Questions and answers about autism spectrum disorders (ASD)


Q: What are autism spectrum disorders?

A: Autism spectrum disorders (ASD) are a group of complex brain development disorders. This umbrella term covers conditions such as autism and Asperger syndrome. These disorders are characterized by difficulties in social interaction and communication and a restricted and repetitive repertoire of interests and activities.

Q: How common are autism spectrum disorders?

A: Reviews estimate that 1 child in 160 has an autism spectrum disorder. This estimate represents an average figure, and reported prevalence varies substantially across studies. Some recent studies have, however, reported rates that are substantially higher.

Q: Do people with an autism spectrum disorder always suffer from intellectual disability?

A: The level of intellectual functioning is extremely variable in persons with an autism spectrum disorder, ranging from profound impairment to superior non-verbal cognitive skills. It is estimated that around 50% of persons with ASD also suffer from an intellectual disability.

Q: How early can an autism spectrum disorder be recognized in children?

A: Identifying an autism spectrum disorder is difficult before the age of about 12 months but diagnosis is generally possible by the age of 2 years. Characteristic features of the onset include delay in the development or temporary regression in language and social skills and repetitive stereotyped patterns of behaviour.

Q: What can parents do to help their child with an autism spectrum disorder?

A: Parents have an essential role in providing support to a child with an autism spectrum disorder. They can help to ensure access to health services and education, and offer nurturing and stimulating environments as their child grows up. Recently, it has been shown that parents can also help deliver psychosocial and behavioural treatments to their own children.

Q: What causes autism spectrum disorders?

A: Scientific evidence suggests that various factors, both genetic and environmental, contribute to the onset of autism spectrum disorders by influencing early brain development.

Q: Are childhood vaccines responsible for autism spectrum disorders?

A: Available epidemiological data show that there is no evidence of a link between measles-mumps-rubella (MMR) vaccine and autism spectrum disorders. Previous studies suggesting a causal link were found to be seriously flawed.

There is also no evidence to suggest that any other childhood vaccine may increase the risk of autism spectrum disorders. In addition, evidence reviews commissioned by WHO concluded that there was no association between the use of vaccine preservatives such as thiomersal and autism spectrum disorders.

Source:WHO

Induced Labor Not Linked to ASD


No relationship between labor induction and an increased risk for autism spectrum disorders (ASD) is seen when family variables are taken into account, a new study suggests. These findings run counter to previous studies, in which an association between induction and ASD was reported.

The difference lies in the use of a family comparison design involving discordant pairs of siblings or first cousins; that is, comparing one child born after induction of labor with a relative born after no induction of labor, lead author Anna Sara Oberg, PhD, and colleagues write in an article published online July 25 in JAMA Pediatrics. This allowed the authors to “control for all shared maternal factors (present across all pregnancies) that are unmeasured in registries but appear to confound the association between labor induction and neurodevelopmental disorders in the offspring.”

The findings suggest that concerns about ASD “should not factor into the clinical decision about whether to induce labor,” they write.

Dr Oberg, from the Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, and coauthors studied all live births in Sweden between 1992 and 2005. Using several nationwide registries that include all Swedish residents, they calculated induced births, ASD diagnoses, and maternal lifestyle and socioeconomic information such as reproductive history, use of tobacco, health history, and cohabitation status. The authors followed all the children born during the study period through the end of 2013 or until they were diagnosed with ASD, died, or emigrated from Sweden.

The baseline analysis accounted for birth year, parity, and maternal age, in addition to induction of labor. The researchers then added other covariates, including stable ones such as maternal educational level, as well as those specific to each pregnancy, such as maternal smoking, multiple gestations, preeclampsia, and urogenital infection, among others. The final model included a “fixed-effect” adjustment to allow for comparison between maternal siblings or maternal first cousins, while continuing to account for the covariates that were unique to each birth.

There were 1,362,950 members of the cohort, including 22,077 who were diagnosed with ASD during follow-up. Labor induction was used in 11% of live births during the study. Of the maternal sibling pairs in the sample, 15.2% were discordant for labor induction, as were 18.2% of the maternal cousin pairs. Primiparity, older maternal age, and higher maternal body mass index all were risk factors for induction, along with pregnancy complications such as gestational diabetes, gestational hypertension, and preeclampsia. By the time the cohort members were 20 years of age, ASD had been diagnosed in 3.5% of the offspring in the induced sample and 2.5% of the offspring in the noninduced sample.

