Aging and gene expression -- possible links to autism and schizophrenia in offspring

Advanced paternal age has been associated with greater risk for psychiatric disorders, such as schizophrenia and autism. With an increase in paternal age, there is a greater frequency of certain types of mutations that contribute to these disorders in offspring. Mutations are changes in the genetic code. Recent research, however, looks beyond the genetic code to "epigenetic effects", which do not involve changes in the genes themselves, but rather in how they are expressed to determine one's characteristics. Such epigenetic changes in sperm, related to ageing, have been linked with psychiatric disorders in offspring. Maria Milekic, PhD, reported today, at the American College of Neuropsychopharmacology annual meeting in Hollywood Florida, that old mice have an epigenetic change ‒ a loss of DNA methylation at the locations where the genetic code starts being transcribed. DNA methylation is a biochemical process that plays an important regulatory role in development and disease. The work was done by a research team in the Department of Psychiatry at Columbia University. Offspring of old fathers showed the same deficit in DNA methylation, and they differed in their behavior from the offspring of the young fathers. They showed less exploratory activity and differed in the startle response and in habituation. Two groups, with 10 breeder mice per group, were tested. The breeders were either old (12 month) or young (3 month) males, each bred with two young (3 month) female mice. Then the behavior of the offspring was tested when they were 3 months old. DNA methylation also was tested in the young and old fathers' sperm, and brains of the offspring were tested for DNA methylation as well as gene expression. "We were interested in understanding the mechanism of the paternal age effect", said Dr. Milekic."The risk for schizophrenia increases 2-fold when a father is over 45 years of age, and the risk for autism increases 2-5-fold. It seemed unlikely that mutation alone could account for this. We therefore speculated that DNA methylation could provide an alternative mechanism." Not only did the offspring of the old fathers differ from their counterparts with young fathers in DNA methylation, they also showed significant differences in the expression of genes that have been implicated in autism spectrum disorders and that are known to regulate the development and function of the brain. These findings point to possible factors that can lead to autism spectrum disorders and schizophrenia, and ultimately may lead to more effective therapeutic interventions. With respect to studies in the immediate future, Dr. Milekic said,"We are trying to evaluate changes in different brain regions. Our studies before did not compare brain regions. Most of the genes that have altered expression are in the cerebellum. We are interested in how DNA methylation in the cerebellum is affected by paternal age." Social Worker CEUs ### The work was supported by grants from NIMH and the Simon Foundation to Jay Gingrich, MD, PhD, and a NARSAD Young Investigator Awa rd from the Brain and Behavior Research Foundation to Dr. Milekic.

Researchers identify dozens of new de novo genetic mutations in schizophrenia

Many newly discovered genes most active during fetal development New York, NY (October 3, 2012) — Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease. The study, the largest and most comprehensive of its kind, was published today in the online edition of the journal Nature Genetics. Although schizophrenia typically onsets during adolescence and early adulthood, many of the mutations were found to affect genes with higher expression during early-to-mid fetal development. Together, the findings show that both the function of the mutated gene and when the gene is expressed are critically important in determining the risk for schizophrenia. The findings inform epidemiologic studies showing that environmental factors, such as malnutrition or infections during pregnancy, can contribute to the development of schizophrenia. "Our findings provide a mechanism that could explain how prenatal environmental insults during the first and second trimester of pregnancy increase one's risk for schizophrenia," said study leader Maria Karayiorgou, MD, professor of psychiatry at CUMC, and acting chief, division of Psychiatric and Medical Genetics, New York State Psychiatric Institute. "Patients with these mutations were much more likely to have had behavioral abnormalities, such as phobias and anxiety in childhood, as well as worse disease outcome." In an earlier study of 53 families, the team of investigators found that spontaneous, or de novo, mutations — genetic errors that are present in patients but not in their parents — play a role in a substantial portion of sporadic cases of schizophrenia. The mutations were found in the part of the genome that codes for proteins, known as the exome. In the larger, current study, the researchers performed whole-exome sequencing on 231 patient "trios" from the United States and South Africa. Each trio consisted of a patient and both of his or her parents, who were unaffected by the disease. By comparing the exomes of the patients with those of their parents, the researchers were able to identify de novo rather than heritable, mutations that may contribute to schizophrenia. This is the first study of this scale to search for single nucleotide variations in the exomes of schizophrenia patients. Previous studies from the Columbia group and others searched for much larger genetic variations, such as gene deletions or duplications. The researchers identified many mutated genes with diverse functions. They also identified four new genes (LAMA2, DPYD, TRRAP, and VPS39) affected by recurrent de novo events within or across the two populations, a finding unlikely to have occurred by chance. The researchers estimate that several hundred loci (genetic locations) can contribute to the development of schizophrenia. "The chance that two patients have exactly the same mutation or combination of mutations is rather small" said Dr. Karayiorgou. "What is intriguing is that despite this variability, people with schizophrenia tend to have, more or less, the same phenotype—that is, the same clinical presentation. Our hypothesis is that many neural circuits are extremely important in schizophrenia and that these circuits are vulnerable to a number of influences. So, when any of the genes involved in these circuits are mutated, the end result is the same." According to the researchers, the challenge remains to identify the affected biological processes and neural circuits, and to determine how they are affected. "Although the genetics of schizophrenia are extremely complex, a coherent picture of the disease is beginning to emerge," said co-director of the study Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center. "Our studies show that dozens, and perhaps hundreds, of different spontaneous mutations can raise one's risk for schizophrenia. On the surface, this is daunting, but using these new findings to understand how these mutations affect the same neural circuits, including during early fetal development, raises hopes that it may be possible to develop effective prevention and treatment strategies for the disease." Social Worker CEUs The paper is titled, "De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia." The other contributors are Bin Xu (CUMC), Iuliana Ionita-Laza (CUMC), J. Louw Roos (University of Pretoria, Pretoria, South Africa), Braden Boone (Hudson Alpha Institute for Biotechnology, Huntsville, Ala.), Scarlet Woodrick (CUMC), Yan Sun (CUMC) and Shawn Levy (Hudson Alpha Institute for Biotechnology). The research was partially supported by National Institute of Mental Health grants MH061399 and MH077235 and the Lieber Center for Schizophrenia Research at Columbia University. The authors declare no financial conflict of interest. About Schizophrenia Contrary to popular belief, schizophrenia is not a split personality; it is a chronic, severe, and disabling brain disorder that affects just over one percent of the adult population and is characterized by loss of contact with reality (psychosis), hallucinations (usually, hearing voices), firmly held false beliefs (delusions), abnormal thinking, a restricted range of emotions (flattened affect) or inappropriate and disorganized behavior, social withdrawal, and diminished motivation. The disease often strikes in the early adult years, and although many individuals experience some recovery, many others experience substantial and lifelong disability. People with schizophrenia often have problems functioning in society and in relationships and are over-represented on disability rolls and among the homeless and imprisoned. The precise causes of schizophrenia are not known, but current research suggests a combination of hereditary and environmental factors. Fundamentally, however, it is a biologic problem (involving changes in the brain), not one caused by poor parenting or a mentally unhealthy environment. Since the causes of schizophrenia are not clear, treatments focus on eliminating disease symptoms. Treatments include antipsychotic medications and various psychosocial treatments. ### Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. www.cumc.columbia.edu Columbia Psychiatry is ranked among the best departments and psychiatric research facilities in the Nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a rich and productive collaborative relationship with physicians in various disciplines at Columbia University's College of Physicians and Surgeons. Columbia Psychiatry is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders. http://columbiapsychiatry.org/

Targeted Behavioral Therapy Can Effectively Control Tics in Adults with Tourette Syndrome

A comprehensive behavioral intervention is more effective than supportive therapy and education in helping adults control the tics associated with Tourette syndrome, according to an NIMH-funded study published in the August 2012 issue of the Archives of General Psychiatry. The study follows a previous study involving children with the disorder, which showed similar results. Background Tourette syndrome (TS) is a chronic neurological disorder associated with motor or vocal tics that can be disruptive and difficult to control. Tics begin in childhood, typically peak in early adolescence and often decrease by adulthood. For some adults, the tics persist and can be difficult to control. Many individuals with TS describe an unwanted urge or sensation prior to the tic that is relieved by performing the tic. TS is commonly treated with an antipsychotic medication such as pimozide or risperidone. But these medications rarely eliminate tics entirely and can cause troubling side effects such as weight gain and sedation. Because of these adverse side effects, many patients decline or discontinue use of these medications. Until now, few large-scale studies have examined the effectiveness of behavioral interventions for TS. A team of investigators from Massachusetts General Hospital/Harvard Medical School; Yale University; University of Texas Health Science Center at San Antonio; University of California, Los Angeles; the University of Wisconsin-Milwaukee; Johns Hopkins Medical Institutions; and the Tourette Syndrome Association tested the effectiveness of a Comprehensive Behavioral Intervention for Tics (CBIT), a therapy based on habit reversal training that includes two concepts: Tic-awareness training, which teaches how to recognize early signs that a tic is about to occur, and Competing-response training, which teaches how to engage in a voluntary behavior that is physically incompatible with the impending tic. For example, a person feeling an urge to jerk his or her shoulder may be taught to tense arm muscles while pushing the elbow against the torso (a competing response). This combination of awareness training and competing response training is intended to disrupt the cycle of premonitory urge and performance of the tic. The researchers randomized 122 adults at three research centers to either CBIT or a control treatment that included supportive therapy and education about TS. Each group received eight sessions over a 10-week period. Those who responded to therapy were assessed three months and six months after the end of the study period to determine if the therapy’s benefits persisted. Results of the Study Overall, 38 percent of patients receiving CBIT showed significant symptom improvement compared to 6 percent receiving the control treatment. The results complement the earlier CBIT study in children, which found that 52 percent of the children who received CBIT showed significant symptom improvement compared to 18.5 percent receiving the control treatment.

