Altered Neural Circuitry May Lead to Anorexia and Bulimia
Anorexia nervosa and bulimia nervosa –disorders characterized by extreme eating behavior and distorted body image – are among the deadliest of psychiatric disorders, with few proven effective treatments.
A landmark study, with first author Tyson Oberndorfer, MD, and led by Walter H. Kaye, MD, professor of psychiatry at the University of California, San Diego School of Medicine, suggests that the altered function of neural circuitry contributes to restricted eating in anorexia and overeating in bulimia. The research, published June 4 in the early on-line edition of the American Journal of Psychiatry, may offer a pathway to new and more effective treatments for these serious eating disorders.
“It has been unknown whether individuals with anorexia or bulimia have a disturbance in the system that regulates appetite in the brain, or whether eating behavior is driven by other phenomena, such as an obsessional preoccupation with body image,” said Kaye, director of the UCSD Eating Disorders Treatment and Research Program. “However, this study confirms earlier studies by our group and others that establish a clear link between these disorders and neural processes in the insula, an area of the brain where taste is sensed and integrated with reward to help determine whether an individual hungry or full.”
The UC San Diego study used functional MRI to test this neurocircuitry by measuring the brain response to sweet tastes in 28 women who had recovered from either anorexia or bulimia.
These photomicrographs depict comparative stained sections of a healthy brain (top) and of patient EP, in which significant structures in the medial temporal lobe are heavily damaged or missing. The letters identify specific brain structures, such as EC and PRC for entorhinal cortex and perirhinal cortex, respectively, both important to memory formation and function.
Gone, But Not Forgotten
UC San Diego scientists recall EP, perhaps the world’s second-most famous amnesiac
An international team of neuroscientists has described for the first time in exhaustive detail the underlying neurobiology of an amnesiac who suffered from profound memory loss after damage to key portions of his brain.
Writing in this week’s Online Early Edition of PNAS, principal investigator Larry R. Squire, PhD, professor in the departments of Neurosciences, Psychiatry and Psychology at the University of California, San Diego School of Medicine and Veteran Affairs San Diego Healthcare System (VASDHS) – with colleagues at UC Davis and the University of Castilla-La Mancha in Spain – recount the case of EP, a man who suffered radical memory loss and dysfunction following a bout of viral encephalitis.
EP’s story is strikingly similar to the more famous case of HM, who also suffered permanent, dramatic memory loss after small portions of his medial temporal lobes were removed by doctors in 1953 to relieve severe epileptic seizures. The surgery was successful, but left HM unable to form new memories or recall people, places or events post-operation.
HM (later identified as Henry Gustav Molaison) was the subject of intense scientific scrutiny and study for the remainder of his life. When he died in 2008 at the age of 82, he was popularized as “the world’s most famous amnesiac.” His brain was removed and digitally preserved at The Brain Observatory, a UC San Diego-based lab headed by Jacopo Annese, PhD, an assistant adjunct professor in the Department of Radiology and a co-author of the PNAS paper.
Like Molaison, EP was also something of a scientific celebrity, albeit purposefully anonymous. In 1992, at the age of 70, he was diagnosed with viral encephalitis. He recovered, but the illness resulted in devastating neurological loss, both physiologically and psychologically.
Not only did he also lose the ability to form new memories, EP suffered a modest impairment in his semantic knowledge – the knowledge of things like words and the names of objects. Between 1994, when he moved to San Diego County, and his death 14 years later, EP was a subject of continued study, which included hundreds of different assessments of cognitive function.
“The work was long-term,” said Squire, a Career Research Scientist at the VASDHS. “We probably visited his house 200 times. We knew his family.” In a 2000 paper, Squire and colleagues described EP as a 6-foot-2, 192-pound affable fellow with a fascination for the computers used in his testing. He was always agreeable and pleasant. “He had a sense of humor,” said Squire.
National Recognition for Three UC San Diego School of Medicine Chairs
Lewis L. Judd, MD, Distinguished Professor and chair of the Department of Psychiatry, Arno J. Mundt, MD, professor and chair of the Department of Radiation Medicine and Applied Sciences, and Robert N. Weinreb, MD, Distinguished Professor of Ophthalmology, chair of the Department of Ophthalmology and director of the Shiley Eye Center have received recognition from national medical societies.
