life through alen spa

life through alen spa

Excessive worrying may have co-evolved with intelligence

What is usually seen as pathology may aid survival of the species

Worrying may have evolved along with intelligence as a beneficial trait, according to a recent study by scientists at SUNY Downstate Medical Center and other institutions. Jeremy Coplan, MD, professor of psychiatry at SUNY Downstate, and colleagues found that high intelligence and worry both correlate with brain activity measured by the depletion of the nutrient choline in the subcortical white matter of the brain. According to the researchers, this suggests that intelligence may have co-evolved with worry in humans.

"While excessive worry is generally seen as a negative trait and high intelligence as a positive one, worry may cause our species to avoid dangerous situations, regardless of how remote a possibility they may be," said Dr. Coplan. "In essence, worry may make people 'take no chances,' and such people may have higher survival rates. Thus, like intelligence, worry may confer a benefit upon the species."

In this study of anxiety and intelligence, patients with generalized anxiety disorder (GAD) were compared with healthy volunteers to assess the relationship among intelligence quotient (IQ), worry, and subcortical white matter metabolism of choline. In a control group of normal volunteers, high IQ was associated with a lower degree of worry, but in those diagnosed with GAD, high IQ was associated with a greater degree of worry. The correlation between IQ and worry was significant in both the GAD group and the healthy control group. However, in the former, the correlation was positive and in the latter, the correlation was negative. Eighteen healthy volunteers (eight males and 10 females) and 26 patients with GAD (12 males and 14 females) served as subjects.

Previous studies have indicated that excessive worry tends to exist both in people with higher intelligence and lower intelligence, and less so in people of moderate intelligence. It has been hypothesized that people with lower intelligence suffer more anxiety because they achieve less success in life.

The results of their study, "The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism," was published in a recent edition of Frontiers in Evolutionary Neuroscience, and can be read at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269637/pdf/fnevo-03-00008.pdf.

The study was selected and evaluated by a member of the Faculty of 1000 (F1000), placing it in their library of the top 2% of published articles in biology and medicine.

SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient's bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, Colleges of Nursing and Health Related Professions, a School of Graduate Studies, a School of Public Health, University Hospital of Brooklyn, and an Advanced Biotechnology Park and Biotechnology Incubator.

SUNY Downstate ranks eighth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school social worker continuing education

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 Southvestern. 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

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realistic optimist

realistic optimist

Antipsychotic drug may be helpful treatment for anorexia nervosa

Mouse model of anorexia offers opportunity to study drugs effective for disorder

Low doses of a commonly used atypical antipsychotic drug improved survival in a mouse model of anorexia nervosa, University of Chicago researchers report this month. The result offers promise for a common and occasionally fatal eating disorder that currently lacks approved drugs for treatment.

Mice treated with small doses of the drug olanzapine were more likely to maintain their weight when given an exercise wheel and restricted food access, conditions that produce activity-based anorexia (ABA) in animals. The antidepressant fluoxetine, commonly prescribed off-label for anorexic patients, did not improve survival in the experiment.

"We found over and over again that olanzapine was effective in harsher conditions, less harsh conditions, adolescents, adults — it consistently worked," said the paper's first author Stephanie Klenotich, graduate student in the Committee on Neurobiology at the University of Chicago Biological Sciences.

The study, published in Neuropsychopharmacology, was the product of a rare collaboration between laboratory scientists and clinicians seeking new treatment options for anorexia nervosa. As many as one percent of American women will suffer from anorexia nervosa during their lifetime, but only one-third of those people will receive treatment.

Patients with anorexia are often prescribed off-label use of drugs designed for other psychiatric conditions, but few studies have tested the drugs' effectiveness in animal models.

"Anorexia nervosa is the most deadly psychiatric disorder, and yet no approved pharmacological treatments exist," said Stephanie Dulawa, PhD, assistant professor of Psychiatry & Behavioral Neuroscience at the University of Chicago Medicine and senior author of the study. "One wonders why there isn't more basic science work being done to better understand the mechanisms and to identify novel pharmacological treatments."

One challenge is finding a medication that patients with anorexia nervosa will agree to take regularly, said co-author Daniel Le Grange, PhD, professor of Psychiatry & Behavioral Neuroscience and director of the Eating Disorders Clinic at the Univershty of Chicago Medicine. Drugs that directly cause weight gain or carry strong sedative side effects are often rejected by patients.

