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A mutation that prevents certain amino acids from entering neurons leads to the cells’ death early in brain development, according to a new study in mice. The findings provide clues to what happens in the brains of people with the mutation, which is linked to autism.

The mutation affects the SLC7A5 gene, which encodes a protein that transports some large amino acids across the blood-brain barrier. Most of these amino acids are essential, meaning the body cannot produce them and has to get them from food. Mice missing the SLC7A5 gene in cells of the blood-brain barrier develop microcephaly, or an unusually small brain, after birth and have motor and social difficulties, a 2016 study showed.

In the new study, published last month in Cell, the same team of researchers discovered that neurons in the mouse brain also express SLC7A5. Knocking the gene out of some of those neurons starves the cells of amino acids and causes them to die.

“Obviously neurons need some fuel,” says lead researcher Gaia Novarino, professor of neuroscience at the Institute of Science and Technology in Klosterneuburg, Austria. It’s interesting “to really see that our neurons are dependent on that level, specifically at certain stages, on those amino acids.

Novarino and her team also filled in a blank in the literature: how metabolism changes as the mouse brain develops.

It was known that, in the developing brain, neural progenitor cells get energy through anaerobic glycolysis — that is, by breaking down glucose in the absence of oxygen. Later, support cells called astrocytes feed mature neurons the vast amounts of energy needed to fire and reset. Surprisingly, there was little information about what happens in between, when neurons begin to fire but do not yet have support from astrocytes.

t turns out that during this transitional period, young neurons get their energy by metabolizing a set of essential amino acids called branched-chain amino acids (BCAAs), Novarino’s team discovered by analyzing the metabolomes of developing mouse neurons.

“That was eye-opening to me, how dramatically the metabolism of the cell seems to change,” says John Jay Gargus, director of the Center for Autism Research and Translation at the University of California, Irvine, who was not involved in the study.

BCAAs are among the amino acids that SLC7A5 transports. In mice, young neurons missing the gene are therefore starved of their primary energy source. These neurons switch to running on lipids, but they fire less frequently than usual and then disappear within 10 days after birth, the team found. As a result, SLC7A5 mice have smaller brains than controls do.

Similar to these mice, two children with SLC7A5 mutations, whom Novarino and her team identified and monitored after their 2016 study, were born with mild microcephaly that became more pronounced within seven months.

He says the research aligns with a larger pattern in the field: About 17 percent of autistic children show an imbalance in their amino acid levels, according to a 2018 study that Amaral led.

Unfortunately, the new insights into SLC7A5 smashed some of the team’s hopes for treatments.

Disrupted levels of molecular compounds in maternal blood and cord blood are linked to later diagnosis of autism spectrum disorder (ASD) according to a new study. The study was led by researchers at Columbia University Mailman School of Public Health and the Norwegian Institute of Public Health. Identification of these compounds sheds light on the biological processes that give rise to ASD and paves a way for earlier diagnosis and treatment for ASD.

The findings are published in Molecular Psychiatry in an article titled, “Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders.”

“The discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into ASD and facilitate early diagnosis,” wrote the researchers.

The researchers analyzed levels of 1,208 different chemical compounds in plasma samples collected from 408 mothers at mid-gestation (17–21 weeks) and in cord blood taken from 418 children at birth through the Norwegian Autism Birth Cohort (ABC). They used chromatography/mass spectrometry-based metabolomics assays to measure levels of chemical compounds. They used machine learning to assess the predictive value of the compounds as biomarkers for ASD.

The researchers found 12 chemical compounds in maternal mid-gestation (MMG) samples of ASD girls, three compounds in MMG samples of ASD boys, eight compounds in cord blood (CB) samples of ASD girls, and 12 compounds in CB samples of ASD boys to be linked to autism, including those that involve inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Machine learning analyses suggested the potential utility of the compounds as biomarkers, especially those in cord blood, for early identification of children at risk for ASD.

Background
Previous studies have reported reduced brain activity with a concomitant increase in cortical temperature, which indicates activation of inhibitory neuronal pathways by elevated temperature. Circadian rhythm disturbances have also been reported among ASD patients; however, large-scale studies investigating the association between circadian rhythm and autistic traits among the general population are limited.

About the study
The survey-based study comprised 2,400 individuals between 20 and 70 years of age. Among the study participants, autistic traits were measured using questionnaires assessing the autism spectrum quotient (AQ), empathy quotient (EQ), and systemizing quotient (SQ), adjusting for self-documented circadian rhythm and age. The composite morning questionnaire (CSM) was completed by the participants to assess circadian rhythms.

Individuals self-documented their axillary temperatures, temperature recording time, wake-up time, and the manufacturing details of the axillary thermometer used. In addition, the participants documented variables that could affect body temperature, including the presence of cold, recording temperatures following exercise, use of antipyretic medications, and coronavirus vaccinations in the prior week. Data were obtained on participants’ age, sex, and residence, and analyzed by performing multiple regression modeling.