New Workshop Helps Doctors Avoid Burnout, Increase Wellbeing
On Saturday, May 11, the Center for Mindfulness at University of California, San Diego School of Medicine is hosting a workshop to help physicians and clinicians increase job satisfaction and prevent burnout. The program will show participants how to incorporate the concept of mindfulness into their daily clinical practice with the long-term goal of enhancing patient-centered care and physician well-being through compassionate communication.
“This is a unique opportunity for clinicians to learn to take better care of themselves and their patients through attentive and mindful interactions in every moment,” said Steven Hickman, PsyD, director, UC San Diego Center for Mindfulness. “Practicing medicine mindfully can increase a clinician’s sense of well-being and the ability to empathize with each patient they encounter. This may result in fewer medical errors, greater self-awareness, and the ability to see a situation from multiple perspectives before reacting.”
The day-long course is designed to introduce participants to the components of mindfulness practice, how awareness of interpersonal communication can improve office dynamics, and how to avoid mental and physical burnout. Experiential exercises will help attendees better respond to the suffering of patients by exploring common reactions to chronic illness and pain and an analysis of personal reactions to it.
Effects of Alcoholism: a Q & A with Marc Schuckit, Distinguished Professor of Psychiatry
The overconsumption of alcohol kills 2.5 million people each year around the globe, according to the World Health Organization. It is a major factor in many neuropsychiatric disorders and a risk factor for cardiovascular diseases, cirrhosis of the liver and various cancers.
The effects of alcohol abuse are felt far beyond the physical and psychological effects of the drinker. From drunk driving fatalities to booze-fueled violence and other behavioral disorders, alcohol abuse leaves a lasting, damaging mark on individuals and society.
Marc Schuckit, MD, is a Distinguished Professor of psychiatry at the University of California, San Diego School of Medicine and editor of the Journal of Studies on Alcohol and Drugs. He has spent his career studying the causes and effects of alcohol use and abuse. We asked for a status report.
Q: Where do you rate alcohol consumption as a social and public health problem? Is it trending up or down? Where do you see the most cause for alarm?
A: It’s close to number one. It’s a worldwide problem. Alcohol use is one of the leading risk factors in the overall burden of disease, especially among men age 15 to 60. The U.S. has an average consumption rate per person per year somewhere between eight and 10 liters of absolute alcohol. That’s somewhere in the middle among countries worldwide, but it’s still one heck of a lot of booze. Alcohol use disorders, such as dependence and the problems associated with these conditions, are much more common than, say, illicit drug disorders, as important as they are.Whether the problem is trending up or down depends upon who you’re reading. Excessive alcohol consumption has been a bad problem for decades. Not a lot has changed. It remains a bad problem.
Q: To what degree can abuse and dependence on alcohol, or alcoholism, be attributed to genetics? Does a biological predisposition outweigh all other factors?
A: If you use the general definition of alcohol abuse and dependence, this basically reflects severe repetitive problems with alcohol. The condition is roughly 60 percent genetic. Nonetheless, that still means the environment and environmental interaction with genetics is almost half the picture.The fact that researchers are now finding some genes related to the disease can help with identifying it and people at higher risk. This knowledge can help start early prevention. It’s also possible that understanding something about the genetics will help with treatment, though not always.
Q: One of your major studies concluded that sensitivity to the effects of alcohol strongly influences risk of alcohol dependence. Can you elaborate?
A: One of the characteristics through which the genes for alcohol abuse and dependence operate is the ability to consume fairly large amounts of alcohol, but have relatively little effect. This is associated with a probability of drinking a lot more per occasion than some other people and carries a higher risk for alcohol problems in the long run. Depending upon a range of factors, including their genetic make-up, other people experience a lot of effects after a few drinks, which means they have a higher sensitivity per drink, a characteristic often related to a lower alcoholism risk.We think we’ve found some of the genes that are associated with the low alcohol sensitivity (or low effect per drink) and that we may be able to use this information to identify people at greater risk and educate them. This would be very useful when working with, say, adolescents.
