Increased production of neurons in hypothalamus found in mice fed high fat diets

Hypothalamic proliferative zone. For more details, Nature Neuroscience (2012) doi:10.1038/nn.3079

(Medical Xpress) -- A research team made up of people from a wide variety of biological sciences has found that mice fed a diet high in fat tend to see an increase in the number of neurons created in the hypothalamus, a region of the brain associated with regulating energy use in the body. The team, as they describe in their paper published in Nature Neuroscience, write that the increase in neurons occurs in a part of the hypothalamus called the median eminence, which lies outside the blood-brain barrier.

Suspecting that something unusual goes on with the hypothalamus and the median eminence in particular, when mice eat more fat, the research team put a group of mice on a diet very high in it. In the lab, mice are usually fed a diet that is approximately thirty five percent fat, which keeps them from gaining weight. In this study, the fat content was raised to sixty percent, which of course caused the mice to get fat. But, the team found, it also caused the creation of new brain cells in the median eminence to increase, from one to five percent.

Next the researchers forced the mouse brains to stop creating new brain cells while continuing to feed the mice the high fat diet. And surprisingly, the mice weight gain slowed and the mice demonstrated more energy. Adding to the good news was the fact that the median eminence lies outside of the blood-brain area (a separation of blood and brain fluid that prevents many materials in blood from reaching brain cells) meaning that the possibility of developing a therapy based on this research to help humans lose weight might be possible.

The researchers are quick to point out, however, that there is no evidence yet that increased neuron production occurs in people who eat extra amounts of fat, or even in any other animal. They also say they don’t yet understand why new neuron growth occurs when mice are fed a high-fat diet but speculate that it may have something to do with detecting chemicals in the bloodstream and responding by sending signals to the rest of the hypothalamus.

More information: Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche, Nature Neuroscience (2012)doi:10.1038/nn.3079

Abstract 

Adult hypothalamic neurogenesis has recently been reported, but the cell of origin and the function of these newborn neurons are unknown. Using genetic fate mapping, we found that median eminence tanycytes generate newborn neurons. Blocking this neurogenesis altered the weight and metabolic activity of adult mice. These findings reveal a previously unreported neurogenic niche in the mammalian hypothalamus with important implications for metabolism.

© 2012 Medical Xpress

"Increased production of neurons in hypothalamus found in mice fed high-fat diets." March 26th, 2012. http://medicalxpress.com/news/2012-03-production-neurons-hypothalamus-mice-fed.html

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Brain 'talks over' boring speech quotes

(Medical Xpress) -- Storytelling is a skill not everyone can master, but even the most crashing bore gets help from their audience’s brain which ‘talks over’ their monotonous quotes, according to scientists.

Researchers from the University of Glasgow’s Institute of Neuroscience and Psychology investigated the ‘voice-selective’ areas of the brain and revealed that when listening to someone monotonously repeating direct speech quotations, the brain will ‘talk over’ the speaker to make the quotes more vivid.

Previously, the researchers had shown the brain ‘talks’ when silently reading direct quotations.

Dr Bo Yao, the principal investigator of the study, said: “You may think the brain need not produce its own speech while listening to one that is already available.

“But, apparently, the brain is very picky on the speech it hears. When the brain hears monotonously-spoken direct speech quotations which it expects to be more vivid, the brain simply ‘talks over’ the speech it hears with more vivid speech utterances of its own.”

Dr Bo Yao explains why the brain 'talks over' boring speech:

The research was conducted by Dr Yao and colleagues Professor Pascal Belin and Professor Christoph Scheepers within the Institute’s Centre for Cognitive Neuroimaging.

The team enlisted 18 participants in the study and scanned their brains using functional magnetic resonance imaging (fMRI) while they listened to audio clips of short stories containing direct or indirect speech quotations. The direct speech quotations -- e.g., Mary said excitedly: “The latest Sherlock Holmes film is fantastic!” – were either spoken ‘vividly’ or ‘monotonously’ (i.e., with or without much variation in speech melody).