"Patients are almost uniformly very skeptical and very reluctant to take any medication that could lower their resolve to refrain from eating," Le Grange said. "There are long-standing resistances, and I think researchers and clinicians have been very reluctant to embark on that course, since it's just littered with obstacles."

Both fluoxetine and olanzapine have been tried clinically to supplement interventions such as family-based treatment and cognitive-behavioral therapy. But their direct effect on anorexia nervosa behavior — in humans or animals — is lacking in sufficient data.

To test the effectiveness of these drugs in laboratory mice, Klenotich adapted the ABA protocol from previously published rat studies: Mice given 24-hour access to a running wheel but only six hours a day of food access become hyperactive, eat less and rapidly lose weight, with a 25 percent reduction from baseline considered to be the "drop-out" survival point.

In Klenotich's study, mice were pretreated with fluoxetine, olanzapine or saline before starting the ABA protocol, and treatment continued throughout the ABA period. Researchers then measured how many mice in each group reached the drop-out point for weight loss over 14 days of food restriction and exercise wheel access. Treatment with the antipsychotic olanzapine significantly increased survival over the control group, while fluoxetine treatment produced no significant effects on survival.

Importantly, a low dose of olanzapine did not decrease overall running activity in the mice, indicating that sedative effects of the drug were minimal. In future experiments, the researchers hope to use different drugs and genetic methods to determine exactly how olanzapine is effective against symptoms of anorexia nervosa, perhaps pointing toward a better drug without the negative image or side effects of an antipsychotic.

"We can dissect the effect of olanzapine and hopefully identify the mechanisms of action, and identify what receptor systems we want to target," Klenotich said. "Hopefully, we can develop a newer drug that we can aim towards the eating disorders clinic as an anorexic-specific drug that might be a little more acceptable to patients."

The study offers support for the clinical use of olanzapine, for which clinical trials are already under way to test in patients. Le Grange said the development of a pharmacological variant that more selectively treats anorexia nervosa could be a helpful way to avoid the "stigma" of taking an antipsychotic while giving clinicians an additional tool for helping patients.

"I think the clinical field is certainly very ready for something that is going to make a difference," Le Grange said. "I'm not saying there's a 'magic pill' for anorexia nervosa, but we have been lacking any pharmacological agent that clearly contributes to the recovery of our patients. Many parents and many clinicians are looking for that, because it would make our job so much easier if there was something that could turn symptoms around and speed up recovery."

Additionally, the study demonstrated the innovative experimental design and translational results that can come from a collaboration of laboratory and clinical experts.

"We don't talk to one another often enough in basic science and clinical science," Le Grange said. "More of that would be helpful for clinicians to understand the neurobiology of this disease. I'm very excited about the way this project is going, and I think it's going to be clinically very informative."


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The paper, "Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice," was published online March 7 by Neuropsychopharmacology (doi: 10.1038/npp.2012.7). In addition to Klenotich, Dulawa and Le Grange, authors include Mariel Seiglie and Priya Dugad of the University of Chicago and Matthew S. McMurray and Jamie Roitman of the University of Illinois at Chicago. Funding for the research was provided by the National Institute of Mental Health.

For more news from the University of Chicago Medical Center, follow us on Twitter at @UChicagoMed, or visit our Facebook page at facebook.com/UChicagoMed, our research blog at sciencelife.uchospitals.edu, or our newsroom at uchospitals.edu/news. counselor ceus

Scripps Research Institute Team Wrests Partial Control of a Memory

News Release

The work advances understanding of how memories form and offers new insight into disorders such as schizophrenia and post traumatic stress disorder

LA JOLLA, CA – March 22, 2012 – Scripps Research Institute scientists and their colleagues have successfully harnessed neurons in mouse brains, allowing them to at least partially control a specific memory. Though just an initial step, the researchers hope such work will eventually lead to better understanding of how memories form in the brain, and possibly even to ways to weaken harmful thoughts for those with conditions such as schizophrenia and post traumatic stress disorder.

Researchers have known for decades that stimulating various regions of the brain can trigger behaviors and even memories. But understanding the way these brain functions develop and occur normally—effectively how we become who we are—has been a much more complex goal.

