The Autism studies/research thread

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Background and Objective
The theory of complexity loss in neurodivergent brain is widely acknowledged. However, the findings of autism research do not seem to align well with this theory. We aim to investigate the brain complexity in children with ASD (Autism Spectrum Disorders) compared with the TD (Typical Developed) children in sleeping state.

Method
42 ASD children and 42 TD children were imaged using sleep-state functional magnetic resonance imaging (ss-fMRI), and brain complexity was analyzed by employing sample entropy (SampEn) and transfer entropy (TE). For the ASD group, we also investigated the relationship of symptom severity with SampEn and with TE.

Results
In compared with TD group, ASD group showed significant increased SampEn in the right inferior frontal gyrus. However, in the group of TD, 13 pairs of brain regions exhibit higher TE compared to the ASD group. In the ASD group, the TE of 5 pairs of brain regions is higher than in the TD group.

Conclusion
This sleeping-state fMRI study provide evidence that ASD children exhibited aberrant brain complexity in compare with the TD children. The complexity of the autistic brain is composed of aberrant randomness in brain activity and anomalous information transmission between brain regions. We believe that brain complexity in ASD is a highly valuable area of research. Differences in the entropy of local brain regions, as well as in the transfer entropy between brain regions, may be related to the brain complexity observed in children with ASD.

The majority of people will, at some point, experience a traumatic event, but only 3.9-5.6% will develop a post-traumatic stress disorder, or PTSD (WHO, 2024).

In autistic people, PTSD may be especially pronounced through maladaptive coping and traumatic memories. Autistic individuals tend to exhibit high avoidance coping, attentional bias towards threatening stimuli, and other autism-associated characteristics or tendencies that, despite being precursors of PTSD, are often dismissed as a ‘normal’ part of ASD (Ehlers & Clark, 2000; Lage et al., 2024).

This can lead to a ‘diagnostic overshadowing’ bias, which means that the PTSD-related challenges and unique features of PTSD in autistic people go unrecognised. Quinton and colleagues (2024) from King’s College London bring this bias into the spotlight in their review of the methods of PTSD assessment and the core symptoms of PTSD in autism.

A new meta-analysis from a Chinese team adds weight to the idea that maternal diabetes can increase the risk of autism and other neurodevelopmental disorders. The study found that when pregnant women have diabetes their children are 28% more likely to be later diagnosed with a neurodevelopmental disorder. The risk of autism, in particular, was 25% higher.

The study was published in Lancet Diabetes & Endocrinology. The lead author is Wenrui Ye, PhD, of Xiangya Hospital, Central South University, in Hunan. This is just the latest report to show a connection between maternal diabetes and neurodevelopmental disorders.

This Chinese meta-analysis of 202 studies included data from more than 56 million mother-child pairs. The team searched PubMed, Web of Science, Embase, and EBSCO databases from inception to Dec 1, 2024, for studies exploring neurodevelopmental outcomes of children born to mothers with diabetes. The primary outcome was neurodevelopmental disorders, per the Diagnostic and Statistical Manual of Mental Disorders.

The study found children exposed to maternal diabetes had a higher risk of any neurodevelopmental disorder, including ASD, attention-deficit hyperactivity disorder, intellectual disability, specific developmental disorders, communication disorder, motor disorder, and learning disorder, compared with unexposed children. Maternal pre-gestational diabetes was more strongly associated with the risk of most neurodevelopmental disorders in children than gestational diabetes.

The risk was 30% higher for attention deficit hyperactivity disorder, 32% higher for intellectual disability, 20% higher for trouble with communication, 17% higher for movement issues, and 16% higher for learning disorders in children whose mothers had gestational diabetes. The researchers also found that having diabetes before pregnancy is linked with a 39% higher risk for one or more of those neurodevelopmental disorders.

A study led by Rutgers University-New Brunswick researchers suggests that tiny facial movements – too slight for the human eye to notice – could help scientists better understand social communication in people with autism.

Published in Frontiers in Psychiatry, the study found that while individuals with autism express emotions like everyone else, their facial expressions may be too subtle for the human eye to detect.

Autistic individuals use the same basic facial movements to express emotions, but their intensity often falls outside the culturally familiar range that most people recognize,” said Elizabeth Torres, a psychology professor at the Rutgers School of Arts and Sciences.

“This disconnect can lead to missed social cues, causing others to overlook or misinterpret their emotions.”