About 62.5 percent of those who responded to CBIT in the trial returned for follow-up assessments at three and six months. About 80 percent of the returning participants continued to show a positive response to CBIT, indicating the treatment has enduring benefits for a significant group. In comparison, about 50 percent of those who responded to the control treatment returned for post-treatment assessment, and only about 25 percent of those continued to show benefits after six months. Significance Given the limited medication options for treating TS and the adverse effects associated with the antipsychotic medications, CBIT provides an alternative treatment to manage tics in children and adults. However, the positive response among adults was lower than among the children. The researchers suggest that people with tics that persist into adulthood may have a more chronic form of the disorder that is more difficult to treat. What’s Next Future research focused on CBIT may uncover the role of behavioral learning in reducing the involuntary movements and tics associated with TS. In the meantime, the researchers are working with the Tourette Syndrome Association and the Centers for Disease Control and Prevention to disseminate this intervention by offering training workshops to clinicians around the country social worker ceus Reference Wilhelm S, Peterson AL, Piacentini J, Woods DW, Deckersbach T, Sukhodolsky DG, Chang S, Liu H, Dziura J, Walkup JT, Scahill L. Randomized trial of behavior therapy for adults with Tourette syndrome. Archives of General Psychiatry. 2012 August.

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).

UCLA study uncovers new tools for targeting genes linked to autism

Findings could lead to future therapeutic targets UCLA researchers have combined two tools – gene expression and the use of peripheral blood -- to expand scientists' arsenal of methods for pinpointing genes that play a role in autism. Published in the June 21 online edition of the American Journal of Human Genetics, the findings could help scientists zero in on genes that offer future therapeutic targets for the disorder. "Technological advances now allow us to rapidly sequence the genome and uncover dozens of rare mutations," explained principal investigator Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics and a professor of neurology at the David Geffen School of Medicine at UCLA. "But just because a particular genetic mutation is rare doesn't mean it's actually causing disease. We used a new approach to tease out potential precursors of autism from the occasional genetic glitch." Geschwind and his colleagues studied DNA contained in blood samples from 244 families with one healthy child and one child on the autism spectrum. The team used a hybrid method that blended tests that read the order of DNA bases with those that analyze gene expression, the process by which genes make cellular proteins. "Monitoring gene expression provides us with another line of data to inform our understanding of how autism develops," said Geschwind, who is also director of the Center for Autism Research and Treatment at the Semel Institute for Neuroscience and Behavior at UCLA. "Integrating this method with the sequencing of DNA bases expands our ability to find mutations leading to the disease." Gene expression offers a molecular signpost pointing scientists in the right direction by narrowing the field and highlighting specific areas of the genome. For example, if a gene is expressed at substantially higher or lower levels in a patient, researchers will review the patient's DNA to check if that gene has changed. "We found that we can use gene expression to help understand whether a rare mutation is causing disease or playing a role in disease development," said Geschwind. "A true mutation will alter a gene's sequence, modifying the protein or RNA it produces -- or preventing the gene from producing them entirely. "A gene mutation accompanied by a change in expression clues us to a hot spot on the genome and directs us where to look next," he added. "Not all mutations will influence gene expression, but this approach improves our ability to pinpoint those that do." The researchers used the combined method to prioritize gene targets that merit closer investigation, potentially explaining why one person develops autism and their sibling does not. Their search turned up new regions in the genome where genetic variations showed strong links to autism and altered expression patterns. Genes in these regions were more likely to be mutated in the autistic children than in their unaffected siblings. "When we looked at genes associated with nervous-system function we found significantly more genes were expressed at higher or lower levels in the children diagnosed with autism than we did in their siblings unaffected by the disorder," said Geschwind. Finally, the research team discovered that the DNA contained in peripheral blood can help shed light on diseases of the central nervous system. Brain cells and genes related to synaptic function are expressed in the blood, offering a window into gene expression. "Brain tissue from people with autism is not readily available for study, and some people are reluctant to use non-neural tissue in psychiatric disease," explained Geschwind. "But our study demonstrates that even peripheral blood can expand our knowledge of neurological disease." The team's next step will be to replicate their findings in a larger population. ### Autism is a complex brain disorder that strikes in early childhood. The condition disrupts a child's ability to communicate and develop social relationships and is often accompanied by acute behavioral challenges. Autism spectrum disorders are diagnosed in one in 110 children in the United States, affecting four times as many boys as girls. Diagnoses have expanded tenfold in the last decade. The research was supported by grants from the Simons Foundation, the National Institute of Mental Health (5R01 MH081754-04), the Wellcome Trust and Autism Speaks. Geschwind's coauthors included first author Rui Luo, Irina Voineagu, Lambertus Klei, Chaochao Cai, Jing Ou, Jennifer Lowe and Matthew State of UCLA; Stephan Sanders of Yale University; Ni Huang and Matthew Hurles of the Wellcome Trust Sanger Institute; and Su Chu and Bernie Devlin of Carnegie Mellon University. The UCLA Center for Autism Research and Treatment provides diagnosis, family counseling, clinical trials and treatment for patients with autism. UCLA is one of eight centers in the National Institutes of Health–funded Studies to Advance Autism Research and Treatment network and one of 10 original Collaborative Programs for Excellence in Autism social worker ceus

Agent Reduces Autism-like Behaviors in Mice

Press Release • April 25, 2012

Agent Reduces Autism-like Behaviors in Mice Boosts Sociability, Quells Repetitiveness – NIH Study National Institutes of Health researchers have reversed behaviors in mice resembling two of the three core symptoms of autism spectrum disorders (ASD). An experimental compound, called GRN-529, increased social interactions and lessened repetitive self-grooming behavior in a strain of mice that normally display such autism-like behaviors, the researchers say. GRN-529 is a member of a class of agents that inhibit activity of a subtype of receptor protein on brain cells for the chemical messenger glutamate, which are being tested in patients with an autism-related syndrome. Although mouse brain findings often don’t translate to humans, the fact that these compounds are already in clinical trials for an overlapping condition strengthens the case for relevance, according to the researchers. “Our findings suggest a strategy for developing a single treatment that could target multiple diagnostic symptoms,” explained Jacqueline Crawley, Ph.D., of the NIH’s National Institute of Mental Health (NIMH). “Many cases of autism are caused by mutations in genes that control an ongoing process – the formation and maturation of synapses, the connections between neurons. If defects in these connections are not hard-wired, the core symptoms of autism may be treatable with medications.” Crawley, Jill Silverman, Ph.D., and colleagues at NIMH and Pfizer Worldwide Research and Development, Groton, CT, report on their discovery April 25th, 2012 in the journal Science Translational Medicine. "These new results in mice support NIMH-funded research in humans to create treatments for the core symptoms of autism,” said NIMH director Thomas R. Insel, M.D. “While autism has been often considered only as a disability in need of rehabilitation, we can now address autism as a disorder responding to biomedical treatments." social worker ceus Crawley’s team followed-up on clues from earlier findings hinting that inhibitors of the receptor, called mGluR5, might reduce ASD symptoms. This class of agents – compounds similar to GRN-529, used in the mouse study – are in clinical trials for patients with the most common form of inherited intellectual and developmental disabilities, Fragile X syndrome, about one third of whom also meet criteria for ASDs. To test their hunch, the researchers examined effects of GRN-529 in a naturally occurring inbred strain of mice that normally display autism-relevant behaviors. Like children with ASDs, these BTBR mice interact and communicate relatively less with each other and engage in repetitive behaviors – most typically, spending an inordinate amount of time grooming themselves. Crawley’s team found that BTBR mice injected with GRN-529 showed reduced levels of repetitive self-grooming and spent more time around – and sniffing nose-to-nose with – a strange mouse. Moreover, GRN-529 almost completely stopped repetitive jumping in another strain of mice. “These inbred strains of mice are similar, behaviorally, to individuals with autism for whom the responsible genetic factors are unknown, which accounts for about three fourths of people with the disorders,” noted Crawley. “Given the high costs – monetary and emotional – to families, schools, and health care systems, we are hopeful that this line of studies may help meet the need for medications that treat core symptoms.” Reference: Silverman JL, Smith DG, Rizzo SJS, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley, JN. Negative allosteric modulation of the MGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. April 25, 2012, Science Translational Medicine.

