Select memories can be erased, leaving others intact

Different types of memories stored in the same neuron of the marine snail Aplysia can be selectively erased, according to a new study by researchers at Columbia University Medical Center (CUMC) and McGill University and published today in Current Biology.

The findings suggest that it may be possible to develop drugs to delete memories that trigger anxiety and post-traumatic stress disorder (PTSD) without affecting other important memories of past events.

During emotional or traumatic events, multiple memories can become encoded, including memories of any incidental information that is present when the event occurs. In the case of a traumatic experience, the incidental, or neutral, information can trigger anxiety attacks long after the event has occurred, say the researchers.

“The example I like to give is, if you are walking in a high-crime area and you take a shortcut through a dark alley and get mugged, and then you happen to see a mailbox nearby, you might get really nervous when you want to mail something later on,” says Samuel Schacher, PhD, a professor of neuroscience in the Department of Psychiatry at CUMC and co-author of the paper. In the example, fear of dark alleys is an associative memory that provides important information — e.g., fear of dark alleys — based on a previous experience. Fear of mailboxes, however, is an incidental, non-associative memory that is not directly related to the traumatic event.

“One focus of our current research is to develop strategies to eliminate problematic non-associative memories that may become stamped on the brain during a traumatic experience without harming associative memories, which can help people make informed decisions in the future — like not taking shortcuts through dark alleys in high-crime areas,” Dr. Schacher adds.

Brains create long-term memories, in part, by increasing the strength of connections between neurons and maintaining those connections over time. Previous research suggested that increases in synaptic strength in creating associative and non-associative memories share common properties. This suggests that selectively eliminating non-associative synaptic memories would be impossible, because for any one neuron, a single mechanism would be responsible for maintaining all forms of synaptic memories.

The new study tested that hypothesis by stimulating two sensory neurons connected to a single motor neuron of the marine snail Aplysia; one sensory neuron was stimulated to induce an associative memory and the other to induce a non-associative memory.

By measuring the strength of each connection, the researchers found that the increase in the strength of each connection produced by the different stimuli was maintained by a different form of a Protein Kinase M (PKM) molecule (PKM Apl III for associative synaptic memory and PKM Apl I for non-associative). They found that each memory could be erased — without affecting the other — by blocking one of the PKM molecules.

In addition, they found that specific synaptic memories may also be erased by blocking the function of distinct variants of other molecules that either help produce PKMs or protect them from breaking down.

The researchers say that their results could be useful in understanding human memory because vertebrates have similar versions of the Aplysia PKM proteins that participate in the formation of long-term memories. In addition, the PKM-protecting protein KIBRA is expressed in humans, and mutations of this gene produce intellectual disability.

“Memory erasure has the potential to alleviate PTSD and anxiety disorders by removing the non-associative memory that causes the maladaptive physiological response,” says Jiangyuan Hu, PhD, an associate research scientist in the Department of Psychiatry at CUMC and co-author of the paper. “By isolating the exact molecules that maintain non-associative memory, we may be able to develop drugs that can treat anxiety without affecting the patient’s normal memory of past events.”

“Our study is a ‘proof of principle’ that presents an opportunity for developing strategies and perhaps therapies to address anxiety,” said Dr. Schacher. “For example, because memories are still likely to change immediately after recollection, a therapist may help to ‘rewrite’ a non-associative memory by administering a drug that inhibits the maintenance of non-associative memory.”

Future studies in preclinical models are needed to better understand how PKMs are produced and localized at the synapse before researchers can determine which drugs may weaken non-associative memories.

No place like home

New research by Steve Posavac, E. Bronson Ingram Professor of Marketing at Vanderbilt’s Owen Graduate School of Management, uncovers another consequence of anxiety symptoms: susceptibility to certain marketing themes.

According to a paper recently published in the Journal of Social and Clinical Psychology, individuals with relatively elevated symptoms of Adult Separation Anxiety Disorder (ASAD) are more favorable to advertisements with home concepts.

“Importantly, our research suggests a vulnerability to persuasion among those with adult separation anxiety disorder symptoms that goes beyond simply the appeal of a product itself,” Posavac and co-author, psychologist Heidi Posavac, write. “Featuring the concept of home as an advertising theme leads to more favorability towards the persuasive attempt.”

The paper says consumer advertising regularly invokes the idea of home, citing recent Super Bowl ads by Jeep and Budweiser as examples.

Adult Separation Anxiety Disorder is a psychological condition in which an individual has excessive anxiety regarding separation from places or people to whom he or she has a strong emotional attachment. The lifetime incidence of adult separation anxiety disorder in the United States is estimated to be 6.6 percent, but a much higher percentage may experience symptoms.

