Category: Autism

New theory may explain the complex set of symptoms seen in autism.

People with autism often display a complex and confusing range of symptoms, including hypersensitivity to sound, problems interacting with others and repetitive behaviours.

Scientist have long wondered what all these — and other, seemingly unrelated symptoms — have in common.

Now MIT researchers are testing a brand new theory: that autistic children have difficulties predicting what is going to happen next, and it’s this problem that is at the root of autism (Sinha et al., 2014).

Without the ability to predict simple events, to an autistic child, life seems to happen randomly and almost magically, with no rhyme or reason.

Professor Pawan Sinha, the lead author of the new paper, explains:

“If we were unable to habituate to stimuli, then the world would become overwhelming very quickly.

It’s like you can’t escape this cacophony that’s falling on your ears or that you’re observing.”

From this point of view, the repetitive behaviours, the preference for highly structured and predictable environments may be coping strategies.

Professor Sinha continued:

“The need for sameness is one of the most uniform characteristics of autism.

It’s a short step away from that description to think that the need for sameness is another way of saying that the child with autism needs a very predictable setting.

At the moment, the treatments that have been developed are driven by the end symptoms.

We’re suggesting that the deeper problem is a predictive impairment problem, so we should directly address that ability.”

Children with autism often have problems understanding other people’s thoughts, motivations and feelings.

This could be a result of failing to use past events to predict future behaviour.

While other theories of autism tend to explain individual symptoms, this theory has a broader ambition: to bring the symptoms together.

To try and show their theory is correct, they are already conducting experiments to test it out.

One study has already suggested that autistic children fail to become habituated to sensory stimuli, which is what the theory suggests.

Set against the deficits, the theory also predicts that autistic children will have advantages when rules rather than predictions are important.

Indeed, activities that draw on just those skills — like math, music and drawing — are often found in autistic children in abundance.

Dr. Leonard Rappaport, chief of the division of developmental medicine at Boston Children’s Hospital, thinks the new theory is:

“…a uniting concept that could lead us to new approaches to understanding the etiology and perhaps lead to completely new treatment paradigms for this complex disorder.

This is not the first theory to explain the complex of symptoms we see every day in our clinical programs, but it seems to explain more of what we see than other theories that explain individual symptoms.”

Image credit: Jose-Luis Olivares/MIT

Simple techniques taught to parents are the key to an effective new therapy for autism.

Very early treatment of infants with the first signs of autism can substantially reduce the symptoms such that, by age 3, most have no developmental delays, a new study finds.

‘Infant Start’ is the name of the new behavioural therapy, mostly delivered by the children’s parents, developed by autism experts at the University of California – Davis and Duke University in North Carolina.

The results of a pilot study of the therapy have just been published in the Journal of Autism and Developmental Disorders (Rogers & Ozonoff, 2014).

Professor Sally J. Rogers, the study’s first author, explained the impressive results of the therapy:

“Most of the children in the study, six out of seven, caught up in all of their learning skills and their language by the time they were 2 to 3.

Most children with ASD are barely even getting diagnosed by then.

For the children who are achieving typical developmental rates, we are essentially ameliorating their developmental delays.

We have speeded up their developmental rates and profiles, not for every child in our sample, but for six of the seven.”

These results were largely down to the parents:

“It was the parents — not therapists — who did that.

Parents are there every day with their babies.

It’s the little moments of diapering, feeding, playing on the floor, going for a walk, being on a swing, that are the critical learning moments for babies.

Those moments are what parents can capitalize on in a way that nobody else really can.”

Infant Start involves parents being coached by therapists to help their children pay attention to social cues, an area in which autistic children typically lack.

During their normal, everyday routines, parents help their children focus on:

• parents’ faces and voices,
• interactions that attract infants’ attention, bringing smiles and delight to both,
• imitation of infant sounds and intentional actions,
• use of toys to support, rather than compete with, the child’s social attention.

One of the keys to the therapy’s success is the early intervention.

Infants in the study were between 6 and 15 months old and were already highly symptomatic and at risk of developing autism.

Intervening at this age is much earlier than most children receive specialised treatment.

Here is how to spot the early signs of autism in infants:

Being such a small study, the findings are hopeful, but need more extensive investigation with larger sample sizes.