Genetic manipulation boosts growth of brain cells linked to learning, enhances antidepressants

DALLAS -- UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants – meaning they needed lower doses of the drugs to affect 'mood' – and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in the Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain's hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain's synapses," said Dr. Parada, an elected member of the prestigious National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada's laboratory has published a series of studies that link the Nf1 gene – best known for mutations that cause tumors to grow around nerves – to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body's immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease social worker ceus

The current study's lead author is former graduate student Dr. Yun Li, now a postdoctoral researcher at the Massachusetts Institute of Technology. Other co-authors include Yanjiao Li, a research associate of developmental biology, Dr. Renée McKay, assistant professor of developmental biology, both of UT Southwestern, and Dr. Dieter Riethmacher of the University of Southampton in the United Kingdom.

The study was supported by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health. Dr. Parada is an American Cancer Society Research Professor.

This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at www.utsouthwestern.edu/receivenews

Pattern Recognition Technology May Help Predict Future Mental Illness in Teens

Pattern Recognition Technology May Help Predict Future Mental Illness in Teens


Source: NIMH

A technique combining computer-based pattern recognition and brain imaging data accurately distinguished teens at risk for mental disorders from those with low risk and may someday be useful in predicting risk in individuals, according to an NIMH-funded study published February 15, 2012, in the journal PLoS One.

Background

Research on risk for mental disorders generally describes risk factors that apply to groups. To date, no biological measures can accurately predict an individual’s risk of future mental disorders.

Mary Phillips, M.D., of the University of Pittsburgh School of Medicine, and colleagues evaluated the use of computer-based techniques that automatically find patterns in data—these techniques are collectively called machine learning—with functional magnetic resonance imaging (fMRI) data. The researchers obtained fMRI data from 32 teens, half of whom had at least one biological parent diagnosed with bipolar disorder and were therefore at genetic risk for future psychiatric disorders. The other half of teens had no history of mental disorders either personally or in their immediate families.

The teens’ brain activity was assessed as they identified the gender of actors depicting various emotional facial expressions (happy, fearful, or neutral) in a series of photographs. Previous research has linked various mental disorders, especially depression and bipolar disorder, with abnormal patterns of brain activity during this task. Based on this fMRI data, the researchers used machine learning to calculate each participant’s odds for future mental illness social worker ceus

The participants were also assessed clinically and with fMRI at the start of the study, and clinically assessed again about two years later, on average. Long-term follow up is ongoing, with successive face-to-face assessments occurring every other year.

Results

Machine learning combined with fMRI accurately identified most of the healthy teens at genetic risk of future mental disorders vs. healthy teens with low genetic risk. Four of the 16 at-risk teens were misidentified as having low risk.

At the two-year follow up, none of the at-risk teens had developed bipolar disorder, but six were diagnosed with major depression or an anxiety disorder. Among all the at-risk teens identified through machine learning, these six had received the highest odds for belonging to the at-risk group.

Three of the four at-risk teens misidentified as belonging to the low risk group at the start of the study remained healthy at the second assessment. Clinical information for the fourth teen was not available at the time of follow-up.

Significance

Though still a very preliminary study, according to the researchers, machine learning combined with fMRI shows promise for predicting individual risk of developing future mental disorders, especially in at-risk populations.

The ongoing follow-up may also yield further insights into the relationship between depression, anxiety disorders, and bipolar disorder. Many studies have shown that bipolar disorder is often preceded by depression or anxiety disorders, and that these disorders may affect the course of subsequent bipolar disorder.

What’s Next

Larger studies using machine learning and fMRI will help to better define the extent to which pattern recognition techniques can accurately identify people at risk for future mental disorders. Research in this area may also inform early treatment or prevention efforts.

Reference

Mourão-Miranda J, Oliveira L, Ladouceur CD, Marquand A, Brammer M, Birmaher B, Axelson D, Phillips ML. Pattern recognition and functional neuroimaging help to discriminate healthy adolescents at risk for mood disorders from low risk adolescents. PLoS One. 2012;7(2):e29482. Epub 2012 Feb 15. PubMed PMID: 22355302; PubMed Central PMCID: PMC3280237.

Related Funding: K01 MH083001-04; R01 MH060952-11

Thinking Globally to Improve Mental Health

Source: NASA Jet Propulsion Laboratory (NASA-JPL)
Mental health experts are calling for a greater world focus on improving access to care and treatment for mental, neurological, and substance use (MNS) disorders, as well as increasing discoveries in research that will enable this goal to be met.

The Grand Challenges in Global Mental Health Initiative, led by the National Institutes of Health and the Global Alliance for Chronic Diseases, has identified the top 40 barriers to better mental health around the world. Similar to past grand challenges, which focused on infectious diseases and chronic, noncommunicable diseases, this initiative seeks to build a community of funders dedicated to supporting research that will significantly improve the lives of people living with MNS disorders within the next 10 years.

Twenty-five of the specific challenges and the process used to derive them are described in an article that will be published on July 7, 2011, in the journal Nature.

"Participating in global mental health research is an enormous opportunity, a means to accelerate advances in mental health care for the diverse U.S. population, as well as an extension of our vision of a world where mental illnesses are prevented and cured," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), the NIH institute heading this effort.

According to the paper's authors, the disorders targeted by the Grand Challenges in Global Mental Health—for example, schizophrenia, depression, epilepsy, dementia, and alcohol dependence—collectively account for more years of life lost to poor health, disability, or early death than either cardiovascular disease or cancer. Yet, compared to illnesses like cardiovascular disease and cancer, there are far fewer effective treatments or preventive methods. In addition, interventions are not widely available to those who need them most.

In recognizing the need to address this imbalance, Pamela Collins, M.D., M.P.H., of the NIMH Office for Research on Disparities and Global Mental Health, and colleagues assembled an international panel of experts to identify research priorities using the Delphi method, a widely accepted consensus-building tool. The panel consisted of 422 experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, and represented more than 60 countries social worker ceus

Over the course of two months, NIMH staff pared the panel's initial list of 1,565 challenges down to 154, with input from a scientific advisory board. From this list, the expert panel selected the top 40, of which the top five challenges identified after the third and final round of ranking are:

Integrate screening and core packages of services into routine primary health care
Reduce the cost and improve the supply of effective medications
Improve children's access to evidence-based care by trained health providers in low- and middle-income countries
Provide effective and affordable community-based care and rehabilitation
Strengthen the mental health component in the training of all health care personnel.
These top five challenges were ranked according to the ability to reduce the burden of disease, ability to reduce inequalities in health and health care, length of time until results can be observed, and the ability for the topic to be researched effectively.

"Addressing these challenges could have far-reaching effects, including increasing access to services and ultimately, reducing the treatment gap associated with these disorders," said Dr. Collins.

The Grand Challenges in Global Mental Health Initiative is led by NIMH and the Global Alliance for Chronic Diseases, in partnership with the Wellcome Trust, the McLaughlin-Rotman Centre for Global Health, and the London School of Hygiene and Tropical Medicine. Other NIH components participating in the Grand Challenges in Global Mental Health include the Fogarty International Center; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

Reference
Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar A, on behalf of the Grand Challenges in Global Mental Health Scientific Advisory Board and Executive Committee. Grand Challenges in Global Mental Health. Nature. 2011 July 7. 474(7354):pp.

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.

Depressed Teens with History of Abuse Less Likely to Respond to Combination Treatment

Adolescents with treatment-resistant depression who have a history of abuse—especially physical abuse—are less likely to respond to combination treatment than to medication alone, according to data from the NIMH-funded Treatment of Resistant Depression in Adolescents (TORDIA) study. The new study was published in the March 2011 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Background
Although the relationship between childhood abuse and risk for depression or other mental disorder is well-established, few studies have examined whether a history of abuse may affect response to treatment, especially among adolescents. Some studies have suggested that a history of abuse is associated with a lower response to cognitive behavioral therapy (CBT), a type of psychotherapy that emphasizes problem-solving and behavior change social worker ceus

In the Treatment of Resistant Depression in Adolescents (TORDIA) study, teens whose depression had not improved after an initial course of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment were randomly assigned to one of four interventions for 12 weeks:

Switch to another SSRI—paroxetine (Paxil), citalopram (Celexa) or fluoxetine (Prozac)
Switch to a different SSRI plus CBT
Switch to venlafaxine (Effexor), a different type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
Switch to venlafaxine plus CBT
As reported in May 2010, about 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of the treatment to which they had initially been assigned. The risk for relapse remained high, however.

About 13 percent of TORDIA participants had a history of physical abuse, 17 percent had a history of sexual abuse, and 5 percent had a history of both. In this most recent study, Wael Shamseddeen, M.D., MPH, of Rosalind Franklin University of Medicine and Sciences in North Chicago, and colleagues examined the association between having a history of physical or sexual abuse and response to combination treatment among TORDIA participants.

Results of the Study
The researchers found that teens without a history of abuse had a higher response rate to combination therapy compared to medication-only therapy (63 percent vs. 37.6 percent). Those with a history of sexual abuse responded similarly to combination and medication-only therapy (48 percent vs. 42 percent). However, those with a history of physical abuse had a much lower response rate to combination therapy (18.4 percent) compared to medication-only (52.4 percent).