The survey forms were distributed twice online at different time points to verify the validity and reproducibility of the study findings. The first survey was conducted between October 23-27, 2021, whereas the second survey was conducted between January 14-19, 2022.

The team excluded individuals reporting menstruation data, measuring body temperatures without axillary thermometers, and those with outlier values for body temperature exceeding ±3.0 standard deviation (SD). Time data exceeding 24 hours were also excluded from the analysis.

Results
For surveys one and two, data were obtained for 3,227 and 3,402 individuals, respectively, residing across 47 prefectures in Japan. The data from 827 and 1,020 participants, respectively, were excluded, as they were obtained using inappropriate strategies and previously established techniques. As a result, data were analyzed for 2,185 and 2,264 individuals, respectively, for the association between ASD and bodily temperature, whereas 2,211 and 2,288 individuals for the other associations.

No statistically significant associations were observed between ASD-associated characteristics and axillary temperatures. However, a significant but negative association was observed between age and AQ that was concordant with reduced cognitive and sensory functions with advancing age. In addition, AQ scores were negatively correlated with CSM, thus indicating that individuals with greater autistic traits (greater AQ scores) had stronger tendencies at night.

Excluding female data of specific age groups yielded statistically significant associations. Significant relationships were observed in the initial survey; however, these results did not replicate in the subsequent survey, despite the survey procedures and dependable variable distribution being similar for both surveys.

Conclusions
Overall, the study findings showed no significant association between autistic traits and body temperature. However, individuals with greater AQ scores had stronger evening tendencies, whereas autistic traits were weaker among older individuals. These observations could improve understanding of age-associated malleability, circadian rhythm irregularities, and difficulties in performing routine activities in association with autistic traits.

Further research is needed to assess the validity of the findings using controlled conditions for bodily temperature recording and/or core temperature measurements. These studies should also consider individual-level alterations in ASD parameters, as well as brain and body temperatures, with time.

by Penny Benford, B. Med, Sci (Hons)
Thesis submitted to the University of Nottingham for the degree
of Doctor of Philosophy
July 2008

I don't understand this threads purpose,

At least half of all autistic children experience some form of aggression, such as hitting, kicking or name-calling, while their parents are tasked with helping them cope and integrate socially. Yet the prevalence and characterization of aggressive behaviors across autistic development are poorly understood.

To address this knowledge gap, researchers in the Family and Community Intervention Lab at the University of Arkansas compared autistic children to non-autistic children on different types of aggressive behaviors over three critical developmental periods and found that parents of autistic children reported more frequent aggression at greater intensities than non-autistic children.

"Aggression represents a pervasive and serious problem faced by autistic youths and their families," said Lauren Quetsch, assistant professor of psychology and lead author of "Understanding aggression in autism across childhood: Comparisons with a non-autistic sample."

"While our knowledge about the unique needs of autistic children has grown exponentially over the last several decades, we still have a long way to go," she said. "And understanding the role aggression plays in autistic youths' lives can help us to better address our gaps in care."

Between December 2020 and March 2021, Quetsch and her colleagues gathered quantitative and qualitative data on 450 autistic and 432 non-autistic children. The data were broken down into three age-matched groups -; younger than six, six to 12 and 13 to 17. The children were compared on multiple caregiver-report measures of aggressive and disruptive behavior across these key developmental periods.

The researchers' analysis of the data revealed higher levels of verbal aggression and disruptive behavioral intensity for autistic children across all three stages of development. Autistic children younger than six had more significant levels of physical aggression than their non-autistic peers. However, these levels became equal to non-autistic peers as the children aged.

In the qualitative study, non-autistic children more frequently expressed anger in a controlled manner, according to parents, whereas autistic children were more apt to quickly lose their temper.

" We surmise that this can be attributed to several factors. Frustration from regularly being misunderstood, challenges with recognizing emotions in others or expressing their own emotions to others, sensory overstimulation, and even co-occurring health challenges, such as physical discomfort from gastrointestinal issues and exhaustion due to irregular sleeping patterns, all likely contribute to aggression."

Lauren Quetsch, Assistant Professor of Psychology

The researchers' study was published April 9 in Autism Research, the official journal of the International Society for Autism Research.

Journal reference:
Quetsch, L. B., et al. (2023). Understanding aggression in autism across childhood: Comparisons with a non‐autistic sample. Autism Research. doi.org/10.1002/aur.2930.

Young children with common ear, nose, and throat (ENT) issues may be at subsequent risk of autism or high levels of demonstrable autism traits, suggests research published online in the open access journal BMJ Open.

Previous research suggests that ENT conditions, such as ear infections, 'glue ear', and sleep disordered breathing, may have a role in the development of autism. But most of this evidence is based on health records, which may have biased these findings, because parents of children with suspected autism may be more likely than other parents to seek medical help for their offspring, explain the researchers.