Rogers is quick to point out that she is not trying to ‘cure’ autism:

“People with ASD contribute greatly to our culture.

The diversity of human nature is what makes us a powerful and strong species.

We are trying to reduce the disability associated with ASD.

“My goal is for children and adults with autism symptoms to be able to participate successfully in everyday life and in all aspects of the community in which they want to participate: to have satisfying work, recreation, and relationships, education that meets their needs and goals, a circle of people they love, and to be generally happy with their lives.”

Image credit: Chris W.

Support for controversial disorder thought to affect 1 in 6 elementary school children.

Children with sensory processing disorders have different structural brain connections in the sensory regions compared with autism, lending weight to a controversial diagnosis, a new study finds.

The study, which is published in the journal PLOS ONE, is the first to compare the brain structures of those with autism with those who have sensory processing disorders (SPD) (Chang et al., 2014).

Those with SPD have significant problems in organising the sensations they experience from the environment and their body.

For example, they may be badly co-ordinated, or under- or over-respond to sensations in the environment, or be inattentive or generally disorganised.

The separate nature of the condition has been questioned since over 90% of children with autism also have some degree of problems processing sensory inputs.

SPD is also not currently listed in the official diagnostic manual used by psychiatrists and psychologists, the Diagnostic and Statistical Manual.

Nevertheless, some claim that upwards of one in six elementary school children have the condition.

Professor Pratik Mukherjee, one of the study’s lead authors, said:

“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct.”

Their study used a type of brain scan called diffusion tensor imaging, which highlights the brain’s ‘white matter’.

The white matter is the brain’s cabling: how it sends messages from one part to another.

From an analysis of 16 boys with SPD, 15 boys with autism and 23 controls, they found decreased connectivity in critical sensory areas of the brain in both autism and SPD,

Crucially, though, there was only decreased connectivity in critical social-emotional processing areas for those with autism.

Dr. Elysa Marco, one of the study’s authors, explained:

“One of the classic features of autism is decreased eye-to-eye gaze, and the decreased ability to read facial emotions.

The impairment in this specific brain connectivity, not only differentiates the autism group from the SPD group but reflects the difficulties patients with autism have in the real world.

In our work, the more these regions are disconnected, the more challenge they are having with social skills.”

She hopes this research will help the children with SPD get the help they deserve:

“These kids, however, often don’t get supportive services at school or in the community because SPD is not yet a recognized condition.

We are starting to catch up with what parents already knew; sensory challenges are real and can be measured both in the lab and the real world.

Our next challenge is to find the reason why children have SPD and move these findings from the lab to the clinic.”

Image credits: Mannaz & UCSJ

The delicate balance between white and grey matter is disrupted by chronic stress.

Long-term stress causes changes in the brain’s white and grey matter which could help explain the link to emotional disorders and anxiety later in life.

In a series of experiments, scientists at UC Berkeley found that chronic stress leads to fewer neurons and more myelin production (Chetty et al., 2014).

Neurons make up the so-called grey matter of the brain; these are used to store and process information.

Myelin, meanwhile, is a fatty white substance which surrounds the connections between neurons — the axons — and which helps information flow around the brain.

We already know that the balance between grey and white matter in the brain is important.

People who have post-traumatic stress disorder, for example, have higher levels of grey matter in comparison to white matter.

It is thought that a change in the balance between the white and grey matter may disrupt the delicate timing involved in how parts of the brain communicate with each other.

This disruption may well be one of the biological underpinnings of serious mental disorders.

One of the study’s authors, Daniela Kaufer of UC Berkeley, said:

“We studied only one part of the brain, the hippocampus, but our findings could provide insight into how white matter is changing in conditions such as schizophrenia, autism, depression, suicide, ADHD and PTSD.”

The results come from the study of rats and cultured rat brain cells.

The researchers found that chronic stress made stem cells turn into oligodendrocytes, which produce the myelin or grey matter of the brain.

At the same time, chronic stress reduced the number of stem cells that became neurons.

Kaufer explained how this shift in the balance between grey and white matter might affect connectivity in the brain:

“You can imagine that if your amygdala and hippocampus are better connected, that could mean that your fear responses are much quicker, which is something you see in stress survivors.

On the other hand, if your connections are not so good to the prefrontal cortex, your ability to shut down responses is impaired.