Q: In your opinion, what has been the most interesting or surprising discovery in alcohol research over the last decade or so?
A: For me, it’s the findings about alcohol sensitivity, which are the opposite of what we initially thought. We had hypothesized that the people at high risk for alcohol abuse and dependence were those with a higher effects, but that’s not what we found. People who can drink a lot without obvious effect tend to drink a lot and they hang out with other people who drink a lot.
Using imaging research, it looks like this low sensitivity to alcohol may be related to how the brain is processing information. People who have a low sensitivity process some kinds of information with a little bit less efficiency than others. They’re as smart as anybody else, it’s just a different intensity in the way the brain is working. That, in turn, might interfere with their ability to recognize effects of more moderate doses of alcohol.
![Paradox of Aging: The Older We Get, the Better We Feel?
Presently, there are about 40 million Americans over the age of 65, with the fastest-growing segment of the population over 80 years old. Traditionally, aging has been viewed as a period of progressive decline in physical, cognitive and psychosocial functioning, and aging is viewed by many as the “number one public health problem” facing Americans today.
But this negative view of aging contrasts with results of a comprehensive study of 1,006 older adults in San Diego by researchers from the University of California, San Diego School of Medicine and Stanford University. Results of the Successful Aging Evaluation (SAGE) study – comprising a 25-minute phone interview, followed by a comprehensive mail-in survey – will be published in the December 7 online issue of the American Journal of Psychiatry.
“While there is a growing public health interest in understanding and promoting successful aging, until now little published research has combined measures of physical health with cognitive and psychological assessments, in a large and randomly selected sample,” said principal investigator Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of UC San Diego’s Stein Institute for Research on Aging, and the current President of the American Psychiatric Association (which was not involved in this study).
The SAGE study included adults between the ages of 50 and 99 years, with a mean age of just over 77 years. In addition to measures which assessed rates of chronic disease and disability, the survey looked at more subjective criteria such as social engagement and participants’ self-assessment of their overall health.
“Sometimes the most relevant outcomes are from the perspective of the subjects themselves,” said Jeste.
The study concludes that resilience and depression have significant bearing on how individuals self-rate successful aging, with effects that are comparable to that of physical health. “Even though older age was closely associated with worse physical and cognitive functioning, it was also related to better mental functioning,“ said co-author Colin Depp, PhD, associate professor of psychiatry at UC San Diego School of Medicine.
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After adjusting for age, a higher self-rating of successful aging was associated with higher education, better cognitive function, better perceived physical and mental health, less depression, and greater optimism and resilience.
Participants were asked to rate the extent to which they thought they had “successfully aged,” using a 10-point scale and using their own concept of the term. The study found that people with low physical functioning but high resilience, had self-ratings of successful aging similar to those of physical healthy people with low resilience. Likewise, the self-ratings of individuals with low physical functioning but no or minimal depression had scores comparable to those of physically healthy people with moderate to severe depression.
“It was clear to us that, even in the midst of physical or cognitive decline, individuals in our study reported feeling that their well-being had improved with age,” Jeste said. This counterintuitive increase in well-being with aging persisted even after accounting for variables like income, education and marriage.
Jeste suggests there’s a take-away message for clinicians, which is that an optimistic approach to the care of seniors may help reduce societal ageism. “There is considerable discussion In public forums about the financial drain on the society due to rising costs of healthcare for older adults – what some people disparagingly label the ‘silver tsunami.’ But, successfully aging older adults can be a great resource for younger generations,” he said.
The findings point to an important role for psychiatry in enhancing successful aging in older adults. “Perfect physical health is neither necessary nor sufficient,” Jeste said. “There is potential for enhancing successful aging by fostering resilience and treating or preventing depression.”](http://25.media.tumblr.com/fc09a27f378f103f1e02372f65e55fa9/tumblr_meo6jbT88r1qievavo1_1280.jpg)
Paradox of Aging: The Older We Get, the Better We Feel?
Presently, there are about 40 million Americans over the age of 65, with the fastest-growing segment of the population over 80 years old. Traditionally, aging has been viewed as a period of progressive decline in physical, cognitive and psychosocial functioning, and aging is viewed by many as the “number one public health problem” facing Americans today.
