Autism ASD: Researchers discover a potential cause

Topoisomerase inhibitors reduce the expression of long genes in neurons, including a remarkable number of genes implicated in Autism Spectrum Disorders -- 200 kb is four times longer than the average gene. 

Credit: Concept: Mark Zylka. Illustration: Janet Iwasa.

Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), according to research announced today in the journal Nature.

Scientists at the University of North Carolina School of Medicine have described a finding that represents a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder's genetic causes.

"Our study shows the magnitude of what can happen if topoisomerases are impaired," said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC.

"Inhibiting these enzymes has the potential to profoundly affect neurodevelopment—perhaps even more so than having a mutation in any one of the genes that have been linked to autism."

The study could have important implications for ASD detection and prevention.

Mark Zylka

"This could point to an environmental component to autism," said Zylka.

"A temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development. "

This study could also explain why some people with mutations in topoisomerases develop autism and other neuro-developmental disorders.

Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes overwound, a common occurrence that can interfere with key biological processes.

Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells.

"If there are additional compounds like this in the environment, then it becomes important to identify them," said Zylka.

"That's really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects—so that pregnant women can avoid being exposed to these compounds."

Zylka and his colleagues stumbled upon the discovery quite by accident while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy.

Investigating the drug's effects in mouse and human-derived nerve cells, they noticed that the drug tended to interfere with the proper functioning of genes that were exceptionally long—composed of many DNA base pairs.

The group then made the serendipitous connection that many autism-linked genes are extremely long.

"That's when we had the 'Eureka moment,'" said Zylka. "We realized that a lot of the genes that were suppressed were incredibly long autism genes."

Of the more than 300 genes that are linked to autism, nearly 50 were suppressed by topotecan. Suppressing that many genes across the board—even to a small extent—means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene.

The study's findings could also help lead to a unified theory of how autism-linked genes work. About 20 percent of such genes are connected to synapses—the connections between brain cells.

Another 20 percent are related to gene transcription—the process of translating genetic information into biological functions.

Zylka said this study bridges those two groups, because it shows that having problems transcribing long synapse genes could impair a person's ability to construct synapses.

"Our discovery has the potential to unite these two classes of genes—synaptic genes and transcriptional regulators," said Zylka.

"It could ultimately explain the biological mechanisms behind a large number of autism cases."

More information: Nature paper dx.doi.org/10.1038/nature12504

Medikidz: Comic books to help children understand chronic pain

Comic book superheroes are being used to help children understand more about older relatives suffering from chronic pain, in an innovative project. 

Northumbria University academic Dr Derek Jones has been working on a project led by Teesside University Professor Denis Martin to explore how comic book superheroes can help children understand what an older adult with chronic pain is experiencing.

The research project, also involving colleagues from the universities of Dundee, Aberdeen, and Greenwich, has seen the academics work with Medikidz – an international company which produces award-winning comics featuring Marvel-inspired superheroes to put medical information into plain words which children can understand – to create a comic book about chronic pain.

The comic is one of the products from a collaboration between the university partners in the UK Research Council-funded £1.2 million EOPIC (Engaging with Older People and Their Carers to Develop Interventions for the Self-management of Chronic Pain) Project.

Dr Derek Jones, Senior Lecturer in Occupational Therapy at Northumbria University, said: "Education about pain is really important; it is increasingly recognised that explaining to people the biological processes underlying their experience results in better pain management.

"We will be carrying out research to investigate the value of the Medikidz comic book; from what we have been told so far we think it will prove to be helpful to anyone who comes into contact with someone with chronic pain."

Professor Martin, from Teesside University, said: "The idea for the comic came about as we were talking to older people to find out their ideas on how to improve the lives of older people living with chronic pain."

"We learned that there was a need to help grandchildren to better understand the experiences of a grandparent living with chronic pain."

"It can be difficult for a child to understand because they can't see the pain which is making their grandparent miserable and feeling unable to do day-to-day things. We wanted to use that information to develop a product which would help younger relatives understand what the older person is going through, given the lack of information available to help that communication."

Medikidz already produces material to explain to children about their own medical conditions, but working with the EOPIC team, they focused on material to inform a child about the older relative's condition.