The results showed that listening to monotonously spoken direct speech quotations increased brain activity in the ‘voice-selective areas’ of the brain. These voice-selective areas – originally discovered by Prof Belin – are certain areas of the auditory cortex which are particularly interested in human voices when stimulated by actual speech sounds perceived by the ears.

However, the present and previous studies also reveal that these areas can be activated by different linguistic reporting styles – such as direct versus indirect speech.

Prof Scheepers said: “Direct speech quotations are generally assumed to be more vivid and perceptually engaging than indirect speech quotations as they are more frequently associated with depictions of voices, facial expressions and co-speech gestures.

“When the brain does not receive actual stimulation of auditory speech during silent reading, it tends to produce its own to enliven written direct speech quotations – a phenomenon commonly referred to as the ‘inner voice’ during silent reading. Now it appears the brain does the same even when listening to monotonously-spoken direct speech quotations.”

Dr Yao added: “This research demonstrates that human speech processing is an active process in which the brain generates models for the incoming speech utterances in order to predict actual auditory input.

“By doing so, the brain attempts to optimise the processing of the incoming speech, ensuring more speedy and accurate responses.

“These predictions are probably grounded in our past experiences in which direct speech is frequently associated with vivid depictions of the reported speaker’s voice whereas indirect speech is usually stated in a more flat and steady tone.

“The brain’s ‘talking over’ monotonously spoken direct quotes seems to reflect that it tries to bridge the incongruence between the expected speech utterances (vivid) and the actually perceived speech (monotonous) by simulating or imagining the expected vivid vocal depictions.

“We believe that such a simulation mechanism is an integral part of language comprehension -- we naturally recruit our sensory and motor systems to interpret the language input. Language processing, in this sense, is embodied.”

The research paper ‘Brain “talks over” boring quotes: Top-down activation of voice-selective areas while listening to monotonous direct speech quotations’ is published in NeuroImage.

Provided by University of Glasgow

"Brain 'talks over' boring speech quotes." March 26th, 2012. http://medicalxpress.com/news/2012-03-brain-speech-quotes.html

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Smokers could be more prone to schizophrenia, study finds

Smoking alters the impact of a schizophrenia risk gene. Scientists from the universities of Zurich and Cologne demonstrate that healthy people who carry this risk gene and smoke process acoustic stimuli in a similarly deficient way as patients with schizophrenia. Furthermore, the impact is all the stronger the more the person smokes.

Schizophrenia has long been known to be hereditary. However, as a melting pot of disorders with different genetic causes is concealed behind manifestations of schizophrenia, research has still not been able to identify the main gene responsible to this day.

In order to study the genetic background of schizophrenia, the frequency of particular risk genes between healthy and ill people has mostly been compared until now. Pharmacopyschologist Professor Boris Quednow from University Hospital of Psychiatry, Zurich, and Professor Georg Winterer's workgroup at the University of Cologne have now adopted a novel approach. Using electroencephalography (EEG), the scientists studied the processing of simple acoustic stimuli (a sequence of similar clicks). When processing a particular stimulus, healthy people suppress the processing of other stimuli that are irrelevant to the task at hand. Patients with schizophrenia exhibit deficits in this kind of stimulus filtering and thus their brains are probably inundated with too much information. As psychiatrically healthy people also filter stimuli with varying degrees of efficiency, individual stimulus processing can be associated with particular genes.

In a large-scale study involving over 1,800 healthy participants from the general population, Boris Quednow and Georg Winterer examined how far acoustic stimulus filtering is connected with a known risk gene for schizophrenia: the so-called "transcription factor 4" gene (TCF4). TCF4 is a protein that plays a key role in early brain development. As patients with schizophrenia often smoke, the scientists also studied the smoking habits of the test subjects.