But this negative view of aging contrasts with results of a comprehensive study of 1,006 older adults in San Diego by researchers from the University of California, San Diego School of Medicine and Stanford University. Results of the Successful Aging Evaluation (SAGE) study – comprising a 25-minute phone interview, followed by a comprehensive mail-in survey – will be published in the December 7 online issue of the American Journal of Psychiatry.
“While there is a growing public health interest in understanding and promoting successful aging, until now little published research has combined measures of physical health with cognitive and psychological assessments, in a large and randomly selected sample,” said principal investigator Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of UC San Diego’s Stein Institute for Research on Aging, and the current President of the American Psychiatric Association (which was not involved in this study).
The SAGE study included adults between the ages of 50 and 99 years, with a mean age of just over 77 years. In addition to measures which assessed rates of chronic disease and disability, the survey looked at more subjective criteria such as social engagement and participants’ self-assessment of their overall health.
“Sometimes the most relevant outcomes are from the perspective of the subjects themselves,” said Jeste.
The study concludes that resilience and depression have significant bearing on how individuals self-rate successful aging, with effects that are comparable to that of physical health. “Even though older age was closely associated with worse physical and cognitive functioning, it was also related to better mental functioning,“ said co-author Colin Depp, PhD, associate professor of psychiatry at UC San Diego School of Medicine.
![Card 10 in Hermann Rorschach’s original inkblot series. You can see the entire series and how Nazi leaders Adolph Eichmann, Hermann Goering and Albert Speer interpreted the images here, courtesy of Cabinet magazine
Judgments after Nuremberg
As a young professor of psychiatry in the 1970s, Joel E. Dimsdale studied concentration camp survivors – and their families – in the years after World War II. What were the psychological consequences of their suffering and trauma? What mechanisms did they use to cope?
One day a man came to visit Dimsdale at his Boston office. He had heard the professor speak and believed Dimsdale should study another group as well: the Nazi perpetrators who had conceived and implemented the camps that resulted in the murder of millions.
The man said he had met some of Nazi leaders.
The man had killed some of them.
“He was one of the executioners at the Nuremberg trials,” recalled Dimsdale, now a professor emeritus in the UC San Diego School of Medicine.
The trials, of course, were a series of highly publicized, history-making military tribunals held by Allied victors to judge and punish the surviving remnants of Nazi German leadership after the war. Scores of political, military and public officials were tried, most notably 22 defendants in the Bavarian city of Nuremberg over several months in 1945 and 1946.
These were some of Nazi Germany’s most notorious leaders: Field Marshall Hermann Goering, deputy Fuhrer Rudolf Hess, army head Wilhelm Keitel, SS leader Ernst Kaltenbrunner, and interior minister Wilhelm Frick, who had co-authored the Nazi’s anti-Semitic Race Laws introduced in 1935 in, ironically, Nuremberg.
Though Dimsdale continued and expanded his psychiatric research, ultimately conducting hundreds of studies about stress, sleep and how patients cope with severe illness over a long and distinguished career, he took the advice of the Nuremberg executioner and eventually wrote a book about the trials and efforts to better understand the psychology of the accused.
“One of the great questions of psychology is the anatomy of malice,” said Dimsdale, “and nowhere is that subject more compelling than in trying to explain the behavior of the accused war criminals at Nuremberg. Were they inherently depraved monsters or ordinary men corrupted by power and circumstances? Were they somewhere on a continuum of human behavior or distinctly different? How did they get that way?”
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Dimsdale’s book – Survivors, Victims and Perpetrators: Essays on the Nazi Holocaust – was published in 1980. It’s now out-of-print, but Dimsdale has recently resumed his ruminations on the subject, speaking at public lectures and grand rounds. The story he tells is a psychological thriller. Sixty-six years after the trials ended, it remains a tale fraught with twists and unanswered mysteries.
In 1945, two American military officers were tasked with profiling the Nazi prisoners at Nuremberg: Major Douglas M. Kelley and Lt. Gustave M. Gilbert. It was, according to Dimsdale, “the collaboration from hell.”