The initial analyses appeared to confirm the findings of earlier studies: Labor induction was associated with a significantly higher risk for ASD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.27 – 1.38) in the baseline model. This did not change substantially after adjustment for stable maternal characteristics (HR, 1.31; 95% CI, 1.26 – 1.37). Additional adjustment for pregnancy-specific factors resulted in a slight reduction in association (HR, 1.19; 95% CI, 1.13 – 1.24), but the association was still significant. However, the association disappeared (HR, 0.99; 95% CI, 0.88 – 1.10) when the authors applied fixed-effects models, “comparing discordant siblings to each other to account for all the factors they share.”

These findings suggest there is some other, still-unknown factor responsible for confounding the relationship between labor induction and ASD seen in earlier studies, Dr Oberg and colleagues write. Genes that govern cellular calcium homeostasis might be one culprit. An environmental factor might be delivery at a higher-intensity medical system, where clinicians might induce labor more readily and diagnose neurodevelopmental disorders more frequently.

Several prenatal and perinatal factors have been studied as possible candidates for ASD risk, but often the result is simply more questions, Daniel L. Coury, MD, writes in an editorial accompanying the article. For example, some evidence implicates maternal use of selective serotonin reuptake inhibitors in the incidence of ASD. “Should pregnant women take these medications, or should physicians advise against?” he asks. Similarly, one study showed a higher risk for intellectual disability among children conceived through assisted reproductive technology, but a later study, which followed a different cohort of children only through 36 months of age, failed to support this finding. “Which study is correct? How should clinicians counsel families regarding the risk?”

To help parents make better decisions, Dr Coury, from the Section of Developmental-Behavioral Pediatrics, Department of Pediatrics, Nationwide Children’s Hospital/The Ohio State University, Columbus, suggests more extensive discussion of research findings in lay terms and weighing the benefits against the risks. “The suicides prevented by [selective serotonin reuptake inhibitor] medications outweigh most concerns of adverse effects. The potential that each child brings to the world outweighs any risk associated with [assisted reproductive technology]. The benefits of labor induction, when performed in accordance with clinical guidelines, include the delivery of a healthy neonate and a healthier outcome for the mother.”

Study limitations include a lack of information on the type of labor induction used and the inability to identify the factors responsible for raising the risk for ASD in this population, the authors write. Still, they conclude, “the findings of this study provide no support for a causal association between induction of labor and offspring development of ASD.”

The Technology That’s Giving Students With Autism a Greater Voice


Last year, Hanna Rosin, a well-known journalist for the Atlantic, wrote an articleabout her son’s Asperger’s diagnosis. He lived with this label for only four months, at which point the disorder was expunged from the DSM V. Now, her son is said to be on the “autism spectrum,” along with one out of every 68 children in the U.S.

Autism spectrum disorder (ASD), a newly popularized term which encompasses a breadth of social impairments, repetitive behaviors and communication “deficits,” reflects this different thinking. The flexibility of the spectrum means that it can be applied to children on either end, from highly functioning individuals to those who can’t speak or communicate even their most basic wishes.

According to Rosin, “the newly explicit spectrum thinking gives at least the illusion that there are no fixed boundaries at all. Taken to its logical extreme, the perspective implies an unbroken continuum among minds that extends from autism all the way into the realm of the normal.”

But with this flexibility comes ambiguity — especially in the classroom. The majority of teachers are not equipped to give students on various points across the autism spectrum the unique attention they require. For help, they have been turning to assistive technology.

Many children with autism learn well from visual media. Scene Speak, reviewed above, allows the user to make their own visual and audio books that can reflect real-life descriptions and relationships.

“Teachers are becoming more comfortable with technology,” Jules Csillag, a speech-language pathologist in New York City who focuses on technology and special education, told The Huffington Post. “More and more, it is allowing them to customize a curriculum for students [with ASD].”

According to Csillag, there are two main types of assistive technology for students with ASD: Teaching technologies and communication technologies. While both tools are exceptionally important, a student’s ability to communicate is tantamount to his or her success. “The tricky thing about classrooms is that there are so many unspoken rules,” she said. “I think one of the difficulties, even for high-functioning children, is knowing what the expectations are.”