Significance
The researchers were unable to identify the specific mechanism that might affect response to combination therapy among teens with a history of physical abuse. They suggest that because abuse can affect a child's brain development, abused youth may need psychotherapeutic approaches that target trauma before engaging in traditional CBT designed to treat depression. The researchers also suggest that abused youth may have a tendency to avoid unpleasant emotions, and therefore may have been averse to CBT. It is possible that therapeutic approaches that focus more on behavior and do not rely heavily on the processing of negative thoughts and emotions may be more acceptable and effective for these youth.

What's Next
The researchers concluded that more research is needed into the ways in which abuse history can confer treatment resistance among teens with hard-to-treat depression, and in developing alternative treatment approaches that are more effective.

Reference
Shamseddeen W, Asarnow JR, Clarke G, Vitiello B, Wagner KD, Birmaher B, Keller MB, Emslie G, Iyengar S, Ryan ND, McCracken JT, Porta G, Mayes T, Brent D. Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescents Study (TORDIA). Journal of the American Academy of Child and Adolescent Psychiatry. 2011 March. 50(3):293-301.

Share |

Cognitive Behavioral Therapy for Eating Disorders

Psychiatr Clin North Am. 2010 September; 33(3): 611–627.
doi: 10.1016/j.psc.2010.04.004. PMCID: PMC2928448

Cognitive Behavioral Therapy for Eating Disorders
Rebecca Murphy, Suzanne Straebler, Zafra Cooper, and Christopher G. Fairburn
Department of Psychiatry, Warneford Hospital, Warneford Lane, Oxford University, Oxford OX3 7JX, UK
redistributed and reused, subject to certain conditions.
This document was posted here by permission of the publisher. At the time of the deposit, it included all changes made during peer review, copy editing, and publishing. The U. S. National Library of Medicine is responsible for all links within the document and for incorporating any publisher-supplied amendments or retractions issued subsequently. The published journal article, guaranteed to be such by Elsevier, is available for free, on ScienceDirect, at: http://dx.crossref.org/10.1016/j.psc.2010.04.004AbstractCognitive behavioral therapy (CBT) is the leading evidence-based treatment for bulimia nervosa. A new “enhanced” version of the treatment appears to be more potent and has the added advantage of being suitable for all eating disorders, including anorexia nervosa and eating disorder not otherwise specified. This article reviews the evidence supporting CBT in the treatment of eating disorders and provides an account of the “transdiagnostic” theory that underpins the enhanced form of the treatment. It ends with an outline of the treatment's main strategies and procedures.Keywords: Cognitive behavioral therapy, Eating disorders, Anorexia nervosa, Bulimia nervosa Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferences The eating disorders provide one of the strongest indications for cognitive behavioral therapy (CBT). Two considerations support this claim. First, the core psychopathology of eating disorders, the overevaluation of shape and weight, is cognitive in nature. Second, it is widely accepted that CBT is the treatment of choice for bulimia nervosa1 and there is evidence that it is as effective with cases of “eating disorder not otherwise specified” (eating disorder NOS),2 the most common eating disorder diagnosis. This article starts with a description of the clinical features of eating disorders and then reviews the evidence supporting cognitive behavioral treatment. Next, the cognitive behavioral account of eating disorders is presented and, last, the new “transdiagnostic” form of CBT is described. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesEating disorders and their clinical featuresClassification and Diagnosis
Eating disorders are characterized by a severe and persistent disturbance in eating behavior that causes psychosocial and, sometimes, physical impairment. The DSM-IV classification scheme for eating disorders recognizes 2 specific diagnoses, anorexia nervosa (AN) and bulimia nervosa (BN), and a residual category termed eating disorder NOS.3The diagnosis of anorexia nervosa is made in the presence of the following features:
1. The overevaluation of shape and weight; that is, judging self-worth largely, or even exclusively, in terms of shape and weight. This has been described in various ways and is often expressed as strong desire to be thin combined with an intense fear of weight gain and fatness.
2. The active maintenance of an unduly low body weight. This is commonly defined as maintaining a body weight less than 85% of that expected or a body mass index (BMI; weight kg/height m2 or weight lb/[height in]2 × 703) of 17.5 or less.
3. Amenorrhea, in postpubertal females not taking an oral contraceptive.
The unduly low weight is pursued in a variety of ways with strict dieting and excessive exercise being particularly prominent. A subgroup also engages in episodes of binge eating and/or “purging” through self-induced vomiting or laxative misuse.For a diagnosis of bulimia nervosa 3 features need to be present:
1. Overevaluation of shape and weight, as in anorexia nervosa.
2. Recurrent binge eating. A “binge” is an episode of eating during which an objectively large amount of food is eaten for the circumstances and there is an accompanying sense of loss of control.
3. Extreme weight-control behavior, such as recurrent self-induced vomiting, regular laxative misuse, or marked dietary restriction.
In addition, the diagnostic criteria for anorexia nervosa should not be met. This “trumping rule” ensures that patients do not receive both diagnoses at one time.There are no positive criteria for the diagnosis of eating disorder NOS. Instead, this diagnosis is reserved for eating disorders of clinical severity that do not meet the diagnostic criteria of AN or BN. Eating disorder NOS is the most common eating disorder encountered in clinical settings constituting about half of adult outpatient eating-disordered samples, with patients with bulimia nervosa constituting about a third, and the rest being cases of anorexia nervosa.4 In inpatient settings the great majority of cases are either underweight forms of eating disorder NOS or anorexia nervosa.5In addition, DSM-IV recognizes “binge eating disorder” (BED) as a provisional diagnosis in need of further study. The criteria for BED are recurrent episodes of binge eating in the absence of extreme weight-control behavior. It is proposed that BED be recognized as a specific eating disorder in DSM-V.6Clinical Features
Anorexia nervosa, bulimia nervosa, and most cases of eating disorder NOS share a core psychopathology: the overevaluation of the importance of shape and weight and their control. Whereas most people judge themselves on the basis of their perceived performance in a variety of domains of life (such as the quality of their relationships, their work performance, their sporting prowess), for people with eating disorders self-worth is dependent largely, or even exclusively, on their shape and weight and their ability to control them. This psychopathology is peculiar to the eating disorders (and to body dysmorphic disorder).In anorexia nervosa, patients become underweight largely as a result of persistent and severe restriction of both the amount and the type of food that they eat. In addition to strict dietary rules, some patients engage in a driven form of exercising, which further contributes to their low body weight. Patients with anorexia nervosa typically value the sense of control that they derive from undereating. Some practice self-induced vomiting, laxative and/or diuretic misuse, especially (but not exclusively) those who experience episodes of loss of control over eating. The amount of food eaten during these “binges” is often not objectively large; hence, they are described as “subjective binges.” Many other psychopathological features tend to be present, some as a result of the semistarvation. These include depressed and labile mood, anxiety features, irritability, impaired concentration, loss of libido, heightened obsessionality and sometimes frank obsessional features, and social withdrawal. There are also a multitude of physical features, most of which are secondary to being underweight. These include poor sleep, sensitivity to the cold, heightened fullness, and decreased energy.Patients with bulimia nervosa resemble those with anorexia nervosa both in terms of their eating habits and methods of weight control. The main feature distinguishing these 2 groups is that in patients with bulimia nervosa attempts to restrict food intake are regularly disrupted by episodes of (objective) binge eating. These episodes are often followed by compensatory self-induced vomiting or laxative misuse, although there is also a subgroup of patients who do not purge (nonpurging bulimia nervosa). As a result of the combination of undereating and overeating the weight of most patients with bulimia nervosa tends to be unremarkable and is within the healthy range, BMI = 20–25. Features of depression and anxiety are prominent in these patients. Certain of these patients engage in self-harm and/or substance and alcohol misuse and may attract the diagnosis of borderline personality disorder. Most have few physical complaints, although electrolyte disturbance may occur in those who vomit or take laxatives or diuretics frequently.The clinical features of patients with eating disorder NOS closely resemble those seen in anorexia nervosa and bulimia nervosa and are of comparable duration and severity.7 Within this diagnostic grouping 3 subgroups may be distinguished, although there are no sharp boundaries among them. The first group consists of cases that closely resemble anorexia nervosa or bulimia nervosa but just fail to meet the threshold set by the diagnostic criteria (eg, binge eating may not be frequent enough to meet criteria for BN or weight may be just above the threshold in AN); the second and largest subgroup comprises cases in which the features of AN and BN occur in different combinations from that seen in the prototypic disorders—these states may be best viewed as “mixed” in character—and the third subgroup comprises those with binge-eating disorder. Most patients with binge-eating disorder are overweight (BMI = 25–30) or meet criteria for obesity (BMI ≥ 30). Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesThe empirical status of cognitive behavioral therapy for eating disordersConsistent with the current way of classifying eating disorders, the research on their treatment has focused on the particular disorders in isolation. Wilson and colleagues8 have provided a narrative review of the studies of the treatment of the 2 specific eating disorders as well as eating disorder NOS, and an authoritative meta-analysis has been conducted by the UK National Institute for Health and Clinical Excellence (NICE).1 This systematic review is particularly rigorous and, as with all NICE reviews, it forms the basis for evidence-based guidelines for clinical management.The conclusion from the NICE review, and 2 other recent systematic reviews,9,10 is that cognitive behavioral therapy (CBT-BN) is the clear leading treatment for bulimia nervosa in adults. However, this is not to imply that CBT-BN is a panacea, as the original version of the treatment resulted in only fewer than half of the patients who completed treatment making a full and lasting recovery.8 The new “enhanced” version of the treatment (CBT-E) appears to be more effective.2Interpersonal psychotherapy (IPT) is a potential evidence-based alternative to CBT-BN in patients with bulimia nervosa and it involves a similar amount of therapeutic contact, but there have been fewer studies of it.11,12 IPT takes 8 to 12 months longer than CBT-BN to achieve a comparable effect. Antidepressant medication (eg, fluoxetine at a dose of 60 mg daily) has also been found to have a beneficial effect on binge eating in bulimia nervosa but not as great as that obtained with CBT-BN and the long-term effects remain largely untested.13 Combining CBT-BN with antidepressant medication does not appear to offer any clear advantage over CBT-BN alone.13 The treatment of adolescents with bulimia nervosa has received relatively little research attention to date.There has been much less research on the treatment of anorexia nervosa. Most of the studies suffer from small sample sizes and some from high rates of attrition. As a result, there is little evidence to support any psychological treatment, at least in adults. In adolescents the research has focused mainly on family therapy, with the result that the status of CBT in younger patients is unclear.Preliminary findings have been reported from a 3-site study of the use of the enhanced form of CBT (CBT-E) to treat outpatients with anorexia nervosa.14 This is the largest study of the treatment of anorexia nervosa to date. In brief, it appears that the treatment can be used to treat about 60% of outpatients with the disorder (BMI 15.0 to 17.5) and that in these patients about 60% have a good outcome. Interestingly and importantly the relapse rate appears low.There is a growing body of research on the treatment of binge-eating disorder. This research has been the subject of a recent narrative review15 and several systematic reviews.1,16,17 The strongest support is for a form of CBT similar to that used to treat BN (CBT-BED). This treatment has been found to have a sustained and marked effect on binge eating, but it has little effect on body weight, which is typically raised in these patients. Arguably the leading first-line treatment is a form of guided cognitive behavioral self-help as it is relatively simple to administer and reasonably effective.18Until recently, there had been almost no research on the treatment of forms of eating disorder NOS other than binge-eating disorder despite their severity and prevalence.7 However, recently the first randomized controlled trial of the enhanced form of CBT found that CBT-E was as effective for patients with eating disorder NOS (who were not significantly underweight; BMI >17.5) as it was for patients with bulimia nervosa with two-thirds of those who completed treatment having a good outcome.2In summary, CBT is the treatment of choice for bulimia nervosa and for binge-eating disorder with the best results being obtained with the new “enhanced” form of the treatment. Recent research provides support for the use of this treatment with patients with eating disorder NOS and those with anorexia nervosa.The remainder of this article provides a description of this transdiagnostic form of CBT. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesThe cognitive behavioral account of eating disordersAlthough the DSM-IV classification of eating disorders encourages the view that they are distinct conditions, each requiring their own form of treatment, there are reasons to question this view. Indeed, it has recently been pointed out that what is most striking about the eating disorders is not what distinguishes them but how much they have in common.19 As noted earlier, they share many clinical features, including the characteristic core psychopathology of eating disorders: the overevaluation of the importance of shape and weight. In addition, longitudinal studies indicate that most patients migrate among diagnoses over time.20 This temporal movement among diagnostic categories, together with the shared psychopathology, has led to the proposal that there may be limited utility in distinguishing among the disorders19 and furthermore that common “transdiagnostic” mechanisms may be involved in their maintenance.The transdiagnostic cognitive behavioral account of the eating disorders19 extends the original theory of bulimia nervosa21 to all eating disorders. According to this theory, the overevaluation of shape and weight and their control is central to the maintenance of all eating disorders. Most of the other clinical features can be understood as resulting directly from this psychopathology. It results in dietary restraint and restriction; preoccupation with thoughts about food and eating, weight and shape; the repeated checking of body shape and weight or its avoidance; and the engaging in extreme methods of weight control. The one feature that is not a direct expression of the core psychopathology is binge eating. This occurs in all cases of bulimia nervosa, many cases of eating disorder NOS, and some cases of anorexia nervosa. The cognitive behavioral account proposes that such episodes are largely the result of attempts to adhere to multiple extreme, and highly specific, dietary rules. The repeated breaking of these rules is almost inevitable and patients tend to react negatively to such dietary slips, generally viewing them as evidence of their poor self-control. They typically respond by temporarily abandoning their efforts to restrict their eating with binge eating being the result. This in turn maintains the core psychopathology by intensifying patients' concerns about their ability to control their eating, shape, and weight. It also encourages more dietary restraint, thereby increasing the risk of further binge eating.Three further processes may also maintain binge eating. First, difficulties in the patient's life and associated mood changes make it difficult to maintain dietary restraint. Second, as binge eating temporarily alleviates negative mood states and distracts patients from their difficulties, it can become a way of coping with such problems. Third, in patients who engage in compensatory purging, the mistaken belief in the effectiveness of vomiting and laxative misuse as a means of weight control results in a major deterrent against binge eating being removed.In patients who are underweight, the physiological and psychological consequences may also contribute to the maintenance of the eating disorder. For example, delayed gastric emptying leads to feelings of fullness even after patients have eaten only modest amounts of food. In addition, the social withdrawal and loss of previous interests prevent patients from being exposed to experiences that might diminish the importance they place on shape and weight.The composite “transdiagnostic” formulation is shown in Fig. 1. This illustrates the core processes that are hypothesized to maintain the full range of eating disorders. When applied to individual patients, its precise form will depend on the psychopathology present. In some patients, most of the processes are in operation (for example, in cases of anorexia nervosa binge-purge subtype) but in others only a few are active (for example, in binge-eating disorder). Thus, for each patient the formulation is driven by their individual psychopathology rather than their DSM diagnosis. As such, the formulation provides a guide to those processes that need to be addressed in treatment. Fig. 1
The composite “transdiagnostic” cognitive behavioral formulation.