In a study conducted at Vanderbilt Business’ Behavioral Research Lab, participants completed a questionnaire to measure ASAD published by the American Psychiatric Institute. Later, they read an internet advertisement for a fictitious airline: one version incorporated a theme of “coming home to family,” the other promoted a message of “seeing new things.” Participants with high ASAD symptoms had more favorable attitudes toward the home-themed ad, while those with little to no symptoms offered no preference.

While the Posavacs’ findings may suggest an opportunity for marketers, they caution that it may also reflect a threat for sufferers of adult separation anxiety disorder. Should marketers be able to identify and target a subgroup of consumers with ASAD or ASAD symptoms, home-themed advertising might increase sales, but the impact on the consumers themselves might not be so positive.

“Whether in individual treatment sessions, or with a psychoeducational approach, individuals experiencing chronic adult separation anxiety may be well served by clinicians who help to inoculate them against the possibility of coming under undue influence by savvy marketers,” the authors write.

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Materials provided by Vanderbilt University. Original written by Ryan Underwood / Nathaniel Austin Luce. Note: Content may be edited for style and length.

AI that can shoot down fighter planes helps treat bipolar disorder

The artificial intelligence that can blow human pilots out of the sky in air-to-air combat accurately predicted treatment outcomes for bipolar disorder, according to a new medical study by the University of Cincinnati.

The findings open a world of possibility for using AI, or machine learning, to treat disease, researchers said.

David Fleck, an associate professor at the UC College of Medicine, and his co-authors used artificial intelligence called “genetic fuzzy trees” to predict how bipolar patients would respond to lithium.

Bipolar disorder, depicted in the TV show “Homeland” and the Oscar-winning “Silver Linings Playbook,” affects as many as six million adults in the United States or 4 percent of the adult population in a given year.

“In psychiatry, treatment of bipolar disorder is as much an art as a science,” Fleck said. “Patients are fluctuating between periods of mania and depression. Treatments will change during those periods. It’s really difficult to treat them appropriately during stages of the illness.”

The study authors found that even the best of eight common models used in treating bipolar disorder predicted who would respond to lithium treatment with 75 percent accuracy. By comparison, the model UC researchers developed using AI predicted how patients would respond to lithium 100 percent of the time. Even more impressively, the UC model predicted the actual reduction in manic symptoms after lithium treatment with 92 percent accuracy.

The study authors found that even the best of the eight most common treatments was only effective half the time. But the model UC researchers developed using AI predicted how patients would respond to lithium treatment with 88 percent accuracy and 80 percent accuracy in validation.

It turns out that the same kind of artificial intelligence that outmaneuvered Air Force pilots last year in simulation after simulation at Wright-Patterson Air Force Base is equally adept at making beneficial decisions that can help doctors treat disease. The findings were published this month in the journal Bipolar Disorders.

“What this shows is that an effort funded for aerospace is a game-changer for the field of medicine. And that is awesome,” said Kelly Cohen, a professor in UC’s College of Engineering and Applied Science.

Cohen’s doctoral graduate Nicholas Ernest is founder of the company Psibernetix, Inc., an artificial intelligence development and consultation company. Psibernetix is working on applications such as air-to-air combat, cybersecurity and predictive analytics. Ernest’s fuzzy logic algorithm is able to sort vast possibilities to arrive at the best choices in literally the blink of an eye.

“Normally the problems our AIs solve have many, many googolplexes of possible solutions — effectively infinite,” study co-author Ernest said.

His team developed a genetic fuzzy logic called Alpha capable of shooting down human pilots in simulations, even when the computer’s aircraft intentionally was handicapped with a slower top speed and less nimble flight characteristics. The system’s autonomous real-time decision-making shot down retired U.S. Air Force Col. Gene Lee in every engagement.

“It seemed to be aware of my intentions and reacting instantly to my changes in flight and my missile deployment,” Lee said last year. “It knew how to defeat the shot I was taking. It moved instantly between defensive and offensive actions as needed.”

The American Institute of Aeronautics and Astronautics honored Cohen and Ernest this year for their “advancement and application of artificial intelligence to large scale, meaningful and challenging aerospace-related problems.”

Cohen spent much of his career working with fuzzy-logic based AI in drones. He used a sabbatical from the engineering college to approach the UC College of Medicine with an idea: What if they could apply the amazing predictive power of fuzzy logic to a particularly nettlesome medical problem?

Medicine and avionics have little in common. But each entails an ordered process — a vast decision tree — to arrive at the best choices. Fuzzy logic is a system that relies not on specific definitions but generalizations to compensate for uncertainty or statistical noise. This artificial intelligence is called “genetic fuzzy” because it constantly refines its answer, tossing out the lesser choices in a way analogous to the genetic processes of Darwinian natural selection.

Cohen compares it to teaching a child how to recognize a chair. After seeing just a few examples, any child can identify the object people sit in as a chair, regardless of its shape, size or color.

“We do not require a large statistical database to learn. We figure things out. We do something similar to emulate that with fuzzy logic,” Cohen said.

