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Saturday, August 31, 2013

Autistic Kids Can Outgrow Critical Sensory Disconnect, Study Finds

From WBUR 90.9 FM's CommonHealth Blog

By Karen Weintraub
August 29, 2013

For many people, the “read-my-lips” phenomenon happens almost unconsciously: in a crowded or noisy room, most of us can hear better by watching the person’s lips form the sounds.

That’s not true for many people with autism. They have long reported being unable to pay attention to words and visuals at the same time — which may explain why some on the spectrum avoid looking others in the eye. They have to limit their visual information so they can hear what the person is saying.

In the last few years, researchers have finally begun to take these reports seriously and to investigate them.

In a paper out this week in the journal Cerebral Cortex, researchers at Albert Einstein College of Medicine in the Bronx showed that children with autism struggle to integrate information from multiple senses. High functioning children with autism, ages 5-12, didn’t get the benefit most people do from watching a person’s lips moving while speaking over background noise, according to research led by professor of pediatrics John Foxe.

Older children with autism did get this benefit, though, Foxe found, suggesting that their ability to integrate senses comes together by the mid-teens – at least in children described as high functioning, which generally means they have fewer language impairments.



Autism is a spectrum of social and communication challenges and repetitive behaviors that can range from a little unusual to completely disabling. Some people are unable to speak or function in society; others are university professors.

This improvement in sensory integration with age may explain why some people seem to recover from or outgrow autism as they reach adolescence, Foxe said, though he didn’t follow the same kids over time, so he can’t be sure that those who fared the best were also the ones who got better at integrating sensory information.

He also can’t yet explain why this improvement happens. “Is it a brain maturation process, is it to do with socialization, is it to do with the interventions these kids are getting? The jury is out right now,” he said.

But he has no doubt that it’s profound.


He suspects that the difference in sensory integration may explain the difference between someone who is described as high- or low-functioning. Improve the sensory integration, and the person may be able function more typically.

That has implications for future treatment, and also how we educate kids on the spectrum today.

Foxe is doing some initial outreach to therapists who could help design methods for improving sensory integration.

He said he also thinks we need to make an effort to improve current classroom situations. If these kids are already struggling, it doesn’t make sense to put them in busy, chaotic classrooms and then expect them to learn, he said. Even simple things like headphones to block out background noise might make a major difference, he said.

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Karen Weintraub is a Cambridge-based health/science journalist and frequent contributor to CommonHealth. She is on Twitter @kweintraub.

Prenatal Pesticide Exposure May Raise Risk of Attention Issues in Kids

From HealthDay.com News via MedicineNet.com

By Amanda Gardner
August 19, 2010

Scientists have noted a possible increased risk for attention disorders in children who were exposed to organophosphate pesticides while in the womb.

The effect was not significant at the age of 3 but clearly showed at age 5, according to the report from California researchers that appears in the August 19 issue of Environmental Health Perspectives.

Bernard Weiss, a professor of environmental medicine at the University of Rochester Medical Center, said the time delay of the effects didn't surprise him.

Monkey studies have shown the same thing, with the actual behavioral problems not manifesting until the "brain had become mature enough to support that kind of complex behavior," he explained.

In kids, "you wouldn't really see [hyperactivity] bloom until the child gets into school," he added.

Although the findings are far from establishing a causal link, Weiss said he thought "these are very significant studies and are another form of warning to us about how many kinds of unrecognized threats there are to child development in the environment."

According to study senior author Brenda Eskenazi, the past five or seven years have seen a number of studies looking at low-dose organophosphate exposure in children's neurodevelopment. Prior to this, researchers' interest had concentrated on high-dose exposure.

Now, including this study, three studies have now found effects of low-dose exposure on neurodevelopment, including one earlier this year that found that exposure to high levels of organophosphate pesticides could raise the odds for attention-deficit/hyperactivity disorder (ADHD).

The current findings were based on attention tests given to more than 300 children of Mexican-American farm workers in the Salinas Valley of California. The researchers also took measures of organophosphate metabolites in the mothers' urine and collected behavioral reports from the mothers and from professional observers.

Although there was only a small link between attention problems and exposure at the younger age, the association became significantly larger at age 5, especially among boys.

"We saw that the children were making more errors on the test, and that it was significantly related to the mother's prenatal metabolite levels for these pesticides," said Eskenazi, who is director of the Center for Children's Environmental Health Research at the University of California Berkeley School of Public Health.

It bears noting that these children had much higher exposure levels than the "average" kid.

And "attention problems are so multifactorial that it would be hard to say that this is a major agent if it is causal at all," she added.

A second paper by the same group of researchers that appears in the same journal reported that "children don't have the level of an enzyme needed to metabolize these organophosphates the same as adults until they're much older than we expected," said Eskenazi. "Their metabolism is different, and now we have hard evidence of that."

There's also "suggestive evidence" that some children may harbor genetic variations that make them more susceptible to the neurocognitive effects of pesticides.

"If research consistently shows that symptoms of ADHD are related to the quantity of the organophosphate pesticide exposure, then it seems prudent for families to at least try to limit exposure," said Dr. Nakia Scott, a clinical assistant professor of psychiatry and behavioral science at Texas A&M Health Science Center College of Medicine and a child psychiatrist with Lone Star Circle of Care.

There are several things people can do to protect themselves.

"You can wash produce thoroughly before you eat and try to invest in organic produce when you can," she added. "This may [also] be a reason to grow your own garden. Or families can consider using less toxic alternatives when taking care of lawns."

