Breakthrough research suggests potential treatment for autism, intellectual disability

A breakthrough in finding the mechanism and a possible therapeutic fix for autism and intellectual disability has been made by a University of Nebraska Medical Center researcher and his team at the Munroe-Meyer Institute (MMI).

Woo-Yang Kim, Ph.D., associate professor, developmental neuroscience, led a team of researchers from UNMC and Creighton University into a deeper exploration of a genetic mutation that reduces the function of certain neurons in the brain.

Dr. Kim's findings were published in this week's online issue of Nature Neuroscience.

"This is an exciting development because we have identified the pathological mechanism for a certain type of autism and intellectual disability," Dr. Kim said.

Recent studies have shown that the disorder occurs when a first-time mutation causes only one copy of the human AT-rich interactive domain 1B (ARID1B) gene to remain functional, but it was unknown how it led to abnormal cognitive and social behaviors.

Autism spectrum disorder (ASD) impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with ASD also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors.

There are no drugs or genetic treatments to prevent ASD or intellectual disability; the only treatment options focus on behavioral management and educational and physical therapies.

The team created and analyzed a genetically modified mouse and found that a mutated Arid1b gene impairs GABA neurons, the 'downer' neurotransmitter, leading to an imbalance of communication in the brain.

GABA blocks impulses between nerve cells in the brain. Low levels of GABA may be linked to anxiety or mood disorders, epilepsy and chronic pain. It counters glutamate (the upper neurotransmitter), as the two mediate brain activation in a Yin and Yang manner. People take GABA supplements for anxiety.

"In normal behavior, the brain is balanced between excitation and inhibition," Dr. Kim said. "But when the inhibition is decreased, the balance is broken and the brain becomes more excited causing abnormal behavior.

"We showed that cognitive and social deficits induced by an Arid1bmutation in mice are reversed by pharmacological treatment with a GABA receptor modulating drug. And, now we have a designer mouse that can be used for future studies."

Next steps for Dr. Kim and his team are to even further refine the specific mechanism for autism and intellectual disability and to identify which of the many GABA neurons are specifically involved.

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Story Source:

Materials provided by University of Nebraska Medical Center (UNMC). Note: Content may be edited for style and length.

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Journal Reference:

1. Eui-Man Jung, Jeffrey Jay Moffat, Jinxu Liu, Shashank Manohar Dravid, Channabasavaiah Basavaraju Gurumurthy, Woo-Yang Kim. Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior. Nature Neuroscience, 2017; DOI: 10.1038/s41593-017-0013-0

Strength exercise as vital as aerobic new research finds

Push ups and sit ups could add years to your life according to a new study of over 80,000 adults led by the University of Sydney.

The largest study to compare the mortality outcomes of different types of exercise found people who did strength-based exercise had a 23 percent reduction in risk of premature death by any means, and a 31 percent reduction in cancer-related death.

Lead author Associate Professor Emmanuel Stamatakis from the School of Public Health and the Charles Perkins Centre said while strength training has been given some attention for functional benefits as we age, little research has looked at its impact on mortality.

"The study shows exercise that promotes muscular strength may be just as important for health as aerobic activities like jogging or cycling," said Associate Professor Stamatakis.

"And assuming our findings reflect cause and effect relationships, it may be even more vital when it comes to reducing risk of death from cancer."

The World Health Organization's Physical Activity Guidelines for adults recommend 150 minutes of aerobic activity, plus two days of muscle strengthening activities each week.

Associate Professor Stamatakis said governments and public health authorities have neglected to promote strength-based guidelines in the community, and as such misrepresented how active we are as a nation.

He cites the example of The Australian National Nutrition and Physical Activity Survey which, based on aerobic activity alone, reports inactivity at 53 percent. However, when the World Health Organization's (WHO) strength-based guidelines are also taken into account, 85 percent of Australians fail to meet recommendations.

"Unfortunately, less than 19 percent of Australian adults do the recommended amount of strength-based exercise," said Associate Professor Stamatakis.

"Our message to date has just been to get moving but this study prompts a rethink about, when appropriate, expanding the kinds of exercise we are encouraging for long-term health and wellbeing."

