Mutations Linked to Autism Spectrum Disorders

Mutations in three new genes have been linked to autism, according to new studies including one with investigators at Mount Sinai School of Medicine. All three studies include lead investigators of the Autism Sequencing Consortium (ASC). The findings, in a trio of papers revealing new genetic targets in autism, are published in the April 4th online issue of the journal Nature. The studies provide new insights into important genetic changes and the many biological pathways that lead to autism spectrum disorders (ASD).

Gene mutations are glitches in DNA which can put you at risk for a particular disease. The genes with mutations identified in the studies -- CHD8, SNC2A, and KATNAL2 -- were discovered with a new state-of-the-art genomics technology known as exome sequencing, where all protein coding regions of the genome, called the exome, are analyzed. The researchers say that with further characterization of the genes and sequencing of genes in thousands of families, they will be able to develop novel therapeutics and preventive strategies for autism.

"We now have a good sense of the large number of genes involved in autism and have discovered about 10 percent of them," said Joseph Buxbaum, PhD, Director of the Seaver Autism Center and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience at Mount Sinai School of Medicine. "We need to study many more parents and their affected children if we are to uncover the genes important in ASD. As these genes are further characterized, this will lead to earlier diagnosis and novel drug development. This work is crucial for advancing autism treatment."

In the study, ASC researchers hypothesized that de novo mutations account for a substantial fraction of the risk for autism. De novo gene mutations are mutations that show up in affected children for the first time and result from mutations in the production of sperm or egg.

Founded by Dr. Buxbaum, the Autism Sequencing Consortium is an international group of autism genetics researchers that is working to identify additional genetic causes of autism through large-scale next-generation sequencing. The institutions involved in this study sequenced data from more than 500 families (both parents and the affected child), examining the protein-enriched areas of the genome.

"When the same mutations are found in multiple affected children and none are found in children without autism, we believe that we have identified mutations that collectively affect a higher proportion of individuals with autism," said Dr. Buxbaum. "Our studies revealed that the proteins encoded by the mutated genes interact with each other far more than expected, demonstrating significantly greater connectivity than would be expected."

Two other papers from groups participating in the Autism Sequencing Consortium are also featured in the same issue ofNature. Led by Matthew State, PhD, Yale School of Medicine, the first identified several highly disruptive mutations in genes associated with ASD. The results show that multiple variants on one gene identify risk factors for ASD. The second study led by Evan Eichler, PhD at the University of Washington discovered that certain mutations associated with ASD are mainly of paternal origin. Their findings also support previous research showing an increased risk of developing ASD in children of older fathers.

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Tips for a Better Night's Sleep if You're Sleepy on the Job

There's no denying that sleep deprivation, and the health issues that result, are becoming more prevalent in our go-go, techno society. But a recent sleep study by the National Sleep Foundation (NSF) grabbed my attention as particular cause for concern.

Every year, the NSF releases a Sleep in America® poll. For its 2012 survey, the NSF examined the specific sleep habits and work performances of transportation workers -- pilots, train operators, and truck, bus, taxi and limousine drivers. The transportation workers were asked about the duration and quality of their sleep, specifically on work nights, and how it affects their work performance.

Some of the results of the survey were:

• About one-fourth of the train operators and pilots polled said that sleepiness has affected their job performance at least once a week.

• One in five pilots polled -- about 20 percent -- said they have made a "serious error" as a result of on-the-job sleepiness.

• One in five pilots and one in six train operators admit to a "near miss" due to on-the-job sleepiness.

• Pilots and train operators are more likely than non-transportation workers to have been involved in a sleep-related car accident while commuting.

• Among all workers surveyed, train operators and pilots report the most work day sleep dissatisfaction.

• Almost two-thirds of train operators and one-half of pilots say they rarely or never get a good night's sleep on work nights.

• About one-third of bus, taxi, and limo drivers said they rarely or never get a good night's sleep on work nights.

The results of the poll are some cause for alarm and reinforce the growing problem of sleep disorders and the potential risks they pose, such as commuter car accidents and errors by public transportation drivers responsible for many people.

Persistent sleep problems left untreated can also lead to myriad health problems, including memory and concentration problems, increased risk of high blood pressure, hypertension, stroke and heart attacks, depression, diabetes and sexual dysfunction. Severe cases of sleep apnea can even be fatal.