To avoid this, the researchers drew on participants in the long term Children of the 90s study, also known as the Avon Longitudinal Study of Parents and Children (ALSPAC). This has tracked the health of more than 14,000 children since birth and that of their parents from the early 1990s onwards.

The current study is based on comprehensive data for more than 10,000 young children who were closely monitored throughout their first 4 years.

Their mothers completed 3 questionnaires when their children were aged 18, 30, and 42 months, which were designed to record the frequency of 9 different signs and symptoms relating to the ear, nose, and throat as well as any hearing problems.

They also completed 3 questionnaires when their children were just over 3, nearly 6, and 9 years old. These were designed to pinpoint speech coherence, social and communication issues, repetitive and abnormal behaviors, and sociability, traits which are characteristic of autism. A diagnosis of autism was confirmed from educational records and parental feedback, among other sources.

Adjustments were made for 10 potentially influential 'environmental' factors: early or late birth; sex; number of mother's previous pregnancies resulting in a live or stillbirth; breast feeding; postnatal depression; mother's educational achievements; mother's smoking at 18 weeks of pregnancy; mother's belief in her own agency; child's exposure to environmental tobacco smoke at 15 months; child's attendance at a crèche/other daycare by the age of 30 months.

In all, 177 children had a probable diagnosis of autism:139 boys and 38 girls. Those with autism traits were defined as the 10% of the sample with the highest trait scores.

Early evidence of breathing through the mouth, snoring, ear pulling or poking, reddened and sore ears, worse hearing during a cold, and rarely listening were all more commonly associated with high scores on each of the 4 autism traits, and with a diagnosis of autism.
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Pus or sticky discharge from the ears was also associated with autism and with poor coherent speech.

Among the different ages tested, strong associations were particularly observed when the child was aged 30 and 42 months. Children with high scores on autistic traits at 30 months had more ENT signs. Autism itself was significantly associated with all signs except for symptoms of sleep apnoea (interrupted breathing during sleep).

Factoring in the 10 environmental features made little difference to the results. For example, children with discharge from their ears were more than 3 times as likely to have autism, while those with impaired hearing during a cold were more than twice as likely to do so. And children who failed to react to nearby noise were more than 6 times as likely to have autism at this age.

However, the researchers point out: "These ENT signs and symptoms are very common in childhood and most children who experience them do not go on to be diagnosed with autism. For example, of the group of around 1700 children who snored at age 30 months, most (1660) weren't diagnosed with autism later on."

The researchers acknowledge various limitations, including the loss of some children to subsequent monitoring, as is the case with any long term study, and the lack of ethnic diversity among the Children of the 90s participants, limiting the wider applicability of the findings.

What's more, the children weren't examined consistently to determine a diagnosis of autism; rather, a strategy to assess the probability of a diagnosis using a variety of different sources was used instead.

They add: "This study adds to the evidence that, compared with a typical population of the same age, early ear and upper respiratory symptoms are more common in those subsequently diagnosed with autism or with extreme levels of autistic traits."

But they caution: "It is not possible to determine whether these ENT conditions have a causal role in the development of autistic traits or are related to an unmeasured factor.

"One possibility, for example, could be the consequence of the increased prevalence of minor physical anomalies in individuals with autism, including anatomical differences in the structure and/or positioning of the ear, with such differences in ear morphology increasing the risk of ENT conditions."

Journal reference:
Hall, A., et al. (2023). Associations between autistic traits and early ear and upper respiratory signs: a prospective observational study of the Avon Longitudinal Study of Parents and Children (ALSPAC) geographically defined childhood population. BMJ Open. doi.org/10.1136/bmjopen-2022-067682.

Kiwi researchers hope to offer a new way to ease distressing stomach problems that many people with autism suffer - by transferring gut bugs from others.

So-called “microbiome transfers” - when gut bacteria is taken from healthy donors - have emerged as a promising approach to treat a wide range of conditions, as scientists have learned more about the communities of beneficial bugs that live within each of us.

Now, in a ground-breaking new trial, University of Auckland researchers want to see if these might alleviate gut problems thought to be experienced by nearly half of New Zealand’s 90,000 autistic people.

Just why that is remains unclear, with studies having explored links from everything from diet to stress and anxiety.

In the trial, designed in collaboration with advocacy groups Altogether Autism and Autism New Zealand, around 50 young autistic people will receive the microbiome treatment, with the same number given a placebo.

The participants - who have been earlier screened to confirm they have stomach problems affecting their daily activities, such as diarrhoea - would then be followed for six months and assessed to see whether their symptoms ease.

If the microbiome transfer was found to be helpful, it will be offered to the participants who received the placebo.

Liggins Institute lead investigator Professor Wayne Cutfield said the study was informed by work that began 15 years ago, exploring the importance of the gut microbiome for a wide range of outcomes.

“However, only now are we at the stage of conducting robust randomised controlled trials in humans,” he said.