Cohen found a receptive audience in Fleck, who was working with UC’s former Center for Imaging Research. After all, who better to tackle one of medical science’s hardest problems than a rocket scientist? Cohen, an aerospace engineer, felt up to the task.

Ernest said people should not conflate the technology with its applications. The algorithm he developed is not a sentient being like the villains in the “Terminator” movie franchise but merely a tool, he said, albeit a powerful one with seemingly endless applications.

“I get emails and comments every week from would-be John Connors out there who think this will lead to the end of the world,” Ernest said.

Ernest’s company created EVE, a genetic fuzzy AI that specializes in the creation of other genetic fuzzy AIs. EVE came up with a predictive model for patient data called the LITHium Intelligent Agent or LITHIA for the bipolar study.

“This predictive model taps into the power of fuzzy logic to allow you to make a more informed decision,” Ernest said.

And unlike other types of AI, fuzzy logic can describe in simple language why it made its choices, he said.

The researchers teamed up with Dr. Caleb Adler, the UC Department of Psychiatry and Behavioral Neuroscience vice chairman of clinical research, to examine bipolar disorder, a common, recurrent and often lifelong illness. Despite the prevalence of mood disorders, their causes are poorly understood, Adler said.

“Really, it’s a black box,” Adler said. “We diagnose someone with bipolar disorder. That’s a description of their symptoms. But that doesn’t mean everyone has the same underlying causes.”

Selecting the appropriate treatment can be equally tricky.

“Over the past 15 years there has been an explosion of treatments for mania. We have more options. But we don’t know who is going to respond to what,” Adler said. “If we could predict who would respond better to treatment, you would save time and consequences.”

With appropriate care, bipolar disorder is a manageable chronic illness for patients whose lives can return to normal, he said.

UC’s new study, funded in part by a grant from the National Institute of Mental Health, identified 20 patients who were prescribed lithium for eight weeks to treat a manic episode. Fifteen of the 20 patients responded well to the treatment.

The algorithm used an analysis of two types of patient brain scans, among other data, to predict with 100 percent accuracy which patients responded well and which didn’t. And the algorithm also predicted the reductions in symptoms at eight weeks, an achievement made even more impressive by the fact that only objective biological data were used for prediction rather than subjective opinions from experienced physicians.

“This is a huge first step and ultimately something that will be very important to psychiatry and across medicine,” Adler said.

How much potential does this have to revolutionize medicine?

“I think it’s unlimited,” Fleck said. “It’s a good result. The best way to validate it is to get a new cohort of individuals and apply their data to the system.”

Cohen is less reserved in his enthusiasm. He said the model could help personalize medicine to individual patients like never before, making health care both safer and more affordable. Fewer side-effects means fewer hospital visits, less secondary medication and better treatments.

Now the UC researchers and Psibernetix are working on a new study applying fuzzy logic to diagnosing and treating concussions, another condition that has bedeviled doctors.

“The impact on society could be profound,” Cohen said.

 

Lingering risk of suicide after discharge from psychiatric facilities

A study that synthesized more than 50 years of research into suicide rates for patients after discharge from psychiatric facilities suggests the immediate period after discharge was a time of marked risk and that the risk remained high years after discharge, according to a new article published by JAMA Psychiatry.

Suicide is among the top 20 causes of death worldwide. The World Health Organization estimated the global suicide rate was 11.4 per 100,000 person-years in 2012. (A person-year is a unit of time.) Mentally ill individuals discharged from psychiatric hospitals and wards appear to have a greater risk for suicide than other mentally ill individuals, although there are no accepted benchmarks for postdischarge suicide rates, according to the article.

The work by Matthew Michael Large, B.Sc., M.B.B.S., F.R.A.N.Z.C.P., D.Med.Sci., of the University of New South Wales, Australia, and coauthors quantified rates of suicide after discharge from psychiatric facilities and included 100 studies reporting 17,857 suicides.

The pooled estimate discharge suicide rate was 484 per 100,000 person-years, according to the results, with the suicide rate the highest within three months after discharge (1,132 per 100,000 person-years) and among those patients admitted with suicidal ideas or behaviors.

Pooled suicide rates were 654 per 100,000 person-years in studies with follow-up from three months to one year; 494 per 100,000 person-years in studies with follow-up from one to five years; 366 per 100,000 person-years in studies with follow-up of five to 10 years; and 277 per 100,000 person-years in studies with follow-up greater than 10 years, the authors report.

The study details its limitations and notes that factors associated with increased suicide risk at an aggregate level should be interpreted with caution and may not necessarily be applicable to individual patients.

“Discharged patients have suicide rates many times that in the general community. Efforts aimed at suicide prevention should start while patients are in hospital, and the period shortly after discharge should be a time of increased clinical focus. However, our study also suggests that previously admitted patients, particularly those with prior suicidality, remain at a markedly elevated risk of suicide for years and should be a focus of efforts to decrease suicide in the community,” the article concludes.