The book, entitled 'What's Up with Moira's Grandad: Medikidz Explains Chronic Pain', portrays a typical scenario, which involves a child not understanding why their grandparent has suddenly cancelled time they'd planned to spend with them.

The child is left upset, thinking the grandparent simply isn't bothered - while the grandparent is frustrated and angry at having felt forced to cancel due to difficulty in coping with chronic pain.

The EOPIC team provided the information and outline of the story to Medikidz, who adapted it to use their superheroes to tell the story.

In the story the child is taken on a journey through the human body, with the Medikidz superheroes explaining about chronic pain and how it impacts on someone's life. The happy conclusion shows the child with a better understanding of their grandparent's situation.

The team now plans to distribute the comics to clinics across the region initially and then to expand nationally and further afield.

Fetal Alcohol Spectrum Disorders (FASD) - South Africa study

Two recently published studies report prevalence data about fetal alcohol spectrum disorders (FASD) in South Africa and find that negative consequences of prenatal exposure to alcohol may be lessened if a child is provided with adequate nutrition and appropriate cognitive and behavioral stimulation in his or her first seven years of life.

Dr. Philip A. May

Dr. Philip A. May, faculty member at the University of North Carolina's Nutrition Research Institute (NRI), research professor of nutrition at the Gillings School of Global Public Health and Principal Investigator at the University of New Mexico's Center on Alcoholism, Substance Abuse, and Addictions (CASAA), is lead author of both papers.

At the NRI, May is conducting a comprehensive study of South African mothers and their children who are affected by FASD.

The work is funded through a $5.3 million grant from the National Institutes of Health's National Institute on Alcohol Abuse and Alcoholism.

The study, titled "Approaching the Prevalence of the Full Spectrum of Fetal Alcohol Spectrum Disorders in a South African Population-Based Study," appeared in the May issue of Alcoholism: Clinical and Experimental Research.

"This is the first population-based study of the prevalence of FASD to diagnose a significant number of alcohol-related disabilities, which are at the mild end of the continuum," Dr. May said of the study.

Employing newly refined diagnostic criteria, the researchers were able to better indicate the scope of the problem.

"There is evidence of advances in diagnosis of the milder effects of alcohol exposure in the prenatal period," Dr. May said. "The rate of FASD is greater than we ever thought in human populations."

In "Maternal Factors Predicting Cognitive and Behavioral Characteristics of Children with Fetal Alcohol Spectrum Disorders," which appeared in the Journal of Developmental and Behavioral Pediatrics in June, May and his colleagues found evidence that good health and nutrition of the pregnant mother provides her child with an advantage for cognitive and behavioral development by age seven.

"In the first seven years of life environmental advantages of cognitive and behavioral stimulation and adequate nutrition can, in many cases, serve to minimize any negative consequences of prenatal alcohol exposure on the children's social, behavioral, and intellectual functioning," May said.

The NIAAA grant is funding a study for children as young as 12 months to improve their development with nutritional supplements and a regimen of cognitive and behavioral interventions.

"There is hope that a good postnatal environment in the early years of life can mitigate some, if not most, of the damage that occurs from alcohol exposure in the prenatal period," May said.

Conclusions
High rates of specific diagnoses within FASD were well documented in this new cohort of children. FASD persists in this community. The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD.

More information: Approaching the Prevalence of the Full Spectrum of Fetal Alcohol Spectrum Disorders in a South African Population-Based Study

Childhood Obesity: Schools can help by serving up better, healthier options

Schools across the country are taking several steps to fight obesity by providing healthier foods, according to a new report from the Centers for Disease Control and Prevention.

The CDC's 2012 School Health Policies and Practices Study (SHPPS) surveyed more than 800 school districts in all 50 states and the District of Columbia, finding a significant trend in prohibiting junk foods and some positive steps in getting students more active.

The report was applauded by Voices for Healthy Kids movement, a joint initiative of the American Heart Association and the Robert Wood Johnson Foundation that works to ensure schools provide an environment that encourages healthy eating.

"Everyone want children to grow up healthy," says Jill Birnbaum, executive director for Voices for Healthy Kids at the American Heart Association.

"As schools serve up better options and keep ads for junk food and sugary drinks out of their schools, kids will be better fueled to learn."