“Up until now, our evidence has come from animal trials and associations. So, this is really important and has the potential to be hugely beneficial.”

Liggins was also researching whether microbiome transfer could be useful for people with obesity, obesity-related disorders and anorexia nervosa.

In one 2020 study, the researchers found the approach appeared to help a group of overweight teens living with metabolic syndrome.

Just as in that trial, the research team would take samples from healthy volunteers, process it to enrich for bacteria and then thoroughly enclose the bacteria in capsules.

The donors would then be screened in a similar way to blood donors to ensure there were no harmful viruses or organisms in their stools.

The microbiome bacteria would then be encapsulated in several cases of digestible coating, so they wouldn’t be digested in the mouth or throat, but when they reached the gut.

The capsules would be administered over two days at the university, with medical supervision, before later testing would be carried out later to see if there’d been changes in gut bacteria.

A new study will investigate whether good bacteria taken from donor poo can help alleviate tummy troubles in people with autism.

Everybody has a microbiome: the collection of microbes, such as bacteria, fungi, viruses that live naturally on our skin and in our nose, throat and gut, and play a “critical role” in our health and wellbeing.

University of Auckland researchers are launching a clinical trial to see whether microbiome transfer – in the form of capsules – can help counter gut problems for those living with autism, including pain, loose and frequent stools and indigestion.

Research has found introducing faeces or stool from a healthy donor can restore healthy bacteria in another person’s gastrointestinal tract – in what’s called faecal microbiota transplantation.

Faecal microbiota transplants (or gut biome transfers) are an emerging therapy being tested in a range of gastrointestinal conditions, including colitis, irritable bowel disease, and even neurological conditions such as multiple sclerosis and Parkinson’s.

Now, Professor Wayne Cutfield​, a paediatric endocrinologist at the Liggins Institute, and co-lead investigator Professor Justin O’Sullivan​ are leading a proof-of-concept trial, trying to answer whether microbiome transfers could improve the gut function of autistic teenagers and young adults.

About 90,000​ people in New Zealand are autistic – and, for reasons that remain unclear, nearly half experience potentially distressing gut problems, the researchers say.

In the trial, about 50​ autistic people with gut issues impacting their day-to-day lives will receive the microbiome treatment, and as many will receive a placebo.

The researchers will take stool (poo) samples from healthy volunteers, process it to enrich for microbiome bacteria, then enclose the bacteria in capsules.

Cutfield said the screening process is stringent, to ensure the stool samples used are free from harmful viruses or organisms.

The bacteria will be encapsulated in two layers of capsules so they have no taste or smell, and are specially designed to release the contents into the gut, rather than the mouth or throat, Cutfield says.

The capsules will be given over two days – 10 on one day, 10 the next – with medical supervision.

If the transfer is found to be helpful, it will be offered to those who get the placebo.

Cutfield says they’re not looking for a cure for autism – they want to see whether changing a person’s gut microbiome can improve their quality of life.

The study, designed in collaboration with advocacy groups Autism New Zealand and Altogether Autism, aims to make people’s guts work better, O’Sullivan said.

Children of women whose drinking water contains lithium are at an elevated risk of developing autism spectrum disorder (ASD), according to the findings of a retrospective study published in JAMA Pediatrics.

In previous studies, incident miscarriage and heart malformation in children were more common after maternal lithium therapy for bipolar disorder. Further concern has been raised about the potential effect of maternal lithium exposure on childrens’ neural development, as lithium crosses both the placenta and the fetus’s blood-brain barrier. Furthermore, lithium alters Wnt/β-catenin signaling; this pathway is crucial in neurologic development and its alteration has been implicated in ASD.

Low levels of lithium occur naturally in groundwater, which is Denmark’s exclusive source of drinking water. This prompted the question whether neurodevelopmental disorders such as ASD are more common in areas with higher groundwater lithium levels.

Researchers conducted a case-control study of Denmark’s birth registry in 8,842 children with ASD, born between 2000 and 2013, and diagnosed with ASD between those dates and 2016. The children were matched with children without an ASD diagnosis, in a 1:5 ratio, by age and birth year.

The researchers linked the mothers’ residential addresses with model estimates of local groundwater lithium concentration. This allowed them to examine risk for an ASD diagnosis, in logistic regression models, with respect to local lithium exposure, adjusted for maternal age, maternal smoking, urban vs rural residence, ambient air pollution, and socioeconomic status. The researchers also conducted analyses stratified by ASD subtype, child sex, and birth year.

The research team found that groundwater lithium exposure was associated, in a dose-dependent manner, with higher odds of ASD developing in offspring. Measured as a continuous variable, each increase in lithium concentration interquartile range (IQR) increased the odds of an ASD diagnosis by 23% (adjusted odds ratio (aOR), 1.23; 95% CI, 1.17-1.29), in the fully adjusted regression model.