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Racial Discrimination during Adolescence Predicts Mental Health Deterioration in Adulthood: Gender Differences among Blacks

Shervin Assari, Ehsan Moazen-Zadeh, Cleopatra Howard Caldwell, Marc A. Zimmerman

Tai chi significantly reduces depression symptoms in Chinese-Americans

A 12-week program of instruction and practice of the Chinese martial art tai chi led to significantly reduced symptoms of depression in Chinese Americans not receiving any other treatments. The pilot study conducted by investigators at Massachusetts General Hospital (MGH) and published in the Journal of Clinical Psychiatry enrolled members of Boston’s Chinese community who had mild to moderate depression.

“While some previous studies have suggested that tai chi may be useful in treating anxiety and depression, most have used it as a supplement to treatment for others medical conditions, rather than patients with depression,” explains Albert Yeung, MD, ScD, of the Depression Clinical and Research Program in the MGH Department of Psychiatry, lead and corresponding author of the report. “Finding that tai chi can be effective is particularly significant because it is culturally accepted by this group of patients who tend to avoid conventional psychiatric treatment.”

Participants were recruited through advertisements offering tai chi for stress reduction, and their eligibility for the study was determined based on in-person interviews and assessments of overall health and depression symptoms. Eligible participants were Chinese-American adults fluent in either Cantonese or Mandarin, with a diagnosis of major depressive disorder in the mild to moderate range, no history of other psychiatric disorders, no recent practice of tai chi or other mind-body interventions, and no current use of other psychiatric treatments.

Participants were randomized into three groups — one that received the tai chi intervention; an active control group that participated in educational sessions that included discussions on stress, mental health and depression; and a passive control, “waitlist” group that returned for repeat assessments during and after the study period. The tai chi intervention involved twice weekly sessions for 12 weeks, in which participants were taught and practiced basic traditional tai chi movements. They were asked to practice at home three times a week and to document their practice. The education group also met twice weekly for 12 weeks, and sessions for both groups were offered in Cantonese or Mandarin. Members of both the education and waitlist groups were able to join free tai chi classes after the initial study period, something they were informed of at the study’s outset.

Of the 50 participants who completed the 12-week intervention period, 17 were in the tai chi group, 14 in the education group and 19 in the waitlist group. The 12-week assessments showed that the tai chi group had significantly greater improvement in depression symptoms than did members of either control group. Follow-up assessment at 24 weeks showed sustained improvement among the tai chi group, with statistically significant differences remaining compared with the waitlist group.

“If these findings are confirmed in larger studies at other sites, that would indicate that tai chi could be a primary depression treatment for Chinese and Chinese American patients, who rarely take advantage of mental health services, and may also help address the shortage of mental health practitioners,” says Yeung, who is an associate professor of Psychiatry at Harvard Medical School. “We also should investigate whether tai chi can have similar results for individuals from other racial and ethnic groups and determine which of the many components of tai chi might be responsible for these beneficial effects.”

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Rates of suicide ‘worrying’ among people with autism, say experts

Suicide rates among people with autism in England have reached “worryingly” high levels, according to experts writing in the Lancet Psychiatry.

Writing ahead of a world-first international summit on suicidality in autism, the researchers — from Coventry and Newcastle universities — say the issue remains poorly understood and that action is urgently needed to help those most at risk.

Dr Sarah Cassidy from Coventry University cites a clinical study she led in 2014 — also published in the Lancet Psychiatry — in which 66% of adults newly diagnosed with Asperger Syndrome (AS) reported having contemplated suicide.

In the same study — which remains the most recent clinical research into suicidality in autism — 35% of the 365 respondents newly diagnosed with AS said they had planned or attempted to end their own life, with 31% reporting that they suffered depression.

A 2016 population study in Sweden also concluded that suicide is a leading cause of premature death in people with autism spectrum disorder.

Dr Cassidy from Coventry University’s Centre for Research in Psychology, Behaviour and Achievement said,”What relatively little we know about suicidality in autism points to a worryingly high prevalence of people with the condition contemplating and attempting to take their own life.

“More concerning still, the small body of research that does exist exposes serious shortcomings in how prepared we are to intervene and provide effective support to those with autism who are most at risk of dying by suicide.

“There are significant differences, for example, in the risk factors for suicide in autism compared with the general population, meaning the journey from suicidal thoughts to suicidal behaviours might be quite different.

“The models we currently consider best practise for assessing and treating suicidality need to be rethought for those with autism, and policy adjusted accordingly so new approaches are reflected across services.”

Co-author Dr Jacqui Rodgers from Newcastle University’s Institute of Neuroscience said,”This unique event is of huge importance. For the first time researchers and clinicians from the fields of autism and suicide research will come together, along with members of the autism community and those bereaved by suicide, to learn from each other and identify clinical and research priorities to address this urgent issue.”