Sources


Brenda Eskenazi, Ph.D., Maxwell professor of maternal and child health and epidemiology, and director, Center for Children's Environmental Health Research, University of California Berkeley School of Public Health; Bernard Weiss, Ph.D., professor, environmental medicine, University of Rochester Medical Center, Rochester, N.Y.; Nakia Scott, M.D., clinical assistant professor, psychiatry and behavioral science, Texas A&M Health Science Center College of Medicine, and child psychiatrist, Lone Star Circle of Care; August 19, 2010, Environmental Health Perspectives

Friday, August 30, 2013

More Links Seen Between Autism and ADHD

From HealthDay.com

By Dennis Thompson
August 26, 2013

Kids with attention-deficit/hyperactivity disorder (ADHD) are 20 times more likely to exhibit some traits of autism than children without ADHD, according to a new study.

One of every five ADHD kids in the study exhibited signs of autism such as slow language development, difficulty interacting with others and problems with emotional control, said study co-author Dr. Joseph Biederman, director of the pediatric psychopharmacology unit at Massachusetts General Hospital.

These kids also showed problems with "executive function," or the ability to plan, organize and conceptualize future action, said Biederman, a professor of psychiatry at Harvard Medical School.

Fewer than 1 percent of kids in the non-ADHD comparison group exhibited any traits linked to autism, according to the study appearing in the September issue of Pediatrics.

"These children are not having the full diagnosis of autism, but they have symptoms of autism," Biederman said. "It may be important to screen children with ADHD for autistic traits because they may need more support, particularly in the educational and interpersonal domains."

Previous studies of children with autism have found that many also have severe ADHD symptoms. This is one of the first studies to turn the tables and see if the reverse is true, said Dr. Alice Mao, an associate professor of psychiatry at Baylor College of Medicine. She was not involved with the study.

"Generally, autistic kids with ADHD are challenging to treat because they don't respond well to ADHD medications," Mao said. "You have to treat the autism symptoms and then treat the ADHD. The conclusion would be that perhaps we should screen these ADHD kids who are not doing well on traditional ADHD treatments to see if they have comorbid autism traits."

The study included 242 kids aged 6 to 18 with ADHD as well as a 227-member "control" group of kids without ADHD. The children were drawn from an existing large-scale sample pool that excluded any kids who had been diagnosed with autism.

The children and their parents filled out a series of questionnaires to grade their behavior and compare it to generally accepted definitions of autistic traits.

The researchers found that 18 percent of kids with ADHD exhibited some behaviors that are common in autism, compared with 0.87 percent of kids from the control group.

The ADHD children with autistic traits had many more social problems than typical ADHD children. They were more likely to fight with and be rejected by other kids, and displayed more school behavior problems, more difficulties using their spare time and more friction with their siblings, the study authors noted.

The children with both ADHD and autistic traits also tended to more frequently suffer additional psychiatric and learning disorders than either kids with only ADHD or children in the control group.

"Those with autism traits have greater severity of symptoms and dysfunction," Mao said. "Certainly it would be useful to screen kids with ADHD who have autism traits to see which kids may need more help socially, as well as to make sure they don't have lower intellectual functioning. You may be able to give other treatments that would be helpful in terms of improving their functioning."

These findings, along with previous research, point to the strong possibility that ADHD and autism share some genetic link, study author Biederman said.

"The genetic markers for ADHD have also been associated with autism," he said. "These autistic traits may be present in other conditions as well. I am quite convinced that these traits may be present in children with mood and anxiety disorders."

Thursday, August 29, 2013

Ritalin Reaction

From SFARI.org - The Simons Foundation Autism Research Initiative

By Laura Geggel
August 23, 2013

The stimulant methylphenidate, commonly marketed as Ritalin, can quiet hyperactive behavior and increase focus among children who have both autism and attention deficit hyperactivity disorder (ADHD).

But some hyperactive children with autism can't tolerate the drug and suffer side effects such as nausea, mood swings and appetite loss after just a few doses.


These children may have a genetic intolerance to the drug, suggests a new study published 16 July in the journal Pharmacogenomics.


Hyperactive drive: About half of children with autism
and hyperactivity respond to Ritalin, according
to ratings from parent and teacher surveys.

Up to 75 percent of children with autism have characteristics of ADHD, including inattention and impulsivity. About one-third of these children take stimulants such as Ritalin for their ADHD symptoms.

In a 2005 study of 72 children with autism, hyperactivity and inattention,
35 children responded well to Ritalin, 14 dropped out after experiencing strong side effects and the rest showed little or no improvement. The children, who were 5 to 14 years of age, were not taking other medications.

The new study examined variants in the genes of 58 of these children. The researchers focused on several genes coding for receptors and transporters of dopamine, norepinephrine and serotonin — chemical signals that regulate mood and higher-order cognitive function.

During the first week of the five-week study in 2005, the children took first a placebo and then increasing doses of Ritalin to test their response to the drug. Over the following four weeks, they received varying doses of Ritalin in a random order, or a placebo, but were unaware which they were taking.

The researchers then asked those who responded well to the Ritalin to continue taking it for the following eight weeks.

The children’s parents and teachers filled out surveys at the start of the study and while it was underway, rating the children’s day-to-day ability to cope and their levels of hyperactivity. Among those who responded to Ritalin, the surveys reported the greatest improvement on higher doses,
confirming results from other studies.

Among the 14 children who could not tolerate Ritalin, many carry certain variants in the dopamine receptors
DRD2 and DRD3, the researchers found.

Some who respond well to Ritalin tend to have other variants in the genes DRD1, DRD3 and DRD4, which code for dopamine receptors, and in the COMT gene, which codes for a chemical that breaks down
neurotransmitters and hormones, such as dopamine and norepinephrine.

Others carry variants in the genes for two transporters of dopamine and serotonin (SLC6A3 and SLC6A4) or ADRA2A, a receptor for norepinephrine.

The study is small, and 90 percent of the participants are male. Also, some of genetic variants identified may not be associated with Ritalin response.

Still, if larger studies confirm that certain genetic variants improve the response to Ritalin, it would help doctors decide whom to treat and how.

Wednesday, August 28, 2013

Omega-3 Reduces ADHD Symptoms in Rats

From ScienceDaily.com

August 23, 2013

A new multidisciplinary study shows a clear connection between the intake of omega-3 fatty acids and a decline in ADHD symptoms in rats.

