Music has a universal ability to tap into our deepest emotions. Unfortunately, for children with Autism , understanding emotions is a very difficult task. Can music help them?

Thanks to funding from the GRAMMY Foundation Grant Program, researchers at UCLA are about to find out. Individuals with ASD have trouble recognizing emotions, particularly social emotions like facial expressions a frown, a smirk, or a smile. This inability can rob a child from being able to communicate and socialize, and often leads to social isolation. In an innovative study led by Istvan Molnar-Szakacs, a researcher at the UCLA Tennenbaum Center for the Biology of Creativity, music will be used as a tool to explore the ability of children with autsim to identify emotions in musical excerpts and facial expressions.

“Music has long been known to touch autistic children,” said Molnar-Szakacs. “Studies from the early days of autism research have already shown us that music provokes engagement and interest in kids with autism. More recently, such things as musical memory and pitch abilities in children with autism have been found to be as good as or better than in typically developing children.”

Also, he said, researchers have shown that because many children with autism are naturally interested in music, they respond well to music-based therapy.

But no one has ever done a study to see if the brains of children with autism process musical emotions and social emotions in the same way that typically developing children do.

In this study, Molnar-Szakacs will use “emotional music” to engage the brain regions involved in emotion processing. “Our hypothesis is that if we are able to engage the brain region involved in emotion processing using emotional music, this will open the doorway for teaching children with autism to better recognize emotions in social stimuli, such as facial expressions.”

The overarching goal of the study, of course, is to gain insights about the causes of autism. Molnar-Szakacs will use neuroimaging functional magnetic resonance imaging, or fMRI to look at the brain activity of children with autism , and compare them to the brains of typically developing kids, while both groups are engaged in identifying emotions from faces and musical excerpts. “The study should help us to better understand how the brain processes emotion in children with autism; that in turn will help us develop more optimal interventions. Importantly, this study will also help us promote the use of music as a powerful tool for studying brain functions from cognition to creativity.”

Approximately 15 children with ASD ranging from 10-13 years of age will participate in this study, which is being conducted under the auspices of The Help Group – UCLA Autism Research Alliance. The Alliance, directed by Elizabeth Laugeson, is an innovative partnership between The Help Group and the UCLA Semel Institute for Neuroscience and Human Behavior, and is dedicated to enhancing and expanding research in autism spectrum disorders. The project is also in collaboration with Katie Overy, Co-Director of the Institute for Music in Human and Social Development at the University of Edinburgh, Scotland.

“The hope, of course, is that this work will not only be of scientific value and interest, but most of all, that it will translate into real-life improvements in the quality of the children’s lives,” said Molnar-Szakacs.

Scientists using a new drug screening method in Drosophila (fruit flies), have identified several drugs and small molecules that reverse the features of fragile X syndrome — a frequent form of mental retardation and one of the leading known causes of autism. The discovery sets the stage for developing new treatments for fragile X syndrome.

The results of the research by lead scientist Stephen Warren, PhD, chair of the Department of Human Genetics at Emory University School of Medicine, are published online in the journal Nature Chemical Biology.

Dr. Warren led an international group of scientists that discovered the FMR1 gene responsible for fragile X syndrome in 1991. Fragile X syndrome is caused by the functional loss of the fragile X mental retardation protein (FMRP). Currently there is no effective drug therapy for fragile X syndrome, and previously no assays had been developed to screen drug candidates for the disorder.

During the past 17 years, intense efforts from many laboratories have uncovered the fundamental basis for fragile X syndrome. Scientists believe FMRP affects learning and memory through regulation of protein synthesis at synapses in the brain. One leading view, proposed by Dr. Warren and colleagues, suggests that over stimulation of neurons by the neurotransmitter glutamate is partly responsible for the brain dysfunction resulting from the loss of FMRP.

In their current experiment, Emory scientists used a Drosophila model lacking the FMR1 gene. These fruit flies have abnormalities in brain architecture and behavior that parallel abnormalities in the human form of fragile X syndrome. When FMR1-deficient fly embryos were fed food containing increased levels of glutamate, they died during development, which is consistent with the theory that the loss of FMR1 results in excess glutamate signaling.

The scientists placed the FMR1-deficient fly embryos in thousands of tiny wells containing food with glutamate. In addition, each well contained one compound from a library of 2,000 drugs and small molecules. Using this screening method, the scientists uncovered nine molecules that reversed the lethal effects of glutamate.

The three top identified compounds were known activators of GABA, a neural pathway already known to inhibit the effects of glutamate. In the study, GABA reversed all the features of fragile X syndrome in the fruit flies, including deficits in the brain’s primary learning center and behavioral deficits. The screening also identified other neural pathways that may have a parallel role in fragile X syndrome and could be targets for drug therapy.