Besides these sobering health risks, an untreated sleep disorder can also be the root cause of poor performance at work or school, car accidents and other activities that require focus and concentration.

Common Symptoms of Sleep Disorders

Many people experience some occasional difficulty sleeping and/or daytime fatigue. But how does a person know if he or she has a temporary sleep problem that can be remedied with some simple behavioral changes or if it is a legitimate disorder, such as snoring, sleep apnea, sinusitis or nasal obstruction that should be diagnosed and treated properly?

The first step is to be aware of some common symptoms of sleep disorders. Keep in mind that symptoms vary between disorders, such as snoring, sleep apnea, insomnia, restless leg syndrome, nasal obstruction, and narcolepsy, so it pays to do some research based on what you are personally experiencing.

Some common symptoms of sleep disorders include:

• Trouble falling asleep at night

• Waking throughout the night

• Chronic snoring

• Morning headaches

• Poor memory

• Daytime sleepiness/falling asleep during the day/low energy

• Bad moods/ irritability

• Increased depression

• Trouble concentrating/driving/making decisions

The Link Between Lifestyle and Sleep Problems

If you or someone you know is experiencing some of the above common symptoms of sleep disorders, the next step is to examine if lifestyle habits are contributing to the difficulty sleeping, fatigue and irritability during the day and other symptoms.

Some behavioral and lifestyle questions to ask include:

• Am I watching TV or using the computer late at night and too close to bedtime?

• Am I consuming too much caffeine during the day?

• Am I taking a medication that may be affecting my sleep quality and duration?

• Is there something particularly stressful going on in my life that is causing me worry and anxiety?

• Am I exercising enough to help alleviate some of that stress and tension?

See a Specialist -- And Be Specific

Many sleep problems can be remedied by making some common-sense behavioral changes. However, if you or someone you know is experiencing one or more of the above symptoms on a regular basis, see a qualified ear, nose and throat doctor or otolaryngologist to get diagnosed and treated properly. There are multiple options and minimally-invasive techniques available today to treat your sleep disorder.

When you see a specialist, be specific about the symptoms you are experiencing. Many times, sleep apnea and other sleep disorders can be misdiagnosed as chronic fatigue, insomnia, depression, or some other non-specific condition. Some doctors, for example, still associate sleep apnea more with men than women, and are too quick to prescribe a medication, rather than do a full sleep disorder work up.

It may help to keep a sleep log (or, more accurately, lack-of-sleep log) next to your bed to write down what you are experiencing, when you wake and some symptoms you experience. Again, to try and avoid misdiagnosis, go to a qualified sleep specialist and be specific about your symptoms. Don't wait -- it could save your life.

To read the full report, see "Sleepy Pilots, Train Operators and Drivers" on the National Sleep Foundation website.

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Improvements in autism symptoms vary by child

A new study suggests that social and communication skills in some kids with autism may improve over time with therapy, but other kids will continue having problems functioning as they get older.

Not surprisingly, kids who had milder symptoms when they were first diagnosed tended to be doing better a few years later than those who started out with more severe autism.

But among close to 7,000 children followed by researchers, there was also a group of so-called "bloomers" who started out with lots of communication and social problems but made fast gains during their elementary-school years.

"There's a wide variety of children with different kinds of symptoms that fall within this (autism) umbrella," said Christine Fountain, the lead author of the study and an autism researcher at Columbia University in New York. "We were interested in how these symptoms play out over time."

The new findings, published Monday in Pediatrics, come just a few days after the Centers for Disease Control and Prevention released new data suggesting that one in 88 kids in the United States now has an autism spectrum disorder, which includes less-debilitating conditions such as Asperger's syndrome (see Reuters story of March 29, 2012).

Using data from California centers responsible for testing and treating kids with autism, Fountain and her colleagues tracked kids ages two to 14 who'd had at least four evaluations. During those approximately annual evaluations, staff recorded kids' symptoms of social and communication difficulties as well as their repetitive behaviors.

The researchers found that especially when it came to social and communication scores, most kids improved over time -- though some much faster than others.