Several school settings improved at prohibiting junk food , according to the report:

• A la carte offerings at breakfast and lunch improved from 23.1 percent of schools banning junk food in 2000 to 41.7 percent in 2012. 
• Vending machines improved from 4.1 percent to 43.4 percent.
• School stores improved from 3.9 percent to 28.3 percent.
• And in after-school programs improvement went from 7.3 percent to 21.4 percent.

Some districts required (9.6 percent) or recommended (32.3 percent) that schools make fruits or vegetables available to students whenever other food is offered or sold.

Additionally, more school districts (26 percent) required the availability of healthy beverages, such as water or low-fat milk, during school events and in their stores.

There is a clear need to continue on the path to making healthy choices easier for children throughout the school day, Birnbaum said.

The marketing of unhealthy food to students remains a problem, Birnbaum said. The report found that only 38.3 percent of school districts prohibit advertisements for junk foods or fast food restaurants on school property.

State departments of education play a key role in providing their school districts with model policies and technical assistance.

Whereas almost all states and the District of Columbia helped school districts increase access to free water, only 76.5 percent assisted schools in limiting student access to less nutritious food and beverages.

As for physical activity, many schools have made promising advances, the report found. However, Birnbaum said, there is room for significant improvement.

Most schools require physical education be taught at all grade levels, however very few require the national recommendations of 150 minutes per week for elementary and middle schools and elementary schools and 225 minutes per week for high school students.

Additionally, only 58.9 percent of districts require scheduled recess in elementary schools and a mere 10.8 percent require a break for physical activity in middle schools.

More school districts (61.6 percent) also have formal agreements that allow another organization to use their facilities.

"Sharing recreational spaces allows both children and adults to get the exercise they need to be healthy by providing a place to be active in their community," Birnbaum said.

"Research has shown that people who have parks or recreational facilities nearby exercise 38 percent more than those who do not have easy access."

Preschoolers who stutter do just fine emotionally and socially

Stuttering may be more common than previously thought, but preschool stutterers fair better than first thought, a study by The University of Melbourne, Murdoch Childrens Research Institute and The University of Sydney has found.

A study of over 1600 children, which followed the children from infancy to four years old, found the cumulative incidence of stuttering by four years old was 11 per cent, more than twice what has previously been reported.

However, the study refutes the long held view that suggests developmental stuttering is associated with a range of poorer outcomes in the preschool period.

Interestingly, the study found the reverse was true, with stuttering associated with better language development, non-verbal skills with no identifiable effect on the child's mental health or temperament at four years old.

Surprisingly, researchers found that recovery from stuttering was low, 6.3 per cent, 12 months after onset.

Rates of recovery were higher in boys than girls, and in those who did not repeat whole words at onset than those who did. The study boys were more likely to develop stuttering.

Sheena Reilly

Lead researcher, Professor Sheena Reilly said parents could be happy in knowing that they can take a 'watch and wait' approach to their child's stuttering and it won't be causing harm to their child's language skills or social and emotional development.

"Current best practice recommends waiting for 12 months before commencing treatment, unless the child is distressed, there is parental concern, or the child becomes reluctant to communicate. It may be that for many children treatment could be deferred slightly further," she said.

"Treatment is effective but is intensive and expensive, this watchful recommendation would therefore help target allocation of scarce resources to the small number of children who do not resolve and experience adverse outcomes, secure in the knowledge that delaying treatment for a year or slightly longer has been shown not to compromise treatment efficacy."

Due to the low rates of recovery in the study, researchers were unable to determine what predicts which kids will recover from stuttering, but say this will be the focus of research moving forward.

The study was published in Pediatrics.

More links seen between autism, ADHD

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.

Joseph Biederman

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 psycho-pharmacology 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."

Alice Mao

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 behaviour 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 behaviour 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."

Depression in Grandmothers who care for Grandchildren

Grandmothers who care for their grandkids fulltime need help for depression and family strains, report researchers from the Case Western Reserve University's Frances Payne Bolton School of Nursing.

Carol Musil, PhD, RN, FAAN, professor of nursing, recently conducted one the longest-running studies on grandmothers in various family situations, from serving as their grandkids' fulltime caregivers to those not caring for their grandchildren as a comparison.