Kelley and Gilbert developed a deep and enduring dislike of each other. In part, it may have been because they came from distinctly different backgrounds: Kelley was a native, upper class San Franciscan. He had a medical degree at UC San Francisco and doctorate in medical science from Columbia University. Gilbert was the New York-born son of Jewish-Austrian immigrants. He attended the School for Ethical Culture on a scholarship, then earned a psychology degree at Columbia.
Not surprisingly, Kelley and Gilbert also came to very different conclusions about their Nazi subjects. Some of that difference derived from one of the tests they conducted at Nuremberg: the Rorschach.
Though eventually eclipsed by shorter, simpler and cheaper methods, the Rorschach test was a common personality assessment tool in the middle decades of the last century. Developed by Swiss psychiatrist Hermann Rorschach, it consists of a series of 10 abstract ink blots, some with color. Test-takers are asked to describe what they see in each image. Test-givers analyze these answers, looking for response patterns that reflect specific personality traits.
The Rorschach test can be effective, said Dimsdale, but it requires carefully controlled testing conditions and expertise in accurately interpreting patient responses. “They have a deceptive air of simplicity, but they’re very complex to score.” Though quite famous in psychological circles, the Rorschach tests at Nuremberg were fundamentally flawed.
“Kelley was an expert on Rorschach testing; Gilbert wasn’t,” said Dimsdale. “Gilbert spoke German; Kelley didn’t. He had to rely upon a translator. In both cases, there are real questions about the validity of the work.”
After conducting their own independent tests, Kelley and Gilbert arrived at different assessments. “Kelley said the Nazis were no different from anyone else with power. They were on a continuum of evil,” said Dimsdale. “Gilbert thought they were vicious, depraved psychopaths who were distinctly evil.”
Gilbert despised all of the Nazis without exception. Kelley got along with several of them, most notably Goering, who would eventually ask Kelley if he would adopt his daughter after Goering’s execution. Kelley declined and Goering, in fact, avoided execution by taking a fatal potassium cyanide pill the night before he was scheduled to be hanged.
(Interestingly, the Nazis at Nuremberg seemed to welcome and enjoy the tests, according to Eric Zillmer, a professor of neuropsychology at Drexel University who wrote his own account in The Quest for the Nazi Personality in 1995. The Nazis, Zillmer said, believed the tests might affirm that they were a superior race. Plus, they were often bored in the weeks leading up to the actual trials. The tests became a sort of amusing competition among them.)
Neither Kelley’s nor Gilbert’s Rorschach results were used in the trials. They never became part of the official court proceedings. Instead, the results became part of a different story.
In 1947, a Rorschach expert named Molly Harrower asked 10 leading psychologists to interpret the test results. All 10 declined. The results remained largely ignored until 1975 when Harrower revisited the issue, provoking a fierce debate between those who thought the Rorschach tests revealed major psychopathology and those who weren’t so certain.
Harrower asked a panel of Rorschach experts to review the Nuremberg test results, which were not identified and which were mixed with test results from contemporary psychiatric patients and Unitarian ministers. The experts found no single, uniform, abnormal personality that could serve to explain Nazi behavior.
“That’s what people would have liked. It would be simpler and more comforting if we could just say the Nazis were different from the rest of us,” said Dimsdale. “But nothing proved that they were consistently, manifestly different. Rather, the results suggest that people will do evil under certain circumstances.”
Kelley said much the same thing in his own 1947 book 22 Cells at Nuremberg. His Nuremberg test results, however, have never been made public. Today, they are stored in the archives of the Chicago Psychoanalytic Society.
In later life, Gilbert continued to focus upon the nature of Nazi psychology. In 1950, he published a psychological profile of Adolf Hitler based upon deductions derived from his interviews at Nuremberg. In 1961, he testified at the Jerusalem trial of the Nazi fugitive Adolf Eichmann, describing again his interviews at Nuremberg that linked Eichmann to the Holocaust killings. The court did not include Gilbert’s psychological analyses as part of his testimony.
Gilbert, who became a psychology professor at Long Island University in Brooklyn, NY, died in 1977 at the age of 66.
Kelley died much earlier and far more mysteriously.