“Our discovery of glutamate toxicity in the Drosophila model of fragile X syndrome allowed us to develop this new screen for potential drug targets,” notes Dr. Warren. “We believe this is the first chemical genetic screen for fragile X syndrome, and it highlights the general potential of Drosophila screens for drug development.

“Most importantly, it identifies several small molecules that significantly reverse multiple abnormal characteristics of FMR1 deficiency. It also reveals additional pathways and relevant drug targets. These findings open the door to development of effective new therapies for fragile X syndrome.”

There may be a way in the future to enhance diabetes treatment – with better control of blood sugar and its use by the brain, and a lower risk for neurological problems – by attaching insulin to a specially designed nanomaterial.

Ohio State University researchers have developed a compound consisting of insulin bound to a string of amino acids that includes an antioxidant group. An earlier study in mice, published in Biomaterials, suggested this nanomaterial’s anti-diabetes properties included improving glucose consumption and availability as fuel for the brain.

In a new study, the team compared the therapeutic effects of the experimental compound to the effects of insulin alone and the nanomaterial alone in mouse models of type 1 diabetes. The measures of blood sugar control and insulin-related gene activity in the brains of mice treated with the combination therapy came close to those of healthy animals, and these same mice did better on tests of their thinking and memory.

Previous research has linked both type 1 and type 2 diabetes to problems with cognitive function and higher risk for dementia, but “neurological complications of diabetes are the least addressed,” said Ouliana Ziouzenkova, associate professor of human sciences at Ohio State and senior author of the study.

“We found in mice that our molecule and insulin combined was better than each treatment alone in reversing diabetes-related problems, and produced a dramatically improved cognitive performance compared to all other groups.”

The research is published in the journal Pharmaceutics.

The molecule the scientists used to bind to insulin’s chemical structure, called AAC2, was developed in the lab of study co-senior author Jon Parquette, professor of chemistry and biochemistry at Ohio State.

Parquette and collaborators created a series of molecules out of small chains of amino acids and, to make AAC2, the addition of a structural fragment of the antioxidant coumarin. The chains are designed to stack like bricks and stick to each other in a way that enables them to self-assemble into nanofibers that carry a positive electrical charge. The electrical forces hold insulin and AAC2 together to form a supramolecular complex.

“That’s important because of lot of things that happen on a biological scale seem to be on the nanometer scale. Proteins, cell surfaces, viruses are all nanoscale objects,” he said. “So if you can make things that function on that scale you have a better ability to intervene in biological processes.”

The bodies of people with type 1 diabetes don’t make a sufficient amount of insulin, and in people with type 2 diabetes, the body cannot properly use insulin to transfer sugar from the blood to muscle and fat cells, and many other cells in the body, that use glucose for energy. The brain, a major organ requiring the use of glucose for fuel, relies on specific transporters to deliver glucose – transporters whose function can be damaged by irregularities in glucose levels such as those that occur in diabetes.

In this study, experiments were conducted in mice that were chemically and genetically engineered to have insulin deficiencies that cause high levels of blood sugar, the hallmark of type 1 or type 2 diabetes. Researchers injected the animals every three days with either human insulin alone (used to distinguish treatment from insulin produced by the mice), the AAC2 molecule alone, or the AAC2 molecule bound to the human insulin as a combination therapy.

The team found that only the combination therapy produced steady glucose levels in the mice over a long period of time and positively influenced gene expression and neurotransmitter transport in their brains. The mice treated with the combination therapy also performed better on cognitive behavioral tests than animals treated with only insulin or the nanofiber AAC2.

Results suggested that these benefits relate to how insulin’s interactions with the nanomaterial influence two aspects of glucose use in the body: the breakdown of glucose for energy metabolism, and the use of glucose for storage and structural needs. Together, these positive impacts of the therapy can reestablish a healthy energy balance, Ziouzenkova said.

“Our concept provided a balanced metabolic effect involving a completely unique pathway that is induced by this supramolecular complex,” she said.

Research will continue on the exact mechanisms affecting the brain, any long-term side effects and how the compound degrades in the body. Ziouzenkova said the promising findings with diabetes suggest this amino acid-based nanofiber platform may be useful in enhancing treatments for other neurological and metabolic disorders. Kristy Townsend, associate professor of neurosurgery, has joined the research team to explore these directions.

Scientists have known for some years that eating yogurt is associated with a reduced risk of diabetes, but the reasons behind this protective effect were unclear. A study published today in Nature Communications by researchers at Université Laval and Danone Nutricia Research reveals that this protection could come partly from the gut microbiota as well as from specific metabolites produced by the lactic bacteria in yogurt.