The researchers said individuals on the autism spectrum – especially those who cannot speak or require significant support for movement – also may have more unpredictable and varied facial expressions, making it more difficult for doctors and caregivers to recognize their emotional cues.

As a result, some may mistakenly assume these individuals aren’t trying to communicate at all.

“But that’s not the case,” said Torres, a computational neuroscientist with more than 17 years of experience working with individuals with autism.

“Their emotions and social signals are there – we just haven’t been able to see them properly. This research could help bridge that gap, fostering a better understanding between autistic and nonautistic individuals.”

This unintentional disconnect can contribute to social isolation and misunderstandings about autistic behavior, she added.

The study, led by Torres and her team at the Rutgers Sensory Motor Integration Lab, used a novel data type she developed called micromovement spikes.

This method captures microscopic facial movements using statistical techniques developed by Torres and nonlinear dynamics methods developed by Theodoros Bermperidis, a postdoctoral associate.

By recording short, five-to-six-second videos on smartphones or tablets, researchers tracked facial micromovements that typically go unnoticed.

“We wanted to investigate whether brief microexpressions appeared during common emotional expressions, like smiling or showing surprise,” Torres said.

“Our goal was to uncover what was really happening beneath the surface when expressions go unnoticed.”

The research team developed an app to guide participants through four stages: practicing video capture, recording a resting face, smiling and making a surprised face. Data was collected in various settings, including schools, therapy gyms and social events, with some participants submitting videos from home.

The study analyzed data from 126 participants, including 55 nonspeaking individuals who communicate by typing. Researchers found that while there were differences in facial micro-movements between autistic and neurotypical individuals – varying by age and sex – the facial muscles responsible for emotional expression were active in both groups.

Torres noted the key difference was in the intensity of these expressions.

“The challenge isn’t a lack of expression – it’s that their intensity falls outside what neurotypical individuals are accustomed to perceiving,” she said.

“This means we are quite literally missing each other’s social cues.”

The implications of this research are far-reaching, said Torres, who also created a mobile application to screen, diagnose and track nervous system disorders. As the chief scientific officer of NeuroInversa LLC, a Rutgers spinoff company co-founded with Chris Dudick, she works on using technology to monitor treatment effectiveness over time.

She said this study challenges common misconceptions about autism and introduces a scalable method for understanding social interactions in autistic individuals.

“This research gives us a powerful tool to expand autism studies beyond simply detecting differences,” Torres said.

“Now, we can work toward bridging the gap—helping neurotypical individuals recognize different expressions of emotion and fostering better social understanding.”

The researchers said their findings could lead to improved diagnostic methods and new ways to support communication between autistic and nonautistic individuals.

By using accessible tools such as smartphone cameras powered by AI, this study paves the way for more inclusive and real-world autism research, Torres added.

Study co-authors included Bermperidis; former and current doctoral students Richa Rai and Joe Vero; and Neel Drain, a student at Robert Wood Johnson Medical School.

Funding: The research was funded by the Nancy Lurie Marks Family Foundation.

What causes autism? Studies with twins show that there is a genetic connection—if one twin has autism, the other twin is more likely to have it as well.

Something else is acting in concert with genes to encourage autism. One of those things is an infection of the mother during pregnancy. Getting measles during pregnancy, for instance, increases the odds of autism. Maternal health issues like obesity and diabetes also increase the odds.

Intriguingly, new research points to the gut-brain axis as another factor. There is also more than one kind of autism, as reflected in the term autism spectrum disorder (ASD). Moreover, each type of autism may have a different cause. As autistic poet Karla Culbertson puts it, "Autism is like a fingerprint, no two are alike."

It’s worth noting that Robert F. Kennedy, the new Secretary of Health and Human Services, disagrees with this research. Along with his friend Andrew Wakefield, he feels that autism is caused by vaccines. RFK’s antipathy to vaccines means that more people are getting measles, which ironically could increase the rate of autism.

The microbial connection
Several new studies show an interesting connection with microbes in the mouth and gut. According to Kathy Kar-man Shum of the University of Hong Kong, there is a microbial “fingerprint” of autism in the mouth microbiome. By analyzing oral microbes, researchers can predict whether or not a child will develop autism with 80 percent accuracy. That’s important for early identification and intervention, when therapy is most effective. A simple oral swab during a regular dental exam might provide an effective early warning.

