Decrease in placental steroid can elevate risk of autism spectrum disorder

 In a new study it has been found that allopregnanolone, one of many hormones produced by the placenta during pregnancy, is so essential to normal fetal brain development that the decrease in the supply can cause Autism.

A children's National Hospital research team reports the findings on Oct 20 at the Neuroscience 2019 annual meeting. Lead author said, "To our knowledge, no other research team has studied how placental allopregnanolone (ALLO) contributes to brain development and long-term behaviours."

"Our study finds that targeted loss of ALLO in the womb leads to long-term structural alterations of the cerebellum - a brain region that is essential for motor coordination, balance and social cognition - and increases the risk of developing autism," added the author. According to the Centers for Disease Control and Prevention, about 1 in 10 infants is born preterm, before 37 weeks gestation; and 1 in 59 children has autism spectrum disorder.

In addition to presenting the research,  the abstract's senior author, will discuss the research with reporters during a Neuroscience 2019 news conference. This Children's National abstract is among 14,000 abstracts submitted for the meeting, the world's largest source of emerging news about brain science and health.

To investigate what happens when ALLO supplies are disrupted, a research team led by Children's National created a novel transgenic preclinical model in which they deleted a gene essential in ALLO synthesis. When the production of ALLO in the placentas of these experimental models declines, offspring had permanent neurodevelopmental changes in a sex- and region-specific manner. "From a structural perspective, the most pronounced cerebellar abnormalities appeared in the cerebellum's white matter," the author adds.

"We found the increased thickness of the myelin, a lipid-rich insulating layer that protects nerve fibres. From a behavioural perspective, male offspring whose ALLO supply was abruptly reduced exhibited increased repetitive behaviour and sociability deficits - two hallmarks in humans who have autism spectrum disorder."

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Novel technique to accurately detect autism in kids

Researchers have developed a new technique to help doctors more quickly and accurately detect autism spectrum disorder (ASD) in children.

Researchers  characterised how children with ASD scan a person's face differently than a neuro-typical child.

They developed a technique that considers how a child with ASD gaze transitions from one part of a person's face to another.

The use of this technology, described in the journal, makes the diagnostic process less stressful for the children and if combined with existing manual methods could help doctors better avoid a false positive autism diagnosis.

"Many people are suffering from autism, and we need early diagnosis especially in children," said a researcher.

"The current approaches to determining if someone has autism are not really child-friendly. Our method allows for the diagnosis to be made more easily and with less possibility of mistakes," she said.

"The new technique can be used in all ASD diagnosis, but we believe it's particularly effective for children,"she said.

The researchers evaluated 17 children with ASD and 23 neuro-typical children.

The mean chronological ages of the ASD and neuro-typical groups were 5.5 and 4.8, respectively.
Each participant was shown 44 photographs of faces on a 19-inch screen, integrated into an eye-tracking system.

The infrared device interpreted and identified the locations on the stimuli at which each child was looking via emission and reflection of wave from the iris.

The images were separated into seven key areas of interest (AOIs) in which participants focussed their gaze: under the right eye, right eye, under the left eye, left eye, nose, mouth and other parts of the screen.

The researchers wanted to know more than how much time the participants spent looking at each AOI, but also how they moved their eyes and scan the faces.

The researchers used four different concepts from network analysis to evaluate the varying degree of importance the children placed on the seven AOIs when exploring the facial features.

The first concept determined the number of other AOIs that the participant directly moves their eyes to and from a particular AOI.

The second concept looked at how often a particular AOI is involved when the participant moves their eyes between two other AOIs as quickly as possible.

The third concept is related to how quickly one can move their eyes from a particular AOI to other AOIs.

The fourth concept measured the importance of an AOI, in the context of eye movement and face scanning, by the number of important AOIs that it shares direct transitions with.

Currently, the two most favoured ways of assessing ASD involve a questionnaire or an evaluation from a psychologist.

"It is much easier for children to just look at something, like the animated face of a dog, than to fill out a questionnaire or be evaluated by a psychologist," said a professor.