The analysis also showed exercises performed using one's own body weight without specific equipment were just as effective as gym-based training.

"When people think of strength training they instantly think of doing weights in a gym, but that doesn't have to be the case.

"Many people are intimidated by gyms, the costs or the culture they promote, so it's great to know that anyone can do classic exercises like triceps dips, sit-ups, push-ups or lunges in their own home or local park and potentially reap the same health benefits."

The research, published in the American Journal of Epidemiologytoday, is based on a pooled population sample of over 80,306 adults with data drawn from the Health Survey for England and Scottish Health Survey, linked with the NHS Central Mortality Register.

The study was observational, however adjustments were made to reduce the influence of other factors such as age, sex, health status, lifestyle behaviours and education level. All participants with established cardiovascular disease or cancer at baseline and those who passed away in the first two years of follow up were excluded from the study to reduce the possibility of skewing results due to those with pre-existing conditions participating in less exercise.

Summary of key findings:

• participation in any strength-promoting exercise was associated with a 23 percent reduction in all-cause mortality and a 31 percent reduction in cancer mortality
• own bodyweight exercises that can be performed in any setting without equipment yielded comparable results to gym-based activities
• adherence to WHO's strength-promoting exercise guideline alone was associated with reduced risk of cancer-related death, but adherence to the WHO's aerobic physical activity guideline alone was not
• adherence to WHO's strength-promoting exercise and aerobic guidelines combined was associated with a greater risk reduction in mortality than aerobic physical activity alone
• there was no evidence of an association between strength-promoting exercise and cardiovascular disease mortality.

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Story Source:

Materials provided by University of Sydney. Note: Content may be edited for style and length.

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Journal Reference:

1. Emmanuel Stamatakis, I-Min Lee, Jason Bennie, Jonathan Freeston, Mark Hamer, Gary O'Donovan, Ding Ding, Adrian Bauman, Yorgi Mavros. Does strength promoting exercise confer unique health benefits? A pooled analysis of eleven population cohorts with all-cause, cancer, and cardiovascular mortality endpoints. American Journal of Epidemiology, 2017; DOI: 10.1093/aje/kwx345

Study reveals how a very low calorie diet can reverse type 2 diabetes

In a new study, a Yale-led research team uncovers how a very low calorie diet can rapidly reverse type 2 diabetes in animal models. If confirmed in people, the insight provides potential new drug targets for treating this common chronic disease, said the researchers.

The study is published in Cell Metabolism.

One in three Americans will develop type 2 diabetes by 2050, according to recent projections by the Center for Disease Control and Prevention. Reports indicate that the disease goes into remission in many patients who undergo bariatric weight-loss surgery, which significantly restricts caloric intake prior to clinically significant weight loss. The Yale-led team's study focused on understanding the mechanisms by which caloric restriction rapidly reverses type 2 diabetes.

The research team investigated the effects of a very low calorie diet (VLCD), consisting of one-quarter the normal intake, on a rodent model of type 2 diabetes. Using a novel stable (naturally occurring) isotope approach, which they developed, the researchers tracked and calculated a number of metabolic processes that contribute to the increased glucose production by the liver. The method, known as PINTA, allowed the investigators to perform a comprehensive set of analyses of key metabolic fluxes within the liver that might contribute to insulin resistance and increased rates of glucose production by the liver -- two key processes that cause increased blood-sugar concentrations in diabetes.

Using this approach the researchers pinpointed three major mechanisms responsible for the VLCD's dramatic effect of rapidly lowering blood glucose concentrations in the diabetic animals. In the liver, the VLCD lowers glucose production by: 1) decreasing the conversion of lactate and amino acids into glucose; 2) decreasing the rate of liver glycogen conversion to glucose; and 3) decreasing fat content, which in turn improves the liver's response to insulin. These positive effects of the VLCD were observed in just three days.

"Using this approach to comprehensively interrogate liver carbohydrate and fat metabolism, we showed that it is a combination of three mechanisms that is responsible for the rapid reversal of hyperglycemia following a very low calorie diet," said senior author Gerald I. Shulman, M.D., the George R. Cowgill Professor of Medicine and Cellular and Molecular Physiology and an investigator at the Howard Hughes Medical Institute.