There is another weird connection to inflammation: For some kids, autistic symptoms fade with a fever. Studies with autistic mice have shown that this weird behavior is related to cytokines, molecules that the immune system uses to sound the alarm of inflammation. The cytokine of interest is called IL-17, and it demonstrates the mind-boggling complexity of nature. Although IL-17 is secreted by immune cells, it also seems to act as a neurotransmitter.

That explains how this immune response can affect the brain. There is a small patch of nerve cells on the surface of the brain that is involved in social behavior. If a mouse has the type of autism caused by maternal illness, IL-17 acts as a neurotransmitter, affecting that altered brain patch and causing the mouse to behave normally, with less repetitive behavior and more adventure-seeking.

How did the researchers cause IL-17 to kick into action? They injected pieces of dead bacteria called LPS, mimicking the action of gut pathogens.

Gut-brain studies
John Cryan and Ted Dinan of University College Cork in Ireland have published widely on a mouse model of autism and have found specific populations of gut bacteria that characterize autism. They have also found microbes that ameliorate symptoms, including Blautia stercoris. (Full disclosure, I wrote a book with Cryan and Dinan called The Psychobiotic Revolution from National Geographic.) Cryan says, “There seems to be something about the social brain in particular that makes it sensitive to signals from the microbiome.”

It’s not just mice. There is a gut microbe signature of autism in humans as well. Autistic children have lower levels of Veillonella, Coprococcus, and Prevotella. These microbes can produce GABA and serotonin, two neurotransmitters that may reduce agitation in autistic people.

A new study by Emeran Mayer, Lisa Aziz-Zadeh, and colleagues at USC and UCLA looked at tryptophan—a precursor to serotonin—produced by gut microbes. They found that children with autism had significantly lower tryptophan levels in their guts than the control group. That was associated with altered brain patterns and an increase in autism severity.

This shows a correlation between gut microbes and autistic behavior. But does that mean that microbes actually cause this behavior?

Finding causality
Studies by Sarkis Mazmanian and colleagues at Cal Tech provide some strong evidence for causality. They took stool samples from autistic and non-autistic people and transferred them to mice. The mice that received the autistic poop started to engage in anti-social and repetitive behaviors, while the control mice acted normally. That is as close to showing causality as biology can come right now.

Autistic kids often stick to a diet of their own devising, whether it is healthy or not. In fact, their abnormal gut microbes may affect their cravings, making it difficult to change. Prebiotics and probiotics may help. A study by Rosa Krajmalnik-Brown and colleagues at Arizona State University found that changing the microbiome with probiotics reduced gastric distress and lowered autism scores by almost 50 percent. That’s a remarkable result and points to future therapies.

Abstract
DDX3X is an X-linked RNA helicase that escapes X chromosome inactivation and is expressed at higher levels in female brains. Mutations in DDX3X are associated with intellectual disability (ID) and autism spectrum disorder (ASD) and are predominantly identified in females (DDX3X syndrome). Using cellular and mouse models, we show that Ddx3x mediates sexual dimorphisms in brain development at a molecular, cellular, and behavioral level. During cortical neuronal development, Ddx3x sustains a female-biased signature of enhanced ribosomal biogenesis and mRNA metabolism. Compared to male neurons, female neurons display larger nucleoli, higher expression of a set of ribosomal proteins, and a higher cytoplasm-to-nucleus ratio of ribosomal RNA. All these sex dimorphisms are obliterated by %Ddx3x loss. Ddx3x regulates dendritic arborization complexity in a sex- and dose-dependent manner in both female and male neurons. Ddx3x modulates the development of dendritic spines but only in female neurons. Further, ablating Ddx3x conditionally in forebrain neurons is sufficient to yield sex-specific changes in developmental outcomes and motor function. Together, these findings pose Ddx3x as a mediator of sexual differentiation during neurodevelopment and open new avenues to understand sex differences in health and disease.

The development of a group of mental disorders, ranging from attention-deficit/hyperactivity disorder to schizophrenia, have been linked to vitamin D deficiencies in newborn babies, a new study found. The research, led by Australian professor John McGrath from the University of Queensland’s Brain Institute, examined the vitamin D status of more than 70,000 people in a population study and was published in the June issue of the peer-reviewed journal The Lancet Psychiatry.