"Also, the challenge many psychologists face is that sometimes behaviours deteriorate over time, so the child might not display signs of autism, but then a few years later, something starts showing up.

"Our technique is not just about behaviour or whether a child is focussing on the mouth or eyes. It's about how a child looks at everything," the Prof. said.

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Discovery of new De novo mutation may lead to better treatment

It has been found in a recent study that developmental disorders affect certain skills of humans like attention, memory, language, and social interaction.

Although many new developmental disorders have been identified in recent years, there are many more which are left undiscovered.

In this study, the researchers analyzed genomic data from over 31,000 parent-child trios obtained from the UK's Deciphering Developmental Disorders Project.

Analysis of these trios yielded more than 45,000 'de novo' mutation (DNMs). They developed an improved method to test for the enrichment (over-representation) of damaging DNMs in individual genes.
 
One of the researchers, said: "We found 307 significantly enriched genes, 49 of which are novel. With all of these genes, we were able to explain about 51 per cent of the DNM burden in our dataset. We then modeled different underlying genetic scenarios to get an idea of where the remaining de novo burden lies and how we can go about finding it."

About 40 per cent of developmental disorders is caused by DNMs, equivalent to about one birth in every 295 in the UK alone. The prevalence of the disease increases with the age of the parents.

The disorders usually become visible during childhood and include severe diseases such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), intellectual disability, and Rett syndrome.

A possible expectation is that the DNMs in the genes which are as yet undiscovered are less penetrant, i.e., they present symptoms in fewer people.

"We may need to adapt our system of gene discovery in order to capture these fewer penetrant genes," said a researcher.

The researchers also hope to increase their sample size in order to try to detect ever more genes associated with developmental disorders.

However, the identification of 40 new genes already provides valuable information to clinicians and to drug developers.

One of the lead researchers of the study, said: "Developmental delay is often caused by new mutations arising during the formation of sperm or eggs."

"By combining data on new mutations identified in the DNA of more than 30,000 patients, the scientists could implicate a role for 49 new genes in developmental delay."

"This study shows the power of large-scale international collaboration to advance our understanding of this disorder and improve diagnostics as well as patient management," added the Prof. 

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Acupuncture helps treat autism spectrum disorders

Autism spectrum disorders (ASDs) are developmental disorders, which have four core characteristics: communication and social impairment, irritability, repetitive behaviour and limited range of interests. There is a wide variance in the type and severity of autism.

Medication is used to help support children with autism. However, the adverse reactions to drugs have led to the increasing popularity of complementary treatments for autism.  

The research set out in this paper used body acupuncture and weekly treatments based on an individual diagnosis using an integrated TCM-Five Element style for each child, depending on their own specific symptoms. The study was conducted in one institute to minimise the variations in treatments.

This pilot control trial took place at a specialist residential school for children with ASD  between September 2012 and July 2013.  While 16 children (aged 9-16 years) accepted the invitation to participate, two withdrew. The remaining 14 students were allocated into two groups. Both groups received weekly treatments. The first group received treatment between September 28, 2012 and February 28, 2013, that made to a maximum of 14 possible sessions. The second group, a delayed control group, commenced treatment from March 1, 2013 and it continued till July 12, 2013, with a maximum of 15 possible session.

All diagnoses and treatments were undertaken by a single acupuncturist, who is the author of this study.  The practitioner has 16-year experience, is fully qualified and specialist in Acupuncture. The appointment duration was 30 minutes and parents were asked to attend the first session. The first four sessions consisted of massage and acupressure (pressing points with fingers, pressing with a metal probe, and progressing on to stimulating the point with the back of the needle in order to accustom children to the process). Needles were used from the fifth session depending on each participant’s acceptance of needles. Seirin 0.16x15mm needles were inserted to a depth of 0.3- 0.5 cun, and were retained for up to 20 minutes for the older and more compliant children. For the remaining participants, needles were not retained.

Children and their parents reported a variety of benefits, including feeling more relaxed, less anxious, less angry and improvement in social behaviour, all of which are common challenges that autistic children face. The majority of children were happy to receive acupuncture, provided they received support and a plenty of preparation and reassurance.  

