Tag: autism

Categories : Mental Health Obstetrics & GynaecologyTags : Leave a comment

Placenta Acts to Shield Foetus from Serotonin

On By ModernMedia
Image by Scientific Animations CC4.0

The placenta has long been thought to produce serotonin during pregnancy. But in a new study, Yale researchers shatter the deep-rooted hypothesis – and show that the placenta doesn’t produce serotonin but instead regulates its delivery to the embryo and foetus. They found that serotonin comes from the pregnant parent, with the placenta acting as a “serotonin shield” that controls how much reaches the embryo and foetus. 

The findings, published in the journal Endocrinology, could offer critical insights into how a parent’s serotonin levels might affect the development of their baby’s body and brain, the researchers say. 

“The placenta is in essence the ‘serotonin shield’ that regulates how much serotonin is ultimately delivered to the embryo and foetus, not the source of serotonin,” said Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine and corresponding author of the study. “Why does this matter? Because now we correctly know where this delivery is regulated.”

Often called a “happiness hormone,” serotonin regulates mood, so it’s often associated with the brain. In reality, less than 5% of serotonin is made in the brain, with 95% of it made in the gut. But serotonin does more than just regulate mood. It’s also a growth hormone. In the gut, it gets taken up by platelets and is delivered to parts of the body that need to grow, including in wound healing. 

During pregnancy, serotonin also helps with growth: It travels into the placenta through a special protein known as the serotonin transporter (SERT) where it plays a critical role in the development of the embryo and foetus. 

Serotonin from the mother is taken up by the foetal placenta, which then produces a myriad of hormones, growth factors, and regulators that are delivered to the foetus.

For the new study, researchers sought to better understand these relationships by using a pure source of placenta cells, unlike in previous studies that looked at either whole animals or isolated mouse placentas. To do so, they first purified human cytotrophoblasts, which are the stem cells that make all the cells of the placenta. They then added serotonin to those cells to see where it would go and discovered it concentrated in the nucleus. Next, they used a selective serotonin reuptake inhibitor (SSRI) that blocked SERT, escitalopram, to show that the normal growth, function, and differentiation of these cells was completely blocked. 

They also used another inhibitor called cystamine to block serotonylation, or the process by which serotonin is added to proteins like histone 3, which turns genes “on” and “off.” Again, that completely blocked the normal growth of the cells. 

Blocking either SERT or serotonylation led to significant changes in gene expression of RNAs in the cytotrophoblasts, they found. Some genes, including ones involved in making, moving, and growing cells, became downregulated, or less active, when serotonin couldn’t enter the cell. Other gene, including ones that help cells stay alive and protect them, became upregulated, or more active. According to the researchers, these findings show that serotonin is critical for the growth of the cytotrophoblasts, the placenta, and by extension, the foetus. 

Additionally, researchers discovered that the cytotrophoblasts don’t contain tryptophan hydroxylase (TPH-1), or the enzyme that makes serotonin, indicating the cells within the placenta can’t produce serotonin on their own. 

“This suggests that factors that either inhibit serotonin transport through the placenta, or increase it, may have a significant impact on the placenta, embryo, foetus, and ultimately, the newborn and its brain,” Kliman said.

For example, Kliman says this explains why taking SSRIs, which decrease the levels of serotonin into the placenta, leads to smaller babies, and why, conversely, increased levels of serotonin may lead to bigger babies, with bigger brains, who may be at increased risk for developmental disabilities like autism.

Kliman and his lab have long investigated the link between placentas and children with autism, specifically the number of trophoblast inclusions (TIs) in the placenta. TIs are like wrinkles or folds in the placenta, caused by cells multiplying more than they should, typically only seen in pregnancies where there are genetic problems with the foetus. 

This new study is the culmination of research first published in 2006 that found significantly more TIs in the placentas from children with autism, and later in 2021, that the genetics of the foetus, and not the parent’s uterine environment, determine how many TIs are in the placenta. 

“This puts a big nail into the theory that vaccines cause autism,” suggested Kliman. “Autism, in essence, starts in the womb, not after delivery, and is most likely due to the genetics of the placenta and to a lesser extent, the maternal environment the placenta finds itself in.”

Source: Yale News

Categories : PaediatricsTags :

Early Developmental Intervention Dramatically Cuts Autism Risk

On By ModernMedia
Photo by Margaret Weir on Unsplash

A first-of-its-kind study has shown that parent-led therapy supporting the social development of babies with early autism signs greatly reduced the odds of a later autism. 

The research, led by CliniKids at the Telethon Kids Institute and published in JAMA Pediatrics, found that a diagnosis of autism at age three was only a third as likely in children who received the pre-emptive therapy (iBASIS-VIPP)compared to those who received usual treatment.

