience at Tufts University School of Medicine and a member of the neuroscience program faculty at the Sackler School. Hines DJ, Schmitt LI, Hines RM, Moss SJ, Haydon PG. Translational Psychiatry. "Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling." (2013) 3, e212; doi:10.1038/tp.2012.136. Published online 15 January 2013. This research was supported by award number R01MH095385 from the National Institute of Mental Health, part of the National Institutes of Health, as well as by award number R01NS037585 from the National Institute of Neurological Disorders and Stroke, both of the National Institutes of Health. Dustin Hines was partially funded by the Heart and Stroke Foundation of Canada. Haydon is co-founder and president of GliaCure Inc., which has licensed a pending patent application filed by Tufts University claiming compounds that modulate the signaling cascades, and related methods of use, described in this paper. About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science. If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine or another Tufts health sciences researcher, please contact Siobhan Gallagher.

Brain Imaging Predicts Psychotherapy Success in Patients with Social Anxiety Disorder

Treatment for social anxiety disorder or social phobia has entered the personalized medicine arena—brain imaging can provide neuromarkers to predict whether traditional options such as cognitive behavioral therapy will work for a particular patient, reported a National Institute of Mental Health (NIMH)-funded study that was published in the January 2013 issue of JAMA Psychiatry. Background Social anxiety disorder (SAD)— the fear of being judged by others and humiliated— is the third most prevalent psychiatric disorder in Americans, after depression and alcohol dependence, according to the National Comorbidity Survey, a U.S. poll on mental health. This fear can be so strong that it interferes with daily life activities like going to work or school. If left untreated, some sufferers use alcohol, food, or drugs to reduce the fear at social events, which often leads to other disorders such as alcoholism, eating disorders, and depression. The NIMH claims that 6.8 percent of U.S. adults and 5.5 percent of 13- to 15-year-olds, the age of onset for this chronic disorder, are annually afflicted Social Worker Continuing Education Although psychotherapy and drugs, such as antidepressants and benzodiazepines, exist as treatments for SAD, current behavioral measures poorly predict which would work better for individual patients. “Half of social anxiety disorder patients have satisfactory response to treatment. There is little evidence about which patient would benefit from a particular form of treatment,” said John D. Gabrieli, Ph.D., lead author of the study. “Currently, there is no rational basis for prescribing one treatment over the other. Which treatment a patient gets depends on whom they see.” Enter personalized medicine, the use of genetic or other biological markers to tailor treatments to those who would actually benefit from them, thus sparing the expense and side effects for those who would not. Brain imaging could identify neuromarkers or targeted areas of the brain that could one day optimize treatment for individual patients. Neuromarkers are being used in other areas of mental illness, for instance, to predict the onset of psychosis in schizophrenia and the likelihood of relapse in drug addiction. In this study, Gabrieli, at the Massachusetts Institute of Technology in Cambridge, and his colleagues, used functional magnetic resonance imaging (fMRI) in 39 SAD patients before a 12-week course of cognitive behavioral therapy. The patients viewed angry versus neutral faces and scenes while undergoing fMRI examination (see first slide). Compared to neutral faces, angry faces convey disapproval and are likely to prompt excessive fear responses and negative connotations in SAD patients; cognitive behavioral therapy teaches these patients ways to downregulate their responses. The patients’ brain images were then compared to their scores on a conventional clinical measure, the Liebowitz Social Anxiety Scale (LSAS), a questionnaire which they took before and after therapy completion. Results of the Study SAD patients responded more to the images of faces and not scenes, which is characteristic for the social basis of this disorder. Patients whose brains reacted strongly to the facial images before treatment benefitted more from the therapy than those who reacted to these the least (see second slide). Specifically, changes in two occipitotemporal brain regions—areas involved in early processing of visual cues such as faces—correlated with positive cognitive behavioral therapy outcome. These neuromarkers predicted treatment outcome better than the currently used LSAS. Significance This study is the first of its kind to use neuroimaging to predict treatment response in SAD patients. Neuromarkers may become a practical clinical tool to guide the selection of optimal treatments for individual patients. Integration of neuromarkers with genetic, behavioral, and other biomarkers is likely to further refine the prediction. What’s Next A larger study comparing people with SAD with normal participants is needed to verify the results. fMRI studies using other facial expressions (disgust or fear) might be better predictors. Studies that look at other treatment options, such as drugs, are also needed to confirm which treatment is optimal. Researchers asked patients with social phobia to undergo functional magnetic resonance imaging (fMRI) while viewing images of neutral versus angry faces and scenes. The patients’ brains showed more activity when they viewed the faces. Source: Gabrieli Lab, MIT Patients with social phobia whose brains “lit” up the most, particularly in two regions towards the back of the brain that process what we see, responded the best to psychotherapy. Source: Gabrieli Lab, MIT Reference Doehrmann O, Ghosh SS, Polli FE, Reynolds GO, Horn F, Keshavan A, Triantafyllou C, Saygin ZM, Whitfield-Gabrieli S, Hofmann SG, Pollack M, Gabrieli JD. Predicting Treatment Response in Social Anxiety Disorder from Functional Magnetic Resonance Imaging. JAMA Psychiatry. January 2013. 70(1):87–97.