“These metabolites, called branched chain hydroxy acids (BCHA), result from the action of yogurt lactic bacteria on naturally occurring amino acids in milk,” explains co-lead author André Marette, who is a professor at Université Laval’s Faculty of Medicine and a researcher at the Québec Heart and Lung Institute. “

The researchers made this discovery when observing the effects of yogurt on mice fed a diet rich in sugars and fats. One of the groups was given the equivalent of two daily servings of yogurt. After the 12-week experiment, the researchers found better control of blood sugar, insulin resistance, and liver function in the yogurt fed group. They then analyzed all the metabolites present in their livers and observed changes in BCHA.

“In the group that was not given yogurt, the amount of these metabolites in the bloodstream and in the liver decreased with weight gain. In the yogurt group, the amount of BCHA was partially maintained,” explains Professor Marette who is also a researcher at the Institute of Nutrition and Functional Foods (INAF) at Laval University. “We also found that an abundance of BCHA in the liver was tied to improved fasting glucose and hepatic triglycerides.” 

“BCHA are found in fermented dairy products and are particularly abundant in yogurt. Our body produces BCHA naturally, but weight gain seems to affect the process,” adds co-lead author Dr. Hana Koutnikova, in charge of this research at Danone Nutricia Research. A next step could now be to determine whether dietary intake of BCHA can offset the decrease associated with weight gain and help restore normal metabolic function in obese people. 

The largest and most rigorous twin study of its kind to date has found that shared environment influences susceptibility to autism more than previously thought.

The study, supported by the National Institutes of Health, found that shared environmental factors – experiences and exposures common to both twin individuals – accounted for 55 per cent of strict autism and 58 per cent of more broadly defined autism s). Genetic heritability accounted for 37 per cent of autism and 38 per cent of autism. Random environmental factors not shared among twins play a much smaller role.

Earlier twin studies had estimated the genetic heritability of autism to be as high as 90 percent, due to much lower estimates of concordance – both members of a twin pair having the disorder – in fraternal twins. The new study found such concordance to be four to five times higher.

“High fraternal twin concordance relative to identical twin concordance underscores the importance of both the environment and moderate genetic heritability in predisposing for autism,” explained Joachim Hallmayer, M.D., of Stanford University, Palo Alto, Calif. a grantee of the NIH’s National Institute of Mental Health.
“Both types of twin pairs are more often concordant than what would be expected from the frequency of autism in the general population. However, the high concordance among individuals who share only half their genes relative to those who share all of their genes implies a bigger role for shared environmental factors.”

Hallmayer, senior co-investigator Neil Risch, Ph.D., of the University of California, San Francisco, and colleagues report on findings of the California Autism Twins Study (CATS) in the July 2011 issue of the Archives of General Psychiatry.

“These new findings are in line with other recent observations supporting both environmental and genetic contributions to autism , with the environmental factors likely prenatal and the genetic factors highly complex and sometimes not inherited,” said NIMH director Thomas R. Insel, M.D.

Studies are underway to determine if autism may be traceable, in part, to environmental exposures early during pregnancy.

The new study is the first to analyze a large sample of twins drawn from the general population; previous twin studies have been based on more limited samples, such as patients in treatment. It is also the first to employ the latest standard in diagnosing autism, which requires structured clinical assessments based on interviews with the parents as well as direct observation of the child.

Drawing upon state records, the researchers initially identified 1,156 twin pairs, with at least one member affected by autismk , born to California mothers between 1987 and 2004. The children were all at least 4 years old, an age when autism can be reliably diagnosed. Ultimately, this group was winnowed to 192 twin pairs – 54 identical and 138 fraternal – for genetic analysis. Since autism disproportionately affects males, males outnumbered females by four to five times, with 80 of the pairs including both sexes.

Concordance for autism was 77 percent among identical male pairs, and 31 percent among fraternal male pairs. In females, concordance for ASD was more closely spaced – 50% for identical and 36% for fraternal pairs. By contrast, previous studies had found concordance rates for fraternal twins that were much lower, ranging only in the single digits.

“Spectrum disorders traditionally thought to have less genetic loading turn out to stem from a similar mix of environmental and genetic heritability as narrowly defined autism,” noted Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch.

Yet, there can also be genetic influences that are not inherited from parents. New evidence emerged last month that rare, spontaneous mutations occur at abnormally high rates in autism.

“Such non-inherited genetic changes were proposed as a major mechanism of autism susceptibility, based on the very low concordance among fraternal twins found in earlier studies and evidence of increased risk associated with older parental age,” explained Risch. “In light of the high fraternal twin concordance observed in our study, such new mutations may play a more limited role, since they would primarily occur in only one member of a fraternal pair, which would not lead to concordance.”