White kids, and those whose parents were more educated, tended to have less severe autism symptoms during treatment. They were also more likely to be among the 10 percent or so of kids deemed bloomers, whose symptoms improved dramatically between ages three and 12.

Kids who had other intellectual disabilities along with autism weren't likely to have very large improvements.

"The conclusion is, if you have mental retardation as a co-occurring condition with autism, your prognosis is worse," said Johnny Matson, who studies autism spectrum disorders and intellectual disabilities at Louisiana State University in Baton Rouge.

That's not new, he said -- previous studies have shown that kids with autism and a normal IQ improve more from intensive therapy than those who have both autism and intellectual disabilities.

Unlike social and communication skills, repetitive behaviors didn't tend to improve or worsen much over time among the majority of kids in the study.

MOST KIDS WILL IMPROVE

The gaps in improvement based on parents' race and education are probably about access to good-quality treatment, according to Matson. The good news is, "those gaps are narrowing very rapidly," he told Reuters Health, because of laws requiring insurance companies to cover intensive treatment for all autistic kids.

Matson, who wasn't involved in the new study, had some doubts about the specific "symptom trajectories" the researchers used to separate kids, and said a lot of autism assessments aren't done correctly to begin with -- which makes interpreting changes over time difficult.

"I think all (kids with autism) are going to improve, it's just a matter of how much they're going to improve," Matson added. "I don't believe you can cure autism. Having said that, you can make it a lot better," especially if kids with autism continue to get therapy as they get older.

Still, another autism specialist not involved in the research said the different patterns in improvement -- or lack thereof -- jibe with his own experience.

"We deal with this problem every day, and we sense that there are different patterns or trajectories... in the kids as they develop," said Dr. Andrew Zimmerman, from the Lurie Center for Autism at Massachusetts General Hospital for Kids in Lexington.

"For some kids, you work very hard and you do a lot of therapy and nothing happens or very little, and then some kids seem to do really well," Zimmerman told Reuters Health.

Fountain said the findings suggest that providing equal access to the best autism treatment for minority and less well-off kids will be important going forward. Some states including California provide services to all kids with autism regardless of their ability to pay, she added, but others don't.

Kids' specific conditions and symptoms may play a role in their long-term improvement, but the treatment they get at certain points in development is also likely to be important, she added.

She and Matson said that parents of children with autism should be persistent in making sure their kids get the help they need, but agreed they can also be optimistic.

"There is a bit of a hopeful note in that we did find that most children get at least a little better over time," Fountain told Reuters Health.

Zimmerman agreed, adding that the idea of some kids being bloomers is especially exciting.

"There's a lot of hope here," he said.

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CDC's New Data on Autism Spectrum Disorders

More children than ever before are being diagnosed with autism spectrum disorders (ASDs). Like the many families living with ASDs, CDC considers ASDs an important public health concern. CDC is committed to continuing to provide essential data on ASDs, search for risk factors and causes, and develop resources that help identify children with ASDs as early as possible.

Tracking the Number of Children Identified with Autism Spectrum Disorders

CDC's National Center on Birth Defects and Developmental Disabilities has been tracking ASDs for over a decade through the Autism and Developmental Disabilities Monitoring (ADDM) Network. The newest estimates from the ADDM Network are based on data collected in 14 areas of the United States during 2008. These 14 communities comprised over eight percent of the United States population of 8-year-olds in 2008. Information was collected on children who were 8 years old because previous work has shown that, by this age, most children with ASDs have been identified for services.

CDC estimates 1 in 88 children (11.3 per 1,000) has been identified with an autism spectrum disorder (ASD).