Kathryn deBros, a special educator in Vermont working with children with behavior disorders, has voiced similar sentiments. “A huge part of going to school is learning how to navigate social situations,” she said. “[Students with ASD] are totally lost without a roadmap. Technology has been huge in allowing them to bridge that gap between them and the other kids.”

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For students with ASD who are especially low-functioning communicators, Csillag recommends a group of apps called Visual Scene Displays — a type of augmentative and alternative communication (AAC) — that give detailed context to common situations. She cited an app called Scene Speak, as well as more dynamic ones likeTouchChat, Look2Learn and Tobii Sono Flex. The latter programs turn symbols into speech, allowing less-verbal children a better way to communicate.

As a more specialized classroom educator, deBros focuses on the tools geared around emotion for classroom support, such as Empatico, and organizational support, likeBoardmaker. “Some of these kids are lost in social situations,” she explained. “But with an iPad in front of them, it really just clicks.”

Assistive technology is helping those with ASD outside the classroom, as well. “Part of the ASD difficulty is that society is not built in a way that is easy [for the child] to be in,” Csillag says. She further explains that even a grocery store or movie theater can be filled with distractions and triggers that will continue to elicit autistic behaviors, regardless of how much improvement the child can make in his or her own communications. However, with a better understanding of what autism is, and newer tools that help those with ASD communicate with others, the societal factor is becoming less of an issue while the unique strengths of those with autism are being spotlighted.

The above tutorial explains how to make a communication board on Boardmaker, a design program that allows students with autism to communicate through symbols.

Despite the fact that employment rates for those with ASD have historically been abysmally low, companies like Microsoft are going out of their way to create work environments more friendly to people with autism. Mary Ellen Smith, a Microsoft VP whose son has ASD, announced the software company’s new hiring program for people with autism in a recent blog post. “People with autism bring strengths that we need at Microsoft,” she said, adding that “some have amazing ability to retain information, think at a level of detail and depth, or excel in math or code.”

Technology isn’t just helping those with autism learn; it is actually allowing them to thrive, and on some level, is becoming a more seamless component of their social selves. deBros compared the evolution of assistive technology to wearable devices: “In the future, technology will be much more integrated with the person,” she predicted. “It will allow them to function without the burden of going back and forth with the technology and the world around them.”

CENTURY-OLD DRUG REVERSES AUTISM-LIKE SYMPTOMS IN FRAGILE X MOUSE MODEL


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Autism spectrum disorders (ASD) affect 1 to 2 percent of children in the United States. Hundreds of genetic and environmental factors have been shown to increase the risk of ASD. Researchers at UC San Diego School of Medicine previously reported that a drug used for almost a century to treat trypanosomiasis, or sleeping sickness, reversed environmental autism-like symptoms in mice.

Now, a new study published in this week’s online issue of Molecular Autism, suggests that a genetic form of autism-like symptoms in mice are also corrected with the drug, even when treatment was started in young adult mice.

The underlying mechanism, according to Robert K. Naviaux, MD, PhD, the new study’s principal investigator and professor of medicine at UC San Diego, is a phenomenon he calls the cellular danger response (CDR). When cells are exposed to danger in the form of a virus, infection, toxin, or even certain genetic mutations, they react defensively, shutting down ordinary activities and erecting barriers against the perceived threat. One consequence is that communication between cells is reduced, which the scientists say may interfere with brain development and function, leading to ASD.

Researchers treated a Fragile X genetic mouse model, one of the most commonly studied mouse models of ASD, with suramin, a drug long used for sleeping sickness. The approach, called antipurinergic therapy or APT, blocked the CDR signal, allowing cells to restore normal communication and reversing ASD symptoms.

“Our data show that the efficacy of APT cuts across disease models in ASD. Both the environmental and genetic mouse models responded with a complete, or near complete, reversal of ASD symptoms,” Naviaux said. “APT seems to be a common denominator in improving social behavior and brain synaptic abnormalities in these ASD models.”