Paradox of aging: The older we get, the better we feel?

Presently, there are about 40 million Americans over the age of 65, with the fastest-growing segment of the population over 80 years old. Traditionally, aging has been viewed as a period of progressive decline in physical, cognitive and psychosocial functioning, and aging is viewed by many as the "number one public health problem" facing Americans today. But this negative view of aging contrasts with results of a comprehensive study of 1,006 older adults in San Diego by researchers from the University of California, San Diego School of Medicine and Stanford University. Results of the Successful Aging Evaluation (SAGE) study – comprising a 25-minute phone interview, followed by a comprehensive mail-in survey – will be published in the December 7 online issue of the American Journal of Psychiatry. "While there is a growing public health interest in understanding and promoting successful aging, until now little published research has combined measures of physical health with cognitive and psychological assessments, in a large and randomly selected sample," said principal investigator Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of UC San Diego's Stein Institute for Research on Aging, and the current President of the American Psychiatric Association (which was not involved in this study). The SAGE study included adults between the ages of 50 and 99 years, with a mean age of just over 77 years. In addition to measures which assessed rates of chronic disease and disability, the survey looked at more subjective criteria such as social engagement and participants' self-assessment of their overall health. "Sometimes the most relevant outcomes are from the perspective of the subjects themselves," said Jeste. The study concludes that resilience and depression have significant bearing on how individuals self-rate successful aging, with effects that are comparable to that of physical health. "Even though older age was closely associated with worse physical and cognitive functioning, it was also related to better mental functioning," said co-author Colin Depp, PhD, associate professor of psychiatry at UC San Diego School of Medicine. After adjusting for age, a higher self-rating of successful aging was associated with higher education, better cognitive function, better perceived physical and mental health, less depression, and greater optimism and resilience. Participants were asked to rate the extent to which they thought they had "successfully aged," using a 10-point scale and using their own concept of the term. The study found that people with low physical functioning but high resilience, had self-ratings of successful aging similar to those of physical healthy people with low resilience. Likewise, the self-ratings of individuals with low physical functioning but no or minimal depression had scores comparable to those of physically healthy people with moderate to severe depression. "It was clear to us that, even in the midst of physical or cognitive decline, individuals in our study reported feeling that their well-being had improved with age," Jeste said. This counterintuitive increase in well-being with aging persisted even after accounting for variables like income, education and marriage. Jeste suggests there's a take-away message for clinicians, which is that an optimistic approach to the care of seniors may help reduce societal ageism. "There is considerable discussion In public forums about the financial drain on the society due to rising costs of healthcare for older adults – what some people disparagingly label the 'silver tsunami.' But, successfully aging older adults can be a great resource for younger generations," he said. The findings point to an important role for psychiatry in enhancing successful aging in older adults. "Perfect physical health is neither necessary nor sufficient," Jeste said. "There is potential for enhancing successful aging by fostering resilience and treating or preventing depression." Aging and Long Term Care (Abridged) CE Course (3 hours) ### Additional contributors to this study include Gauri N. Savla, PhD, Wesley K. Thompson, PhD, Ipsit V. Vahia, MD, Danielle K. Glorioso, MSW, A'verria Sirkin Martin, PhD, Barton W. Palmer, PhD, David Rock, BA, and Shahrokh Golshan, PhD, UC San Diego; and Helena C. Kraemer, PhD, professor of biostatistics in psychiatry at Stanford University. This work was supported, in part, by NIMH grants T32 MH-019934 and P30 MH-066248, by NIH National Center for Research Support grant UL1 RR-031980, by the John A. Hartford Foundation, and by the Sam and Rose Stein Institute for Research on Aging.