The next step for the researchers will be to confirm whether the findings can be replicated in type 2 diabetic patients undergoing either bariatric surgery or consuming very low calorie diets. His team has already begun applying the PINTA methodology in humans.

"These results, if confirmed in humans, will provide us with novel drug targets to more effectively treat patients with type 2 diabetes," Shulman said.

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Story Source:

Materials provided by Yale University. Original written by Ziba Kashef. Note: Content may be edited for style and length.

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Journal Reference:

1. Rachel J. Perry, Liang Peng, Gary W. Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D. Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, Kitt Falk Petersen, Gerald I. Shulman. Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes. Cell Metabolism, November 2017 DOI: 10.1016/j.cmet.2017.10.004

Consumption of antioxidant-rich foods is associated with a lower risk of type 2 diabetes, study shows

A lower risk of type 2 diabetes has been observed among individuals consuming food rich in antioxidants. This effect is largely contributed by fruit, vegetables, tea and other hot beverages, as well as moderate consumption of alcohol, as shown in a recent study from an Inserm research group, published in Diabetologia, the journal of the European Association for the Study of Diabetes (EASD)

A diet rich in fruit and vegetables has previously been associated with a lower risk of certain cancers and cardiovascular conditions. An Inserm team (Health across generations, Center of Research in Epidemiology and Population Health, Villejuif, France) has now shown that such a diet is similarly associated with a reduced risk of type 2 diabetes.

The team already suspected there might be a link on the basis of previous studies showing that certain antioxidants, such as vitamins C and E, lycophenes or flavonoids, were associated with a reduction in type 2 diabetes risk. However, these studies looked only at isolated nutrients, not at the total antioxidant capacity of the diet. The researchers therefore wanted to verify whether overall diet, according to its antioxidant capacity, is associated with diabetes risk. Using data from the E3N cohort comprising French women recruited from 1990, then aged between 40 and 65 years, they followed 64,223 women from 1993 to 2008, all of whom were free from diabetes and cardiovascular disease at the time of inclusion in the study. Each participant completed a dietary questionnaire at the beginning of the study, including detailed information on more than 200 different food items. Using this information, together with an Italian database providing the antioxidant capacity of a large number of different foods, the Inserm researchers calculated a score for 'total dietary antioxidant capacity' for each participant. The group then analysed the associations between this score and the risk of diabetes occurrence during the follow-up period.

The results show that diabetes risk diminished with increased antioxidant consumption up to a level of 15 mmol/day, above which the effect reached a plateau. Increasing dietary antioxidants to this level could be achieved through eating antioxidant-rich foods such as dark chocolate, tea, walnuts, prunes, blueberries, strawberries or hazelnuts, to name just a few. Women with the highest antioxidant scores had a reduction in diabetes risk of 27% compared with those with the lowest scores. 'This link persists after taking into account all the other principal diabetes risk factors: smoking, education level, hypertension, high cholesterol levels, family history of diabetes and, above all, BMI, the most important factor', clarifies Francesca Romana Mancini, the first author of this study. The foods and drinks that contributed the most to a high dietary antioxidant score were fruits and vegetables, tea and red wine (consumed in moderate quantities). The authors excluded coffee from the analysis, despite its high antioxidant levels, because the antioxidants in coffee have already been shown to be associated with reduced type 2 diabetes risk, and might therefore mask the effects of antioxidants from other sources.

'This work complements our current knowledge of the effect of isolated foods and nutrients, and provides a more comprehensive view of the relationship between food and type 2 diabetes' explains Guy Fagherazzi, the lead researcher in charge of diabetes research in the E3N study. 'We have shown that an increased intake of antioxidants can contribute to a reduction in diabetes risk'. This now raises the question why: 'We know that these molecules counterbalance the effect of free radicals, which are damaging to cells, but there are likely to be more specific actions in addition to this, for example an effect on the sensitivity of cells to insulin. This will need to be confirmed in future studies', concludes Francesca Romana Mancini.

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Story Source:

Materials provided by Diabetologia. Note: Content may be edited for style and length.

