Scientist find Gene linked to Asperger Syndrome and empathy

Scientists have confirmed that variations in a particular gene play a key role in the autism spectrum condition known as Asperger Syndrome.

They have also found that variations in the same gene are also linked to differences in empathy levels in the general population.

A study to be published later this month in the journal Molecular Autism confirms previous research that people with Asperger Syndrome (AS) are more likely to carry specific variations in a particular gene.

More strikingly, the study supports existing findings that the same gene is also linked to how much empathy typically shown by individuals in the general population.

The research was carried out by a team of researchers led by Professor Baron-Cohen at the Autism Research Centre at Cambridge University.

Asperger Syndrome is an autism spectrum condition. The researchers looked for sequence variations (called single nucleotide polymorphisms, SNPs) in the gene known as GABRB3 in a total of 530 adults - 118 people diagnosed with AS and 412 people without a diagnosis.

The team found that certain SNPs in GABRB3 were significantly more common in people with AS.

They also discovered that additional genetic variations in the same gene were linked to scores on an empathy measure called the Empathy Quotient in the general population.

AS is diagnosed when a person struggles with social relationships and communication, and shows unusually narrow interests and resistance to change, but has good intelligence and language skills.

Most genetic studies of autistic spectrum conditions treat autism as if they are all very similar, whereas in reality there is considerable variation (e.g., in language level and intellectual ability).

Rather than studying people on the autistic condition spectrum, this new study looked only people with AS, as a well-defined subgroup of individuals within this range.

The researchers examined the gene GABRB3 which regulates the functioning of a neurotransmitter called gamma-aminobutyric acid (GABA) and which contains a number of SNPs that vary across the population.

The volunteers were tested for 45 SNPs within this key gene. The team had previously found that SNPs in this gene were more common in adults with AS and also showed a relationship with empathy levels and tactile sensitivity (how sensitive people are to being touched) in the general population.

Testing a new sample of volunteers who had not taken part in previous studies, the researchers found that three of the SNPs were again more common in adults with AS, and two different SNPs in the same gene were again related to empathy levels in the general population, confirming that the gene is involved in autism spectrum conditions.

Professor Baron-Cohen said: "We are excited that this study confirms that variation in GABRB3 is linked not just to AS but to individual differences in empathy in the population.

Many candidate genes do not replicate across studies and across different samples, but this genetic finding seems to be a solid result.

Research now needs to focus on where this gene is expressed in the brain in autism, and how it interacts with other genetic and non-genetic factors that cause AS."

The team was co-led by Dr Bhismadev Chakrabarti from the Department of Psychology at Reading University. He commented: "Genes play an important role in autism and Asperger Syndrome."

"This new study adds to evidence that GABRB3 is a key gene underlying these conditions."

"This gene is involved in the functioning of a neurotransmitter that regulates excitation and inhibition of nerve cell activity so the research gives us vital additional information about how the brain may develop differently in people with Asperger Syndrome."

Varun Warrier, who carried out the study as part of his graduate research at Cambridge University, added: "The most important aspect of this research is that it points to common genetic variants in GABRB3 being involved in both AS and in empathy as a dimensional trait."

"Although GABRB3 is not the only gene to be involved in this condition and in empathy levels, we are confident that we have identified one of the key players."

"We are following this up by testing how much protein GABRB3 produces in the brain in autism, since a genetic finding of this kind becomes more explanatory when we can also measure its function."

More information: "Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism." Varun Warrier, Simon Baron-Cohen and Bhismadev Chakrabarti. Molecular Autism 2013, 4:48 DOI: 10.1186/2040-2392-4-48

FASD: Association found between poor academic achievement and maternal drinking

Education records from the WA Literacy and Numeracy Assessment statewide testing program were compared with maternal alcohol consumption data. Credit: iStock

Researchers from WA and the UK have linked heavy drinking and binge drinking, even occasionally during pregnancy, to children's academic achievement in reading, writing and spelling; and this impact is related to the trimester in which the exposure occurred.

These results lend further support to other international studies which have found prenatal alcohol exposure increases the risk of a range of neurodevelopmental disorders, including Fetal Alcohol Spectrum Disorder (FASD).

Lead author Colleen O'Leary, from Curtin's Centre for Population Health Research, says this study is a first.

"This is the first population-based study that utilises linked cohort and state-wide education test data to examine the effect of prenatal alcohol exposure on educational achievement," Dr O'Leary says.

The cohort of 4056 children aged 8-9 years-old were from the Randomly Ascertained Sample of Children born in Australia's Largest State study; a 10 per cent random sample of infants born in WA between 1995 and 1997.

FASD Indications

Information about maternal alcohol consumption was catergorised into dosage and pattern; low (1-2 standard drinks on occasion, less than 7 per week), moderate (3-4 standard drinks on occasion, 7 per week), binge drinking (more than 50g per occasion), and heavy drinking (more than 7 standard drinks per week).