Weekly treatment with suramin in the Fragile X genetic mouse model was started at nine weeks of age, roughly equivalent to 18 years in humans. Metabolite analysis identified 20 biochemical pathways associated with symptom improvements, 17 of which have been reported in human ASD. The findings of the six-month study also support the hypothesis that disturbances in purinergic signaling – a regulator of cellular functions, and mitochondria (prime regulators of the CDR) – play a significant role in ASD.

Naviaux noted that suramin is not a drug that can be used for more than a few months without a risk of toxicity in humans. However, he said it is the first of its kind in a new class of drugs that may not need to be given chronically to produce beneficial effects. New antipurinergic medicines, he said, might be given once or intermittently to unblock metabolism, restore more normal neural network function, improve resilience and permit improved development in response to conventional, interdisciplinary therapies and natural play.

“Correcting abnormalities in a mouse is a long way from a cure in humans,” cautioned Naviaux, who is also co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, “but our study adds momentum to discoveries at the crossroads of genetics, metabolism, innate immunity, and the environment for several childhood chronic disorders. These crossroads represent new leads in our efforts to understand the origins of autism and to develop treatments for children and adults with ASD.”

ASD And Circumcision Linked, With Thoughts Of Brain Development As A Factor


A new study from the Statens Serum Institut, in Denmark, has found a link between autism spectrum disorder (ASD) and circumcision in boys aged 0 to 9 years. Though no specific mechanism has been established, the team speculates that a malformed stress response, stemming from the procedure, may alter or delay brain development.

Just within the last decade, ASD rates have more than doubled in the U.S. Without a single cause to pin it to, science has seen a rush to draw links between the disorder and a range of environmental, social, and genetic factors. The best that ASD researchers can surmise at this point is it comes from some mix of the three, though in which proportions and at what time still remains unknown.

“Our investigation was prompted by the combination of recent animal findings linking a single painful injury to lifelong deficits in stress response and a study showing a strong, positive correlation between a country’s neonatal male circumcision rate and its prevalence of ASD in boys,” said Professor Morten Frisch of the Statens Serum Institut, who led the research.

The team tracked more than 340,000 boys between 1994 and 2013. Nearly 5,000 cases of ASD were diagnosed during that time. Regardless of background, the team explains, “circumcised boys were more likely than intact boys to develop ASD before age 10 years.” What’s more, “risk was particularly high for infantile autism before age 5 years.”

Controversies surrounding circumcision are as fraught with uncertainty as the science behind the practice. Much of the data on circumcision is conflicting, as one study last year found the benefits outweighed the risks 100 to one and was, as the researchers put it, “equivalent to childhood vaccination.” A separate investigation put the chances of newborn boys getting a urinary tract infection at 50/50 if they stayed uncircumcised.

But while the U.S. circumcision rates are largely declining as the decades pass, worldwide the story is much different. Without access to the same anesthetics and trusted procedures, circumcision in foreign countries tends to earn a less favorable opinion among the public. By the World Health Organization’s most recent estimate, approximately 33 percent of the world’s males aged 15 years or older are circumcised. That number may be so low due to overwhelming beliefs that the practice equates to genital mutilation, while stateside it may be considered more comparable to dental braces.

In the latest study, Frisch and his colleague Jacob Simonsen relied on past research that suggests early pain in neonates has been shown to have long-lasting effects in pain perception, which crop up at greater rates in kids with ASD. “Possible mechanisms linking early life pain and stress to an increased risk of neurodevelopmental, behavioral, or psychological problems in later life remain incompletely conceptualized.” Frisch said. The findings are slightly complicated by earlier work that found autism emerges in utero, which suggests circumcision could only intensify a preexisting deficiency.

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At any rate, the findings may hold great promise for other countries to adopt formal anesthetic protocol to avoid, or at least minimize, the pain children experience. “Given the widespread practice of non-therapeutic circumcision in infancy and childhood around the world,” Frisch concluded, “our findings should prompt other researchers to examine the possibility that circumcision trauma in infancy or early childhood might carry an increased risk of serious neurodevelopmental and psychological consequences.”

Source: Frisch M, Simonsen J. Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark. JRSM. 2015.

RITUAL CIRCUMCISION: INCREASED RISK OF AUTISM?