Jon Spiers, chief executive of autism research charity Autistica, said, “For years society and the healthcare system have ignored the voices of families who have lost autistic loved ones unnecessarily, and far too young. Recent research revealing the sheer scale of the problem proves that we cannot let that continue.

“National and local government, research funders and industry, as well as the NHS and service providers all have a responsibility to tackle the issue of suicide in autism. Autistica is committed to playing a major part by funding mental health research programmes. This suicide summit will kick-start our campaign for change in this severely overlooked area.”

Coventry and Newcastle universities are running the international summit on suicide in autism — the first of its kind anywhere in the world — over the next two days, with funding from Autistica and the James Lind Alliance.

The aim is to develop recommendations for changes in government policy and practise that can be implemented quickly to reduce suicide in autism, and to decide on priorities for future research in the field.

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Parent training on ADHD using volunteers can help meet growing treatment needs

Using volunteers to train parents concerned about attention deficit/hyperactivity disorder (ADHD) in their children can improve capacity to meet increasing ADHD treatment needs, finds a new study by NYU’s Steinhardt School of Culture, Education, and Human Development.

The study, published in the Journal of Abnormal Child Psychology, highlights an innovative approach to embracing community resources — tapping volunteers to act as therapists.

“Given the prevalence of ADHD in many countries and the limited access to evidence-based, non-medication treatment, there is a pressing need to expand service delivery systems. Our findings demonstrate that the service model of behavioral parent training we studied can effectively provide training to many families of youth with concerns about ADHD and is likely highly sustainable,” said Anil Chacko, associate professor of counseling psychology at NYU Steinhardt and the study’s author.

Behavioral parent training is a well-established therapeutic approach in which parents are taught how to improve interactions with their child, increase a child’s desirable behavior, and reduce misbehavior. Research has looked at behavioral parent training for addressing the problems associated with ADHD among youth. Behavioral parent training has been shown to improve parenting behavior and stress, as well as children’s disruptive behavior. The American Academy of Pediatrics advises that behavioral parent training be used as the first line approach to treating preschoolers with ADHD.

While behavioral parent training is a widely accepted intervention for children with ADHD, there are limited therapists available to provide this training. When compounded with the growing prevalence of ADHD, models to improve access to behavioral parent training are needed, particularly those that can be readily implemented in community settings.

“Given the well-documented benefits of behavioral parent training as an intervention for ADHD, widespread availability and access to behavioral parent training delivered by volunteers and paraprofessionals should have direct public health benefits in bending the curve on costs and outcomes associated with ADHD,” Chacko said.

ADHD-foreningen, a Danish ADHD advocacy organization, developed and delivered Caring in Chaos, a parenting intervention drawn from evidence-based behavioral parent training approaches. It focuses on three core elements: education about ADHD, positive behavior, and tools for managing disruptive behavior and conflict prevention. The model relies on trained volunteers, who meet with parents in small groups over 12 weekly evening sessions.

The current study evaluated Caring in Chaos for parents with concerns about their children’s ADHD. (Unlike other studies of ADHD, the children did not undergo an assessment for an ADHD diagnosis, and as such, included children with a range of ADHD symptoms).

The study included 161 Danish families who were randomized to either receive Caring in Chaos or were put on a waitlist, acting as a control group. The researchers collected data on the families before the intervention, immediately after, and four months later. Parents rated their own parenting behavior, competence, stress, and depressive symptoms, as well as their child’s ADHD symptoms and functional impairments at home, such as getting dressed independently or doing chores.

The researchers found that Caring in Chaos resulted in significant improvement in all parenting measures — behavior, competence, stress, and depressive symptoms — as well as children’s functional impairment compared to the wait-listed families immediately after the intervention. Most of the gains were maintained at the four-month follow-up.

This study aligns with other studies demonstrating that behavioral parent training has a consistent impact on key parenting outcomes and children’s functional impairments.

The results of the study suggest that efficient behavioral parent training models, such as Caring in Chaos, can be implemented by a variety of individuals in the community — not just therapists. These models have potential for increasing access to behavioral parent training, which is necessary for addressing the growing and often unmet needs of families of youth with ADHD.

“The model we studied in Denmark can and should be translated here in the United States, given the large disparities in access to evidence-based treatments and significant number of children with ADHD,” said Chacko.

Chronic childhood illness linked with later life mental health problems

A new study into the effects of chronic physical illness in children on their life-long mental health has found that such experiences appear to increase the chances of them having depression and anxiety in adulthood.

Researchers at the University of Sussex and University College London systematically reviewed evidence from a large number of medical studies, looking for associations between eight chronic physical illnesses in childhood, such as arthritis, asthma and cancer, and emotional problems experienced by the sufferers in later life.