Guide Offers a Blueprint for End-of-Life Conversation With Youth

Enlisting the advice of adolescents and young adults with serious illness, researchers at the National Institutes of Health have developed a guide to help young people and their families address issues surrounding end-of-life care. Voicing My CHOICES is the first guide designed to help adolescents and young adults express how they would like to be comforted, supported, and cared for in the course of serious illness, and how they would like to be remembered if they do not survive. The guide is aimed at helping families and health professionals open difficult conversations, and was written using language and questions tailored to the particular needs and preferences of young people. A paper in the November 2012 issue of the journal Pediatrics reported on a study in which young people with serious illnesses read and commented on pages from two existing advance care planning guides. The study found that adolescents and young adults do want to be involved in end-of-life planning. Almost all of the 52 participants in the study felt that having such a guide was helpful and important. Their comments on specific questions shaped the content of Voicing My CHOICES. Lori Wiener, Ph.D., director of the pediatric psychosocial support and research program at the National Cancer Institute, is lead author of the Pediatrics study and developed the prototype for Voicing My CHOICES that the young participants evaluated. She collaborated with Maryland Pao, M.D., clinical director of the National Institute of Mental Health, whose staff provides psychiatric consultation at NIH’s research hospital for patients of all ages with serious illness. Developing Voicing My CHOICES began with focus groups in which young people with serious illness endorsed the need for an advance care planning guide for persons their age. Out of this came a study, reported in 2008, in which a group of 20 adolescents and young adults living with cancer or perinatally acquired HIV disease were asked to read and evaluate the publication Five Wishes, an advanced directive for adults, along with additional topics identified during the focus groups. The study team used their feedback to create a new guide for young people called My Thoughts, My Wishes, My Voice. In the current study, youth reviewed pages from this publication and Five Wishes. Their comments were incorporated in the final Voicing My CHOICES. “Adolescents and young adults often stay silent, not sharing their fears—as they do not want to further upset their parents,” said Wiener. “And parents don’t bring up end-of-life issues for the same reasons.” The research studies showed, however, that teens and young adults are interested in these issues and value the opportunity to express their preferences. The guide also serves a developmental purpose. “At a stage of life where they would normally be seeking identity and a way to leave their mark on the world, they are in a situation where they can’t make decisions,” said Pao. Youth are concerned, she said, with how they will be cared for and remembered and, true to their age, about peer relationships. They want to be heard. Voicing My CHOICES includes questions about making medical care decisions and the types of life support a young person would or would not want. In response to comments, changes were made to make the language in Voices My CHOICES less technical, and to offer both yes/no and open-ended questions. Participants in the study endorsed a section in which they can indicate whether they would like to donate their body to science or have an autopsy, which speaks powerfully, said Wiener, to their sense of altruism and the need to find meaning in their experience Aging and Long Term Care CE Course “Adolescents and young adults can feel very frightened and alone when their bodies are no longer responding to medical interventions and decisions are being made around them,” said Wiener. “Allowing them to be involved in decisions, and to document how they wish to be remembered, enhances the trust in parent and medical provider relationships and provides them with the opportunity to give meaning to their life.” The product of a collaboration between clinical research teams representing two different areas of focus within NIH’s research hospital—pediatric oncology and psychiatry—Voicing My CHOICES can be used to help patients, families, caregivers, and health care providers. Voicing My CHOICES is available from Aging With Dignity (www.agingwithdignity.org), a nonprofit that provides the advanced directive document for adults, Five Wishes. References Wiener L, Zadeh S, Battles H, Baird K, Ballard E, Osherow J, Pao M. Allowing adolescents and young adults to plan their end-of-life care. Pediatrics. 2012 Nov;130(5):897-905. doi: 10.1542/peds.2012-0663. Epub 2012 Oct 8. Wiener L, Ballard E, Brennan T, Battles H, Martinez P, Pao M. How I wish to be remembered: the use of an advance care planning document in adolescent and young adult populations. Journal of Palliative Medicine. 2008 Dec;11(10):1309-13.