After Nuremberg, Dimsdale said Kelley “seemed to get on with his life.” He returned to California and became a noted professor of psychiatry and criminology at UC Berkeley. But he also reportedly began drinking and occasionally flew into rages. On New Year’s Day in 1958, the 45-year-old Kelley appeared in front of his family at home with a cyanide pill between his teeth. He bit down and died.
Kelley’s death was eerily similar to Goering’s suicide a dozen years earlier. The source of Kelley’s cyanide has never been determined.](http://25.media.tumblr.com/tumblr_mebb0wynp21qievavo1_1280.jpg)
Card 10 in Hermann Rorschach’s original inkblot series. You can see the entire series and how Nazi leaders Adolph Eichmann, Hermann Goering and Albert Speer interpreted the images here, courtesy of Cabinet magazine
Judgments after Nuremberg
As a young professor of psychiatry in the 1970s, Joel E. Dimsdale studied concentration camp survivors – and their families – in the years after World War II. What were the psychological consequences of their suffering and trauma? What mechanisms did they use to cope?
One day a man came to visit Dimsdale at his Boston office. He had heard the professor speak and believed Dimsdale should study another group as well: the Nazi perpetrators who had conceived and implemented the camps that resulted in the murder of millions.
The man said he had met some of Nazi leaders.
The man had killed some of them.
“He was one of the executioners at the Nuremberg trials,” recalled Dimsdale, now a professor emeritus in the UC San Diego School of Medicine.
The trials, of course, were a series of highly publicized, history-making military tribunals held by Allied victors to judge and punish the surviving remnants of Nazi German leadership after the war. Scores of political, military and public officials were tried, most notably 22 defendants in the Bavarian city of Nuremberg over several months in 1945 and 1946.
These were some of Nazi Germany’s most notorious leaders: Field Marshall Hermann Goering, deputy Fuhrer Rudolf Hess, army head Wilhelm Keitel, SS leader Ernst Kaltenbrunner, and interior minister Wilhelm Frick, who had co-authored the Nazi’s anti-Semitic Race Laws introduced in 1935 in, ironically, Nuremberg.
Though Dimsdale continued and expanded his psychiatric research, ultimately conducting hundreds of studies about stress, sleep and how patients cope with severe illness over a long and distinguished career, he took the advice of the Nuremberg executioner and eventually wrote a book about the trials and efforts to better understand the psychology of the accused.
“One of the great questions of psychology is the anatomy of malice,” said Dimsdale, “and nowhere is that subject more compelling than in trying to explain the behavior of the accused war criminals at Nuremberg. Were they inherently depraved monsters or ordinary men corrupted by power and circumstances? Were they somewhere on a continuum of human behavior or distinctly different? How did they get that way?”
Four Common Antipsychotic Drugs Found to Lack Safety and Effectiveness in Older Adults
In older adults, antipsychotic drugs are commonly prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications – schizophrenia and bipolar disorder. The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia, some of which carry FDA warnings on prescription information for these drugs.
In a new study – led by researchers at the University of California, San Diego School of Medicine, Stanford University and the University of Iowa, and funded by the National Institute of Mental Health – four of the antipsychotics most commonly prescribed off label for use in patients over 40 were found to lack both safety and effectiveness. The results will be published November 27 in The Journal of Clinical Psychiatry.
The study looked at four atypical antipsychotics (AAPs) – aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) – in 332 patients over the age of 40 diagnosed with psychosis associated with schizophrenia, mood disorders, PTSD, or dementia.
“Our study suggests that off-label use of these drugs in older people should be short-term, and undertaken with caution,” said Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of the Stein Institute for Research on Aging at UC San Diego.
Results of the five-year study led by Jeste, who is also current president of the American Psychiatric Association (which was not involved in this research), showed that within one year of treatment, one-third of the patients enrolled in the study developed metabolic syndrome (medical disorders that can increase the risk of cardiovascular disease or diabetes). Within two years, nearly a quarter of the patients developed serious adverse effects and just over half developed non-serious adverse effects.
Because the patients enrolled in the study were all diagnosed with conditions with psychotic symptoms that required antipsychotic drug treatment according to their treating physicians, no placebo was used in the trial. Instead, the researchers used a technique called “equipoise stratified randomization” which is a hybrid of complete randomization and a clinician’s choice method.