The paper, published today in the Journal of Child Psychology and Psychiatry (JCPP), reveals that the sufferers of all chronic conditions reviewed were at increased risk of developing depression or anxiety, emotional problems that persisted beyond childhood and adolescence and into adult life.

The results suggest that mental health prevention and intervention strategies which specifically target chronic illness sufferers in youth could be vital in treating mental health issues before they develop into more serious long term conditions.

Speaking about the findings, psychologist Dr Darya Gaysina, senior researcher on the project at the University of Sussex said: “Very little is known about life-long effects of childhood chronic physical illness on mental health. Our results show that childhood chronic physical illness was significantly associated with adult depression in the total sample of more than 45,000 participants we studied.

“In particular, we found that cancer was significantly associated with adult depression. Although the research on other chronic conditions is very limited, when we removed cancer from the sample, the link was still there. So it is not only cancer that’s associated with adult emotional problems.”

Dr Gaysina feels that this connection could help mental health practitioners approach young patients with chronic conditions in a different way.

“It seems that if there is a higher risk of mental health issues in adulthood for those with childhood-onset chronic physical illnesses, further in-depth research in this area could help change the way practitioners work with youth with chronic conditions, ensuring that there is as much a focus on the patient’s mental health as their physical health.”

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For anorexia nervosa, researchers implicate genetic locus on chromosome 12

A landmark study led by UNC School of Medicine researchers has identified the first genetic locus for anorexia nervosa and has revealed that there may also be metabolic underpinnings to this potentially deadly illness.

The study, which is the most powerful genetic study of anorexia nervosa conducted to date, included genome-wide analysis of DNA from 3,495 individuals with anorexia nervosa and 10,982 unaffected individuals.

If particular genetic variations are significantly more frequent in people with a disorder compared to unaffected people, the variations are said to be “associated” with the disorder. Associated genetic variations can serve as powerful pointers to regions of the human genome where disorder-causing problems reside, according to the National Human Genome Research Institute.

“We identified one genome-wide significant locus for anorexia nervosa on chromosome 12, in a region previously shown to be associated with type 1 diabetes and autoimmune disorders,” said lead investigator, Cynthia Bulik, PhD, FAED, founding director of the UNC Center of Excellence for Eating Disorders and a professor at Karolinska Institutet in Stockholm, Sweden.

“We also calculated genetic correlations — the extent to which various traits and disorders are caused by the same genes,” said Bulik.

“Anorexia nervosa was significantly genetically correlated with neuroticism and schizophrenia, supporting the idea that anorexia is indeed a psychiatric illness.”

“But, unexpectedly, we also found strong genetic correlations with various metabolic features including body composition (BMI) and insulin-glucose metabolism. This finding encourages us to look more deeply at how metabolic factors increase the risk for anorexia nervosa,” Bulik said.

This study was conducted by the Psychiatric Genetics Consortium Eating Disorders Working Group — an international collaboration of researchers at multiple institutions worldwide.

“In the era of team science, we brought over 220 scientists and clinicians together to achieve this large sample size. Without this collaboration we would never have been able to discover that anorexia has both psychiatric and metabolic roots,” said Gerome Breen, PhD, of King’s College London.

“Working with large data sets allows us to make discoveries that would never be possible in smaller studies,” said Laramie Duncan, PhD, of Stanford University, who served as lead analyst on the project.

The researchers are continuing to increase sample sizes and see this as the beginning of genomic discovery in anorexia nervosa. Viewing anorexia nervosa as both a psychiatric and metabolic condition could ignite interest in developing or repurposing medications for its treatment where currently none exist.

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Virtual reality for psychiatric treatment? Research shows promise for VR and other technologies in mental health care

A growing body of evidence suggests that virtual reality (VR) technology can be an effective part of treatment for phobias, posttraumatic stress disorder, and other mental health conditions, according to a research review in the May/June issue of the Harvard Review of Psychiatry.

“Virtual reality is potentially a powerful tool for the psychiatric community,” comments lead author Jessica L. Maples-Keller, PhD, of University of Georgia. “It allows providers to create computer-generated environments in a controlled setting, which can be used to create a sense of presence and immersion in the feared environment for individuals suffering from anxiety disorders.” The review appears as part of a special theme issue of Harvard Review of Psychiatry, focusing on Emerging Technology and Telehealth in Psychiatric Care.

Virtual Reality and Other Technologies Poised to Aid Mental Health Treatment

Dr. Maples-Keller and colleagues review the current state of research on VR technology for psychiatric treatment. So far, research in this area has focused on exposure-based treatment for certain types of anxiety disorders. Studies have evaluated VR applications for progressive exposure to frightening situations in patients with specific phobias — especially fear of flying. Other studies have evaluated the use of VR for treatment of post-traumatic stress disorder in combat veterans.

Virtual reality applications can simulate exposures that would be costly or impractical to re-create in real life, such as airplane flight or combat conditions. It also enables the therapist to control the “dose” and specific aspects of the exposure environment. For example, the patient can “virtually” experience repeated takeoffs and landings without going on an actual flight.