They then matched this data with education records from the WA Literacy and Numeracy Assessment statewide testing program, and also examined absenteeism at these tests.

Resulting learning problems varied depending on the dose, timing, and drinking pattern of the prenatal alcohol exposure.

"Children exposed to heavy prenatal alcohol exposure during the first trimester were over twice as likely as comparison children to not achieve the reading benchmark," Dr O'Leary says.

"Prenatal exposure to occasional binge drinking in late pregnancy [second and/or third trimester] increased the risk of not achieving the benchmark for writing.

"Children of mothers binge drinking occasionally or drinking heavily at any stage during pregnancy were more likely to have been absent for the spelling test."

Dr O'Leary says results are particularly pertinent given the high rate of pregnancies reported to be unplanned – around 50 per cent – and thus associated risk of unintentional prenatal alcohol exposure.

While low or moderate levels of prenatal alcohol exposure was not associated with academic underachievement, Dr O'Leary stresses that other studies have demonstrated adverse offspring effects, even at very low doses.

As such, "we cannot conclusively state that any amount of alcohol is 'safe'."

She recommends exploring the impact of whether supportive family and school systems can improve academic achievement of children exposed prenatally to alcohol.

More information: www.ncbi.nlm.nih.gov/pubmed/23837182

Autism: Hyperconnectivity found in children's brains

The brains of children with autism show higher-than-normal connectivity along many neural networks, a new study from the Stanford University School of Medicine has found.

The study's results may contribute to the development of a brain-based test that could be used to diagnose autism at an early stage.

The findings, published June 26 in JAMA Psychiatry, were unexpected because they contradict prior reports of reduced brain connectivity in adults with autism.

Vinod Menon

"We found that in the brains of children with autism there is a surprisingly high level of hyperconnectivity," said Vinod Menon, PhD, senior author of the study.

Menon is a professor of psychiatry and behavioral sciences at Stanford and a member of the Child Health Research Institute at Lucile Packard Children's Hospital.

Based on measurements taken when the brain was at rest—while study participants were awake but had their eyes closed—at least five major brain networks were hyperconnected in kids with autism.

But the finding was not uniform across the brain; some networks were underconnected.

"We found that there are major differences in the way the brain is functionally organized in children with autism—in how different brain areas are talking to each other," Menon said.

"The challenge is to figure out how these differences contribute to the complex profile of clinical symptoms that characterise autism."

The research team collected functional and structural magnetic resonance imaging scans from 20 children with autism and 20 typically developing children.

Assessment of connectivity was based on observing whether different areas of the brain were activated simultaneously: "Spontaneous synchronization of brain signals across long distances is what underlies the hyperconnectivity we detected," Menon said.

Hyperconnected systems in the brains of children with autism included the salience, default mode, fronto-temporal, motor and visual networks.

The salience network, which was the most heavily hyperconnected in autism, integrates information about outside stimuli with information about internal states, allowing the brain to decide which external stimuli to pay attention to.

Menon's team suggests that the hyperconnected salience network may contribute to decreased interest in social interactions among children with autism.

The new study also raises the possibility that brain scans could someday be used to diagnose autism: It found that hyperconnectivity in the salience network distinguished children with autism with 83 percent accuracy.

The team confirmed this finding with a second, independent set of brain scans from 15 children with autism and 15 typically developing children, which were obtained from a public database.

No diagnostic test based on biological markers currently exists for autism; at present, the diagnosis is based solely on observations of a child's behavior, which means that many children are diagnosed later than would be ideal.

Lucina Uddin

"We are optimistic that the brain network metrics we have identified may be used to help in developing strategies for earlier diagnosis, leading to the possibility of earlier interventions," said Lucina Uddin, PhD, an instructor in psychiatry and behavioural sciences and the study's lead author.

The complete implications of brain hyperconnectivity in children with autism are not entirely clear. In the new study, for instance, the degree of hyperconnectivity in the salience network predicted the severity of a child's restricted and repetitive behaviours—such as intense focus on a particular object or interest—frequently seen in autism.

"We think there might be a relative inability for certain types of external stimuli to engage the brain's attentional system," Menon said.

"As a result, a child with autism may be engrossed in a narrow range of behaviours instead of adaptively responding to external stimuli. That's a hypothesis we plan to test."

It's possible that hyperconnectivity could also contribute to epileptic seizures, which are more common in individuals with autism than in the general population.

Future research could also explore whether hyperconnectivity explains unusual skills seen in some individuals with autism, such as outstanding mnemonic, mathematical or spatial abilities.

"Whether hyperconnectivity can lead to exceptional skills, albeit in restricted domains, is an open question," Menon said. "We don't have answers to that yet."