Emergency Department Suicide Screening Tool Accurately Predicts At Risk Youth

A set of four questions that takes emergency department nurses or physicians less than 2 minutes to administer can successfully identify youth at risk for attempting suicide, reported a study by National Institute of Mental Health (NIMH) researchers that was published in the December 2012 issue of the Archives of Pediatrics and Adolescent Medicine Aspira Continuing Education Online Courses Background Each year as many as 5 to 8 percent of U.S. children and young adults attempt suicide, according to the U.S. Centers for Disease Control and Prevention. In 2010, 4867 youths between ages 10 and 24 died by suicide, making it the second leading cause of death for people in this age group. Most individuals who die by suicide have visited a health care provider 3 months to 1 year before their death. Typically these patients saw an emergency department (ED) nurse and physician for some other health concern such as abdominal pain or headaches. These at-risk individuals often go unrecognized by ED staff who either lack the time or training to properly screen patients. The Joint Commission, a leading U.S.-based nonprofit healthcare accreditation organization, and the American Academy of Pediatrics have previously recommended the creation and use of suicide screening tools for adult and pediatric patient populations. To date there are no screening instruments to assess suicide risk in children and adolescents who visit EDs for medical or surgical reasons. “Many families use the emergency department as their sole contact in the healthcare system,” said Lisa M. Horowitz, Ph.D., M.P.H., lead author of the study. “Most people don’t show up to the emergency department and say ‘I want to kill myself.’ Rather they show up with physical complaints and do not discuss their suicidal thoughts. But studies have shown that if you ask directly, the majority will tell you. Nurses and physicians need to know what questions to ask.” Horowitz, a clinician and researcher with NIMH, and her colleagues developed a quick questionnaire that ED nurses and physicians could use to assess suicide risk among youth. Their study tested 17 candidate questions in 524 patients ages 10 to 21 years who visited one of three academically-affiliated pediatric EDs and had either psychiatric problems—suicidal ideation, intense anxiety, post-traumatic stress disorder—or medical/surgical concerns—gastrointestinal diseases, sickle cell anemia, cystic fibrosis. The questions—focusing on suicidal thoughts and behavior—were reviewed and revised by a panel of mental health clinicians, health services researchers, and survey specialists. The patients also completed one of two versions of the Suicidal Ideation Questionnaire (SIQ), the “gold standard,” 30-question suicide-screening tool that is used by pediatric and adolescent psychiatrists, but which is too long for ED visits and requires additional training. As part of the study’s safety plan, individuals whose responses indicated that they were at risk for attempting suicide were referred to mental health professionals—social workers, psychiatrists, psychologists—for further evaluation Suicide Prevention CE Course Results of the Study Of the 17 candidate questions, four (used as a set) stood out as having the most accuracy for predicting suicide attempts: current thoughts of being better off dead, current wish to die, current suicidal ideation, and history of suicide attempt. Positive responses to 1 or more of these 4 questions identified 97% of the youth at risk for suicide, regardless of whether these patients came in for psychiatric or general medical concerns. Based on results from the new questionnaire, 18.7% of the ED patients (98 of the 524) screened positive for suicide risk; most of whom had come to the ED with psychiatric concerns (84 of the 524). Elevated suicide risk was detected in 4.1% of the ED patients (14 of the 344) with medical/surgical concerns. Had it not been for the new screening tool, the suicide risk in these 14 patients most likely would have gone undetected. Significance The instrument based on these 4 questions, called the Ask Suicide-Screening Questions (ASQ), is the first time such a screen has been validated for pediatric and young adult patients evaluated in EDs for medical/surgical reasons. Although the number of these patients identified as high risk for suicide is small, the screen takes less than 2 minutes to administer. The tool is freely available and accessible online (pdf). What’s Next Additional research assessing the impact of suicidal screening in pediatric EDs on referral rates to mental health services and future suicidal behavior are needed. The accuracy of the ASQ among diverse demographic populations also needs examination. Additionally, a cost-benefit analysis for the screening tool is needed, as is research studying its use in other healthcare settings such as in-patient and out-patient care. Reference Horowitz LM, Bridge JA, Teach SJ, Ballard E, Klima J, Rosenstein DL, Wharff EA, Ginnis K, Cannon E, Joshi P, Pao M. Ask Suicide-Screening Questions (ASQ). A Brief Instrument for the Pediatric Emergency Department. Archives of Pediatrics and Adolescent Medicine. December 2012. 166(12):1170–1176.