• This marks a 23% increase since our last report in2009. And, a 78% increase since our first report in2007. Some of the increase is due to the way children are identified, diagnosed and served in their local communities, although exactly how much is due to these factors in unknown.
• The number of children identified with ASDs varied widely across the 14 ADDM Network sites, from 1 in 47 (21.2 per 1,000) to 1 in 210 (4.8 per 1,000).
• ASDs are almost 5 times more common among boys (1 in 54) than among girls (1 in 252).
• The largest increases over time were among Hispanic children (110%) and black children (91%). We suspect that some of this increase is due to greater awareness and better identification among these groups. However, this finding explains only part of the increase over time, as more children are being identified in all groups.
• There were increases over time among children without intellectual disability (those having IQ scores above 70), although there were also increases in the estimated prevalence of ASDs at all levels of intellectual ability.
• More children are being diagnosed at earlier ages—a growing number of them by age 3. Still, most children are not diagnosed until after they reach age 4, even though early identification and intervention can help a child access services and learn new skills. This is why CDC's Learn the Signs. Act Early. program is essential. Through this program, CDC provides free tools to help parents track their child's development and free resources for doctors and educators. CDC is also working with states and communities to improve early identification.
• CDC also provided leadership in establishing Healthy People 2020 objectives and supporting the American Academy of Pediatrics recommendation that all children be screened by age 2, because early screening and diagnosis improve access to services during a child's most critical developmental period.

Understanding Risk Factors and Causes

CDC knows that people want answers to what is causing the increase in the number of children identified with ASDs and so do we. To find out what is causing ASDs, we need to better understand the risk factors. The search for risk factors is a prominent, rapidly growing field of research. Each year, the Interagency Autism Coordinating Committee reviews study findings to help direct the national research agenda for ASDs. CDC's work is a key part of this larger, coordinated effort.

Most scientists who study ASDs believe there is no single cause. Studies suggest that both genetic and non-genetic factors play a role in developing an ASD. Studies also suggest the following:

• Children born to older parents are at slightly higher risk.
• A small percentage of children who are born prematurely or with low birth weight are at greater risk for having ASDs.
• Some harmful drugs taken during pregnancy have been linked with a higher risk of ASDs; for example, the prescription drugs thalidomide and valproic acid.

Study to Explore Early Development (SEED)

SEED is currently the largest study in the United States to help identify what might put children at risk for ASDs. It is being conducted by CDC's Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE). SEED is studying potential risk factors that may be related to genes, health conditions and other events during the mother's pregnancy and the child's first few years of life. So far, SEED has enrolled more than 3,700 children, and more than 2,200 children and their parents have completed the study.

Read more about the SEED study methods >>

Learn the Signs. Act Early.

The "Learn the Signs. Act Early." program aims to change perceptions about the importance of identifying developmental concerns early and gives parents and professionals the tools to help.

From birth to 5 years, children reach milestones in how they play, learn, speak and act. A delay in any of these areas could be a sign of an ASD or other developmental disabilities.

• CDC provides free materials to help parents and early educators track young children's developmental milestones, tips [PDF - 5.10MB] for encouraging children's growth and development, and information about what to do if there's a concern about a child's development. There are also free resources for health professionals.
• National, state and local programs that serve parents of young children can add "Learn the Signs." materials to their resources for parents. Programs can customize CDC's materials with their own contact information and distribute them to the populations they serve.

CDC also works with representatives from public health, medicine, education, and advocacy organizations in every state to improve early identification, screening, and referral practices so children and their families can get the services and support they need.

CDC partners with the Health Resources and Services Administration, the Association of University Centers on Disabilities, the Association of Maternal and Child Health Programs and other partners in the delivery of this program.

Looking Back, Moving Forward

Through CDC's work in ASDs over the past 15 years, we know more about which children are more likely to have ASDs, at what age they are likely to be diagnosed, and whether progress has been made in diagnosing children with ASDs early. This is the information communities need to plan for services and understand where improvements can be made to help children.

Although there are still many unanswered questions about what causes ASDs and how to treat them, the data tell us one thing with certainty—there are more children and families that need help. The emotional and financial toll on families and communities is staggering. Therapy costs alone run in the thousands, costs that are beyond the reach of many families.

CDC is committed to the important work of understanding ASDs—committed to tracking ASDs, committed to research to identify risk factors and causes, and committed to developing resources that help identify children with ASDs as early as possible—so that children can get the help they need.

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Parents of Children With Autism More Likely to Get Ailments

Parents of Children With Autism More Likely to Get Ailments




Parents of children with autism are more likely to get common ailments such as colds, coughs and headaches as a direct result of the increased stresses linked to their caring duties, according to research from Northumbria University.

The research is published in the journal Psychoneuroendocrinology, this April which is also National Autism month.