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Journal Reference:

1. Francesca Romana Mancini, Aurélie Affret, Courtney Dow, Beverley Balkau, Fabrice Bonnet, Marie-Christine Boutron-Ruault, Guy Fagherazzi. Dietary antioxidant capacity and risk of type 2 diabetes in the large prospective E3N-EPIC cohort. Diabetologia, 2017; DOI: 10.1007/s00125-017-4489-7

Mushrooms are full of antioxidants that may have antiaging potential

Mushrooms may contain unusually high amounts of two antioxidants that some scientists suggest could help fight aging and bolster health, according to a team of Penn State researchers.

In a study, researchers found that mushrooms have high amounts of the ergothioneine and glutathione, both important antioxidants, said Robert Beelman, professor emeritus of food science and director of the Penn State Center for Plant and Mushroom Products for Health. He added that the researchers also found that the amounts the two compounds varied greatly between mushroom species.

"What we found is that, without a doubt, mushrooms are highest dietary source of these two antioxidants taken together, and that some types are really packed with both of them," said Beelman.

Beelman said that when the body uses food to produce energy, it also causes oxidative stress because some free radicals are produced. Free radicals are oxygen atoms with unpaired electrons that cause damage to cells, proteins and even DNA as these highly reactive atoms travel through the body seeking to pair up with other electrons.

Replenishing antioxidants in the body, then, may help protect against this oxidative stress.

"There's a theory -- the free radical theory of aging -- that's been around for a long time that says when we oxidize our food to produce energy there's a number of free radicals that are produced that are side products of that action and many of these are quite toxic," said Beelman. "The body has mechanisms to control most of them, including ergothioneine and glutathione, but eventually enough accrue to cause damage, which has been associated with many of the diseases of aging, like cancer, coronary heart disease and Alzheimer's."

According to the researchers, who report their findings in a recent issue of Food Chemistry, the amounts of ergothioneine and glutathione in mushrooms vary by species with the porcini species, a wild variety, containing the highest amount of the two compounds among the 13 species tested.

"We found that the porcini has the highest, by far, of any we tested," said Beelman. "This species is really popular in Italy where searching for it has become a national pastime."

The more common mushroom types, like the white button, had less of the antioxidants, but had higher amounts than most other foods, Beelman said.

The amount of ergothioneine and glutathione also appear to be correlated in mushrooms, the researchers said. Mushrooms that are high in glutathione are also high in ergothioneine, for example.

Cooking mushrooms does not seem to significantly affect the compounds, Beelman said.

"Ergothioneine are very heat stable," said Beelman.

Beelman said that future research may look at any role that ergothioneine and glutathione have in decreasing the likelihood of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease.

"It's preliminary, but you can see that countries that have more ergothioneine in their diets, countries like France and Italy, also have lower incidents of neurodegenerative diseases, while people in countries like the United States, which has low amounts of ergothioneine in the diet, have a higher probability of diseases like Parkinson's Disease and Alzheimer's," said Beelman. "Now, whether that's just a correlation or causative, we don't know. But, it's something to look into, especially because the difference between the countries with low rates of neurodegenerative diseases is about 3 milligrams per day, which is about five button mushrooms each day."

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Story Source:

Materials provided by Penn State. Note: Content may be edited for style and length.

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Journal Reference:

1. Michael D. Kalaras, John P. Richie, Ana Calcagnotto, Robert B. Beelman. Mushrooms: A rich source of the antioxidants ergothioneine and glutathione. Food Chemistry, 2017; 233: 429 DOI: 10.1016/j.foodchem.2017.04.109

spectrum disorders and motor skills

ln addition to the three core difficulties of ASD (social interaction, and  communication challenges and repetitive behaviors) children on the autistic spectrum often have difficulties with posture, coordination and motor planning. In fact recent studies show that movement difficulties are very common in children on the autistic spectrum, and importantly, poor motor skills are associated with;greater difficulties with social communication.