The data collected shows that psychiatrically healthy carriers of the TCF4 gene also filter stimuli less effectively – like people who suffer from schizophrenia. It turned out that primarily smokers who carry the risk gene display a less effective filtering of acoustic impressions. This effect was all the more pronounced the more the people smoked. Non-smoking carriers of the risk gene, however, did not process stimuli much worse. "Smoking alters the impact of the TCF4 gene on acoustic stimulus filtering," says Boris Quednow, explaining this kind of gene-environment interaction. "Therefore, smoking might also increase the impact of particular genes on the risk of schizophrenia." The results could also be significant for predicting schizophrenic disorders and for new treatment approaches, says Quednow and concludes: "Smoking should also be considered as an important cofactor for the risk of schizophrenia in future studies." A combination of genetic (e.g. TCF4), electrophysiological (stimulus filtering) and demographic (smoking) factors could help diagnose the disorder more rapidly or also define new, genetically more uniform patient subgroups.

More information: Boris B. Quednow et al. Schizophrenia risk polymorphisms in the TCF4 gene interact with smoking in the modulation of auditory sensory gating. In: PNAS, March 26, 2012. DOI: 10.1073/pnas.1118051109

Provided by University of Zurich

"Smokers could be more prone to schizophrenia, study finds." March 26th, 2012. http://medicalxpress.com/news/2012-03-smokers-prone-schizophrenia.html

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Internet does not make young people abandon traditional media: study

Almost all 9- to 24-year-old Swedes use the internet. Most of them do so daily, and the older they are, the more they use it. Yet, this does not mean that they have ceased using traditional media, says Professor Olle Findahl, who has conducted a study on young people's media habits on behalf of NORDICOM at the University of Gothenburg, Sweden.

Admittedly, people in this age group do watch TV and listen to radio and recorded music somewhat less today than 30 years ago. The same trend can be observed for reading, especially when it comes to educational textbooks and nonfiction. However, children and adolescents still use traditional media more than the internet. In fact, schoolchildren (age 9-14) spend a whole 75 percent of their media time on traditional media; for the age group 15-24 the proportion is 60 percent.

Similar to what happened when television came about in the 1950s, it seems like people use the internet to complement and not substitute older media. The internet provides young people with music and films. Then there is the entirely new behaviour that is made possible through social networks – contacts with like-minded individuals who share the same interests.

The social network Facebook has a greater reach among young people than newspapers, and almost the same reach as TV. And the reach of the digital music service Spotify comes close to that of radio. However, this does not mean that everything that has to do with the internet automatically becomes popular. For example, relatively few young individuals use tablet computers, e-books and the Twitter microblog service. Yet the use of so-called smartphones has increased by several hundred percent in only two years.

It should be noted that there is no direct negative correlation between internet use and the use of traditional media. Instead, the most intense internet users are also heavy consumers of traditional media.

Provided by University of Gothenburg

"Internet does not make young people abandon traditional media: study." March 26th, 2012.http://www.physorg.com/news/2012-03-internet-young-people-abandon-traditional.html

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Rising Of Great Universal Warrior Shree Surya Narayanan - Shirdi Baba's ...

First-ever link between tiny genetic structures, imminent heart attack risk discovered

 by Biomechanism 

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Findings by Intermountain Medical Center Heart Institute team an important step forward.

SALT LAKE CITY — Researchers at the Intermountain Medical Center Heart Institute have, for the first time ever, made a connection between tiny genetic molecules called microRNAs and the imminent threat of a heart attack, according to a new study.

The findings are an important first step toward developing a method for predicting heart attacks in people who show no outward signs, but may be at great risk of having a heart attack. The research group presented study results yesterday (March 25) at the American College of Cardiology’s 61st Annual Scientific Session in Chicago.

“About half of all heart attacks occur in patients with no previous signs of heart disease. The heart attack is a surprise, and very often it’s deadly,” says Jeffrey L. Anderson, MD, chief of cardiovascular research at the Intermountain Medical Center Heart Institute and one of the study’s authors. “This project has a lot of promise in helping us develop a way to identify these patients who don’t show any obvious signs but are at imminent risk of suffering a heart attack.”