When exposures were categorized by quartile, this dose-dependent increase in diagnosis was largest in the highest quartile (lithium concentrations higher than 16.8 μg/L); these most-exposed children had 46% higher odds compared to the lowest quartile of exposure (aOR, 1.46; 95% CI, 1.35-1.59). Children in the second and third quartiles were between 24% and 26% more likely to receive an ASD diagnosis than those in the lowest exposure quartile. These associations remained present among subtypes of ASD, including autism, Asperger syndrome, and pervasive developmental disorder, and were slightly stronger for families living in urban areas than in smaller municipalities.

There are several study limitations that warrant mention, including a lack of information on dietary and lifestyle factors, such as habits of water consumption, not measuring the actual sources of water mothers consumed, and not considering childhood exposure.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies.

For children with greater predisposition to autism-related behaviors and who have mothers with prepregnancy overweight or obesity, gestational weight gain (GWG) is associated with autism spectrum disorder (ASD), according to a study published online April 26 in Obesity.

Marisa A. Patti, from Brown University in Providence, Rhode Island, and colleagues used data from the Early Autism Risk Longitudinal Investigation (EARLI) study, including 136 mothers who had a previous child with ASD, and the Health Outcomes and Measures of the Environment (HOME) study, a general population cohort with 253 participants, to assess influences on the association between GWG and ASD. The prevalence and severity of ASD was assessed using the Social Responsiveness Scale (SRS) in children aged 3 to 8 years.

The researchers found that in the HOME study, GWG z scores and SRS were positively associated in children with more ASD-related traits (higher SRS scores), but not in those with fewer ASD-related traits, among mothers who had overweight or obesity prepregnancy body mass index values. In the EARLI study, similar patterns were seen among mothers with prepregnancy obesity.

One author was compensated for serving as an expert witness in litigation relating to per- and polyfluorinated substance-contaminated drinking water.

Abstract
Objective
Excessive gestational weight gain (GWG) has been associated with autism spectrum disorder (ASD). This study sought to examine whether familial susceptibility for autism, intensity of ASD-related behaviors, or prepregnancy BMI influences the association of GWG with ASD-related behaviors.
Methods

Using data from the Early Autism Risk Longitudinal Investigation (EARLI) study (n = 136), a familial enriched cohort of mothers who had a previous child with ASD, and the Health Outcomes and Measures of the Environment (HOME) study (n = 253), a general population cohort, gestational age and prepregnancy BMI category-specific GWG z scores were calculated. Caregivers completed the Social Responsiveness Scale (SRS) to assess the presence and severity of ASD-related traits in children aged 3 to 8 years. Using quantile regression, the association between GWG z scores and ASD-related behaviors in children was estimated.

Results
In HOME, among mothers who had overweight or obesity prepregnancy BMI values, GWG z scores and SRS scores were positively associated in children with more ASD-related traits (higher SRS scores), but not in children with fewer ASD-related traits. Similar patterns were observed in EARLI among mothers with prepregnancy obesity.

Conclusions
GWG may be associated with autism-related behaviors among children who have a greater predisposition to these behaviors and who have mothers with prepregnancy overweight or obesity.

A new study by UC Davis MIND Institute researchers and others finds that an autism screening tool used widely in the U.S. and around the world is effective but has limitations. The findings highlight the need for providers to use their own judgment and be clear with parents about the limits of the tool, called the M-CHAT-R/F (Modified Checklist for Autism in Toddlers, Revised with Follow-Up).

The researchers analyzed more than a dozen studies of the screening tool from around the world, which included tens of thousands of children. Their work was published today in Pediatrics.

The M-CHAT-R/F is a tool commonly used by pediatricians to screen children for autism around the world. It includes a set of questions that providers ask parents or caregivers about their child’s development, and usually takes about five minutes to administer. If the child receives a positive screening result, a provider usually recommends further evaluation.

The team found that the tool commonly flagged children as positive for autistic traits, who, after a full assessment, did not receive an autism diagnosis, though most did have other developmental challenges. In addition, a significant portion of children who were flagged as negative for autistic traits were later diagnosed with autism.

“Although the M-CHAT-R/F has a clear role in autism screening, these results remind clinicians that a positive screen is not equivalent to an autism diagnosis,” said lead author Aishworiya Ramkumar, assistant professor in the Department of Pediatrics at the National University of Singapore. Ramkumar is also a former ITPND (International Training Program in Neurodevelopmental Disabilities) fellow at the MIND Institute.

“When clinicians counsel parents and caregivers after a positive screening they must be clear that the child still needs to have a definitive assessment.”

Study design and results
The meta-analysis included 15 studies, covering a total of 49,841 children from 10 countries. Studies took place between January 2014 and November 2021 and included standard scoring of the M-CHAT-R/F and a diagnostic assessment for autism following the screening result.