In the first study to look at the physical and psychological well-being of these carers, psychologists Dr Mark Wetherell, Dr Mark Moss and PhD researcher Brian Lovell also discovered higher levels of C-reactive protein in the carers, a marker of inflammation that is linked to increased risk of developing coronary heart disease and diabetes.

Dr Wetherell said: "Parents of children with autism face tremendous physical, financial, emotional and social pressures and these can lead to prolonged activation of stress responses which might place them at greater risk of adverse health outcomes.

"The consequences of these effects are far-reaching and can influence the ability of the caregiver to provide consistent, effective and sustainable care for their child."

In a separate study, published in the April edition of Research in Developmental Disabilities the team discovered that carers with lower levels of social support experienced greater levels of stress, depression and anxiety and more common ailments.

The team is now to embark on a new research project looking at how writing about their emotions can have a positive impact on carers' wellbeing. Those taking part in the research will be asked to provide saliva and blood samples and write for 20 minutes for three days on an assigned topic.

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Surprising Child Concussion Myths and Facts

Suppose your son or daughter has just been brought home from an athletic field with a concussion, complains of being tired and wants to go to sleep. Should you let that happen?

"There was a time when it was considered life-threatening to let someone suffering from a concussion to fall asleep," said Chris Hummel, a certified athletic trainer and clinical associate professor in Ithaca College's Department of Exercise and Sport Sciences. "But current research shows that sleeping is actually the best thing for a concussed player. Getting physical and mental rest helps an athlete recover from a concussion. But athletes should not be left alone the first night and should be seen by the sports medicine staff the next day."

Concussion management, Hummel added, is very complicated and should only be undertaken by athletic trainers, sports medicine physicians and others with specialized concussion training. Still, it's important for coaches, parents and athletes to know the difference between fact and fiction when applied to concussion basics.

Fictions

•A normal CT scan rules out a concussion. "A concussion results from a neuro-metabolic event brought on by the trauma," Hummel said. "Simply put, there is an imbalance of the needed chemicals or fuel that helps the brain function when an athlete is concussed. That's not a structural injury, so a CT scan won't pick it up. CT scans can only view structural damage."

•A player who has been knocked unconscious will suffer a worse concussion than a player who didn't lose consciousness. "A player doesn't have to be knocked out to sustain a serious concussion," Hummel said. "In some cases, individuals who are knocked out may suffer less severe trauma. In either case, the severity of the concussion might not be known for days or weeks."

•Male athletes sustain more concussions than female ones. "Male athletes sustain concussions at similar rates as female ones," Hummel said. "However, recent studies have shown that symptoms might vary by gender, as males with concussions experience more physiological issues such as balance problems while females experience more psychosocial issues such as fatigue or low energy."

•A grade-one concussion is less serious than one that's a grade-three. "We used to grade concussions during the initial diagnosis, but we no longer do that because we now know it's difficult to accurately assess the severity of a concussion right away," Hummel said. "We have to wait and see how the symptoms resolve over time before we can determine how significant the concussion is or is not."

•The harder someone is hit, the worse the concussion. "It doesn't always take a big hit to produce a concussion," Hummel said. "Any contact to the head or body that causes rapid head movement can cause a concussion. It's also important to point out that several lower impacts over time might be more serious than a single collision of great force. For example, offensive linemen in football, who experience contact on almost every play, could be more at risk for permanent brain damage than a wide receiver who absorbs a single hard hit once or twice a game."

•Athletes can soldier through a concussion. "No," Hummel said. "Typically, it takes one to two weeks for concussion symptoms to resolve and for the brain to begin operating back at full capacity. Just because an athlete states his or her head has cleared, it's no indication that he or she should go back into the game. It is not safe to go back on the field the same day after experiencing concussion-like symptoms."

•Concussions are the same for adults and adolescents."Adolescent brains are still developing," Hummel said. "The effects of a concussion on young athletes are more dynamic than on mature ones and may take longer to recover from."

•Helmets prevent concussions. "Helmets are designed to prevent skull fractures, not concussions," Hummel said. "If a helmet is fitted properly, it might reduce the risk or severity of concussions, but no one helmet is capable of preventing a concussion, yet!"