Eight of the 14 children were unable to communicate verbally. Of the six who could communicate, only three children could articulate how they felt. In addition, parents only gave their feedback at the end of the five-month treatment. Parents suggested that treatment had made a positive impact on kids’ social behaviour but it was also suggested that regular treatment was needed to maintain its efficacy.

This treatment is now being made available in India.

 

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Autism Rates Higher in Women with PCOS And their Children

Autism Spectrum Disorder (ASD) is about four times as likely to occur in males than in females. Because of that trend, scientists have suspected an association between ASD and testosterone. Elevated testosterone levels during gestation have been linked to an array of neurological conditions – including ASD – in both male and female children.

What’s New: A new study explored the association between ASD and poly-cystic ovary syndrome (PCOS), a condition in which women of reproductive age produce excess testosterone. The researchers examined existing data from the electronic health records of more than 60,000 women in the UK – 26,000 with PCOS and 1,000 with ASD – from 1990 to 2014. They also looked at the data from more than 8,000 children born to mothers with PCOS.

The researchers found:

• Women with ASD were more than twice as likely than their peers with typical development to have PCOS.
• Women with PCOS were nearly twice as likely than their peers without to condition to have ASD.
• The odds of having a child with ASD significantly increased among women with PCOS.

Why it’s important: This study suggests a connection between PCOS and ASD. Future research could lead to improved screening and treatment based on this finding.

• Genetic factors in autism
• Environmetal factors in autism

Autism Spectrum Disorder (ASD) can be caused by multiple conditions, called risk factors,that have been linked to an increased likelihood of developing ASD. Risk factors can be genetic or environmental.
Genetic risk factors relate to inborn problems in our DNA, such as a gene depletion or duplication. Genetic risk factors are present at birth.
Environmental risk factors, however, stem from social, physical, or chemical exposures and can be present during fetal development or months to years after birth.
In the Risk Factors section of the Autism Reading Room, scientific experts discuss the interaction between environment and genetic risk factors as well as misconceptions about the causes of ASD.

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Foli acid during pregnancy may help to prevent a type of autism

By taking folic acid around the time of conception, mothers-to-be may reduce their child's risk of pesticide-related autism, a new study suggests.

"We found that if the mom was taking folic acid during the window around conception, the risk associated with pesticides seemed to be attenuated," said study first author.

"Mothers should try to avoid pesticides. But if they live near agriculture, where pesticides can blow in, this might be a way to counter those effects," said  an assistant professor.

It's estimated that one in 68 children has an autism spectrum disorder, which can range from mild to severe. There is no single cause, but research suggests a combination of genetic and environmental influences plays a role.

The new study included about 300 children aged 2 to 5 with autism and 220 without the developmental disorder. Children whose mothers took 800 or more micrograms of folic acid (the amount in most prenatal vitamins) had a much lower risk of developing autism, even when their mothers were exposed to household or agricultural pesticides, the researchers said.

Autism risk was higher among children whose mothers were repeatedly exposed to pesticides or whose mothers had low folic acid intake and exposure to agricultural pesticides between three months preconception and three months afterward, the findings showed.

Those two factors combined were associated with higher risk of autism than either low folic acid intake or pesticide exposure alone, said an author.

"The mothers who had the highest risk were the ones who were exposed to pesticides regularly," she added.

Folic acid is the synthetic form of vitamin B9, found in supplements and fortified foods. While taking it reduced the associated risk of pesticide-related autism in children, it did not entirely eliminate it, the report noted.

"It would be better for women to avoid chronic pesticide exposure if they can while pregnant," Schmidt said.

Folic acid plays a critical role in DNA repair and synthesis, and in determining which genes are turned on or off, she said . "These are all really important during periods of rapid growth when there are lots of cells dividing, as in a developing fetus. Adding folic acid might be helping out in a number of these genomic functions," she added.

The study doesn't show a causal link, and there are limitations. For one, participants relied on their memory to report folic acid intake and household pesticide exposure.
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