Fig. 1The composite “transdiagnostic” cognitive behavioral formulation. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesEnhanced cognitive behavioral therapy“Enhanced” cognitive behavioral therapy (CBT-E) is based on the transdiagnostic theory outlined earlier and was derived from CBT-BN. It is designed to treat eating disorder psychopathology rather than an eating disorder diagnosis, with its exact form in any particular case depending on an individualized formulation of the processes maintaining the disorder. CBT-E is designed to be delivered on an individual basis to adult patients with any eating disorder of clinical severity who are appropriate to treat on an outpatient basis. It is described as “enhanced” because it uses a variety of new strategies and procedures to improve outcome and because it includes modules to address certain obstacles to change that are “external” to the core eating disorder, namely clinical perfectionism, low self-esteem, and interpersonal difficulties.There are 2 forms of CBT-E. The first is the “focused” form (CBT-Ef) that exclusively addresses eating disorder psychopathology. Current evidence suggests that this form should be viewed as the “default” version, as it is optimal for most patients with eating disorders.2 The second, a broad form of the treatment (CBT-Eb), addresses external obstacles to change, in addition to the core eating disorder psychopathology. Preliminary evidence suggests that this more complex form of CBT-E should be reserved for patients in whom clinical perfectionism, core low self-esteem, or interpersonal difficulties are pronounced and maintaining the eating disorder.2There are also 2 intensities of CBT-E. With patients who are not significantly underweight (BMI above 17.5), it consists of 20 sessions over 20 weeks. This version is suitable for the great majority of adult outpatients. For patients who have a BMI below 17.5, a commonly used threshold for anorexia nervosa, treatment involves 40 sessions over 40 weeks. The additional sessions and treatment duration are designed to allow sufficient time for 3 additional clinical features to be addressed, namely, limited motivation to change, undereating, and being underweight.In addition CBT-E has been adapted for younger patients22 and for inpatient and day patient settings treatment.23,24 Limitations on space preclude a description of these other forms of CBT-E. Further details of these adaptations of CBT-E, together with a comprehensive account of the treatment and its implementation, can be found in the main treatment guide.25 Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesAn overview of the core aspects of treatmentCBT-E is a form of cognitive behavioral therapy and in common with other empirically supported forms of CBT it focuses primarily on the maintaining processes, in this case those maintaining the eating disorder psychopathology. It uses specified strategies and a flexible series of sequenced therapeutic procedures to achieve both cognitive and behavioral changes. The style of treatment is similar to other forms of CBT, that of collaborative empiricism. Although CBT-E uses a variety of generic cognitive and behavioral interventions (such as addressing cognitive biases), unlike some forms of CBT, it favors the use of strategic changes in behavior to modify thinking rather than direct cognitive restructuring. The eating disorder psychopathology may be likened to a house of cards with the strategy being to identify and remove the key cards that are supporting the eating disorder, thereby bringing down the entire house. Following, we summarize the core features of the focused and broad versions of CBT-E, including adaptations that need to be made for patients who are underweight. The treatment has 4 defined stages. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesPreparation for treatment and changeAn evaluation interview assessing the nature and extent of the patient's psychiatric problems is conducted before starting treatment.26 This interview usually takes place over 2 or more appointments. The assessment process is collaborative and designed to put the patient at ease and begin to engage the patient in treatment and in change. Information from the assessment informs how best to proceed and, in particular, whether CBT-E is appropriate. If CBT-E is deemed to be appropriate, the main aspects of the therapy are described and patients are encouraged to make the most of the opportunity to overcome their eating disorder.It is important that from the outset of CBT-E the patient is in a position to make optimum use of treatment. For this reason any potential barriers to benefiting from CBT-E should be explored. Important contraindications to beginning treatment immediately are physical features of concern, the presence of severe clinical depression, significant substance abuse, major distracting life events or crises, and competing commitments. Such factors should be addressed first before embarking on treatment. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesStage oneIt is crucial that treatment starts well. This is consistent with evidence that the magnitude of change achieved early in treatment is a good predictor of treatment outcome.27,28 This initial intensive stage, designed to achieve initial therapeutic momentum, involves approximately 8 sessions held twice weekly over 4 weeks. The aims of this first stage are to engage the patient in treatment and change, to derive a personalized formulation (case conceptualization) with the patient, to provide education about treatment and the disorder, and to introduce and implement 2 important procedures: collaborative “weekly weighing” and “regular eating.” The changes made in this first stage of treatment form the foundation on which other changes are built.Engaging the Patient in Treatment and Change
Many patients with eating disorders are ambivalent about treatment and change. Getting patients “on board” with treatment is a necessary first step. Engagement can be enhanced by conducting the assessment of the eating disorder in a way that helps the patient to become involved in, and hopeful about, the possibility of change and encourages the patient to take “ownership” of treatment.Jointly Creating the Formulation
This is usually done in the first treatment session and is a personalized visual representation of the processes that appear to be maintaining the eating problem. The therapist draws out the relevant sections of Fig. 1 in collaboration with the patient, incorporating the patient's own experiences and words. It is usually best to start with something the patient wishes to change (eg, binge eating). The formulation helps patients to realize both that their behavior is comprehensible and that it is maintained by a series of interacting self-perpetuating mechanisms that are open to change. It is explained that “the diagram” provides a guide to what needs to be targeted in treatment if patients are to achieve a full and lasting recovery. At this early stage in treatment the therapist should explain that it is provisional and may need to be modified as treatment progresses and understanding of the patient's eating problem increases.Establishing Real-time Self-monitoring
This is the ongoing “in-the-moment” recording of eating and other relevant behavior, thoughts, feelings, and events (Fig. 2 is an example of a monitoring record). Self-monitoring is introduced in the initial session and continues to occupy an essential and central role throughout most of treatment. Therapists should clearly explain the reasons for self-monitoring. First, that it enables further understanding of the eating problem and it identifies progress. Second, and more importantly, it helps patients to be more aware of what is happening in the moment so that they can begin to make changes to behavior that may have seemed automatic or beyond their control. Fundamental to establishing accurate recording is jointly reviewing the patient's records each session and discussing the process of recording and any difficulties with this. The records also help inform the agenda for the session: it is best to save any problems identified in the records for the main part of the session. Fig. 2
An example monitoring record.