Among all children, the pooled predictive value, or accuracy of the M-CHAT-R/F at correctly identifying autism, was 57.7%. This means that there was a 57.7% chance of an autism diagnosis following a “positive” screen. The number varied when children were sorted into groups. For example, in children who had a higher likelihood of autism, such as those with an autistic sibling, the predictive value was 75.6%. Among children with no increased likelihood, the predictive value was 51.2%.

The overall negative predictive value was 72.5%. This means that nearly a quarter of those flagged as “negative” following screening received an autism diagnosis after further assessment.

Ramkumar emphasizes that providers should not view the screening tool as definitive.

“Clinical assessment is important, regardless of the M-CHAT-R/F results. It’s also critical to remember that not all children with autism have features in early childhood and instead, they may become apparent only later. A negative screening at a single point in time does not necessarily rule out autism,” she said.

The M-CHAT-R/F is the most common autism screening tool, but most previous studies have focused on or included earlier versions of it in their analysis.

What do the findings mean for health care providers?
The M-CHAT-R/F is a tool that is frequently used in pediatric offices at the 18- and 24-month well child visits,” said senior author on the paper Heidi Feldman, professor and chief of the Division of Developmental-Behavioral Pediatrics at Stanford University. “It is so important for clinicians to think carefully about the results of the screening test, to neither unnecessarily concern parents nor to inaccurately reassure parents.”

The authors all emphasize that individual provider judgment is key.

“I think the most important takeaway from this study is that the M-CHAT-R/F is a screening tool with limitations,” Ma explained. It has a role in screening for autism but is not meant to replace clinical judgment and comprehensive diagnostic assessment.”

Other study authors included Susan Stewart and Randi Hagerman of UC Davis.

Funding was provided by the National Institutes of Health (UL1 TR001860, P50HD103526) and the Health Resources and Services Administration (T77MC25733, T77MC09796).

A comprehensive study on sleep problems in children with autism revealed elevated rates of sleep disturbance within this population. Sleep problems are prevalent among children with autism, significantly affecting their quality of life and overall functioning.

Investigators led by Andrea Smith, PhD, RN, Sam Houston State University, sought to further expand the understanding related to sleep behavior in children.

Their study aimed to identify the subgroup of children with autism, aged 3–17 years who were referred for polysomnography and describe the types and frequency of clinical encounters for sleep problems observed in this population with and without the diagnosis of autism.

Evaluating Sleep Behaviors
The study utilized a secondary data analysis approach, drawing upon the de-identified Nationwide Children's Hospital Sleep DataBank. The database comprised encounters of children referred for polysomnography, a diagnostic test that records physiological variables during sleep.

The study sample consisted of 2838 unique participants, with an average age of 10.5 years, and a total of 172,167 encounters recorded between 2017-2019. Among the participants, 198 (7%) had been diagnosed with Autism Spectrum Disorder, Asperger's Syndrome, or Pervasive Developmental Disorder.

The analysis revealed several prevalent sleep problems across all participants, including apnea, snoring, non-specified sleep disorders like restless sleep, circadian rhythm disorder (CRD), and insomnia.

The study noted the subgroup of participants diagnosed with autism exhibited a higher frequency of various sleep problems compared with those without an autism diagnosis. Restless sleep, CRD, and insomnia were particularly prevalent among children with autism, indicating a specific association between autism and these sleep issues.

Researchers from the Hebrew University of Jerusalem have published a first-of-its-kind study revealing a potential future method for reducing the symptoms of autism among those diagnosed with the common developmental disorder.

Dr. Haitham Amal and his team from the School of Pharmacy in the Faculty of Medicine discovered a direct connection between levels of nitric oxide (NO) in the brain and autism, the university said in a statement.

The study, conducted on mice and published Monday in the peer-reviewed Advanced Science journal, demonstrates that autism indicators increases as NO increases in the brain, and that autism indicators and behavior decrease as the levels of NO in the brains of murine models of autism are lowered “in a proactive and controlled manner.”

Researchers from the Hebrew University of Jerusalem have published a first-of-its-kind study revealing a potential future method for reducing the symptoms of autism among those diagnosed with the common developmental disorder.

Dr. Haitham Amal and his team from the School of Pharmacy in the Faculty of Medicine discovered a direct connection between levels of nitric oxide (NO) in the brain and autism, the university said in a statement.

The study, conducted on mice and published Monday in the peer-reviewed Advanced Science journal, demonstrates that autism indicators increases as NO increases in the brain, and that autism indicators and behavior decrease as the levels of NO in the brains of murine models of autism are lowered “in a proactive and controlled manner.”

“This research is a significant breakthrough in autism research, with the first direct connection made between an increase in the concentration of NO in the brain and autistic behavior,” Amal said.

“Our research showed – in an extraordinary way – that inhibiting the production of NO, specifically in brain neuron cells in mouse models of autism, causes a decrease in autism-like symptoms,” he said. “By inhibiting the production of NO on laboratory animals, they became more ‘social’ and less repetitiveness was observed in their behavior. Additionally, the animals showed interest in new objects and were less anxious. Finally, the decrease in NO levels led to a significant improvement in neuronal indices.”