“The question we’re ultimately interested in is: How does the activity of the brain represent the world?” said Scripps Research neuroscientist Mark Mayford, who led the new study. “Understanding all this will help us understand what goes wrong in situations where you have inappropriate perceptions. It can also tell us where the brain changes with learning.”

On-Off Switches and a Hybrid Memory

As a first step toward that end, the team set out to manipulate specific memories by inserting two genes into mice. One gene produces receptors that researchers can chemically trigger to activate a neuron. They tied this gene to a natural gene that turns on only in active neurons, such as those involved in a particular memory as it forms, or as the memory is recalled. In other words, this technique allows the researchers to install on-off switches on only the neurons involved in the formation of specific memories.

For the study’s main experiment, the team triggered the “on” switch in neurons active as mice were learning about a new environment, Box A, with distinct colors, smells and textures continuing education for counselors

Next the team placed the mice in a second distinct environment—Box B—after giving them the chemical that would turn on the neurons associated with the memory for Box A. The researchers found the mice behaved as if they were forming a sort of hybrid memory that was part Box A and part Box B. The chemical switch needed to be turned on while the mice were in Box B for them to demonstrate signs of recognition. Alone neither being in Box B nor the chemical switch was effective in producing memory recall.

“We know from studies in both animals and humans that memories are not formed in isolation but are built up over years incorporating previously learned information,” Mayford said. “This study suggests that one way the brain performs this feat is to use the activity pattern of nerve cells from old memories and merge this with the activity produced during a new learning session.”

Future Manipulation of the Past

The team is now making progress toward more precise control that will allow the scientists to turn one memory on and off at will so effectively that a mouse will in fact perceive itself to be in Box A when it’s in Box B.

Once the processes are better understood, Mayford has ideas about how researchers might eventually target the perception process through drug treatment to deal with certain mental diseases such as schizophrenia and post traumatic stress disorder. With such problems, patients’ brains are producing false perceptions or disabling fears. But drug treatments might target the neurons involved when a patient thinks about such fear, to turn off the neurons involved and interfere with the disruptive thought patterns.

In addition to Mayford, other authors of the paper, “Generation of a Synthetic Memory Trace,” are Aleena Garner, Sang Youl Hwang, and Karsten Baumgaertel from Scripps Research, David Rowland and Cliff Kentros from the University of Oregon, Eugene, and Bryan Roth from the University of North Carolina (UNC), Chapel Hill.

This work is supported by the National Institute of Mental Health, the National Institute on Drug Abuse, the California Institute for Regenerative Medicine, and the Michael Hooker Distinguished Chair in Pharmacology at UNC.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation. For more information, see www.scripps.edu.

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Possibld Causes of Sudden Onset OCD in Kids Broadened

NIH Immune-Based Treatment Study Underway

Criteria for a broadened syndrome of acute onset obsessive compulsive disorder (OCD) have been proposed by a National Institutes of Health scientist and her colleagues. The syndrome, Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), includes children and teens that suddenly develop on-again/off-again OCD symptoms or abnormal eating behaviors, along with other psychiatric symptoms – without any known cause nursing ceus

PANS expands on Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS), which is limited to a subset of cases traceable to an autoimmune process triggered by a strep infection. A clinical trial testing an immune-based treatment for PANDAS is currently underway at NIH and Yale University (see below).

“Parents will describe children with PANS as overcome by a ‘ferocious’ onset of obsessive thoughts, compulsive rituals and overwhelming fears,” said Susan Swedo, M.D., of the NIH’s National Institute of Mental Health (NIMH), who first characterized PANDAS two decades ago. “Clinicians should consider PANS when children or adolescents present with such acute-onset of OCD or eating restrictions in the absence of a clear link to strep.”

Swedo, James Leckman, M.D., of Yale University, and Noel Rose, M.D., Ph.D. of Johns Hopkins University, propose working criteria for PANS in February 2012 in the open source journal Pediatrics & Therapeutics.

“As the field moves toward agreement on this broadened syndrome, affected youth will be more likely to receive appropriate care, regardless of whether they are seen by a neurologist, pediatrician or child psychiatrist,” said NIMH Director Thomas R. Insel, M.D.