The findings were the first evidence showing that a pre-emptive intervention during infancy could result in such a significant improvement in children’s social development that they then fell below the threshold for an autism diagnosis.

Study leader Professor Andrew Whitehouse, Telethon Kids Institute, said: “The use of iBASIS-VIPP resulted in three times fewer diagnoses of autism at age three. No trial of a pre-emptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now.”

Professor Whitehouse said many therapies for autism tried to replace developmental differences with more ‘typical’ behaviours. Instead, iBASIS-VIPP attempts to work with each child’s unique differences, creating a social environment around the child helping them learn in a way optimised for them.

“The therapy uses video-feedback to help parents understand and appreciate the unique abilities of their baby, and to use these strengths as a foundation for future development,” said Professor Whitehouse. “By doing so, this therapy was able to support their later social engagement and other autistic-related behaviors such as sensory behaviors and repetitiveness, to the point that they were less likely meet the ‘deficit-focused’ diagnostic criteria for autism.”

“We also found increased parental sensitivity to their baby’s unique communication and an increase in parent-reported language development. Other general aspects of development were not affected.” The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years.”

The four-year randomised clinical trial enrolled babies aged 9-14 months, all of whom having shown early behavioural signs of autism. Over five months, half received the video intervention, while a control group received current best practice treatment.

Eighty-nine children completed an assessment at the start of the study, at the end of the therapy period, and when they were two and three years of age. With the high prevalence of autism worldwide, the implications of the findings were enormous, said Professor Whitehouse. Around 2% of all children in Australia have an autism diagnosis.
“Autism is not typically diagnosed until three years of age, however, interventions commencing during the first two years of life, when the first signs of development difference are observed and the brain is rapidly developing, may lead to even greater impact on developmental outcomes in later childhood,” Professor Whitehouse said.

Professor Whitehouse said that a follow-up of study participants in later childhood, when autism behaviours may be more apparent, would be critical to determining the longer-term significance of the video intervention.

Source: Telethon Kids Institute

Categories : Neurology PaediatricsTags :

Internal Body Sensing Ability Varies with Age

On By ModernMedia
Photo by Daniil Kuželev on Unsplash

A Chinese study has found that the ability to sense nervous signals such as heartbeat varies with age, peaking in young adulthood, but does not seem to be associated with autism.

Interoception is the ability to process and integrate internal signals originating from one’s body, such as heartbeats and breathing patterns. This ability is important for maintaining homeostasis. Recent findings have suggested that autism spectrum disorders are associated with a wide range of sensory integration impairments including interoceptive accuracy.

However, it is still not clear whether individuals with subclinical features of autism, which only moderately impact daily life, also exhibit similar impairments in interoceptive accuracy. It is also not clear how interoceptive ability and its association with autistic traits varies with age.

In order to address this issue, Dr Raymond Chan’s team from the Institute of Psychology of the Chinese Academy of Sciences (CAS) has developed an innovative paradigm involving eye-tracking measures to examine the multidimensional interoception and autistic traits in different age groups.

In so doing, they recruited 114 healthy university students aged 19–22 and explored the correlations among autistic traits and interoceptive accuracy using an “Eye-tracking Interoceptive Accuracy Task” (EIAT), which presents two bouncing shapes and requires participants to look at the one whiches bounces in time with their heartbeat.

Since this task requires no verbal report or button-pressing, it enables the exploration of interoceptive accuracy in preschool children and individuals with psychiatric disorders or speech impairments.

However, while autistic traits correlated significantly with the ability to describe and express emotion (alexithymia) but not with the different dimensions of interoception such as interoceptive accuracy (performance of interoceptive ability on behavioural tests), interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires) and interoceptive awareness (personal insight into interoceptive aptitude).

They then recruited 52 preschool children aged four to six, 50 adolescents aged 12–16 and 50 adults aged 23–54 to specifically examine the relationship of autistic traits and interoceptive accuracy across these three age groups. The researchers found that interoceptive accuracy evolves from childhood to early adulthood, and then declines with age. The highest average accuracy was seen in 12-16 year olds. The dataset showed that the developmental trajectory of interoceptive accuracy has a reverted U-shape trend peaking around early adulthood.

The findings suggest that interoceptive accuracy significantly differs between typically-developing preschool children, adolescents and adults. The study also highlights the need for future study into preschool children with suspected autism spectrum disorders.

Source: Medical Xpress

Categories : Mental HealthTags :

Autism Theory Treats its Characteristic Traits as Favoured by Society

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For decades, scientists have fruitlessly sought a unifying aetiology for autism and an explanation for its prevalence, but now a new theoretical model describes the condition as a combination of traits that are common in autism and which are socially valued, combined with co-occurring disabilities.