Facts

•An athlete who has had one concussion is more likely to have another than an athlete who hasn't been concussed."Once an athlete has experienced one concussion, the threshold for sustaining another concussion can be diminished. Also, if a player sustains another blow before he or she is fully recovered, the resultant symptoms can be worsened and result in a prolonged recovery. There is also a rare phenomenon called Second Impact Syndrome that can cause impaired brain blood flow or even death if an athlete suffers another trauma before fully recovering."

•Concussions should be treated and managed on an individual basis. "The brain is an incredibly complex organ, and so are the neurochemical processes that govern it," Hummel said. "No two concussions are exactly alike anymore than the brains of any two individuals are identical. Concussion management begins by obtaining individual baseline (pre-injury) testing for each athlete. Once a concussion occurs you will then know what is 'normal' for that athlete. Once the athlete has become symptom-free and is back to his or her baseline test scores, a progressive return to play plan should be followed. This progression should consist of rest, light exercise, noncontact drills and then full practice before returning to game competition. Each level of recovery should take 24 hours. An athlete has to continue being symptom-free to proceed to the next level."

•If you suspect a student-athlete of having a concussion, assume it's a concussion. "If an athlete describes having a headache or dizziness, shows signs of balance problems, or difficulty remembering, assume that player is concussed and have him or her evaluated by an athletic trainer or a physician trained in sports medicine," Hummel said.

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Required Sleep Disorder Tests for Truck Drivers

I applaud the effort to increase driver safety.

While convenient, these devices are not 100% sensitive. They can have artifact. And in some the results may not be valid given the person's medical history and exam. 

Sleep apnea is best treated with a face-to-face with a physician. This is a high risk population that needs close follow up with a specialist.

Success with CPAP is best at devoted sleep center. Many people are still very sleepy even after CPAP has started. 

Are we selling CPAP's or improving road safety?

Eyes Open.

JR

Required Sleep Disorder Tests for Truck Drivers

Truck drivers should be required to undergo medical tests for sleep disorders before getting a licence, experts say, after a study that has revealed a high number with sleep apnea.

The study, published on Sunday in the Journal of Sleep, surveyed 517 long-haul drivers of B-doubles, semi-trailers and road trains in NSW and Western Australia.

It found 41 per cent had undiagnosed obstructive sleep apnoea (OSA), a condition in which the airways close, causing people to stop breathing during sleep.

OSA can increase drivers' risk of crashing by two to seven-fold, the study said.

Currently, truck drivers are required only to fill out a questionnaire about their sleep patterns in order to pass a medical to obtain their heavy vehicle licence.

However, researchers found that only 12 per cent of truck drivers reported struggling with tiredness using this questionnaire, called the Epworth Sleepiness Scale(ESS).

The OSA sufferers in the study were diagnosed using a take-home monitoring device, which has been proven to identify sleep apnea accurately.

The report's authors concluded that the questionnaires alone were not sufficient to assess drivers' crash risk.

Prof Mark Stevenson, the director of Melbourne's Monash University Accident Research Centre, said the current licensing requirements would not identify those with sleep disorders.

"We know there is an elevated risk of crashing in drivers with untreated OSA, therefore it is important that truck drivers - behind the wheels of the largest vehicles on the road network, at times with combustible freight - should be tested with a diagnostic tool that does not rely on self reporting."

Industry body the Australian Trucking Association fully reported the study's conclusions.

Communications manager Bill McKinley said the association in 2009 recommended diagnostic testing for truck drivers to the National Transport Commission, which develops licensing guidelines.

However he said the recommendation was ignored in the most recent guidelines, in place since March 1.

"The ATA fully agrees that there should be a diagnostic tool for sleep apnea included in the medical standards for truck drivers," Mr McKinley told AAP.

The National Transport Commission declined to comment.

The study also found that 50 per cent of truck drivers surveyed were overweight and 49.5 per cent were smokers.

Eighteen per cent had hypertension but only 13 per cent took medication for the condition.

Truck drivers worked an average of 65.4 hours a week, 40 per cent reported trouble sleeping in the past month and 17 struggled with tiredness at least twice a week.

The study, the largest of its kind, involved the universities of Sydney, NSW, Queensland, Monash University Accident Research Centre, The George Institute for Global Health, and Curtin University.

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