So, when you are in a stressful situation, the inhibitory pathways from the prefrontal cortex telling you not to get stressed don’t work as well as the amygdala shouting to the hippocampus, ‘This is terrible!’ You have a much bigger response than you should.”

Image credit: Sander van der Wel

“Alarming” rise in autism has been blamed on environmental factors.

Abnormal levels of lipid molecules in the brain, which can be sparked by exposure to common medications, may contribute to autism, a new study finds.

The researchers at York University in Canada found that two key neural pathways were affected by abnormal lipid levels (Wong et al., 2014).

One of the study’s authors, Professor Dorota Crawford, explains:

“We have found that the abnormal level of a lipid molecule called Prostaglandin E2 in the brain can affect the function of Wnt proteins.

It is important because this can change the course of early embryonic development.”

The study, published in the journal Cell Communication and Signaling, is a reminder that the causes of autism are both genetic and environmental.

Professor Crawford continues:

“It’s even more apparent from the recent literature that the environment might have a greater impact on vulnerable genes, particularly in pregnancy.

Our study provides some molecular evidence that the environment likely disrupts certain events occurring in early brain development and contributes to autism.”

One of the biggest challenges with autism, however, is that both the genetic and environmental causes are exceedingly complex.

This study may provide another piece in that puzzle.

Its first author, Christine Wong, said:

“Using real-time imaging microscopy, we determined that higher levels of PGE2 can change Wnt-dependent behaviour of neural stem cells by increasing cell migration or proliferation.

As a result, this could affect how the brain is organized and wired.

Moreover, we found that an elevated level of PGE2 can increase expression of Wnt-regulated genes — Ctnnb1, Ptgs2, Ccnd1, and Mmp9.”

Interestingly, all these genes have been previously implicated in various autism studies.”

Professor Crawford referred to the rise in autism is “alarming”:

“It’s 30 per cent higher than the previous estimate of 1 in 88 children, up from only two years earlier.

Perhaps we can no longer attribute this rise in autism incidence to better diagnostic tools or awareness of autism.”

Image credit: bies

Arrows show areas of disorganised neurons in the brains of autistic children.

A new analysis of children’s brain tissue has revealed that autism begins during pregnancy with patches of disorganised neurons.

The study, to be published in the New England Journal of Medicine, compared 25 genes in the post-mortem brain tissue of children with and without autism (Stoner et al., 2014).

What they found was focused disorganisation in how the autistic brain forms.

The Director of the Autism Center of Excellence at UC San Diego, Professor Eric Courchesne, explained:

“Building a baby’s brain during pregnancy involves creating a cortex that contains six layers.

We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.”

These six layers of the brain each have their own type of brain cells and connectivity.

Each has a major role: one layer becomes the frontal cortex, the part of the brain most associated with higher-level processes like making plans and understanding complex social situations, amongst many others.

Another layer becomes the temporal cortex, the part of the brain associated with language, along with other complex functions.

The study found that, in children with autism, key genetic markers were missing, indicating that the development of the crucial six layers of the brain, with specific types of brain cells and connectivity, had been disrupted.

These early developmental defects were most common in the temporal and frontal cortex, perhaps helping to explain why children with autism have problems with language and social situations.

In comparison, the visual cortex, which is associated with perception, was largely free of disrupted development.

Perception is not an area in which children with autism normally have problems.

Another of the study’s authors, Ed S. Lein, continued:

“The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder.”

The authors say that in children with autism the brain may be able to rewire connections to combat these disrupted cortical patches.

Courchesne added:

“The finding that these defects occur in patches rather than across the entirety of [the] cortex gives hope as well as insight about the nature of autism.”

Image credit: Rich Stoner, Ph.D., University of California, San Diego

New drug given during pregnancy may help treat fragile X syndrome, a leading genetic cause of autism.

The most common form of intellectual disability is caused by a mechanism which shuts of an associated gene, a new study finds.

Scientists at the Weill Cornell Medical College have also shown that a drug can block the silencing mechanism, thereby preventing the most common form of mental disability: fragile X syndrome (Colak et al., 2014).

This points the way towards a therapy for fragile X syndrome — a leading genetic cause of autism — and possibly for 20 other diseases.

Fragile X syndrome causes a wide range of emotional, behavioural and physical problems and occurs mostly in boys.