Autism: Higher Levels of Several Toxic Metals Found in Children

In a recently published study in the journal Biological Trace Element Research, Arizona State University researchers report that children with autism had higher levels of several toxic metals in their blood and urine compared to typical children.

The study involved 55 children with autism ages 5-16 years compared to 44 controls of similar age and gender.

The autism group had significantly higher levels of lead in their red blood cells (+41 percent) and significantly higher urinary levels of lead (+74 percent), thallium (+77 percent), tin (+115 percent), and tungsten (+44 percent).

Lead, thallium, tin, and tungsten are toxic metals that can impair brain development and function, and also interfere with the normal functioning of other body organs and systems.

A statistical analysis was conducted to determine if the levels of toxic metals were associated with autism severity, using three different scales of autism severity.

It was found that 38-47 percent of the variation of autism severity was associated with the level of several toxic metals, with cadmium and mercury being the most strongly associated.

In the paper about the study, the authors state "We hypothesize that reducing early exposure to toxic metals may help ameliorate symptoms of autism, and treatment to remove toxic metals may reduce symptoms of autism; these hypotheses need further exploration, as there is a growing body of research to support it."

James Adams

The study was led by James Adams, a President's Professor in the School for Engineering of Matter, Transport and Energy, one of ASU's Ira A. Fulton Schools of Engineering.

He directs the ASU Autism/Asperger's Research Program.

Adams previously published a study on the use of DMSA, an FDA-approved medication for removing toxic metals.

The open-label study found that DMSA was generally safe and effective at removing some toxic metals.

It also found that DMSA therapy improved some symptoms of autism. The biggest improvement was for children with the highest levels of toxic metals in their urine.

Overall, children with autism have higher average levels of several toxic metals, and levels of several toxic metals are strongly associated with variations in the severity of autism for all three of the autism severity scales investigated.

The study was funded by the Autism Research Institute and the Legacy Foundation.

Journal Reference:

1. James B. Adams, Tapan Audhya, Sharon McDonough-Means, Robert A. Rubin, David Quig, Elizabeth Geis, Eva Gehn, Melissa Loresto, Jessica Mitchell, Sharon Atwood, Suzanne Barnhouse, Wondra Lee. Toxicological Status of Children with Autism vs. Neurotypical Children and the Association with Autism Severity. Biological Trace Element Research, 2012; 151 (2): 171 DOI:10.1007/s12011-012-9551-1

Industrial Chemicals Found in US Food Samples

A sample of 72 commonly consumed foods including pizza, meats and beverages from supermarkets in Albany, N.Y., were purchased and tested for the presence of phthalates. 

Researchers detected some level of phthalate in every food product they sampled. 

Credit: © cristi lucaci / Fotolia

Researchers at The University of Texas Health Science Center at Houston (UTHealth) have discovered phthalates, industrial chemicals, in common foods purchased in the United States. Phthalates can be found in a variety of products and food packaging material, child-care articles and medical devices.

"Although it's not completely understood how phthalates get into our food, packaging may be a contributor to the levels of the toxin in food," said lead investigator Arnold Schecter, M.D., M.P.H., professor of environmental health at The University of Texas School of Public Health Dallas Regional campus, part of UTHealth.

The study is published in the online edition of Environmental Health Perspectives. Schecter believes this is the first study to compile an analysis of phthalates in foods found in the United States. National Institutes of Health researcher Linda Birnbaum, Ph.D., is the senior author on the study publication.

"It's unfortunate that we have these toxic chemicals in our bodies," said Schecter. "However, this is not a cause for alarm because the amount of phthalates found in the food falls below what the Environmental Protection Agency considers safe. But it is cause for concern because these toxins and others previous reported by this group do not belong in our food or our bodies."

Phthalates are synthetic compounds that are used as a plasticizers and in personal care products such a shampoo, soap, perfumes and other common household products. According to Schecter, exposure to phthalates has been reported to be associated with harmful effects including reproductive changes such as damage in sperm, premature breast development in girls and premature birth.

A sample of 72 commonly consumed foods including pizza, meats and beverages from supermarkets in Albany, N.Y., were purchased and tested for the presence of phthalates. Researchers detected some level of phthalate in every food product they sampled, Schecter said.

Schecter believes further research is necessary to fully characterize phthalates in U.S. foods.

The study was funded by the Gustavus and Louise Pfeiffer Research Foundation.

In other studies, Schecter and his colleagues have found bisphenol A (BPA), a chemical produced in large quantities for use primarily in the production of polycarbonate plastics and epoxy resins, and hexabromocyclododecane (HBCD), a widely-used flame retardant, in foods.

Polybrominated diphenyl ether (PBDE), another kind of flame retardant, was found in butter and its paper wrapping, which led to butter contamination.