An estimated 1 in 54 people have autism, which has been on the increase in developed countries. TA Meridian McDonald, PhD, a research instructor in Neurology at Vanderbilt University Medical Center, said: “Up until now there have been a lot of theories about the possible causes of autism but none of those theories account for the majority of autism cases. There are also a lot of theories as to why the prevalence of autism has been increasing in the population but, to date, there hasn’t been a theory that provides an explanatory model that accounts for all of those phenomena, including the genetics, social history, or characteristics of autism.”

She has worked on autism for 25 years, culminating in a theory called, “The Broader Autism Phenotype Constellation-Disability Matrix Paradigm (BAPCO-DMAP) Theory”, a focuses on the genetic basis of autism in line with current science but shifts the emphasis to positive traits selected for by events occurring over the past century.”The BAPCO-DMAP theory describes how people are attracted to other people who are very similar. They are attracted to certain traits that are very common in the population, and this leads to offspring who are more likely to have certain traits, as well as a greater intensity of traits,” said McDonald.

“The [BAPCO] traits are not what people expect. They expect the traits to be about challenges or difficulties, but instead there are six main traits—increased attention, increased memory, a preference for the object world vs. the social world and their environment, increased nonconformity, increased differences in sensory and perception, as well as systemising.”

These BAPCO traits are thus not necessarily negative, and can be combined with social skills. Counterintuitively, babies with increased memory and attention spans learn language later, because babies normally rely on their tiny attention span to break words down into their simplest sounds. With greater memory and attention spans, infants engage in echolalia, speaking long phrases without understanding them.

“You can often see children with autism engaging in sense-making activities, such as watching the same show over and over and memorising information,” McDonald said.The BAPCO traits are not by themselves significant impediments, but when combined with a disability such as an information processing disorder, then the combination leads to greater difficulties.

According to McDonald, the increased prevalence of autism in developed countries is due to men and women with BAPCO traits being able to pursue similar careers and passions, as opposed to being limited by circumstance, and results in relationships. This effectively concentrates BAPCO traits in any children they have.Since the BAPCO traits are socially valued, there simply is no “cure” for them, according to McDonald.”When we talk about autism we need to address the developmental disabilities that these individuals are experiencing but also find way to support and enhance their broader autism trait constellations,” she concluded.

Source: Medical Xpress

Journal information: T.A. Meridian McDonald, The broader autism phenotype constellations–disability matrix paradigm: Theoretical model for autism and the broader autism phenotype, Medical Hypotheses (2020). DOI: 10.1016/j.mehy.2020.110456

Categories : UncategorizedTags :

Unmedicated Autism Associated With Substance Abuse

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A Taiwanese study has shown that individuals diagnosed with untreated autism spectrum disorder (ASD) have higher rates of substance abuse compared to those on treatment.

The researchers used inpatient and outpatient data of 6 599 individuals with ASD who had at least 3 outpatients visits for ASD, drawn from the Taiwan National Health Insurance Research Database. They found an increased risk of substance use disorder (SUD) among those who were not receiving medication for ASD (adjusted hazard ratio 2.33, 95% CI 1.89-2.87). The risk for drug abuse was three times higher, and the risk for alcohol abuse was two times higher.

Additionally, those with comorbid SUD had over a three times greater risk of death over a follow-up period of 8.1 years.Those taking psychotropic agents had a 40% reduction for SUD risk when taking one agent, and a 63% reduction with a multiagent.

There were several comorbidities of psychiatric disorders seen in patients with ASD, such as intellectual disability, attention deficit hyperactivity disorder, tic disorder, epilepsy, obsessive-compulsive disorder, mood disorder, anxiety disorder, and impulse control disorder. However, individuals with ASD had a higher risk of SUD even compared with matched controls with the same comorbidities. SUD risk was highest with certain comorbidities; untreated ASD with comorbid tic disorder was 6 times higher; with a comorbid impulse control disorder, it was five times higher.

The researchers stated that these are critical findings, but of limited use due to the “umbrella term” of substance use disorder, and further studies will be needed to examine the specific types of drug use amongst individuals with ASD. Future research could investigate whether non-pharmaceutical treatments such as behavioural therapy had the same effect.They conclude that screening  individuals with ASD for SUD is important, given the findings of the study.

Source: MedPage Today

Journal information: Huang J, Yang F, Chien W, et al. Risk of Substance Use Disorder and Its Associations With Comorbidities and Psychotropic Agents in Patients With Autism. JAMA Pediatr. Published online January 04, 2021. doi:10.1001/jamapediatrics.2020.5371