Fig. 2An example monitoring record.Establishing Collaborative “Weekly Weighing”
The patient and therapist check the patient's weight once a week and plot it on an individualized weight graph. Patients are strongly encouraged not to weigh themselves at other times. Weekly in-session weighing has several purposes. First, it provides an opportunity for the therapist to educate patients about body weight and help patients to interpret the numbers on the scale, which otherwise they are prone to misinterpret. Second, it provides patients with accurate data about their weight at a time when their eating habits are changing. Third, and most importantly, it addresses the maintaining processes of excessive body weight checking or its avoidance.Providing Education
From session 1 onward, an important element of treatment is education about weight and eating, as many patients have misconceptions that maintain their eating disorder. Some of the main topics to cover are as follows:
• The characteristic features of eating disorders including their associated physical and psychosocial effects
• Body weight and its regulation: the body mass index and its interpretation; natural weight fluctuations; and the effects of treatment on weight
• Ineffectiveness of vomiting, laxatives, and diuretics as a means of weight control
• Adverse effects of dieting: the types of dieting that promote binge eating; dietary rules versus dietary guidelines.
To provide reliable information on these topics, patients are asked to read relevant sections from one of the authoritative books on eating disorders29,30 and their reading is discussed in subsequent treatment sessions.Establishing “Regular Eating”
Establishing a pattern of regular eating is fundamental to successful treatment whatever the form of the eating disorder. It addresses an important type of dieting (“delayed eating”); it displaces most episodes of binge eating; it structures people's days and, for underweight patients, it introduces meals and snacks that can be subsequently increased in size. Early in treatment (usually by the third session) patients are asked to eat 3 planned meals each day plus 2 or 3 planned snacks so that there is rarely more than a 4-hour interval between them. Patients are also asked to confine their eating to these meals and snacks. They should choose what they eat with the only condition being that the meals and snacks are not followed by any compensatory behavior (eg, self-induced vomiting or laxative misuse). The new eating pattern should take precedence over other activities but should not be so inflexible as to preclude the possibility of adjusting timings to suit the patients' commitments each day.Patients should be helped to adhere to their regular eating plan and to resist eating between the planned meals and snacks. Two rather different strategies may be used to achieve the latter goals. The first involves helping patients to identify activities that are incompatible with eating and likely to distract them from the urge to binge eat (eg, taking a brisk walk) and strategies that make binge eating less likely (eg, leaving the kitchen). The second is to help patients to recognize that the urge to binge eat is a temporary phenomenon that can be “surfed.” Some “residual binges” are likely to persist, however, and these are addressed later.Involving Significant Others
The treatment is primarily an individual treatment for adults. Despite this, “significant others” are seen if this is likely to facilitate treatment and the patient is willing for this to happen. There are 2 reasons for seeing others: if they could help the patient in making changes or if others are making it difficult for the patient to change, for example, by commenting adversely on eating or appearance. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesStage twoStage two is a brief, but essential, transitional stage that generally comprises 2 appointments, a week apart. While continuing with the procedures introduced in Stage one, the therapist and patient take stock and conduct a joint review of progress, the goal being to identify problems still to be addressed and any emerging barriers to change, to revise the formulation if necessary, and to design Stage three. The review serves several purposes. If patients are making good progress they should be praised for their efforts and helpful changes reinforced. If patients are not doing well, the explanation needs to be understood and addressed. If clinical perfectionism, core low self-esteem or relationship difficulties appear to be responsible, this would be an indication for implementing the broad version of the treatment. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesStage threeThis is the main body of treatment. Its aim is to address the key processes that are maintaining the patient's eating disorder. The mechanisms addressed, and the order in which these are tackled, depend upon their role and relative importance in maintaining the patient's psychopathology. There are generally 8 weekly appointments.Addressing the Overevaluation of Shape and Weight
Identifying the overevaluation and its consequences
The first step involves explaining the concept of self-evaluation and helping patients identify how they evaluate themselves. The relative importance of the various domains that are relevant may be represented as a pie chart (Fig. 3 is an example of a pie chart with extended formulation), which for most patients is dominated by a large slice representing shape and weight and controlling eating. Fig. 3
The overevaluation of shape and weight and their control: an extended formulation.