Factors that affect motor skills in children with autism Differences in brain wiring  Affect sensorimotor integration, motor learning and coordination Difficulties with prediction and anticipation Affect motor planning and motor learning Also affects postural stability and balance Joint hypermobility/low muscle tone Affect stability and muscle strength Associated with toe walking Anxious/fearful temperament  Affects willingness to participate in challenging tasks Leads to avoidance and limited experience

Difference in brain wiring 

Learning a new motor skill depends on the brain's ability to form rich connections between the different parts of the brain involved in controlling movement, including  the ability to use sensory information from the environment and from the body to predict what is going to happen next, to plan actions and adapt the actions as needed. 

Typically developing children make these brain connections, and learn new motor tasks, easily in the course of everyday experience. They are motivated to take on new challenges, explore different ways of achieving their goals and expect to master new skills with repeated practice. This gives them a sense of self-efficacy and I-can-do. 

Children with autism, and those with developmental coordination disorder, do not learn new motor skills in the same easy way, possibly because of differences in the way their brains form new connections.  

How differences in brain wiring affect motor skills

Motor skill performance and learning depend on forming rich connections between different parts of the brain that link:

• sensory information from the body – skin, joints, muscles, vestibular system
• sensory information from the environment: vision and hearing
• intentions, goals and feelings

This information is used for predicting what will happen next, planning movements to achieve goals, executing the movements and evaluating the outcome: was I successful, did I achieve my goal, what needs to be changed to improve?

Because of the differences in how the brain is wired, children with autism do not easily integrate all the information needed for task learning, may use different pathways which are less efficient and may need extra practice and guidance to learn new motor skills.

However, given the right opportunities all children with autism can improve their motor skills: it just takes time, patience and know how. 

Read more:
How brain wiring affects motor control  
Jason learns to catch a ball - a teaching session 
Task based training for autism and DCD

Movement difficulties related to anxiety and attention issues

Good motor control is learned through experience. Typically developing children spend a lot of time working on learning and improving motor skills as part of their everyday activities.  They explore different ways to achieve a goal,  persist in the face of failure and learn from their mistakes.  Through lots of repeated experience young children learn how to use sensory information to plan and adapt their actions to achieve their goals. 

Autistic children are not as good at exploring different ways to achieve a goal, have difficulty sorting through and selecting the right sensory information for a task and are not as good at learning through experience. 

Movement difficulties caused by joint hypermobility

​Although there is no research that has looked at the prevalence of generalized joint hypermobility (GJH) in autistic children, anecdotal evidence suggests that it is a fairly common feature. 

GJH  simply means that the child has joints that are more flexible than usual. This happens when the connective tissue which makes up the joint structures (capsule and ligaments) is more compliant (more easily stretched) than usual. Muscles are also affected, with a tendency to weakness (sometime mistakenly called low muscle tone).

Hypermobile joints are less stable than usual; this means that the child needs stronger muscles to support the body. Fortunately strength training will improve both joint stability and muscle strength.

The increased compliance (give) in the connective tissue also affects the blood vessels and internal organs which can lead to low blood pressure, trouble with bladder control and voiding, and constipation.

Interestingly, children with joint hypermobility tend to have a fearful/anxious temperament which affects their behaviour. 

How joint hypermobility affects motor function

Joint hypermobility affects the development of motor control in several ways. Because the joints inherently less stable, more muscle work is needed for good posture and movement control. Children with joint hypermobility often have difficulty sitting erect for working at a table, hypermobile finger joint affect pencil grip for drawing and handwriting, leg weakness affects walking distances, running speed, managing stairs, climbing on the climbing frame and hanging from monkey bars. 

Loose joint, some tight muscles 

In addition children with GJH often have some tight muscles in the hips and shoulders. This affects sitting comfortably on a chair or cross legged on the floor, as well as shoulder movements needed for drawing and handwriting. 

• Strength, flexibility and general fitness training all help children with hypermobile joints to get better at everyday activities such as sitting for working at a table, shoulder control for handwriting, going up and down stairs, walking distances, running speed and fitness, enjoying climbing frames and monkey bars. 

Night pain and joint hypermobility 

Children with joint hypermobility and tightness in the hip muscles often experience pain in the legs following exercise, or when they are going through a growth spurt. Children with autism often have an increased tendency to respond negatively to discomfort, which can make night pain related to exercise very bothersome. Read more about night pain in hypermobility

• Fitness training that includes stretching and strengthening goes along way to improving pain following exercise. Some gentle stretching before going to sleep at night also helps to alleviate knee pain that occurs during growth spurts.   