Researchers at the University of Oslo have observed the behaviour of rats and have analyzed biochemical processes in their brains. The results show a clear improvement in ADHD-related behaviour from supplements of omega-3 fatty acids, as well as a faster turnover of the signal substances dopamine, serotonin and glutamate in the nervous system.

There are, however, clear sex differences: a better effect from omega-3 fatty acids is achieved in male rats than in female.

Unknown Biology Behind ADHD

Currently the psychiatric diagnosis ADHD (Attention Deficit/Hyperactivity Disorder) is purely based on behavioural criteria, while the molecular genetic background for the illness is largely unknown. The new findings indicate that ADHD has a biological component and that the intake of omega-3 may influence ADHD symptoms.

"In some research environments it is controversial to suggest that ADHD has something to do with biology. But we have without a doubt found molecular changes in the brain after rats with ADHD were given omega-3," says Ivar Walaas, Professor of Biochemistry.

The fact that omega-3 can reduce ADHD behaviour in rats has also been indicated in previous international studies. What is unique about the study in question is a multi-disciplinarity that has not previously been seen, with contributions from behavioural science in medicine as well as from psychology, nutritional science and biochemistry.

Hyperactive Rats

The rats used in the study are called SHR rats -- spontaneously hypertensive rats. Although this is primarily a common type of rat, random mutations in their genes have resulted in genetic damage that produces high blood pressure. It is therefore first and foremost blood-pressure researchers who have so far been interested in these rats.

However, the rats do not suffer from high blood pressure until they have reached puberty. Before that age they present totally different symptoms -- namely hyperactivity, poor ability to concentrate and impulsiveness. It is exactly these three criteria that form the basis for making the ADHD diagnosis in humans.


The animals also react to Ritalin, the central nervous system stimulant, in the same way as humans with ADHD: the hyperactive responses are stabilized. SHR rats are therefore increasingly used in research as a model for ADHD.

Supplements as Early as the Fetal Stage

Researchers believe that omega-3 can have an effect from the very beginning of life.


Omega-3 was therefore added to the food given to mother rats before they were impregnated, and this continued throughout their entire pregnancy and while they fed their young. The baby rats were also given omega-3 in their own food after they were separated from their mother at the age of 20 days.

Another group of mother rats were given food that did not have omega-3 added, thus creating a control group of SHR offspring that had not been given these fatty acids at the fetal stage or later.

The researchers started to analyze the behaviour of the offspring some days after they were separated from the mother. They studied behaviour driven by reward as well as spontaneous behaviour. Substantial differences were noted for both types of behaviour between the rats that had been given the omega-3 supplement as foetuses and as baby rats and those that had not.

Rewards Made Male Rats Better Able to Concentrate

The reward-driven behaviour was such that the rats were allowed access to a drop of water each time they pressed an illuminated button. The ADHD rats that had not been given omega-3 could not concentrate on pressing the button, whereas the rats that had been brought up on omega-3 easily managed to hold their concentration for the seconds this takes and were able to enjoy a delicious drop of water as a reward.

Surprisingly enough, it was only male rats that showed an improvement in reward-driven behaviour. However, with regard to the rats' spontaneous behavior, the same type of reduction in hyperactivity and attention difficulties was noted in both male and female rats that had been given the omega-3 supplement.

Changes in Brain Chemistry

Professor Walaas and his research group became involved in the study at this point in order to analyze the molecular processes in the rats' brains.

The group analyzed the level of the chemical connections in the brain, the so-called neurotransmitters that transfer nerve impulses from one nerve cell to another. The researchers measured how much of the neurotransmitters such as dopamine, serotonin and glutamate was released and broken down within the nerve fibres.


A key player in this work was Kine S. Dervola, Ph.D. candidate, who reports clear sex differences in the turnover of the neurotransmitters -- just as there had been in the reward-driven behaviour.

"We saw that the turnover of dopamine and serotonin took place much faster among the male rats that had been given omega-3 than among those that had not. For serotonin the turnover ratio was three times higher, and for dopamine it was just over two and a half times higher. These effects were not observed among the female rats. When we measured the turnover of glutamate, however, we saw that both sexes showed a small increase in turnover," Ms. Dervola tells us.

Transferrable to Humans?

The researchers are cautious about drawing conclusions as to whether the results can be transferred to humans.

"In the first place there is of course a difference between rats and humans, and secondly the rats are sick at the outset. Thirdly the causes of ADHD in humans are in no way mapped sufficiently well. But the end result of what takes place in the brains of both rats and humans with ADHD is hyperactivity, poor ability to concentrate and impulsiveness," says Professor Walaas, and concludes:

"Giving priority to basic research like this will greatly increase our detailed knowledge of ADHD."


Journal Reference


Kine S Dervola, Bjørg Å Roberg, Grete Wøien, Inger Lise Bogen, Torbjørn H Sandvik, Terje Sagvolden, Christian A Drevon, Espen Borgå Johansen, Sven Ivar Walaas. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD. Behavioral and Brain Functions, 2012; 8 (1): 56 DOI: 10.1186/1744-9081-8-56

Tuesday, August 27, 2013

Meditation Stimulates Long-Lasting Brain Changes

From Higher Perspectives via Waking Times

By David Wilder, Reality Sandwich
July 15, 2013

The effects gained from meditation continue to affect brain function for a long time after meditation is over, according to new research.

“This is the first time meditation training has been shown to affect emotional processing in the brain outside of a meditative state,” said Gaelle Desbordes, Ph.D., a research fellow at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and at the Boston University Center for Computational Neuroscience and Neural Technology.

“Overall, these results are consistent with the overarching hypothesis that meditation may result in enduring, beneficial changes in brain function, especially in the area of emotional processing.”

Before beginning the study, the researchers hypothesized that meditation assists in controlling emotional responses, even in a non-meditative state.