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Research published today by the Journal of the Royal Society of Medicine suggests that circumcised boys are more likely than intact boys to develop autism spectrum disorder (ASD) before the age of 10. Risk is particularly high for infantile autism before the age of five. The research was carried out in Denmark among a cohort of all children born between 1994 and 2003. During the study over 340,000 boys were followed up to the age of nine between 1994 and 2013 and almost 5,000 cases of ASD were diagnosed. The study showed that regardless of cultural background circumcised boys may run a greater risk of developing ASD. The researchers also made an unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families.

Professor Morten Frisch of the Statens Serum Institut, Copenhagen, who led the research, said: “Our investigation was prompted by the combination of recent animal findings linking a single painful injury to lifelong deficits in stress response and a study showing a strong, positive correlation between a country’s neonatal male circumcision rate and its prevalence of ASD in boys.”

Today it is considered unacceptable practice to circumcise boys without proper pain relief but none of the most common interventions used to reduce circumcision pain completely eliminates it and some boys will endure strongly painful circumcisions. The researchers say that the pain associated with circumcision in very young babies is likely to be more severe during the operation and post-operatively.

Painful experiences in neonates have been shown in animal and human studies to be associated with long-term alterations in pain perception, a characteristic often encountered among children with ASD.

“Possible mechanisms linking early life pain and stress to an increased risk of neurodevelopmental, behavioural or psychological problems in later life remain incompletely conceptualised,” said Professor Frisch. “Given the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, our findings should prompt other researchers to examine the possibility that circumcision trauma in infancy or early childhood might carry an increased risk of serious neurodevelopmental and psychological consequences.”

Genetic Test for Autism Refuted.


A team of Australian scientists claimed to have developed a genetic test that predicts a person’s risk of developing autism spectrum disorder (ASD) with 72 percent accuracy. Writing in Molecular Psychiatry, the team led by Stan Skafidis and Carlos Pantelis from the University of Melbourne said that their panel of 237 genetic markers could “correctly classify ASD from non-ASD individuals” and “may provide a tool for screening at birth or during infancy to provide an index of at-risk status.”

But a new study, led by Benjamin Neale from Massachusetts General Hospital, suggests that those claims were overblown. Neale’s team replicated the Australian group’s research in a larger sample, and found that the proposed panel of markers did not accurately predict ASDs.

“The claims in the original manuscript were quite bold. If they were true, it really would have been quite a major advance for the field, with serious ramifications for patients and other risk populations,” said Neale. “I think it’s important to ensure that this kind of work is of the highest quality.”

“This is a convincing refutation that calls into question the original results on specific technical grounds, rather than simply a non-replication that leaves a puzzling discrepancy between the two studies,” said Leonid Kruglyak, a geneticist from the University of California, Los Angeles, who was not involved in either study.

In 2012, Skafidis’s team compared the genes of 732 European people with ASD from the Autism Genetic Resource Exchange database, with those of 123 neurotypical people from a different cohort. They searched for single nucleotide polymorphisms (SNPs) that were linked to ASD, especially those in genes with roles in relevant cellular pathways.

They eventually settled on 237 SNPs in 146 genes, which they used to create a classifier for predicting ASD risk. When they tested the classifier on 243 cases and 42 controls from the same databases, it correctly predicted ASD with an accuracy of 85.6 percent.

The team then tested the classifier on an independent group of people—525 with ASD taken from the Simons Foundation Autism Research Initiative and 2,620 controls from the Wellcome Trust Birth Cohort. It identified the ASD cases with an accuracy of 71.7 percent.

But to other geneticists, these results seemed too good to be true. They implied that this small set of SNPs can explain around 11 percent of the variation in ASD risk—an unprecedented figure for any psychiatric condition. If the set truly had such strong effects, genome-wide association studies (GWAS) should have identified those SNPs by now—and they had not. It will likely take a sample of hundreds of thousands of people to find SNPs with such predictive power, as has been the case for other traits like height. “The magnitude of the study you need is dramatically larger than what was presented,” said Neale.

Neale wrote to Skafidis’s team asking for the full list of 237 SNPs, but did not receive it. (Skafidis told The Scientist that they offered the code that they used to generate their results, which should have been even better.) As such, they focused on the 30 most important SNPs, which were detailed in the published paper.