Based on available evidence, VR has significant benefits in these types of anxiety disorders. Studies of flight phobia have reported significant and lasting reductions in flight-related anxiety. Patients report satisfaction with VR-based therapy, and in some cases find it more acceptable than traditional therapy.

Virtual reality has been studied in a wide range of conditions as well, including panic disorder, schizophrenia, acute and chronic pain, addictions (including smoking), and eating disorders. However, research on VR applications has important limitations including small numbers of patients and lack of comparison groups. The authors note that mental health care providers will need specific training before integrating VR approaches into clinical practice.

“With the cost of head-mounted displays coming down and smaller smartphone applications being developed, it is likely that virtual reality applications will proliferate,” Dr. Maples-Keller and colleagues conclude. “It will be important that these are treated as tools and therapists are properly trained in their applications.” The authors also note the exciting possibility VR provides to conduct methodologically rigorous and controlled clinical research.

The special issue highlights other emerging uses of technology for mental health treatment. These include internet-based approaches to cognitive-behavioral therapy for depression, “telemental” health approaches enabling remote mental health visits, technology-based interventions for substance abuse and accompanying disorders, and standards for evaluating the quality of smartphone applications designed for patients with schizophrenia. Guest Editors Dawn E. Sugarman, PhD, Scott L. Rauch, MD, and Isabelle M. Rosso, PhD of McLean Hospital and Harvard Medical School write, “In this rapidly evolving field, research is striving to leverage new advances in technology as quickly as they emerge.”

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First clear-cut risk genes for Tourette disorder revealed

Tourette disorder (also known as Tourette syndrome) afflicts as many as one person in a hundred worldwide with potentially disabling symptoms including involuntary motor and vocal tics. However, researchers have so far failed to determine the cause of the disorder, and treatments have only limited effectiveness, in part because the genetics underlying the disorder have remained largely a mystery.

Now, as reported online May 3, 2017 in Neuron, a consortium of top researchers — led by scientists at UC San Francisco, Rutgers University, Massachusetts General Hospital, the University of Florida, and Yale School of Medicine — has made a significant advance, identifying the first “high-confidence” risk gene for Tourette disorder as well as three other probable risk genes. These findings are a step forward in understanding the biology of the disorder, the authors said, which will aid in the search for better treatments.

“In the clinic, I have seen again and again the frustration that patients and families experience because of our lack of understanding and the limitations of our current treatments. But we have now taken a major initial step forward in changing this reality, thanks to new genomic technologies and a very successful long term collaboration between clinicians and geneticists,” said Matthew State, MD, PhD, Oberndorf Family Distinguished Professor and chair of the Department of Psychiatry at UCSF and a co-senior author on the new paper.

Studying Rare Variants to Illuminate Disease Biology

For their new paper, the researchers used an approach that State and colleagues have pioneered in studies of the genetic basis of autism spectrum disorders, and which has led to important discoveries in that field over the past five years.

As in this earlier research, the scientists involved in the Neuron study compared the protein-coding regions of the genomes of children with Tourette disorder to the genomes of their parents to identify so-called de novo variants — rare genetic mutations that are not inherited from parents, but rather occur spontaneously at conception. De novo variants often have stronger biological effects than inherited variants passed from generation to generation, said Jeremy Willsey, PhD, an assistant professor of psychiatry at UCSF and co-lead author of the new paper.

“We study de novo variants even though they are rare because they generally have more extreme effects than inherited mutations and can provide us much information about the underlying causes of a disease,” Willsey said. “This also translates to developing therapies: if these variants greatly increase a child’s risk of Tourette disorder, we would expect that understanding these changes could potentially lead to very effective treatments for the disorder.”

The team analyzed genomic data from 311 “trios” — children with Tourette disorder and their parents, most of whom were unaffected by the disorder — collected by the Tourette International Collaborative Genetics group (TIC Genetics), and found strong evidence that de novo variants can play a significant role in triggering the disorder. To be certain of what they were seeing, the team conducted a replication study in 173 trios from the Tourette Association of America International Consortium for Genetics (TAAICG), and found the same results.

Extrapolating from the number of de novo variants they observed in these relatively small datasets, the researchers were able to estimate that approximately 12 percent of Tourette disorder cases are likely to involve de novo variants, and that these variants probably strike about 400 different key risk genes.

Four Brain-Expressed Genes are Likely Tourette Disorder Risk Factors

In order to gain sufficient statistical power to identify specific genes in which de novo variants disrupt function and contribute to risk of Tourette disorder, the researchers combined the genetic data from the TIC Genetics and TSAICG cohorts — a complex effort led by State, Willsey, and their team at UCSF. The resulting dataset allowed the researchers to zero in on four genes expressed in the brain in which de novo variants were significantly associated with the disorder.