During meditation, the area of the brain that contains the amygdala showed decreased activity. The amygdala is a mass of gray matter inside of each cerebral hemisphere that is involved with the experiencing of emotions.

When the subjects were shown images of other people that were good, bad, or neutral for a mindfulness technique known as “compassion meditation,” the amygdala was extraordinarily responsive.

The participants were able to focus their attention and significantly reduce their emotional reactions. The study found that they were able to retain this ability for eight weeks after the testing concluded. The subjects demonstrated subdued emotional response and increased compassion for others when faced with disturbing images, even when they were no longer in the meditative state.

Another group of Harvard Medical School researchers studied the effect of meditation on retaining information. Their hypothesis was that meditators have more intentional influence over alpha rhythm – a brain wave believed to screen out everyday distractions.

“Mindfulness meditation has been reported to enhance numerous mental abilities, including rapid memory recall,” said Catherine Kerr of the Martinos Center for Biomedical Imaging and the Osher Research Center, both at Harvard Medical School.

“Our discovery that mindfulness meditators more quickly adjusted the brain wave that screens out distraction could explain their superior ability to rapidly remember and incorporate new facts.”

Both studies used participants that did not have prior experience with meditation. Over the course of a two-month period and a three-month period, both groups showed significant change in their daily normal brain function.

This research supports a belief held by some researchers – that meditation may help reduce dependency on pharmaceutical drugs.

“The implications extend far beyond meditation,” said Kerr. “They give us clues about possible ways to help people better regulate a brain rhythm that is deregulated in attention-deficit hyperactivity disorder and other conditions.”

Large Study Links Autism to Autoimmune Disease in Mothers

From SFARI.org

By Sarah DeWeerdt
August 22, 2013

About one in ten women who have a child with autism have immune molecules in their bloodstream that react with proteins in the brain, according to a study published 20 August in Molecular Psychiatry (1).

Several research groups have found these immune molecules, called antibodies, in mothers of children with autism, and have shown that prenatal exposure to the antibodies alters social behavior in mice and monkeys.

The new study, which includes more than 2,700 mothers of children with autism, is the largest survey yet on the prevalence of these anti-brain antibodies.

Brain-bound: Immune molecules in mothers who have
children with autism target neurons in the frontal cortex,
cerebellum and hippocampus of mouse brains.

“It’s a very large sample size,” says study leader Betty Diamond, head of the Center for Autoimmune and Musculoskeletal Disorders at The Feinstein Institute for Medical Research in Long Island, New York. The scale gives a clearer impression of the prevalence of these antibodies, she says.

Antibodies help the body’s immune system recognize and fight off disease-causing microorganisms such as bacteria and viruses, but sometimes the body mistakenly produces antibodies to its own proteins. In some people, this results in autoimmune diseases such as rheumatoid arthritis and lupus, in which the body attacks its own tissues.

Researchers say anti-brain antibodies do not harm the brains of the women who produce them because of the blood-brain barrier, a filter that prevents most molecules from entering the brain. But the immature blood-brain barrier of a developing fetus may let them through, allowing them to damage the brain and perhaps cause autism.

Diamond’s team also found that women who have autism-linked antibodies are more likely to have other markers of autoimmunity compared with those who don’t carry these antibodies. Studies have shown that women with an autoimmune disease also have an increased risk of having a child with autism (2).

“This ties together the epidemiological finding that women who have autoimmune disease are more likely to have kids with autism, with the idea that there are actually antibodies against fetal brain in their serum,” says Paul Patterson, professor of biology at the California Institute of Technology, who was not involved in the work.

Sample Size

In the new study, Diamond’s team screened blood plasma samples from 2,431 mothers enrolled in the Simons Simplex Collection (SSC). The SSC is a registry of families with one child affected by autism and unaffected parents and siblings, and is funded by SFARI.org’s parent organization.

The researchers found that plasma from 260 of the women, or 10.5 percent, reacts strongly with mouse brain tissue, a signal that the blood contains anti-brain antibodies.

They also screened samples from 318 mothers enrolled in a different autism registry, the Autism Genetic Resource Exchange, and found that 28, or 8.8 percent, of them also have anti-brain antibodies.

In contrast, among a group of 653 controls drawn from the general population of women of childbearing age in New York City, only 17, or 2.6 percent, carry the autism-linked antibodies.

This means that the prevalence of anti-brain antibodies is about four times greater among mothers of children with autism than among the controls.

However, “The control population could have had mothers of children with autism in it,” notes Judy Van de Water, professor of clinical immunology at the University of California, Davis, who was not involved in the work. In fact, some of the women in the control group may not have children at all.

Still, Van de Water says, the study “corroborates, from an independent investigator, that women in this population have a higher incidence” of the antibodies.

Van de Water has found anti-brain antibodies in autism mothers who are part of the Childhood Autism Risk from Genetics and the Environment study using a different methodology (3), known as Western blotting, and says that the differences in study design make the similar results more persuasive. “It’s further support for this potential pathway to autism,” she says.

However, she cautions that measuring reactivity to mouse brain tissue also has drawbacks, because of the action of chemicals used in preparing the brain tissue for analysis. “The perfusion and fixation process that you have to go through is going to alter some of the antigens,” the proteins to which the antibodies bind, she says. This may ‘mask’ some of the binding patterns that occur in live brains.

Using the mouse brain enabled Diamond’s team to pinpoint which regions of the brain the antibodies affect. They found that the antibodies bind primarily to neurons in the frontal cortex, hippocampus and cerebellum, all areas that have been implicated in autism.

Fetal Findings

Patterson notes that the researchers tested binding of the antibodies to adult mouse brain, but protein expression in the adult brain is often very different from that in the fetal brain. “Optimally, one would like to know what the binding is to fetal human brain or fetal monkey brain,” he says.