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The research group from Intermountain Medical Center, the flagship facility for the Intermountain Healthcare system, examined blood samples for the presence of six microRNA molecules that had previously been identified in patients after a heart attack. These genetic structures serve as an “on-off switch” for regulating the expression of a host of genes. When their levels drop, the genes they help to control are no longer regulated and can go “rogue.”

The blood samples came from 85 patients who were sorted into four groups:

• Pre-heart attack patients, whose blood was drawn one to seven days before a heart attack
• Post-heart attack patients, whose blood was drawn within 36 hours after a heart attack
• Patients with cardiac problems, but no heart attack within one year before or after blood sample collection
• Healthy patients with no cardiac problems

“We found that three of those six microRNA molecules were present in significantly lower levels in patients who had a heart attack within the next seven days compared to the two groups who didn’t have a heart attack,” says Oxana Galenko, who holds a doctorate in biomedical science and is lead author of the study.

The researchers believe the low levels of microRNA and the resulting genetic dysfunction may herald the heart attack. The three microRNAs are known as miR-122, miR-145, and miR-375.

“We don’t know exactly which genes are controlled by these microRNAs, but this study gives us a good starting point for looking more deeply into the ways they influence the heart,” says John Carlquist, PhD, director of Intermountain Healthcare’s Cardiovascular Molecular and Genetic Laboratory at LDS Hospital and one of the study’s authors.

The researchers envision a day in the not-too-distant future when a patient with cardiac risk factors does regular blood testing to watch for signs of imminent heart attack. Developments in nanotechnology one day may make it possible to continuously monitor an individual’s blood for changes in these markers and alert a physician at any sign of danger.

The group says this study was possible only at Intermountain Healthcare, which helped to pioneer computerized health data collection in the 1950s and continues today. Intermountain is home to the world’s largest cardiovascular DNA and plasma bank repository, which includes samples from more than 20,000 consenting patients. Combining these resources allowed researchers to search medical records for patients who had a heart attack and also had a frozen blood sample in storage that was drawn in the days before the heart attack.

“Because of this trove of patient records and specimens, we’re uniquely equipped to do a study like this,” says Dr. Carlquist.

The group will continue their research into microRNAs and heart attack with another study looking at a larger sample of patients, says Dr. Galenko.

_________

Members of the research team include: Oxana Galenko, Tyler Miyawaki, Staci Gunter, Stacey Knight, John Carlquist and Jeffrey L. Anderson.

High-Throughput Screening Finds Surprising Properties for Antioxidants: Some Compounds Can Damage DNA, but May Treat Cancer

Researchers have demonstrated that some antioxidants damage DNA and kill cells instead of protecting them. The findings also suggest that this surprising capability may be good for treating cancer, but may prove cautionary when using antioxidant-based medicines to treat other disorders, such as diabetes.

Science Daily  — Antioxidants have long been thought to have anti-aging properties, primarily by protecting a person's genetic material from damaging chemicals. The story, however, now appears to be much more complicated.

"It's an unexpected discovery," says Kyungjae Myung, Ph.D., a senior investigator in the Genetics and Molecular Biology Branch of the National Human Genome Research Institute (NHGRI), and the senior author on the report. "It may have important clinical applications in treating people with cancer, especially if they have failed previous treatments."National Institutes of Health researchers from two institutes and one center have demonstrated that some antioxidants damage DNA and kill cells instead of protecting them. The findings, published in theProceedings of the National Academy of Sciences on March 19, 2012, also suggest that this surprising capability may be good for treating cancer, but may prove cautionary when using antioxidant-based medicines to treat other disorders, such as diabetes.

Many people attempt to boost their levels of antioxidants by eating fruits and vegetables, nuts and grains, or by taking vitamins such as A, C, E and beta-carotene, among others. Some research suggests that antioxidants soak up compounds called free radicals produced by burning oxygen during normal respiration. Free radicals cause random chemical reactions that can damage cellular components, including DNA, leading to disease. By adding antioxidants to the diet, many people hope to slow down the process that some believe contributes to the normal process of aging.