This analysis identified variants of the gene WWC1, also called KIBRA (for “KIdney- and BRAin-expressed protein) — which is involved in brain development, memory, and the brain’s response to the hormone estrogen — as having a greater than 90 percent probability of contributing to Tourette disorder. Three other genes were flagged as having at least 70 percent probability of contributing to the disorder. Of these, two — FN1 and CELSR3 — are also known to be involved in the development of brain circuitry. The third probable risk gene, called NIPBL or Delangin, is involved in regulation of gene expression in the brain, and has previously been associated with the developmental disorder Cornelia de Lange syndrome, as well as anxiety, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder in humans.

The authors anticipate that future studies of de novo variants in a larger number of families affected by Tourette disorder will result in dozens more promising genetic leads, just as State and colleagues have been able to generate for autism spectrum disorders: those findings are driving an explosion in research into the biology of autism that was not possible before the identification of these molecular clues.

“We’ve now done in Tourette disorder what we began five years ago in autism spectrum disorders. These findings shows that Tourette disorder has same path forward, which means there is a very bright future for understanding genetics of the disorder,” said State, who is also director of the Langley Porter Psychiatric Institute and Hospital at UCSF and a member of the Steering Committee for the UCSF Weill Institute for Neurosciences. “The very first study I did as a geneticist was of Tourette disorder, so this has been a 20-year odyssey — and it is deeply gratifying to see this long-term effort across multiple sites and countries lead to real progress.”

Close Collaboration Between Geneticists, Clinicians Made Study Possible

The new study represents a collaborative effort across the two international Tourette disorder genetics consortia: TIC Genetics, founded by State and Jay Tischfield, PhD, of Rutgers, and now led by State, Tischfield and Gary Heiman, PhD, also at Rutgers; and the TSAICG, led by Jeremiah Scharf, MD, PhD, of Massachusetts General Hospital and Carol Mathews, MD, of the University of Florida. Tischfield, Heiman, Scharf, and Mathews are all co-senior authors of the new paper.

“The success of this project, and the identification of an increased burden of rare variants in Tourette disorder reinforces the importance of collaborative science and open data sharing, to which both consortia are strongly committed,” Scharf and Matthews wrote in an email.

The study also depended on a tight collaboration between genetic researchers and the clinicians who work directly with the patients and families whose DNA were central to the new findings, State said. “Our collaborators in this effort are all clinical experts, deeply devoted to Tourette patients and families, in the U.S., Europe and Asia, all of whom have tenaciously worked to keep this project moving forward over the last seven years.”

Adjusting medications may reduce fall risk in older adults

Simply adjusting the dose of an older adult’s psychiatric medication could reduce their risk of falling, a new University of Michigan study suggests.

The study found that a moderate increase in depressive symptoms among people over 65 was associated with a 30 percent increase in experiencing a fall over the next two years, said Geoffrey Hoffman, research fellow and assistant professor at the U-M School of Nursing.

This association appeared, in part, to reflect greater use of psychiatric medications, he said. The study didn’t formally measure the impact of medication use on falls, but when psychiatric medication was included in the experimental model, the relationship between falls and depressive symptoms became nonsignificant, he said.

“We’ve pinpointed that we think the relationship between depression and falls involves medication use with important implications for patient safety and fall risk reduction,” Hoffman said. “Many interventions to prevent falls are expensive and time-intensive, but this is a simple and inexpensive matter of encouraging continued use of psychiatric medication while improving monitoring of fall risk and adjusting medication appropriately.”

While Hoffman and colleagues found that depressive symptoms among older adults preceded falls, they didn’t find the reverse — that a fall is followed by symptoms of depression over the next two years. This is positive in the sense that depression didn’t seem to set in — at least in the time period researchers examined in this study.

The team looked at the risk of falls between 2006 and 2010 among those 65 and older surveyed for the National Health and Retirement Study. When they examined medication use, the strength of the relationship between depressive symptoms and falls decreased.

The takeaway for older adults? Stay active and always be careful to reduce fall risks. Talk to a family member or a physician if you think you’re depressed, and talk to a physician if you have questions about medications.

For families and physicians? Watch for depressive symptoms, and trust that physicians are weighing the risks and benefits of psychiatric medication use. Physicians should pay special attention to properly choosing and dosing medication, and ask older patients about symptoms that indicate fall risks. For purposes of the study, those medications included tranquilizers, antidepressants, and pills for nerves.

Hoffman also said that specialty geriatric societies should highlight depression and medication use in fall risk assessment protocols and encourage physicians treating older adults to be sensitive to fall risks.

Falls among the elderly cost about $30 billion a year, and up to half of nursing home admissions follow a fall. About one-third of Americans 65 or older fall annually and about 10 percent of all elderly people are injured during falls.

The study, “Depressive symptomatology and fall risk among community-dwelling older adults,” appeared in the journal Social Science and Medicine.

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