According to Diamond, the team did find that the antibodies also bind to fetal human brain extracts and to whole fetal mouse brain. However, she says, it wasn’t possible to see which regions of fetal mouse brain they bind to because the brains are too small.

Her team performed several other analyses that uncovered tantalizing links between autism-linked antibodies and autoimmunity more generally.

First, they screened the blood of study participants for anti-nuclear antibodies (ANAs), which bind to molecules found in the cell nucleus and are commonly found in people with a variety of different autoimmune disorders. They found that 52 percent of autism mothers who carry anti-brain antibodies also have ANAs. In contrast, only 13.4 percent of autism mothers without anti-brain antibodies have ANAs, as do 15 percent of controls.

Mothers with anti-brain antibodies are also more likely to have autoimmune diseases, especially rheumatoid arthritis and lupus, compared with mothers who don’t have these antibodies.

Finally, the team screened a group of 363 women with rheumatoid arthritis for autism-linked antibodies. They found that 13.5 percent of these women have anti-brain antibodies, similar to the prevalence among mothers of children with autism and much higher than that of controls.

That’s a rather puzzling finding, Patterson says. “If they’re just as likely to be found in rheumatoid arthritis women, that means they’re not especially specific to autism,” he says.

But a link between rheumatoid arthritis and autism isn’t unheard of, Diamond says. In a separate series of experiments, she has found that antibodies that cause kidney damage in women with lupus also cause cognitive impairment in mice exposed to the antibodies in utero (4).

Diamond says she has unpublished data indicating that some of the brain proteins that bind the antibodies are already implicated in autism or other neurodevelopmental disorders — but declined to reveal details. Are any of the targets she has identified the same as those reported by Van de Water and her colleagues in July? “It’s sort of interesting,” Diamond says. “They’re not.”

References

1: Brimberg L. et al. Mol. Psychiatry Epub ahead of print (2013) PubMed

2: Atladóttir H.O. et al. Pediatrics 124, 687-694 (2009) PubMed

3: Braunschweig D. et al. Transl. Psychiatry 3, e277 (2013) PubMed

4: Lee J.Y. et al. Nat. Med. 15, 91-96 (2009) PubMed

Monday, August 26, 2013

FDA Warns Against Alternative Autism Therapy

From DisabilityScoop.com

By Michelle Diament
August 23, 2013

The Food and Drug Administration is warning consumers that a therapy often marketed for treating autism, cerebral palsy and other conditions is unproven and may “endanger their health.”

Federal regulators said Thursday that contrary to many claims on the Internet, hyperbaric oxygen therapy is not clinically proven to cure or effectively treat the developmental disorders and many other conditions.


“Patients may incorrectly believe that these devices have been proven safe and effective for uses not cleared by the FDA, which may cause them to delay or forgo proven medical therapies...”

“Patients may incorrectly believe that these devices have been proven safe and effective for uses not cleared by the FDA, which may cause them to delay or forgo proven medical therapies,” said Nayan Patel, a biomedical engineer at the FDA’s anesthesiology devices branch. “In doing so, they may experience a lack of improvement and/or worsening of their existing conditions.”

Despite limited research, hyperbaric oxygen therapy has become a popular alternative treatment for autism and cerebral palsy. For the therapy, individuals spend time in a pressurized chamber allowing the lungs to take in as much as three times the normal amount of oxygen.

Hyperbaric oxygen therapy is FDA approved for thirteen different uses including the treatment of thermal burns, carbon monoxide poisoning and decompression sickness that’s sometimes experienced by divers.

But, in issuing the consumer alert this week, regulators listed more than a dozen conditions ranging from autism and cerebral palsy to cancer, AIDS, Alzheimer’s disease and hepatitis for which the therapy is marketed even though the FDA has not approved such uses.

Patel indicated that the agency has received 27 complaints in the last three years from consumers or health care professionals about treatment centers promoting hyperbaric oxygen therapy for uses that are not approved.

Possible risks of hyperbaric oxygen therapy include sinus pain, ear pressure or joint pain as well as more serious problems like paralysis or air embolism, which can obstruct circulation in the body, the FDA said.

This is not the first time a treatment advertised as helping those with autism has been specifically called out by the FDA. In 2010, the agency told eight businesses to stop marketing chelation products to those with autism and other conditions citing serious side effects including death.


..................................................................................

From Forbes Magazine's Health & Pharma

FDA Warns Consumers About Common Off-Label Autism Therapy

By Emily Willingham
August 23, 2013

The FDA minces no words in its consumer alert about hyperbaric oxygen therapy :

"No, hyperbaric oxygen therapy (HBOT) has not been clinically proven to cure or be effective in the treatment of cancer, autism, or diabetes. But do a quick search on the Internet, and you’ll see all kinds of claims for these and other diseases for which the device has not been cleared or approved by FDA."

Evidently, the list of conditions HBOT purveyors have promised the therapy will treat is a long one and includes Parkinson’s disease, hepatitis, and multiple sclerosis, in addition to autism and cerebral palsy.

Of course, none of these conditions has been linked to a lack of access to oxygen for your tissues, which is the only indicated use of HBOT as a therapy. In fact, the FDA approves use of HBOT for 13 specific conditions, all of them related to helping boost the body’s access to oxygen. They include HBOT for carbon monoxide poisoning and for burns resulting from heat or fire.


Like any medical intervention, HBOT carries risks, according to the FDA, including mild effects such as ear pressure or sinus pain all the way to very serious adverse effects such as paralysis and embolisms. Oxygen, feeding fire the way it does [correction], also means a fire risk for anyone undergoing HBOT, which have been involved in about 80 deaths worldwide.

Not something you want to do with any old street corner practitioner.

In addition to these risks, the FDA cautions that people turning to HBOT for autism or cerebral palsy or for cancer or Parkinson’s might well be delayed from receiving effective therapies and interventions while they waste time and money on HBOT.