For around twenty years scientists have known that the cause of fragile X syndrome is the excess repetition of a sequence of genetic code.

The problem was understanding how this code caused the disease.

Now, in a new study, published in the prestigious journal Science, researchers have discovered that this code halts the production of a protein which is crucial to communication within the brain.

To find out how to fix this problem, the researchers used human stem cells from embryos that had tested positive for fragile X syndrome to create brain neurons in the lab.

This gave them a model of how the embryonic brain develops in which to test a new drug developed by Dr. Matthew Disney of the Scripps Research Institute.

After adding the drug, they found that the gene continued to produce the vital protein, instead of being deactivated as it is in fragile X syndrome.

This points the way towards a treatment for fragile X syndrome. One of the study’s authors, Dr. Samie Jaffrey, explained:

“If a pregnant woman is told that her fetus carries the genetic mutation causing fragile X syndrome, we could potentially intervene and give the drug during gestation.

This may delay or prevent the silencing of the fragile X gene, which could potentially significantly improve the outcome of these patients.”

Huntington’s disease

The findings have implications for a range of other diseases because of the biological mechanism that has been discovered.

Other diseases including Jacobsen syndrome, an intellectual disorder, and Huntington’s disease, a neurodegenerative disorder, involve similar repetitions of DNA sequences and so may be amenable to similar treatments.

Dr. Jaffrey said:

 “This completely new mechanism by which RNAs can direct gene silencing may be involved in a lot of other diseases. Our hope is that we can find drugs that interfere with this new type of disease process.”

Image credit: Neil Palmer

Autism research finds link between this vitamin and serotonin production.

Many scientists have speculated that the problematic social behaviour of people with autism is related to low vitamin D and serotonin levels.

Now a new study has found a causal link between vitamin D and three hormones which are important in social behaviour: serotonin, oxytocin and vasopressin.

Genetic research has shown that vitamin D hormone activates a gene which produces an enzyme leading to higher levels of serotonin (Patrick & Ames, 2014).

In the brain, serotonin acts as a neurotransmitter, helping to modulate social behaviour and even affecting the wiring and structure of the brain.

However, the research also found that the gene affected by vitamin D tends to decrease serotonin production in the gut and other tissues.

High levels of serotonin in the gut — where 90% is usually located — can cause intestinal problem, which is often associated with autism.

The study may help answer two mysteries (amongst others) about autism:

1. The ‘serotonin anomaly’. This is the finding that people with autism tend to have low levels of serotonin in the brain, but high levels in the blood — which is linked to the intestinal problems.
2. Why more males than females have autism. The hormone estrogen can boost serotonin levels.

The majority of vitamin D made in the body is produced by UVB radiation hitting the skin.

It is thought that fully 70% of the U.S. population have inadequate levels of vitamin D. It is particularly low amongst people who live in northern climes, such as northern parts of the United States.

The problem is especially strong for those with darker skin pigmentation as this blocks the UVB rays.

It’s also interesting to note that a rise in the rates of autism has happened at a time when there have been large drops in average levels of vitamin D.

In autism, the authors argue for dietary supplementation with vitamin D, tryptophan (which is converted to serotonin) and omega-3 fatty acids — all of which are relatively inexpensive.

They also argue that in prenatal care, the monitoring of vitamin D levels should become standard practice.

→ Read on: Autism: 10 Facts You Should Know

Image credit: Colin Dunn

“…children worldwide are being exposed to unrecognised toxic chemicals that are silently eroding intelligence, disrupting behaviours, truncating future achievements, and damaging societies…”

The rise in disorders like autism, ADHD and dyslexia could be linked to the industrial use of neurotoxic chemicals, according to new research published in The Lancet (Grandjean & Landrigan, 2014).

The epidemiologists have identified six chemicals that could have negative effects on children’s development.

This is on top of a previous report in 2006 which listed five potentially dangerous chemicals.

The six chemicals include fluoride, manganese, a solvent called tetrachloroethylene, DDT (a pesticide) and a flame retardant containing polybrominated diphenyl ethers.

Author Philippe Grandjean, from the Harvard School of Public Health, explained:

“The greatest concern is the large numbers of children who are affected by toxic damage to brain development in the absence of a formal diagnosis. They suffer reduced attention span, delayed development, and poor school performance. Industrial chemicals are now emerging as likely causes.”