Fig. 3The overevaluation of shape and weight and their control: an extended formulation.
The patient and therapist then identify the problems inherent in this scheme for self-evaluation. Briefly there are 3 related problems: first, self-evaluation is overly dependent on performance in one area of life with the result that domains other than shape and weight are marginalized; second, the area of controlling shape and weight is one in which success is elusive, thus undermining self-esteem; and third, the overevaluation is responsible for the behavior that characterizes the eating disorder (dieting, binge eating, and so forth).31The final step in the consideration of self-evaluation is the creation of an “extended formulation” depicting the main expressions of the overevaluation of shape and weight: dieting, body checking and body avoidance, feeling fat, and marginalization of other areas of life. The therapist uses this extended formulation to explain how these behaviors and experiences serve to maintain and magnify the patient's concerns about shape and weight and thus they need to be addressed in treatment.Enhancing the importance of other domains for self-evaluation
An indirect, yet powerful, means of diminishing the overevaluation of shape and weight is helping patients increase the number and significance of other domains for self-evaluation. Engaging in other aspects of their life that may have been pushed aside by the eating disorder results in these other areas becoming more important in the patient's self-evaluation. Briefly, this involves identifying activities or areas of life that the patient would like to engage in and helping them do so.A second, direct, strategy is to target the behavioral expressions of the overevaluation of shape and weight. This is done at the same time as enhancing the other domains for self-evaluation and it involves tackling body checking, body avoidance, and feeling fat.Addressing body checking and avoidance
Patients are often not aware that they are engaging in body checking and that it is maintaining their body dissatisfaction. The first step is therefore to obtain detailed information about their checking behavior by asking patients to monitor it. Patients are then educated about the adverse effects of repeated body checking as the way in which they check tends to provide biased information that leads them to feel dissatisfied. For example, scrutinizing parts of one's body magnifies apparent defects, and only comparing oneself to thin and attractive people leads one to draw the conclusion that one is unattractive. Most patients need substantial and detailed help to curb their repeated body checking and invariably attention needs to be devoted to their mirror use.Patients who avoid seeing their bodies also need considerable help. They should be encouraged to progressively get used to the sight and feel of their body. This may take many successive sessions.Addressing “feeling fat”
“Feeling fat” is an experience reported by many women but the intensity and frequency of this feeling appears to be far greater among people with eating disorders. Feeling fat is a target for treatment because it tends to be equated with being fat (irrespective of the patient's actual shape and weight) and hence maintains body dissatisfaction. Although this topic has received little research attention, clinical observation suggests that feeling fat is a result of mislabeling certain emotions and bodily experiences. Consequently, patients are helped to identify the triggers of their feeling fat experiences and the accompanying feelings. These typically are negative mood states (eg, feeling bored or depressed) or physical sensations that heighten body awareness (eg, feeling full, bloated, or sweaty). Patients are then helped to view “feeling fat” as a cue to ask themselves what else they are feeling at the time and once recognized to address it directly.Exploring the origins of overevaluation
Toward the end of Stage three it is often helpful to explore the origins of the patient's sensitivity to shape, weight, and eating. A historical review can help to make sense of how the problem developed and evolved, highlight how it might have served a useful function in its early stages, and the fact that it may no longer do so. If a specific event appears to have played a critical role in the development of the eating problem, the patient should be helped to reappraise this from the vantage point of the present. This review helps patients distance themselves further from the eating disorder frame of mind or “mindset.”Addressing Dietary Rules
Patients are helped to recognize that their multiple extreme and rigid dietary rules impair their quality of life and are a central feature of the eating disorder. A major goal of treatment is therefore to reduce, if not eliminate altogether, dieting. The first step in doing so is to identify the patient's various dietary rules together with the beliefs that underlie them. The patient is then helped to break these rules to test the beliefs in question and to learn that the feared consequences that maintain the dietary rule (typically weight gain or binge eating) are not an inevitable result. With patients who binge eat, it is important to pay particular attention to “food avoidance” (the avoidance of specific foods) as this is a major contributory factor. These patients need to systematically re-introduce the avoided food into their diet.Addressing Event-related Changes in Eating
Among many patients with eating disorders, eating habits change in response to outside events and changes in their mood. The change may involve eating less, stopping eating altogether, overeating, or binge eating. If these changes are prominent, patients need help to deal directly with the triggers. Generally this may be achieved by training them in “proactive” problem solving coupled with the use of functional means of modulating mood.Addressing Clinical Perfectionism, Low Self-esteem, and Interpersonal Problems
As noted earlier, there are 2 main forms of CBT-E. The components of the focused version are described previously. The “broad” version also includes these strategies and procedures but, in addition, addresses one or more “external” (to the core eating disorder) processes that may be maintaining the eating disorder. It is designed for patients in whom clinical perfectionism, core low self-esteem, or marked interpersonal problems are pronounced and appear to be contributing to the eating disorder. If the therapist decides, in the review of progress (Stage two), to use one or more of these modules, they should become a major component of all subsequent sessions. In the original version of the broad form of CBT-E a fourth module, “mood intolerance,” was included but this has since been integrated in to the standard, focused, form of the treatment as part of addressing events and moods. A description of the main elements of the 3 modules follows. A more detailed account is available in the main treatment guide.32Addressing clinical perfectionism
The psychopathology of clinical perfectionism is similar to that of an eating disorder.33 Its core is the overevaluation of striving to achieve and achievement itself. People with clinical perfectionism judge themselves largely, or exclusively, in terms of working hard toward, and meeting, personally demanding standards in areas of life that they value. If they have a coexisting eating disorder such extreme standards are applied to their eating, weight, and shape. This intensifies key aspects of the eating disorder including dietary restraint, exercise, and shape checking. It is usually evident from the patient's behavior and it can interfere with important aspects of treatment, leading to, for example, overly detailed recording and a strong resistance to relaxing dietary restraint.The strategy for addressing clinical perfectionism mirrors that used to address the overevaluation of shape and weight and the two can be addressed more or less at the same time. The first step is to add perfectionism to the patient's formulation and to consider the consequences of this for the patient and his or her life, including the self-evaluation pie-chart. Patients are then encouraged to take steps to enhance the importance of other, nonperformance related, domains for self-evaluation.It is helpful to consider collaboratively patients' goals in areas of life that they value, which are usually multiple, rigid, and extreme, and whether these goals are in fact counterproductive and impairing their actual performance. Performance checking is addressed similarly to shape checking, beginning by first asking patients to record times when they are checking their performance. Then the therapist helps them appreciate that the data they obtain is likely to be skewed as a result of using biased assessment processes, such as selective attention to failure. Avoidance and procrastination also need to be addressed, as they interfere with patients being able to assess their true ability with the result that their fears of failure are maintained.Addressing core low self-esteem
People with core low self-esteem (CLSE) have a longstanding and pervasive negative view of themselves. It is largely independent of the person's actual performance in life (ie, it is unconditional) and is not secondary to the presence of the eating disorder. The presence of CLSE results in the individual striving especially hard to control eating, weight, and shape to retain some sense of self-worth. It is generally a barrier to engaging in treatment as patients do not feel they deserve treatment nor do they believe that they can benefit from it.If it is to be directly addressed in treatment, it is added to the patient's formulation in Stage two and tackled alongside, although slightly later than, the steps addressing the overevaluation of shape and weight. This involves educating patients about the role of CLSE in maintaining the eating disorder and contributing to other difficulties in their life. Patients are helped to identify and modify the main cognitive maintaining processes, including discounting positive qualities and the overgeneralization of apparent failures. Previous views of the self are reappraised, using both cognitive restructuring and behavioral experiments, to help patients to reach a more balanced view of their self-worth.Addressing interpersonal problems