Dr. Myung did not set out to challenge this anti-aging strategy, and the new findings may not fundamentally alter the approach; much more study will be needed. Instead, his lab studies DNA repair, the enzyme systems within a cell that fix mistakes and other damage that routinely accumulate in DNA as cells simply live and divide to make daughter cells. Researchers know that naturally occurring defects in DNA repair can lead to a number of disorders, including cancer.

To study DNA repair, Dr. Myung's group sought a new way to easily identify chemicals that damage DNA and then use those chemicals to study cellular repair mechanisms, a basic research question. Using a laboratory grown cell line from human kidneys, the NHGRI team, which included Jennifer Fox, Ph.D., lead author and post-doctoral fellow, developed a novel laboratory test, or assay, that readily shows when a chemical exposure damages DNA.

With the test developed, Dr. Myung's team formed collaborations with two other NIH research groups: The first was with what is now the NIH National Center for Advancing Translational Sciences (NCATS). Over the last several years, a team led by Christopher Austin, M.D., head of the NCATS laboratories, has developed high-throughput chemical screening systems using robotics. Dr. Austin agreed to use Dr. Myung's assay to rapidly test thousands of chemicals for their ability to damage DNA. But what chemicals should they test?

In 2008, the NIH Chemical Genomics Center, then part of NHGRI and now at NCATS, the National Institute of Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (EPA) formed an initiative called Tox21 to develop high-throughput screening tests that measure cellular harm caused by environmental chemicals. The Tox21 team created a library of some 2,000 compounds and agreed to test them against Dr. Myung's assay. The NHGRI researchers also added a commercially available chemical collection to the screening runs for a total of some 4,000 chemicals.

The screening runs produced surprises, identifying 22 antioxidants that damaged DNA. Three of the antioxidants -- resveratrol, genistein and baicalein -- are currently used -- or being studied -- to treat several disorders, including heart disease, type 2 diabetes, osteopenia and osteoporosis and chronic hepatitis, as well as serving as an anti-aging treatment.

Not only did the antioxidants damage the DNA, the researchers found, but also, in dividing cells (such as in tumors), the antioxidants can be lethal, killing the disease-causing cells.

"This is what's cool about biology," Dr. Austin said. "Just when we think we understand something, it turns out to be more complex than we thought. Not only did the NHGRI team produce a novel way to measure DNA damage, but their test has given us insights into the effects of chemical compounds that were not seen in more conventional strategies."

The discovery opens up several new lines of research. As a first step, the collaborators are dramatically expanding the number of compounds -- more than 300,000 -- that will be tested with the new assay. The Tox21 team also has decided to include the NHGRI test in its standard screen for biological harm produced by environmental chemicals.

The clinical implications for these findings are more complicated. This initial discovery is only in lab-grown cell lines, not even in intact organisms. The relevance for humans has yet to be demonstrated.

Still, there is plenty of work already underway. Other researcher teams had launched various studies of these DNA-damaging antioxidants in various diseases. For example, 44 studies are currently listed in www.clinicaltrials.gov for resveratrol, which is found in many foods, including red grapes and wine, peanuts and chocolate. The studies focus on treating Alzheimer's disease, type 2 diabetes, obesity, inflammation, colon cancer, multiple myeloma, and testing other anti-aging strategies, among others. The newly reported study does not suggest that resveratrol in red wine is harmful; the dose is probably too low to be significant, Dr. Myung said.

Researchers also have launched 43 studies on genistein, including trials to treat cancers of the prostate, pancreas, bladder, breast, kidney and skin (metastatic melanoma) and as adjunct treatments for rare diseases such as cystic fibrosis.

Even though the antioxidants damaged the DNA, the researchers reported that the chemicals did not cause genetic mutations, another surprise. "Because they don't cause genetic mutations, antioxidants may be useful for treating cancer," Dr. Myung said. "Standard chemotherapy mutates the tumor's DNA, speeding its evolution and sometimes allowing it to escape the toxic treatment intended to kill it. This leads to multi-drug resistance in some cancer patient's disease."