The study results were also based on tests conducted using human stem cells and clinical blood samples from children with low-functioning autism, the statement said.

“I am hopeful that with our new understanding of the NO mechanism, we can begin to develop therapeutic drugs and help millions of children and adults living with autism around the world,” he added.

According to Amal, the discovery could also have implications on the ties between NO and other neurological diseases, such as Alzheimer’s, or psychiatric diseases, including schizophrenia and bipolar disorder.

Researchers working to unlock the mysteries of autism report they have discovered differences among children when two in a family have the condition versus just one.

Scientists from Cold Spring Harbor Laboratory in New York have been researching the genetic origins of autism for two decades. Their discoveries have included thousands of genes that, when damaged, may cause a child to be born with an autism spectrum disorder.

They still couldn’t account for all cases, so they analyzed the genomes of more than 6,000 volunteer families.

The researchers discovered that in families that have two or more children with autism, the siblings shared more of their father’s genome -- the complete set of DNA.

Conversely, in families where only one sibling had autism, the children shared less of their father’s genome.

It’s not clear how the father’s genome has this impact.

Scientists had previously thought that siblings with autism shared more of their mother’s genome than their father’s.

One theory now is that some fathers may carry protective mutations that fail to get passed on.

It’s also possible that fathers may pass down mutations that trigger the mother’s immune system to attack the developing embryo, said co-author Ivan Iossifov, an associate professor at Cold Spring.

These theories may offer some hope for parents of children with autism and other neurological disorders like schizophrenia.

The research was published recently in Cell Genomics.

Researchers from Cold Spring Harbor Laboratory (CSHL) have recently revised the commonly held genetic assumptions about autism spectrum disorder (ASD).

For many years, scientists believed that siblings diagnosed with ASD tended to inherit more genetic traits from their mother than their father. However, Associate Professor Ivan Iossifov and Professor Michael Wigler from CSHL have demonstrated that it could often be the father who has a more significant genetic contribution in numerous instances.

Over the last two decades, CSHL scientists have led a multimillion-dollar effort to uncover the genetic origins of autism. They discovered thousands of genes that, when damaged, may cause a child to be born with ASD. But their work was not able to account for all cases of ASD. So Iossifov and Wigler set out to find the missing sources.

The duo analyzed the genomes of over 6,000 volunteer families. They found that in families that have two or more children with ASD, the siblings shared more of their father’s genome. Meanwhile, in families where only one sibling had ASD, the children shared less of their father’s genome. While the discovery reveals a new potential source of ASD, it also poses a provocative question. Could other disorders play by the same genetic rules?

No one is sure how dad’s genome makes its mark on children with ASD. But Iossifov has a couple of interesting ideas. He thinks some fathers may carry protective mutations that fail to get passed on. Or fathers may pass down mutations that trigger the mother’s immune system to attack the developing embryo. Both theories offer hope for parents of children with ASD and other neurological disorders like schizophrenia.

“Our future research is exciting,” Iossifov says. “If one of those theories or two of them prove to be true, then it opens different treatment strategies, which can, in the future, affect quite a lot of families.”

The study was funded by the Simons Center for Quantitative Biology, the Simons Foundation Autism Research Initiative, the Centers for Common Disease Genomics, the National Human Genome Research Institute, and the National Heart, Lung, and Blood Institute.

Autism scientists have long been on a quest to crack the condition’s sleep conundrum. Problems with falling and staying asleep are not typically considered a core trait of autism, but they are exceedingly common among autistic people and have compound effects: They can exacerbate a range of autism traits and are linked to greater difficulties with daily functioning.

But to track and assess what goes on in the body during sleep — historically at least — research participants have had to sleep in a lab, tucked up in a web of cumbersome equipment: The gold-standard approach, polysomnography, temporarily turns a sleeper into something resembling the prey of a giant electrical spider, bound in electrodes and wire leads that capture brain activity via electroencephalography (EEG), and breathing and body position, among other measures.

This scenario is uncomfortable enough for neurotypical people, never mind someone with autism who may also have anxiety and sensory, communication or behavioral difficulties, notes Beth Ann Malow, professor of neurology and pediatrics at Vanderbilt University in Nashville, Tennessee.

“The question is, are you really getting a valid night’s sleep [under those conditions]?”

Some study participants with autism may not be able to sleep at all, notes Thomas Frazier, professor of psychology at John Carroll University in University Heights, Ohio, as was the case when Frazier’s teenage autistic son went to a clinic for an overnight EEG study. “Getting good data and then scaling that up so you can actually use it in a real, meaningful way is tough,” he says.