By comparing 5,417 cases and 5,417 controls from the Psychiatric Genomics Consortium, Neale’s team found that none of the 30 SNPs were significantly associated with ASD risk. The researchers also combined the SNPs into a classifier, using methods detailed in the original paper, and tested it on 4,623 cases and 4,623 controls from the same group. Again, the set failed to predict ASDs any better than chance. Finally, they also showed that the cellular pathways which the Australian team identified are not significantly associated with ASDs. The team’s results were published as a letter to the editor on 22 October, also in Molecular Psychiatry.

Several factors could explain the differences between the two studies. The Melbourne team initially tested the accuracy of their risk classifier on the same group of people whom they used to identify their SNP set. This is bad practice. “To appropriately assess the accuracy of a classifier, the sample which is used to develop it must be fully distinct from the sample on which it is tested,” said Kruglyak.

The Australian researchers also drew their cases and controls from separate populations with subtly different ethnic compositions. The SNPs they identified could have reflected reflect random ancestral differences between the two groups, rather than meaningful differences in ASD risk. Daniel Geschwind from the University of California, Los Angeles, made the same argument in a letter regarding Skafidis’s paper, which was published in the same journal this April.

Kruglyak added a third possible explanation: “batch effects, in which cases and controls are genotyped at different times and on different technology platforms,” he proposed. This problem also plagued a similar recently-retracted paper, which identified a panel of SNPs that could supposedly predict longevity.

But Skafidis said that Neale’s team may have come to different conclusions because the group did not use the full set of SNPs, nor the code that was provided. His team has submitted a response to the new study, which is in revision with Molecular Psychiatry (and does list the full set of 237 SNPs).

Meanwhile, Neale emphasized that other research into the genetics of autism are yielding stronger results. Several studies have identified loss-of-function mutations, and differences in the number of copies of certain genes, that are linked to ASD risk. Promising GWAS results have been presented at conferences and are making their way into published papers. “Autism genetics shouldn’t be tarnished by science that hasn’t been robustly proven,” he said. “There are successes beginning to emerge, and that’s really exciting and important.”

Psychotropics Still Commonly Prescribed for Autism.


Children with autism spectrum disorder (ASD) are still commonly prescribed psychotropic medications alone and in combinations despite “minimal evidence” of their effectiveness, new research suggests.

A retrospective study of more than 33,000 children with ASD showed that 64% had been prescribed at least 1 psychotropic. In addition, 35% had been prescribed 2 or more classes of psychotropics concurrently, and 15% had been prescribed 3 or more classes.

“Our results indicate the need to develop standards of care around the prescription of psychotropic medications to children with ASD,” write Donna Spencer, PhD, from OptimumInsight, Life Sciences, in Eden Prairie, Minnesota, and colleagues.

They note that the study participants who had comorbidities such as bipolar disorder or attention-deficit disorders, who were older, or who had visited a psychiatrist were significantly more likely to use psychotropics.

New standards of care should be based on “a coordinated, multidisciplinary approach to improving the health and quality of life of children with ASD and their families,” write the investigators.

The study was published online October 21 in Pediatrics.

Few Treatment Options

As reported at the time by Medscape Medical News, a systematic review of 33 randomized controlled trials, which was published in 2011, showed that only 3 psychotropics (all of which were antipsychotics) “have established evidence” in treating symptoms of ASD.

These included aripiprazole and risperidone for irritability and hyperactivity, aripiprazole for stereotypy, and haloperidol for negative behavioral symptoms. Promising evidence of benefit was shown for methylphenidate, and preliminary evidence was shown for 5 other agents, including naltrexone and atomoxetine.

However, “the humbling or sobering news is that we still have no medicines that treat the core features of autism — social/interaction and language impairments and repetitive behaviors,” said Matthew Siegel, MD, medical director of the developmental disorders program at Spring Harbor Hospital, Maine Medical Center, in Westbrook, at the time.

Yet other studies have shown “increasing rates of psychotropic use and [polypharmacy] among children overall” as well as in children with ASD, note the current investigators.

Because there is a wide variance in use estimates of psychotropic medications and because many reports are based on a period of 1 year or less, are based on parent reports, and include small sample sizes, the researches sought to conduct a study that answered these concerns.

They assessed data from medical and pharmacy claims for 33,565 insured children and adolescents younger than 21 years with ASD (82% boys; 60% between the ages of 6 and 10 years, 22% between the ages of 11 and 17 years, 17% between the ages of 0 and 1 year).