To test whether the antioxidants might help, the NHGRI team borrowed some multi-drug resistant cancer cells from Dr. Michael Gottesman, a National Cancer Institute researcher and NIH Deputy Director for Intramural Research. Although these cells are very resistant to anti-cancer drugs, treatment with resveratrol appeared to sensitize the cancer cells, leading to their death. "Resveratrol," Dr. Myung said, "could prove useful in treating multi-drug resistant cancers."

The findings do raise concerns about using antioxidants to treat disorders, as treatment with high doses may cause unexpected DNA damage that leads to other problems. "Clearly," Dr. Myung said, "much more study will be needed."

Highly flexible despite hard-wiring -- even slight stimuli change the information flow in the brain

Images or cups? Due to the rapid reorganisation of networks in the brain, we perceive different image elements. Credit: Demian Battaglia/ MPI for Dynamics and Self-Organization

One cup or two faces? What we believe we see in one of the most famous optical illusions changes in a split second, and so does the path that the information takes in the brain. In a new theoretical study, scientists of the Max Planck Institute for Dynamics and Self-Organization, the Bernstein Center Göttingen and the German Primate Center now show how this is possible without changing the cellular links of the network. The direction of information flow changes depending on the time pattern of communication between brain areas. This reorganisation can be triggered even by a slight stimulus, such as a scent or sound, at the right time.

The way how the different regions of the brain are connected with each other plays a significant role for information processing. This processing can be changed by the assembling and disassembling of nerve fibres joining distant brain circuits. But such events need to be faster to explain rapid changes in perception. From experimental studies it was known that the responsible actions must be at least two orders of magnitude faster. The Göttingen scientists now show for the first time that it is possible to change the information flow in a tightly interconnected network in a simple manner.

Many areas of the brain display a rhythmic nerve cell activity. "The interacting brain areas are like metronomes that tick at the same speed and in a distinct temporal pattern," says the physicist and principal investigator Demian Battaglia. The researchers were now able to demonstrate that this temporal pattern determines the information flow. "If one of the metronomes is affected, e.g. through an external stimulus, then it changes beat, ticking in an altered temporal pattern compared to the others. The other areas adapt to this new situation through self-organisation and start playing a different drum beat as well. It is therefore sufficient to impact one of the areas in the network to completely reorganize its functioning, as we have shown in our model," explains Battaglia.

The applied perturbation does not have to be particularly strong. "It is more important that the 'kick' occurs at exactly the right time of the rhythm," says Battaglia. This might play a significant role for perception processes: "When viewing a picture, we are trained to recognize faces as quickly as possible – even if there aren't any," points out the Göttingen researcher. "But if we smell a fragrance reminiscent of wine, we immediately see the cup in the picture. This allows us to quickly adjust to things that we did not expect, changing the focus of our attention."

Next, the scientists want to test the model on networks with a more realistic anatomy. They also hope that the findings inspire future experimental studies, as Battaglia says: "It would be fantastic if, in some years, certain brain areas could be stimulated so finely and precisely that the theoretically predicted effects can be measured through imaging methods."

More information: Battaglia D, Witt A, Wolf F, Geisel T (2012): Dynamic effective connectivity of inter-areal brain circuits. PLoS Comp Biol, 10.1371/journal.pcbi.1002438

Provided by Max-Planck-Gesellschaft

"Highly flexible despite hard-wiring -- even slight stimuli change the information flow in the brain." March 23rd, 2012.http://medicalxpress.com/news/2012-03-highly-flexible-hard-wiring-slight.html

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Possible causes of sudden onset obsessive compulsive disorder in kids broadened

Children with PANS and PANDAS sometimes experience sudden loss of fine motor skills. Source: Susan Swedo, M.D., NIMH Pediatric and Developmental Neuroscience Branch

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.

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.

Provided by National Institutes of Health

"Possible causes of sudden onset obsessive compulsive disorder in kids broadened." March 23rd, 2012. http://medicalxpress.com/news/2012-03-sudden-onset-obsessive-compulsive-disorder.html

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