Differing causes sharing a “common presentation”

The PANS criteria grew out of a PANDAS workshop convened at NIH in July 2010, by the NIMH Pediatric and Developmental Neuroscience Branch, which Swedo heads. It brought together a broad range of researchers, clinicians and advocates. The participants considered all cases of acute-onset OCD, regardless of potential cause.

Clinicians reported that evaluations of more than 400 youth diagnosed with PANDAS confirmed that affected boys outnumbered girls 2:1, with psychiatric symptoms, always including OCD, usually beginning before 8 years.

Although debate continues about the fine points, the field is now of one mind on the core concept of “acute and dramatic” onset of a constellation of psychiatric symptoms. There is also broad agreement on the need for a “centralized registry” that will enable the research community to analyze evidence from studies that will eventually pinpoint causes and treatments. Such a registry is currently under development by members of the International Obsessive Compulsive Foundation (IOCDF).

Since a diagnosis of PANS implies no specific cause, clinicians will have to evaluate and treat each affected youth on a case-by-case basis.

“PANS will likely turn out to include a number of related disorders with different causes that share a common presentation,” explained Swedo.

The authors propose that a patient must meet 3 diagnostic criteria for a diagnosis of PANS:
1.Abrupt, dramatic onset of OCD or anorexia.
2.Concurrent presence of at least two additional neuropsychiatric symptoms with similarly severe and acute onset. These include: anxiety; mood swings and depression; aggression, irritability and oppositional behaviors; developmental regression; sudden deterioration in school performance or learning abilities; sensory and motor abnormalities; somatic signs and symptoms.
3.Symptoms are unexplainable by a known neurologic or medical disorder.

Among the wide range of accompanying symptoms, children may appear terror stricken or suffer extreme separation anxiety, shift from laughter to tears for no apparent reason, or regress to temper tantrums, “baby talk” or bedwetting. In some cases, their handwriting and other fine motor skills worsen dramatically. Leckman’s team at the Yale Child Study Center is in the process of developing assessment tools for diagnosing the syndrome.

PANDAS treatment study targets errant antibodies

Meanwhile, Swedo, Leckman, and Madeleine Cunningham of the University of Oklahoma, and colleagues, are collaborating on a new, multi-site placebo-controlled study, testing the effectiveness of intravenous immunoglobulin (IVIG) for reducing OCD symptoms in children with PANDAS.

Previous human and animal research suggested mechanisms by which strep-triggered antibodies mistakenly attack specific brain circuitry, resulting in obsessional thoughts and compulsive behaviors.

“Strep bacteria has evolved a kind of camouflage to evade detection by the immune system,” Swedo explained. “It does this by displaying molecules on its cell wall that look nearly identical to molecules found in different tissues of the body, including the brain. Eventually, the immune system gets wise to this ‘molecular mimicry,’ recognizes strep as foreign, and produces antibodies against it; but because of the similarities, the antibodies sometimes react not only with the strep, but also with the mimicked molecules in the human host. Such cross-reactive ‘anti-brain’ antibodies can cause OCD, tics, and the other neuropsychiatric symptoms of PANDAS.”

IVIG, a medication derived from normal antibodies, neutralizes such harmful antibodies, restoring normal immune function. It is used to treat other autoimmune illnesses and showed promise in a pilot study with PANDAS patients.

“We predict that IVIG will have striking benefits for OCD and other psychiatric symptoms, and will prove most effective for children who show high levels of anti-brain antibodies when they enter the study,” said Swedo.

Prospective study participants are first screened by phone by investigators at the NIH or the Yale Child Study Center. Those who meet eligibility requirements are then randomized to receive either active IVIG or a placebo procedure during a brief inpatient stay at the NIH Clinical Center. The researchers remain blind to which children received the active medication; after 6 weeks of placebo control, they give any children whose symptoms fail to improve the option to receive open-label active treatment.

In addition to assaying for antibodies that attack brain cells, the researchers use magnetic resonance imaging to see if the treatment reduces inflammation in an area of the brain known as the basal ganglia, which is thought to be the target of the errant antibodies. They also analyze levels of immune system chemical messengers (cytokines) in cerebrospinal fluid and blood – with an eye to identifying biomarkers of disease activity and potential predictors of treatment response.

The study was launched with support from the NIH Clinical Center’s Bench to Bedside program, which encourages such intramural-extramural collaborations in translational science.