"Although we expected the primary caregiver grandmothers raising grandchildren would have more strain and depressive symptoms, " Musil said, "we were surprised at how persistent these were over the years examined in the study."

Results of the study, funded by a grant from the National Institute of Nursing Research, were reported in Nursing Outlook, the journal of the American Academy of Nursing and the Council for the Advancement of Nursing Science.

Some 6.2 million, or 5.3 percent of all U.S. households, have a grandparent living in the house, according to U.S. Census data.

Musil said over 1 million grandmothers are responsible for raising grandchildren whose parents do not live in the home.

Musil tracked and focused on the health and wellbeing of 240 grandmothers they studied for 6 1/2 years to see how the responsibilities of caring for their grandchildren 16 years and younger affected their health over time.

The subjects were surveyed about their physical and mental health annually for the first three years, and two more times, 2- 2 ½ years apart at the end of study.

The grandmothers, who averaged 57.5 years old at study onset, were in three caregiving situations: those who are fulltime caregivers for their grandchildren, living in multigenerational homes or non-caregivers.

They were randomly selected throughout Ohio, representing rural, suburban and urban backgrounds.

Despite the signs of depression and family stress, researchers also found that the grandmothers, especially those raising grandchildren, were generally open to receiving various forms of help.

That implies, Musil said, that grandmothers might be open to resourcefulness training, which has helped to reduce depressive symptoms in grandmothers in pilot studies conducted with Jaclene Zauszniewski.

"They need support from others," she said, "but the most important thing is to maintain and perhaps develop new cognitive and behavioral skills and approaches for handling some very challenging family issues."

Boys suffer from their fathers' absence and long working hours

Fathers' extremely long working hours can be detrimental to their sons´ wellbeing.

This is the key finding of a longitudinal study by Jianghong Li (senior researcher at the WZB Berlin Social Science Center) and four Australian co-authors, published in the Journal of Marriage and Family.

The longitudinal study is based on data of more than 1,400 children in Western Australia. Around 19 percent of Western Australian fathers work 55 or more hours per week when their children are 5 years of age.

Almost 20 percent of Australian fathers work so long when their children are 8 years old.

Boys whose fathers worked 55 or more hours per week later exhibited more delinquent and aggressive behaviours than boys whose fathers worked fewer hours.

Their fathers' long work hours did not appear to affect girls' behaviours.

Mothers' work hours did not seem to matter, although few Australian mothers worked long hours and no firm conclusions can be drawn yet from this comparison.

The culture of working long hours which has crept into many jobs in the new economy should be the next policy frontier.

In Germany 15 percent of fathers of children with similar age (3-4) work 55 or more hours per week in 2011.

The data come from the cohort study called "Western Australian Pregnancy Cohort Study" well-known under the name Raine Study. The Study has been following children from pregnancy to adulthood.

More information: Johnson, S. et al. Mothers' and Fathers' Work Hours, Child Gender and Behavior in Middle Childhood. Journal of Marriage and Family, 2013, 75: 56-74.

Antipsychotic drug use in children for mood, behaviour disorders increases type 2 diabetes risk

Prescribing of "atypical" antipsychotic medications to children and young adults with behavioral problems or mood disorders may put them at unnecessary risk for type 2 diabetes, a Vanderbilt University Medical Center study shows.

Young people using medications like risperidone, quetiapine, aripiprazol and olanzapine led to a threefold increased risk of developing type 2 diabetes within the first year of taking the drug, according to the study published Aug. 21 in the journal JAMA Psychiatry.

Wayne A. Ray

While other studies have shown an increased risk for type 2 diabetes associated with the use atypical antipsychotic medications, this is the first large, well-designed study to look at the risk in children, said Wayne A. Ray, Ph.D., professor of Preventive Medicine, and senior author of the study.

The authors note the use of these drugs for non-psychosis-related mood, attention or behavioral disorders in youth/children now accounts for the majority of prescriptions.

"Because we wanted to address this question of risk for indications for which there were therapeutic alternatives, we deliberately excluded those taking antipsychotics for schizophrenia and other psychoses; thus, our entire sample consisted of patients for whom there were alternatives to antipsychotics," Ray said.