To address the issue, multiple labs are working to deploy minimally invasive sleep-tracking devices — both “wearables” that someone puts on and “nearables” that take measurements from a distance. These devices tend to collect fewer types of data than polysomnography can, but their creators say they do enough to get the job done, tracking sleep stages and certain aspects of a sleeper’s physiology and brain activity.

Dreem sleep
During the day, our experiences accumulate in our memory, and at night, they are consolidated while we sleep. This consolidation is mediated by sleep spindles generated in the thalamus, slow waves that propagate from the cortex and ripples that radiate from the hippocampus, says Dimitrios Mylonas, instructor in psychology and a researcher in Dara Manoach’s lab at Massachusetts General Hospital in Boston. “You have a discussion between these different structures of the brain.”

Mylonas and his colleagues in the Manoach lab are eavesdropping on this conversation via the Dreem headband, which contains EEG sensors to track sleep architecture and an accelerometer to track a wearer’s respiration, head motion and head position. Their overarching goal is to spot where there’s miscommunication so they can correct it and maybe even ease core autism traits or improve cognition.

The crosstalk among sleep oscillations is disrupted in the brains of children with autism, according to a 2022 study Manoach and her team published in Sleep last year. By way of traditional polysomnography, they found altered spindles in the autistic children compared with their neurotypical peers, indicating some difference in the circuit that unites the thalamus and cortex. Now they plan to use the Dreem to dig deeper, and they have received funding from the Autism Science Foundation’s new profound autism grant and the Simons Foundation.

To start, they plan to use immediate feedback from the Dreem’s EEG readout to conduct the chorus of sleep oscillations by way of closed loop auditory stimulation. Such auditory stimulation accelerated slow oscillations in non-autistic people, and the magnitude of oscillation change correlated with memory improvements in the participants in one 2018 study.

The 2022 Sleep study set them on this path but was limited by a small sample size, Mylonas says.

Night watch
Smartwatches may also help researchers better understand the link between autism and sleep difficulties. The relationship has been widely reported, but its direction — whether poor sleep contributes to any autism-linked traits or vice versa — remains unclear, says Ilan Dinstein, associate professor of psychology at Ben-Gurion University of the Negev in Israel.

Smartwatch option: The EmbracePlus gives researchers access to the raw data it collects.
Past research has suggested that sleep is important for cognitive abilities. But when he and his colleagues ran a study of the relationship between autism traits and poor sleep in autistic children, they found that sensory sensitivities and irritability were more strongly tied to disturbed sleep than were cognitive ability or core autism traits. “I was really surprised by this,” Dinstein says.

The study assessed children’s sleep habits using parent reports, which are subjective measures, so Dinstein and his colleagues sought a more objective way to evaluate different sleep parameters.

They turned to actigraphy monitors — wearable devices, such as Fitbits, that track a person’s movements. The monitors are small and can be worn on a wrist or ankle, or even taped to another body part, making them ideal for continuously tracking movement and establishing a person’s circadian rhythms, Dinstein says. But standard actigraphy monitors can provide only a rough snapshot of sleep duration and awake periods; for example, they cannot reliably identify when a person first falls asleep, he says. “The limitation is that you could be inactive for multiple reasons, and not necessarily because you’re sleeping.”

Instead they adopted a newer actigraphy monitor that reports additional physiological data to more accurately determine whether a person is awake or asleep: The EmbracePlus smartwatch tracks a person’s movement, skin conductance, body temperature and heart rate, among other metrics, and provides the researchers with access to the device’s raw data.

They also plan to combine the actigraphy with another measure, such as EEG from the Dreem headband, to create an even fuller portrait of a person’s sleep behavior — and more akin to the data obtained in a traditional sleep study.

Making waves
Even in short studies on sleep, having participants wear EEG headbands was a challenge, says Dina Katabi, director of the Center for Wireless Networks and Mobile Computing at the Massachusetts Institute of Technology. “Without even knowing about it, they just rip it off their head while they sleep.”

But what if a sleep tracker didn’t even need to touch the body of the person it tracks? The Emerald, which mounts on a wall and resembles a wireless internet router, was born in Katabi’s lab to test that question. The device sends radio waves into the surrounding space and tracks how a person’s movements distort the waves’ return, not unlike how sonar maps what lies below a ship.

Unlike polysomnography, the Emerald does not create a real-time readout of someone’s brain activity, heart rate, motion or breathing. Instead, the device feeds its data through an artificial intelligence processing program trained on polysomnography data. The lab has validated the device in neurotypical people, and it can measure disease severity and medication responses in people with Parkinson’s disease, according to a pair of 2022 papers from Katabi’s lab that used the Emerald to track gait and nighttime breathing. The device can also track sleep and breathing in people with Rett syndrome, Katabi says, but those data are not yet published.

People with Rett syndrome tend to have trouble getting to sleep and staying asleep, and their breathing can be especially shallow, which leads to hyperventilation. They may also temporarily stop breathing — a phenomenon known as sleep apnea — and the Emerald can detect these changes in breathing, Katabi says.