Proponents of HBOT as a treatment for autism argue that the controversy around it is “political, not scientific.” But that’s not actually the case. In addition to the risks associated with HBOT, all of which at the least involve pain and discomfort, research suggests that the therapy is ineffectual, and the costs suggest that it’s enormously expensive for an unproven, “off-label” intervention that parents could just “try and see.”

A 2012 review of studies evaluating HBOT and autism a review of the available research at the time found no replications of the limited studies suggesting some effectiveness. The review authors called for a “sham controlled” study of the intervention, and just such a study appeared a few months later. Those authors compared HBOT and “sham air” and found improvement in both groups–control and treatment–and no difference between the groups in outcome.

The FDA reports having received 27 complaints in the past three years about HBOT centers offering up the “treatment” for conditions that the FDA has not approved.

Saturday, August 24, 2013

Mood Influenced by Immune Cells Called to the Brain in Response to Stress

From ScienceDaily.com

August 21, 2013

New research shows that in a dynamic mind-body interaction during the interpretation of prolonged stress, cells from the immune system are recruited to the brain and promote symptoms of anxiety.

The findings, in a mouse model, offer a new explanation of how stress can lead to mood disorders and identify a subset of immune cells, called monocytes, that could be targeted by drugs for treatment of mood disorders.

The Ohio State University research also reveals new ways of thinking about the cellular mechanisms behind the effects of stress, identifying two-way communication from the central nervous system to the periphery -- the rest of the body -- and back to the central nervous system that ultimately influences behavior.

Unlike an infection, trauma or other problems that attract immune cells to the site of trouble in the body, this recruitment of monocytes that can promote inflammation doesn't damage the brain's tissue -- but it does lead to symptoms of anxiety.

The research showed that the brain under prolonged stress sends signals out to the bone marrow, calling up monocytes. The cells travel to specific regions of the brain and generate inflammation that causes anxiety-like behavior.

In experiments conducted in mice, the research showed that repeated stress exposure caused the highest concentration of monocytes migrating to the brain. The cells surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus, and their presence led to anxiety-like behavior in the mice.

"In the absence of tissue damage, we have cells migrating to the brain in response to the region of the brain that is activated by the stressor," said John Sheridan, senior author of the study, professor of oral biology and associate director of Ohio State's Institute for Behavioral Medicine Research (IBMR).

"In this case, the cells are recruited to the brain by signals generated by the animal's interpretation of social defeat as stressful."

The research appears in the August 21, 2013, issue of The Journal of Neuroscience.

Mice in this study were subjected to stress that might resemble a person's response to persistent life stressors. In this model of stress, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours. This elicits a "fight or flight" response in the resident mice as they are repeatedly defeated. The experience of social defeat leads to submissive behaviors and the development of anxiety-like behavior.

Mice subjected to zero, one, three or six cycles of this social defeat were then tested for anxiety symptoms. The more cycles of social defeat, the higher the anxiety symptoms; mice took longer to enter an open space and opted for darkness rather than light when given the choice. Anxiety symptoms corresponded to higher levels of monocytes that had traveled to the animals' brains from the blood.

Additional experiments showed that these cells did not originate in the brain, but traveled there from the bone marrow. In previous studies, this same research group showed that cells in the brain called microglia, the brain's first line of immune defense, are activated by prolonged stress and are partly responsible for the signals that call up monocytes from the bone marrow.

"There are different moving parts from the central and peripheral components, and what's novel is them coming together to influence behavior," said Jonathan Godbout, a senior co-author of the paper and an associate professor of neuroscience at Ohio State.

Exactly what happens at this point in the brain remains unknown, but the research offers clues. The monocytes that travel to the brain don't respond to natural anti-inflammatory steroids in the body and have characteristics signifying they are in a more inflammatory state. These results indicate that inflammatory gene expression occurs in the brain in response to the stressor.

"The monocytes are coming out of the bone marrow and they are not responsive to steroid regulation, so they overproduce proinflammatory signals when they're stimulated. We think this is the key to the prolonged anxiety-like disorders that we see in these animals," Sheridan said.

These findings do not apply to all forms of anxiety, the scientists noted, but they are a game-changer in research on stress-related mood disorders.

"Our data alter the idea of the neurobiology of mood disorders," said Eric Wohleb, first author of the study and a predoctoral fellow in Ohio State's Neuroscience Graduate Studies Program. "These findings indicate that a bidirectional system rather than traditional neurotransmitter pathways may regulate some forms of anxiety responses. We're saying something outside the central nervous system -- something from the immune system -- is having a profound effect on behavior."

This work was supported by the National Institute of Mental Health (NIMH), the National Institute on Aging and an NIMH Predoctoral Fellowship. Nicole Powell of the Division of Oral Biology at Ohio State is an additional co-author of the study. Sheridan and Godbout also are investigators in the IBMR and Center for Brain and Spinal Cord Repair.


Journal Reference

E. S. Wohleb, N. D. Powell, J. P. Godbout, J. F. Sheridan.Stress-Induced Recruitment of Bone Marrow-Derived Monocytes to the Brain Promotes Anxiety-Like Behavior. Journal of Neuroscience, 2013; 33 (34): 13820 DOI:10.1523/JNEUROSCI.1671-13.2013

Thursday, August 22, 2013

Guest Blog: Classroom Quality

From SFARI.org - The Simons Foundation Autism Research Initiative

By Brian Boyd and Samuel Odom
August 13, 2013

Brian Boyd, left, and Samuel Odom
‘Evidence-based practice’ has become a widespread and commonplace term among school-based practitioners, families and policymakers. As Connie Kasari noted in her guest blog, much of the research on effective programs for children with autism has taken place in laboratory or clinical settings, and there are questions about its application in the real world of public schools. Yet, this is the setting in which so many children with autism spend much of their time.