Claims for all participants had been made at least 6 months prior to baseline, and all had at least 6 months of continuous care between January 2001 and December 2009.

For this study, the psychotropic medication classes included antidepressants, both stimulants and nonstimulants for treating attention-deficit disorder (ADD), antipsychotics, anxiolytics, lithium, anticholinergics, and anticonvulsants/antiepileptics.

“Polypharmacy was defined as at least 1 episode of multiclass polypharmacy,” explain the investigators, noting that “an episode of multiclass polypharmacy” denoted prescriptions that overlapped 2 or more classes for at least 30 days.

Increasing Use

Results showed that 63.56% of the participants had any psychotropic use, whereas 34.36% showed evidence of multiclass polypharmacy.

Psychotropic or polypharmacy use increased with the age of the children. A total of 34% of the 0- to 1-year age group had use of any psychotropic, and 10% had polypharmacy use.

These numbers jumped dramatically to 64% and 32%, respectively, for those in the 2- to 10-year age group; to 84% and 57% for those in the 11- to 17-year age group; and to 87% and 62% for those in the 18- to 20-year age group.

Of those in the polypharmacy subgroup, total episodes of multiclass polypharmacy averaged 5.63 per child. The average maximum number of medications per episode was 2.6, and the average maximum number of classes per episode was 3.3.

In addition, 10.4% of the entire study group had 3-class polypharmacy, and 4.5 had polypharmacy with 4 or more classes.

“Common class combinations were antidepressants and ADD medications (38% of subjects), antipsychotics and ADD medications (28%), antipsychotics and antidepressants (20%), and antipsychotic, antidepressant, and ADD medications (18%),” report the investigators.

The average total days of all episodes of polypharmacy was 525. The median was 346 days.

Interestingly, use of either psychotropics or polypharmacy was lower in the participants from the northeast and western regions of the United States and highest in the southern regions.

This raises questions “about the availability of nonpharmacologic, behaviorally based services and treatments in the south, where other health outcomes and health care services have been found to be poorer than in other parts of the country,” note the researchers.

The strongest predictor of psychotropic and polypharmacy use was having a comorbid condition, especially seizures, bipolar disorder, and ADD. Household income was not found be a significant factor.

Overall, the findings emphasize the need for more research of psychotropics in kids with ASD “to assess the value of these medications when weighed against their potential for harm,” conclude the investigators.

Source: Medscape.com

 

 

Unique Brain Pattern May Explain Superior Math Skills in Autism.


A unique pattern of brain organization may explain why children with autism spectrum disorder (ASD) often possess superior math skills.

A small brain imaging study showed that children between the ages of 7 and 12 years with ASD had significantly superior numerical problem-solving abilities, including the use of more sophisticated strategies to figure out single-digit addition questions, than their age-, sex-, and IQ-matched healthy peers.

In addition, participants with ASD showed different activation patterns in the ventral temporal-occipital cortex (VTOC), the posterior parietal cortex, and the medial temporal lobe during mathematical problem solving — with activation patterns in the VTOC region actually predicting these superior abilities.

“Our findings suggest that altered patterns of brain organization in areas typically devoted to face processing may underlie the ability of children with autism to develop specialized skills,” lead author Teresa Iuculano, PhD, from the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, in California, and from the Stanford Cognitive and Systems Neuroscience Laboratory, said in a release.

She told Medscape Medical News that because children with ASD are often bad at recognizing faces, this particular area was recruited instead for math abilities in this patient population.

“However, this isn’t a universal finding, and we know that the spectrum is very broad. So there could be many different talents discovered, including music and drawing, and should be assessed on a case-by-case basis,” said Dr. Iuculano.

“If a parent sees that a child is strongly interested in something, they should help them to follow their passion. This is important for all children, but especially those with autism. It can be used as a relaxation tool and to help them to enjoy life more.”

The study was published online August 19 in Biological Psychiatry.

Mostly Anecdotal Evidence

The investigators note that although past research has suggested that individuals with ASD often have high mathematical skills, the evidence has been “mostly anecdotal and descriptive.”

For the current study, they sought to assess both the cognitive and neural characterizations of these skills.

“We thought that because math is such a concrete discipline, and with many rules, it could represent a good way to look at superiorities in a group of children on the spectrum,” said Dr. Iuculano.