The researchers identify studies providing evidence for connections between six chemicals and problems in children’s psychological development, including:

• Manganese has been associated with reduced intellectual function, reduced achievement in mathematics and increased hyperactivity.
• Flouride at higher levels in drinking water has been associated with seven point decrements in IQ.
• Pesticides like DDT, which are banned in richer countries, are still used elsewhere and have been associated with neurodevelopmental disorders.

These substances have been added to a growing list of chemicals which are well-known neurotoxins, like lead and methylmercury.

The authors suspect there may be many more chemicals in regular industrial use which may be damaging to children’s developing brains.

These include Phthalates and bisphenol A, which are used in plastics and cosmetics and air pollutants like carbon monoxide.

For example, one study of pollution in California has linked pollution from car exhausts to higher rates of autism spectrum disorders (Volk et al., 2013).

Very few of these potentially dangerous chemicals are regulated simply because little effort has been made to look at the dangers and the very high standards of proof that are required.

The authors argue that:

“The presumption that new chemicals and technologies are safe until proven otherwise is a fundamental problem. Classic examples of new chemicals that were introduced because they conveyed certain benefits, but were later shown to cause great harm, include several neurotoxicants, asbestos, thalidomide, diethylstilboestrol, and the chlorofluorocarbons.” (Grandjean & Landrigan, 2014).

The authors say that in order to protect children’s brains–which are highly sensitive–a new agency should be established to screen and test new chemicals used in industrial processes.

They end on a worrying note:

“…the total number of neurotoxic substances now recognised almost certainly represents an underestimate of the true number of developmental neurotoxicants that have been released into the global environment. Our very great concern is that children worldwide are being exposed to unrecognised toxic chemicals that are silently eroding intelligence, disrupting behaviours, truncating future achievements, and damaging societies, perhaps most seriously in developing countries.” (Grandjean & Landrigan, 2014).

Image credit: Josh Pesavento

New research ‘gives autism’ to mice, then cures it with probiotic therapy.

One of the many curious things about autism is that it is often accompanied by gastrointestinal issues, despite it being primarily thought of as a brain disorder.

For example, many people with autism also have inflammatory bowel disease and other gastrointestinal problems like constipation and abdominal cramps.

This has led scientists to wonder how much the gut might have to do with the brain.

A new study, published in the journal Cell, tests out this link in autism between the gut and the brain in a mouse model (Hsiao et al., 2013).

Curing a leaky gut

The Caltech study created mice with autistic behaviours by exposing them to a virus-like structure which provokes an immune response.

Like humans with autism, the mice also developed intestinal problems. They had ‘leaky guts’: material was allowed to pass from their intestines into their blood stream.

The question is: could they fix the problem?

One experimental treatment for autism that has had some success is the use of probiotic therapy.

So the researchers then treated the mice with Bacteroides fragilis, which has been used in probiotic therapy.

After the treatment, the mice’s leaky guts were fixed.

Not only that, but their behaviour also changed. They were much less likely to engage in repetitive digging behaviours. This is a good sign since repetitive behaviours are a common feature of autism in humans.

They also displayed reduced anxiety and were more likely to communicate with other mice–similarly, communication difficulties are a core feature of autism in humans.

Mind-altering microbes

The lead author of the study, Elaine Hsiao, explained:

“The B. fragilis treatment alleviates GI problems in the mouse model and also improves some of the main behavioral symptoms. This suggests that GI problems could contribute to particular symptoms in neurodevelopmental disorders.”

The scientists think that the therapy works because it stops certain metabolites leaking into the bloodstream, which then affect the brain and behaviour.

After this success, their next step will be to try the therapy on humans. However, another of the study’s authors, Professor Sarkis K. Mazmanian, said:

“Autism is such a heterogeneous disorder that the ratio between genetic and environmental contributions could be different in each individual. Even if B. fragilis ameliorates some of the symptoms associated with autism, I would be surprised if it’s a universal therapy–it probably won’t work for every single case.”

Nevertheless, it’s a fascinating finding about what continues to prove a baffling disorder.

Here is Elaine Hsiao talking about mind-altering microbes at a TEDx event at Caltech (link):

→ Now read on: Autism: 10 Quick Facts You Should Know

Image credit: Elaine Hsiao