Interpersonal problems are common among patients with eating disorders, although they generally improve as the eating disorder resolves. Such problems may include conflict with others and difficulties developing close relationships. If these problems, and the resulting effects on mood, directly influence the patient's eating, they may be addressed through the use of proactive problem solving and functional mood modulation and acceptance (as described earlier). However, in some cases interpersonal problems powerfully maintain the eating disorder through a variety of direct and indirect processes or they interfere with treatment itself. Under these circumstances, they need to become a focus of treatment in their own right.The strategy used in CBT-E is to use a different psychological treatment to achieve interpersonal change, namely Interpersonal Psychotherapy (IPT). This is an evidence-based treatment that helps patients identify and address current interpersonal problems. In style and content IPT is very different from CBT-E. For this reason it is not “integrated” with CBT-E as such: rather, each session has a CBT-E component and an IPT one. More detailed information about IPT and its use with patients with eating disorders is available in a recent book chapter.34 Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesStage fourStage four, the final stage in treatment, is concerned with ending treatment well. The focus is on maintaining the progress that has already been made and reducing the risk of relapse. Typically there are 3 appointments about 2 weeks apart. During this stage, as part of their preparation for the ending of treatment, patients discontinue self-monitoring and begin weekly weighing at home.To maximize the chances that progress is maintained, the therapist and patient jointly devise a personalized plan for the following few months until a posttreatment review appointment (usually about 20 weeks later). Typically this includes further work on body checking, food avoidance, and perhaps further practice at problem solving. In addition, patients are encouraged to continue their efforts to develop new interests and activities.There are 2 elements to minimizing the risk of relapse. First, patients need to have realistic expectations regarding the future. Expecting never to experience any eating difficulties again makes patients vulnerable to relapse because it encourages a negative reaction to even minor setbacks. Instead, patients should view their eating problem as an Achilles heel. The goal is that patients identify setbacks as early as possible, view them as a “lapse” rather than a “relapse,” and actively address them using strategies that they learned during treatment. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesUnderweight patientsThe strategies and procedures described so far are also relevant to patients who are underweight (mostly cases of anorexia nervosa but some cases of eating disorder NOS). However, CBT-E has to be modified to address certain characteristics of these patients.The first priority is to address motivation, as often these patients do not view undereating or being underweight as a problem. This may be done in several ways and relies on a good therapeutic alliance. The patient is provided with a personalized education about the psychological and physical effects of being underweight. This helps them to understand that some of the things that they find difficult (eg, being obsessive and indecisive, being unable to be spontaneous, being socially avoidant, lacking sexual appetite) are a direct consequence of being a low weight rather than being a reflection of their true personality. The patient is helped to think through the advantages and disadvantages of change, including a consideration of how things are likely to be in the future if they choose not to change and how this would fit with their aspirations. The therapist shows intense interest in the patient as a person, beyond the eating disorder, and helps them to reflect on the state of all aspects of their life, including their relationships, their physical and psychological well-being, their work, and their personal values. The patient is encouraged to experiment with making changes to learn more about the pros and cons of their current behavior. The goal is for patients themselves to decide to regain weight rather than this decision being imposed by the therapist. If this is successful, it greatly assists subsequent weight regain.Second, the undereating and the consequent state of starvation must be addressed. It is important to help patients to realize that undereating, and being underweight maintain the eating disorder and this is illustrated in a personalized formulation. Once the patient has agreed to regain weight it is explained that weight regain should be gradual and steady and that they should aim to maintain an average energy surplus of 500 calories each day to regain an average of 0.5 kg (1.1 lb) per week. The therapist helps the patient to devise and implement a daily plan of eating (which may be supplemented by energy-rich drinks) that meets this target.Treatment needs to be extended from the typical 20 weeks to about 40 weeks to allow sufficient time for patients to decide to change, to reach a healthy weight, and then practice maintaining it. It can be helpful to involve others in the weight-gain process to facilitate the patient's own efforts. This is especially so with young patients who are living at home with their parents. Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesFinal commentsHopefully it will be clear from this brief account of CBT for eating disorders that major advances have been made and are continuing to be made. Perhaps most prominent among these is the adoption of a transdiagnostic approach to treatment whereby treatment is no longer for a specific eating disorder (eg, bulimia nervosa) but is directed at eating disorder psychopathology and the processes that maintains it. As a result, an empirically supported treatment approach has evolved that is suitable for all forms of eating disorder and one that is highly individualized.Many challenges remain. First and foremost, treatment outcome needs to be further improved, especially in the case of patients who are substantially underweight. Second, understanding more about the way in which treatment works, and the active ingredients of treatment, could inform the design of a more potent version. Doubtless some elements could be discarded whereas others may need to be enhanced.35 We need treatments that are effective and efficient. Last, we need to facilitate the dissemination of evidence-based practice. Many patients receive suboptimal treatment. There are several possible reasons for this but prominent among them is the fact that few therapists have received the necessary training.FootnotesC.G.F. is supported by a Principal Research Fellowship from the Wellcome Trust (046386). R.M., S.S., and Z.C. are supported by a program grant from the Wellcome Trust (046386). Other Sections▼
AbstractEating disorders and their clinical featuresThe empirical status of cognitive behavioral therapy for eating disordersThe cognitive behavioral account of eating disordersEnhanced cognitive behavioral therapyAn overview of the core aspects of treatmentPreparation for treatment and changeStage oneStage twoStage threeStage fourUnderweight patientsFinal commentsReferencesReferences1. National Institute for Clinical Excellence (NICE) NICE; London: 2004. Eating disorders—core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders.http://www.nice.org.uk Available at: Accessed October 2009. NICE Clinical Guidance No. 9.
2. Fairburn C.G., Cooper Z., Doll H.A. Transdiagnostic cognitive behavioral therapy for patients with eating disorders: a two-site trial with 60-week follow-up. Am J Psychiatry. 2009;166:311–319. [PubMed]
3. American Psychiatric Association 4th edition. American Psychiatric Association; Washington, DC: 1994. Diagnostic and statistical manual of mental disorders.
4. Fairburn C.G., Bohn K. Eating disorder NOS (EDNOS): an example of the troublesome “not otherwise specified” (NOS) category in DSM-IV. Behav Res Ther. 2005;43:691–701. [PMC free article] [PubMed]
5. Dalle Grave R., Calugi S. Eating disorder not otherwise specified on an inpatient unit. Eur Eat Disord Rev. 2007;15:340–349. [PubMed]
6. Miller G., Holden C. Proposed revisions to psychiatry's canon unveiled. Science. 2010;327(5967):770–771. [PubMed]
7. Fairburn C.G., Cooper Z., Bohn K. The severity and status of eating disorder NOS: implications for DSM-V. Behav Res Ther. 2007;45(8):1705–1715. [PMC free article] [PubMed]
8. Wilson G.T., Grilo C.M., Vitousek K.M. Psychological treatment of eating disorders. Am Psychol. 2007;62(3):199–216. [PubMed]
9. Shapiro J.R., Berkamn N.D., Brownley K.A. Bulimia nervosa treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007;40(4):321–336. [PubMed]
10. Hay P.P.J., Bacaltchuk J., Stefano S. Psychological treatments for bulimia nervosa and binging. Cochrane Database Syst Rev. 2009;4 CD000562.
11. Fairburn C.G., Jones R., Peveler R.C. Psychotherapy and bulimia nervosa: the longer-term effects of interpersonal psychotherapy, behaviour therapy and cognitive behaviour therapy. Arch Gen Psychiatry. 1993;50:419–428. [PubMed]
12. Agras W.S., Walsh B.T., Fairburn C.G. A multicenter comparison of cognitive behavioral therapy and interpersonal psychotherapy for bulimia nervosa. Arch Gen Psychiatry. 2000;57:459–466. [PubMed]
13. Wilson G.T., Fairburn C.G. Treatments for eating disorders. In: Nathan P.E., Gorman J.M., editors. A guide to treatments that work. 3rd edition. Oxford University Press; New York: 2007. pp. 581–583.
14. Fairburn CG. Transdiagnostic CBT for eating disorders “CBT-E”, presented at association for behavioral and cognitive therapy. New York; 2009.
15. Mitchell J., Devlin M., de Zwaan M. Guilford; New York: 2008. Binge eating disorder. Clinical foundations and treatment. p. 65–9.
16. Brownley K.A., Berkman N.D., Sedway J.A. Binge eating disorder treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007;40:337–348. [PubMed]
17. Sysko R., Walsh T. A critical evaluation of the efficacy of self-help interventions for the treatment of bulimia nervosa and binge-eating disorder. Int J Eat Disord. 2008;41:97–112. [PubMed]
18. Wilson G.T., Wilfley D.E., Agras W.S. Psychological treatments of binge eating disorder. Arch Gen Psychiatry. 2010;67(1):94–101. [PubMed]
19. Fairburn C.G., Cooper Z., Shafran R. Cognitive behaviour therapy for eating disorders: a “transdiagnostic” theory and treatment. Behav Res Ther. 2003;41:509–528. [PubMed]
20. Fairburn C.G., Harrison P.J. Eating disorders. Lancet. 2003;361:407–416. [PubMed]
21. Fairburn C.G., Cooper Z., Cooper P. The clinical features and maintenance of bulimia nervosa. In: Brownwell K.D., Foreyt J.P., editors. Physiology, psychology and treatment of eating disorders. Basic Books; New York: 1986. pp. 389–404.
22. Cooper Z., Stewart A. CBT-E and the younger patient. In: Fairburn C.G., editor. Cognitive behavior therapy and eating disorders. Guilford Press; New York: 2008. pp. 221–230.
23. Dalle Grave R., Bohn K., Hawker D. Inpatient, day patient, and two forms of outpatient CBT-E. In: Fairburn C.G., editor. Cognitive behavior therapy and eating disorders. Guilford Press; New York: 2008. pp. 231–244.
24. Dalle Grave R, Fairburn CG. Intensive CBT for eating disorders. New York: Guilford Press, in press.
25. Fairburn C.G. Guilford Press; New York: 2008. Cognitive behavior therapy and eating disorders.
26. Fairburn C.G., Cooper Z., Waller D. The patients: their assessment, preparation for treatment and medical management. In: Fairburn C.G., editor. Cognitive behavior therapy and eating disorders. Guilford Press; New York: 2008. pp. 35–40.
27. Fairburn C.G., Agras W.S., Walsh B.T. Prediction of outcome in bulimia nervosa by early change in treatment. Am J Psychiatry. 2004;161:2322–2324. [PubMed]
28. Agras W.S., Crow S.J., Halmi K.A. Outcome predictors for the cognitive-behavioral treatment of bulimia nervosa: data from a multisite study. Am J Psychiatry. 2000;157:1302–1308. [PubMed]
29. Fairburn C.G. Guilford Press; New York: 1995. Overcoming binge eating.
30. Schmidt U., Treasure J. Psychology Press; Hove (UK): 1993. Getting better bit(e) by bit(e). A survival guide for sufferers of bulimia nervosa and binge eating disorders.
31. Fairburn C.G., Cooper Z., Shafran R. Enhanced cognitive behavior therapy for eating disorders: the core protocol. In: Fairburn C.G., editor. Cognitive behavior therapy and eating disorders. Guilford Press; New York: 2008. pp. 47–193.
32. Fairburn C.G., Cooper Z., Shafran R. Clinical perfectionism, core low self-esteem and interpersonal problems. In: Fairburn C.G., editor. Cognitive behavior therapy and eating disorders. Guilford Press; New York: 2008. pp. 47–123.
33. Shafran R., Cooper Z., Fairburn C.G. Clinical perfectionism: a cognitive-behavioural analysis. Behav Res Ther. 2002;40:773–791. [PubMed]
34. Murphy R., Straebler S., Cooper Z. Interpersonal psychotherapy (IPT) for eating disorders. In: Dancyger I.F., Fornari V.M., editors. Evidence based treatments for eating disorders. Nova Science Publishers; New York: 2009. pp. 257–274.
35. Kazdin A.E., Nock M.K. Delineating mechanisms of change in child and adolescent therapy: methodological issues and research recommendations. J Child Psychol Psychiatry. 2003;44:1116–1129. [PubMed]
--------------------------------------------------------------------------------
Continuing Education for Social Workers