The researchers enrolled 18 children with ASD (78% boys) and 18 children without the disorder, who were considered the “control group” (also 78% boys).

Standardized tests given during the study’s recruitment stage showed that all of the participants had IQs considered to be in the normal range; and those with ASD had “normal” verbal and reading skills. Standardized math tests were also administered.

While undergoing functional magnetic resonance imaging (fMRI) scans, all children were asked to solve addition problems, one at a time.

During the scans, the researchers also interviewed the participants to determine which of the following types of problem-solving strategies were being used: remembering an answer already known (retrieval), counting on fingers or in their heads, or decomposition.

The latter strategy is a comparatively sophisticated method and consists of breaking down a problem into several components.

Significant Differences

Results showed that the group with ASD had significantly higher scores on the numerical operations subscale of the Weschsler Individual Achievement Test–Second Edition for mathematics (WIAT-II) than the control group (P= .012).

They also displayed significantly greater use of decomposition (P = .033), “suggesting that more analytic strategies, rather than rote memory, were the source of their enhanced abilities,” the investigators note.

There were no between-group differences in use of counting or retrieval strategies or on any of the 4 working memory measures assessed.

The MRI scans showed “several cortical regions where arithmetic complexity-related activity patterns differed significantly” between the 2 groups.

“Notably, high cross-validation classification accuracies (80% to 90%) were in [VTOC], including bilateral inferior lateral occipital cortex and fusiform gyrus, as well as posterior parietal cortex, including the left intraparietal sulcus, angular gyrus, and the left precuneus,” write the researchers.

Significant differences in activity patterns were also found in medial temporal lobe regions.

Finally, “numerical abilities in the ASD group were predicted by the pattern of neural activity in an area of the left VTOC encompassing the left fusiform gyrus and lateral occipital cortex,” whereas numerical abilities in the control group were predicted by activity patterns in the left dorsolateral prefrontal cortex.

Not Universal

Overall, “there appears to be a unique pattern of brain organization that underlies superior problem-solving abilities in children with autism,” senior author Vinod Menon, PhD, professor of psychiatry and behavioral sciences at Stanford and from the Child Health Research Institute at the Lucile Packard Children’s Hospital, said in a release.

He added that although instant recall of calendar dates (a skill often found in individuals with ASD) is not likely to help with academic and professional success, “developing good mathematical skills could make a big difference in the life of a child with autism,” including possibly leading to future employment.

“Our study supports the idea that the typical brain development in autism can lead not just to deficits but also to some remarkable cognitive strengths. We think this can be reassuring to parents,” said Dr. Menon.

However, he noted that it is important to realize that not all children with ASD have superior math skills. So future research should examine the neural basis of variations in problem-solving abilities.

Dr. Iuculano added that she is excited about the current study’s findings on both research and clinical levels.

“As a scientist, it’s great that we’re understanding how the brain works in children with autism. And on a practical level, it’s important because it can raise awareness of the fact that these individuals can be contributing in a very good way to society,” she said.

Not Limited to Math

“I think this is not new as such, but it’s a very good study and important because it extends some things we already know,” Laurent Mottron, MD, PhD, professor of psychiatry at the University of Montreal, Quebec, Canada, and scientific director of the University’s Center of Excellence in Pervasive Development Disorders, toldMedscape Medical News.

He added that mathematic cognition has not been really studied before in ASD; but the take-away message is not that these findings are specific only to mathematics.

“This overactivation of the occipital region, and specifically the fusiform gyrus, is found in all tasks involving any visual information,” said Dr. Mottron, who was not involved with this research.

As reported at the time by Medscape Medical News, his investigative team published findings from a meta-analysis in Human Brain Mapping 2 years ago. Their analysis of 26 fMRI studies and more than 700 individuals showed that those with ASD had higher activity in the temporal and occipital regions in relation to visual-based tasks than those without the disorder.

“As scientists, we are happy when something is replicated. Here it’s more than replication, it’s specification. But I think if you want to see the big picture, you need to realize this isn’t only related to mathematics. Because autistics, when reasoning in general, use more of their perceptual expertise than other people,” he said.

“And I’m quite happy that now it’s become a kind of consensual message about autistic intelligence.”

Source: Medscape.com