Toe walking and hypermobility

Toe walking is associated with tightness in the calf muscles as well as the muscles crossing over the back and sides of the hips and legs. In most cases children who walk on the toes have hypermobile joints.  (Some tight muscles is a common feature of joint hypermobility).

The toe walking is probably more related to muscle tightness along with poor motor planning , rather than be a sensory issue. Children who walk on their toes often have tightness in the muscles crossing the sides of their hips. They stand with their legs wide apart and the feet turned out. This tightness makes it uncomfortable to stand with the feet close together and the heels flat on the floor, or to walk with the heels flat on the floor.

Depending on how tight the calf muscles are, a program of stretching exercises that target the hip muscles in particular, along with foot balance training will improve toe walking.

 Read more:  Idiopathic toe walking in children  and  Idiopathic toe walking: for therapists

Low muscle tone 

The problem with the  term "low muscle tone" is that it is a bit of a catch-all idea.  It seems to mean different things to different people. Mostly it is a box into which any movement difficulty can be thrown without really pin-pointing what the underlying causes of the child' difficulties are.

In many cases the underlying reason for the appearance of low muscle tone can be attributed to joint hypermobility. The distinction is important because it affects the choice of remedial activities.  Movement difficulties caused by joint hypermobility are improved by exercises that improve strength and general fitness. 

Read more: My child has been diagnosed with low muscle tone. What does this mean? 

SfA Fitness and Coordination Training Guide 
All the information you need to be your child's coach and advocate. Designed by a master physical therapist

 

  

     

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For therapists

Autism notes and abstracts 
Covering latest research on motor control and brain connectivity in autism 

Why take a task based approach to physical therapy?
A video tutorial 

Joan, mother of 8 year old autistic Zak Your website is the only site I have found that has answered all my questions and provided practical solutions for my son's challenges with posture, muscle strength, hand writing and muscle tone. I am really looking forward to starting the handwriting work with him as I have known for ages that it was linked to muscular strength/flexibility problem but did not have the tools to work on it. Previous occupational therapy made differences in other  areas but not that one. Now I can test him and have the tools to help him. Brilliant.

Here's what losing weight does to your body and brain

Special thanks to John Gunstad, professor with the Department of Psychological Sciences at Kent State University, for speaking with us about his cutting-edge research on how losing weight affects brain function. Following is a transcript of the video. 

Here’s what losing weight does to your body and brain.

During the first week, you may find it easy to lose weight by simply switching to a healthier diet. But as your metabolism adjusts, you won’t burn as many calories as you used to.

So losing additional weight will become harder.

Making matters worse, as the fat melts away, you’ll start to experience an increase in appetite. After a meal, fat cells release a hormone called leptin into the bloodstream.

This surge in leptin levels signals to your brain you’re full and should stop eating. But with less overall fat, people who lose weight show a measurable dip in leptin.

Brain scans of obese patients who had lost 10% of their body weight revealed that less leptin leads to increased activity in regions of the brain that control our desire to eat.

The result isn’t just an increased appetite but an even stronger urge to eat fatty, high-calorie foods, because your brain is trying to restore the body’s leptin levels to normal. 

However, fighting that early impulse to gorge on pizza and donuts is worth it in the long run.

Besides the decreased risk of heart disease, hypertension, high cholesterol and type 2 diabetes, scientists studying overweight people discovered that losing just one pound of body weight reduces four pounds of pressure on knee joints.

Losing excess weight also reduces strain on the blood vessels, increases blood flow to the brain, and boosts overall brain function.

Several studies have shown that people who underwent weight-loss surgery saw an improvement in memory, concentration, and problem-solving skills in as soon as three months.

Plus, brain scans indicate that people who lost weight and kept it off for nine months reacted differently when shown images of high-calorie foods than before they lost the weight.

The brain regions that process reward, motivation, and taste didn’t react as strongly, whereas the areas that promote overall self-control had a boost in activity.

So fighting those cravings early on might make them easier to control later. Turns out — like anything else — losing weight can get easier with practice.