In a study published 28 June in the Journal of Autism and Developmental Disorders, we examined the effects of two established comprehensive treatment programs for preschool children with autism, when they were delivered in traditional public-school settings
1. Importantly, we compared these programs not only with one another but also with high-quality ‘eclectic’ special education programs, in which teachers do not use a specific treatment program to guide their instruction.

We found that preschool-aged children with autism make developmental and behavioral gains, regardless of the type of classroom in which they are enrolled.

The good news from this study, we believe, is that there are established programs that can foster positive growth and learning in children with autism, and that can take place in public schools, if the schools choose to adopt these programs.


TEACCH, one of the programs we studied, is historic because it was one of the first program models established for children with autism. It follows a structured teaching approach to create a specialized learning environment to address characteristics of autism that interfere with children’s ability to participate in the classroom.

LEAP (Learning Experiences and Alternative Program for Preschoolers and their Parents), also a program with a long history, focuses on adapting a typical early childhood education model to accommodate the learning and social needs of young children with autism. One of LEAP’s core features is the inclusion of typically developing preschool children as classmates.

Although both of these programs have been around for a long time — TEACCH since the 1970s and LEAP since the 1980s — we have no evidence as to which one works better.
Classroom conditions:

The general purpose of our study was to determine whether these two approaches work better than usual classroom practice in public schools.

We studied 75 special education preschool classrooms in North Carolina, Florida, Colorado and Minnesota, involving 198 children diagnosed with autism. We followed teachers and children over the course of one school year.

We chose not to follow a design in which teachers (or students) would be randomly assigned, because previous research told us that teachers have different beliefs about which practices to use in their classes, and random assignment to a classroom condition that runs counter to those beliefs can be counterproductive as well as stressful.

Rather, we identified teachers who had already been trained in the program models or were conducting high-quality eclectic practices in their classrooms. Because of this quasi-experimental approach, we had to be vigilant about selecting teachers and programs, and we had to make sure that the general level of quality was high for all programs.

At the beginning and end of the school year, we used a broad set of developmental and behavioral assessments, such as the Mullen Scales of Early Learning and the Repetitive Behavior Scale-Revised, to determine the children’s progress.

We found that preschool-aged children with autism make developmental and behavioral gains, regardless of the type of classroom in which they are enrolled. Also, we generally did not find differences in the children’s performance between the three programs: Children in TEACCH, LEAP and eclectic special education programs all made fairly similar gains across the school year.

Although these classes were taking place under ‘normal’ circumstances in public schools (i.e., they were not model classrooms or special programs run by researchers), we would say they have a better quality of practice than is typically seen in a public school. We believe this is an important point that may ultimately help to explain the findings.

In counseling and clinical psychology, there is a term referred to as ‘common factors.’ This means that there are some components that define good therapeutic practice that should be implemented with all clients. It may be that there are some components of good, or rather ‘high-quality,’ classrooms that should be implemented for all students with autism, and the classrooms in our study shared some of these components. The similar findings for all three sets of programs may reflect the commonalities across these classrooms instead of their differences.

TEACCH and LEAP are prime examples of programs that work, and there may well be others. Importantly, teachers can construct eclectic programs that may have positive effects for preschool children with autism, as long as they provide a high level of program quality and select evidence-based instructional practices
2.

It is important in future research to identify the features these programs have in common that may explain the similar findings. In short, if classroom quality matters, what constitutes a high-quality classroom, and how do we ultimately support classroom teachers to improve the quality of the children’s learning environment?


..........................................................................

Brian Boyd is assistant professor of occupational science and fellow at the University of North Carolina at Chapel Hill’s Frank Porter Graham Child Development Institute. Samuel Odom is director of the institute and professor in the School of Education.

References
 

1: Boyd B.A. et al. J. Autism Dev. Disord. Epub ahead of print (2013) PubMed

2: Odom S. et al. Behav. Modif. 36, 270-297 (2012) PubMed

An Opportunity for Young Adults with ASD: MAC's Young Adult Leaders Fellowship


By Catherine Mayes, Autism Project Advocate
August 20, 2013

Massachusetts Advocates for Children invites young adults 18-26 on the Autism Spectrum to apply for an innovative "Young Adult Leaders Fellowship," which provides opportunities to learn the professional skills needed to advocate on behalf of other youth with disabilities.

The Fellowship is a partnership between Massachusetts Advocates for Children and the Institute for Community Inclusion at UMass Boston. The Young Adult Leaders Fellowship consists of one year part-time advocacy training under the supervision of the Autism Project Advocate and senior attorney. A small stipend is provided.

Please help us get the word out to young adults who might be interested in this Fellowship. We would appreciate it if you would forward this information to inform other individuals, families, and organizations. For an application or if you have questions, please feel free to contact me at 617-357-8431 ext. 241, or by email to cmayes@massadvocates.org.

The deadline for return of application materials is September 20, 2013.

Wednesday, August 21, 2013

Mobile Lab Brings Research Studies to Schools

From AutismDailyNewscast.com

By
August 19, 2013

A grant from the Health Resource and Services Administration of the U.S. Department of Health and Human Services and the National Institute for Child Health and Human Development has funded a new mobile laboratory for the Shriver Center, a division of the University of Massachusetts Medical School that develops research, education, and service programs aimed at improving the quality of life for people with intellectual and developmental disabilities.


The new mobile lab will allow researchers to bring the lab different schools they’ve partnered with in recruiting individuals for their research studies. The lab was purchased from a company in Ohio that offers custom services vehicles for specialized uses, including SWAT and medical mobile vehicles.

The mobile lab, called CAMEL (Community Access Mobile Evaluation Laboratory), will be used to study eye tracking movements and EEG scans from children with autism and other developmental disabilities, in the hopes of developing appropriate interventions that will enhance their quality of life. The eye tracking equipment allows researchers to track exactly where an individual’s eye gaze is falling while looking at videos of a human face.


This allows researchers to determine which nonverbal cues are being missed. This is especially useful for children on the autism spectrum, who often cannot effectively communicate to the researcher about what they are looking at. EEG scans are used to measure tiny changes in the electrical activity of the brain.