State-provided, de-identified medical records were examined for TennCare youths ages 6-24 from 1996 through 2007.

During that time children and youth who were prescribed treatment with atypical antipsychotics for attention, behavioral or mood disorders, were compared with similar youth prescribed approved medications for those disorders.

Even with the further elimination of certain disorders that are commonly associated with diabetes, like polycystic ovarian syndrome, those taking antipsychotics had triple the risk of developing type 2 diabetes in the following year, with the risk increasing further as cumulative dosages increased.

The increased risk persisted for at least a year after the medications were stopped.

Ray and his colleagues point out developing type 2 diabetes is still rare in this age group. Of the nearly 29,000 children and youth in the antipsychotic medication group and 14,400 children in the control group, 106 were ultimately diagnosed and treated for type 2 diabetes.

"That's why this study had to be so large, in order to detect clinically meaningful differences in the risk of type 2 diabetes, a relatively uncommon, but serious condition for children and youth," Ray said.

The take-away message for providers, said Ray, is to carefully examine alternatives to antipsychotic use.

"This is particularly important for high-risk children, for example, those with elevated weight. Children should be monitored carefully for metabolic effects predisposing them to diabetes, and use of the drug should be at the lowest possible dose for the shortest possible time," he said.

More Information:  Antipsychotics and the Risk of Type 2 Diabetes Mellitus in Children and Youth -

Giving preschoolers choice increases sharing behaviour

Getting kids to share their toys is a never-ending battle, and compelling them to do so never seems to help.

New research suggests that allowing children to make a choice to sacrifice their own toys so they can share with someone else, makes them share more in the future.

The new findings are published in Psychological Science, a journal of the Association for Psychological Science.

Nadia Chernyak

These experiments, conducted by psychological scientists Nadia Chernyak and Tamar Kushnir of Cornell University, suggest that sharing when given a difficult choice leads children to see themselves in a new, more beneficent light.

Perceiving themselves as people who like to share makes them more likely to act in a prosocial manner in the future.

Previous research has shown that this idea – as described by the over-justification effect—explains why rewarding children for sharing can backfire.

Children come to perceive themselves as people who don't like to share since they had to be rewarded for doing so. Because they don't view themselves as "sharers" they are less likely to share in the future.

Chernyak and Kushnir were interested in finding out whether freely chosen sacrifice might have the opposite effect on kids' willingness to share.

"Making difficult choices allows children to infer something important about themselves: In making choices that aren't necessarily easy, children might be able to infer their own prosociality."

Tamar Kushnir

To test this, the researchers introduced 3-5 year-old children to Doggie, a puppet, who was feeling sad.

Some of the children were given a difficult choice: Share a precious sticker with Doggie, or keep it for themselves.

Other children were given an easy choice between sharing and putting the sticker away, while children in a third group were required by the researcher to share.

Later on, all the children were introduced to Ellie, another sad puppet.

They were given the option of how many stickers to share (up to three).

The kids who earlier made the difficult choice to help Doggie shared more stickers with Ellie.

The children who were initially confronted with an easy choice or who were required to give their sticker to Doggie, on the other hand, shared fewer stickers with Ellie.

"You might imagine that making difficult, costly choices is taxing for young children or even that once children share, they don't feel the need to do so again," Chernyak says.

"But this wasn't the case: Once children made a difficult decision to give up something for someone else, they were more generous, not less, later on."

Another experiment supported these findings, illustrating that children are more generous after choosing to share valuable toy frogs compared to non-valuable ripped pieces of paper.

Those who initially shared the frogs with Doggie shared more stickers with Ellie later on. Those who readily shared the paper, on the other hand, shared fewer stickers with Ellie.

Therefore, children did not benefit from simply choosing to give something up, but rather from willingly choosing to give something up of value.

"Given the high amount of emphasis we place on choice during early childhood, especially in this culture, it is important to delineate specifically what choice might do—and not do—for young children," Chernyak says.

"Children are frequently taught to share, be polite, and be kind to others. To bring us closer to one day figuring out how to best teach children these skills, it is important to figure out which factors may aid in young children's sharing behaviour," Chernyak concludes.

"Allowing children to make difficult choices may influence their sharing behaviour by teaching them greater lessons about their abilities, preferences, and intentions towards others."