“Our goal was to ensure clinical relevance,” said Jeste. Patients had to agree to be randomized to 2, 3 or 4 of the study drugs, as they or their physicians were allowed to exclude one or two of the study AAPs, due to past experience or anticipated risk of the particular drug. Treating clinicians could determine the optimal dosage. “We attempted to make the study as ‘user-friendly’ as possible, to allow the drugs the best chance of success, while seeking to minimize the amount of bias,” he explained.
While the researchers’ intent was to continue the patients on the randomized medications for two years, the average length turned out to be only six months, after which the medications were halted or switched because they didn’t work and/or had side effects.
Because of a notably high incidence of serious adverse events, quetiapine had to be discontinued midway through the trial. The researchers found that there were significant differences among patients willing to be randomized to different AAPs – thus, treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with existing metabolic problems. Yet, the different AAP groups did not appreciably differ in most outcome measures.
Using a common scale called the Brief Psychiatric Rating Scale (BPRS), to measure symptoms such as delusions, hallucinations, unusual behavior, depression, and anxiety, assessments were made at 6 weeks, 12 weeks, and then every 12 weeks. Results using “blind” raters showed no significant improvement in BPRS over a six-month period.
“While there were a few significant differences among the four drugs, the overall risk-benefit ratio for the AAPs in patients over age 40 was not favorable, irrespective of diagnosis and drug,” said Jeste.
Jeste points out that clinicians, patients, and caregivers are often left with difficult and unclear choices for treatment for older persons with psychosis, such as that associated with dementia. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there are no FDA-approved alternatives to antipsychotics for this population, and the high cost of newer AAPs also makes their use problematic.
While the researchers say their findings do not suggest that these AAPs should be banned in older patients with psychiatric disorders, they do indicate that considerable caution is warranted in off-label, long-term use of the drugs in older persons.
“When these medications are used off-label, they should be given in low dosages and for short durations, and their side effects monitored closely,” said Jeste. “Clearly, there is also a critical need to develop and test new interventions that are safe and effective in older people with psychotic disorders.”
“Bridging the Hearts and Minds of Youth Conference” Opens Registration
UCSD Center for Mindfulness helps raise compassionate generation with Jon Kabat-Zinn
The Center for Mindfulness at University of California, San Diego School of Medicine announces early registration for the 2013 Bridging the Hearts and Minds of Youth Conference, February 1 – 3 in San Diego, California. Mindfulness leader Jon Kabat-Zinn, PhD – along with his wife Myla and experts from across the U.S. – will show participants how to support and foster the growth of mindfulness and happiness, especially among youths.
“The topic of bringing mindfulness to youth has virtually exploded in recent years as people realize the toll that modern society and technology is putting on our kids and families,” said Steven D. Hickman, PsyD, clinical psychologist, director of the UC San Diego Center for Mindfulness. “Our presenters practice mindfulness at home, in classrooms and therapy rooms. They will share their key findings, challenges and successes with each other to help raise a generation of healthier children and students.”
The 2013 program, hosted at the Catamaran Hotel in San Diego, California, will be headlined by noted mindfulness teacher, Kabat-Zinn, author of Wherever You Go There You Are, Coming to Our Senses and Full Catastrophe Living. His keynote lecture, “Befriending Your Mind, Befriending Your Life: Mindfulness and the Endless Adventure of Growing into Yourself,” will benefit the UC San Diego Family & Child Programs. Kabat-Zinn and his wife, Myla, will also host a 3-hour workshop on Mindful Parenting, based on their book Everyday Blessings.
Image courtesy of Dan Anderson www.danandersonphoto.com
Using Biomarkers to Identify and Treat Schizophrenia
Researchers say lab-based tests may be boon to both clinicians and researchers
In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder.
“A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes,” said Gregory A. Light, PhD, associate professor of psychiatry and the study’s first author. “Diagnoses are currently based on a clinician’s ability to make inferences about patients’ inner experiences.”
Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors.
“Schizophrenia is among the most severe and disabling conditions across all categories of medicine,” said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System.
The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families.
Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient’s inner experiences. That is, their ability to describe what’s happening inside their minds.