This data is useful in evaluating brain activity in people with developmental disabilities. The changes are very minute, so this equipment requires a clean environment without computers and other electrical equipment that could interfere with the readings. Having a mobile lab eliminates the need for researchers to carry fragile equipment and find spaces within the partner schools that are appropriate for the EEG studies.

Before the CAMEL lab was approved, participants either had to travel to the lab, or researchers had to set up lab space at one of their partner schools. “CAMEL can go anywhere – we just need power and parking,” said Teresa Mitchell, assistant professor of psychiatry. “We partner with schools that serve developmentally disabled students, and while many students and their families want to participate in studies that improve outcomes, getting to the Shriver labs in Waltham in the middle of a school and work day is impossible. So now, these families can participate. Now the research facility will come to the children, and the mobile lab will allow them to travel further, and to include a wider variety of subjects in their research studies."


CAMEL has allowed researchers to branch out into new communities on the Cape and Rhode Island border. Mitchell hopes to expand the research geographically, and to include a wider variety of subjects from different socio-economic groups as well.

Mobile labs like CAMEL will allow researchers to expand into populations that had previously been unable to participate in research studies. The use of mobile labs could be expanded across the country.

NAC for Autism: A Case Study

From Questioning-Answers

By Paul Whitely
August 17, 2013

NAC or N-acetlycysteine has appeared a couple of times on this blog, in relation to both autism (see here) and schizophrenia (see here). Not bad for a compound which more readily finds a home in modern medicine following paracetamol (acetaminophen) overdose or as a consequence of its mucolytic properties.

As one might imagine, the autism link is of particular interest to this blog, focused specifically on the findings of Hardan and colleagues* when it came to putting NAC to the [albeit preliminary] experimental test. The results, by the way, were encouraging, for at least some parts of the presentation of childhood autism, with the promise of more to come.

As a sort of follow-up to the Hardan paper, I'm talking today about a case report offered by Ghanizadeh and Derakhshan** (open-access) highlighting a little more individual detail following the use of NAC with an 8-year old boy diagnosed with autism.

I know the word 'case report' sends a shudder down many a scientific shoulder, but as I've said quite a few times before, we ignore the N=1 in autism at our peril given the wide, wide heterogeneity present and all that associated comorbidity to contend with. Real personalised medicine you might say.

If I have managed to persuade you to listen to the rest of my ramblings on this paper and topic, there are a few important points to make about/from the Ghanizadeh paper:
  • From the description provided, the child in question seemed quite floridly autistic with the important add-ons of hyperactivity and inattention present from an early age. Although we aren't told what exactly it means, the authors note: "His laboratory examination was unremarkable".
  • Oral NAC (800mg per day) was begun as part of another trial by the authors to counteract nail-biting***. As unusual as it might sound, mail-biting has been a focus of some NAC research coincident to the presence of anxiety.
  • Indeed, the boy's nail-biting behaviours did seem to subside alongside the installation of NAC, but perhaps of greater interest were the reports that "there was a marked reduction in his autism symptoms 30 days after the onset of NAC administration". OK so this report did come from the boy's parents, and without causing any offence, the issue of objectivity might come into play.
  • The types of 'changes' reported however were in core areas such as his verbal skills, social interaction and a quite unusual preoccupation with having his hair cut (I say unusual because a visit to the barber or hairdresser described by many parents about their child with autism, is often characterised by entirely the opposite reaction).
  • Aside from "a mild abdominal pain" the authors importantly say that "nothing worsened after the administration of NAC," which I take to indicate that side effects were minimal over the course of the intervention.

I should have perhaps mentioned at the beginning that there is some sound logic why NAC might have some effect on cases of autism. The amino acid cysteine, as well as containing sulfur, so potentially tied into to that most forgotten areas of autism research, sulfur chemistry (see here), is also the precursor to another important compound, glutathione.

I know my regular readers are probably getting a little bored of me going on about this 'elephant in the room' and in particular, that glutathione overview paper by Main and colleagues (see here), but a possible link is a possible link.

I was also interested to read the authors' discussions on how NAC might also have the ability to decrease "high glutamate levels". As any good biochemist will tell you, glutathione, which is dependent on cysteine, is a tripeptide, which also incorporates the amino acids glycine and glutamate into its triadic manufacture.

From that point of view, circumstances where any of the three amino acids were low or not optimally biologically available might affect the production of glutathione.

If that happens to mean you have low cysteine levels, glutathione would be low but also this might mean levels of glutamate or glycine could be higher as a result of not being used up to make glutathione. Glutamate is another compound finding some significant interest with regards to autism and conditions presenting with autistic symptoms.

Reiterating that the Ghanizadeh paper is a case report, I do find there to be some interesting observations reported. With my speculating hat on, I do wonder whether that link with nail-biting and onwards anxiety suggested for NAC might also be part and parcel of the effect observed in this case given the quite considerable link suggested between autism and anxiety (see here)?

And by the looks of things NAC is in the research ascendancy perhaps even with a prophylactic effect****.

References

* Hardan AY. et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014.

** Ghanizadeh A & Derakhshan N. N-acetylcysteine for treatment of autism, a case report. J Res Med Sci. 2012 Oct;17(10):985-7.

*** Ghanizadeh A. et al. N-acetylcysteine Versus Placebo for Treating Nail Biting, A Double Blind Randomized Placebo Controlled Clinical Trial. Antiinflamm Antiallergy Agents Med Chem. 2013 May 6. [Epub ahead of print]

**** Beloosesky R. et al. Prophylactic maternal N-acetylcysteine in rats prevents maternal inflammation-induced offspring cerebral injury shown on magnetic resonance imaging. Am J Obstet Gynecol. 2013 Mar;208(3):213.e1-6. doi: 10.1016/j.ajog.2013.01.023.