Vitamin D is important for a baby’s brain development, and low vitamin D levels are common in pregnant women across the globe,” McGrath said in a May 15 news release from the University of Queensland. “This is why many countries recommended the use of vitamin D supplements during pregnancy.” The vitamin comes most often from sun exposure but is also present in some food and dietary supplements, researchers said. Previous research linked neonatal, or newborn, vitamin d deficiencies with increased risk of developing schizophrenia, according to the study, but there was a gap in examining other mental disorders commonly diagnosed in childhood.

The Study
Using national health registers in Denmark between 1981 and 2005, the research team looked for individuals diagnosed with at least one of six disorders: major depressive disorder, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and anorexia nervosa, according to the study. The cohort was pulled from the entire population of Denmark born during that time frame, researchers said, all of whom underwent a routine screening test at birth that collected dried blood spots.

These blood spots were then tested for 25(OH)D, or the primary form of vitamin D that circulates in the blood and helps regulate calcium and phosphate levels within the body, according to the study. When the researchers compared the vitamin D levels of those who had developed the mental disorders included in the study, they found a link.

The Findings
Those with lower levels of vitamin D immediately after birth had an increased risk of developing schizophrenia, supporting what had been suspected in previous research, according to the study. But the cohort also revealed links with other conditions. Higher concentrations of vitamin D were associated with decreased risk of autism spectrum disorder and ADHD, according to the study. On the other side of the spectrum, vitamin D deficiency seemed to act as a protective factor against anorexia nervosa, an eating disorder, researchers said. “Risk factors traditionally linked to increased risks of schizophrenia, ADHD and ASD, such as lower intelligence and worse school performance, and childhood adversities, are paradoxically protective for anorexia nervosa,” according to the study. The research team noted one vitamin is likely not the only factor impacting the development of these mental disorders, as genetics and behavior of the mother also impact early childhood development, but something as simple as a prenatal vitamin may help decrease the risk.

Similar to how folate supplements are recommended during pregnancy to prevent spina bifida, our research suggests that optimizing vitamin D levels in early life may reduce the risk of several neurodevelopmental disorders,” McGrath said in the release. The findings were part of a larger study founded in 2012, known as iPSYCH, designed to investigate mental disorders in Denmark, according to the study.

Males are more than four times more likely to receive an autism diagnosis than females. But a new study by researchers at UC San Diego School of Medicine has found no clinical differences in autistic traits between the sexes in toddlers when they are first diagnosed with autism. The study was published in Nature Human Behavior on May 26, 2025. The findings have potential implications for early diagnosis and intervention for autistic children.

Between 2002 and 2022, the researchers assessed more than 2,500 male and female toddlers between 12 and 48 months of age. Of these toddlers, 1,500 were autistic, 600 were typically-developing, and 475 were developmentally delayed. The assessments included 19 different measures of language development, social and motor skills, core autism traits such as repetitive behaviors, cognitive skills, and other developmental characteristics. The study also examined social attention using eye tracking technology. All assessments were conducted at a single site — the UC San Diego Autism Center of Excellence — by licensed clinical psychologists.

The researchers found:

No clinical differences between male and female autistic toddlers on all but one of the metrics. The sole exception was a measure of daily living skill development based on parent reporting, such as getting dressed and feeding themselves, which females scored just slightly higher on than males.

When clustered into low, medium and high-ability subtypes across the autism spectrum based on robust state-of-the-art methods, there were also no major clinical differences between males and females within these subtypes.

No clinical differences between the sexes between 12 and 48 months when the researchers followed the trajectory of development in autistic toddlers over time.
Few sex differences between developmentally delayed toddlers.

“ There is no consensus in the field about whether females are more or less impacted than males, and that is probably because there haven't been really large-scale studies at the earliest ages."
Karen Pierce, Ph.D.

A number of previous studies with fewer than 100 participants each have shown differences between the sexes in autistic toddlers. However, the current study is the largest and most comprehensive of its kind to date, and one of very few studies to assess children with autism at a very early age, according to senior author Karen Pierce, Ph.D., professor of neurosciences and  director of the Autism Center of Excellence at UC San Diego School of Medicine.

“ There is no consensus in the field about whether females are more or less impacted than males, and that is probably because there haven't been really large-scale studies at the earliest ages,” said Pierce. “ Based on previous small studies, we had anticipated there would be some sex differences. So we were a little bit surprised to find nothing at all.”

The researchers did, however, find sex differences between typically developing female and male toddlers, with females performing at significantly higher levels than males on more than half of the tests, especially those measuring social skills, language development, and daily living skills.

“This is consistent with the literature; female toddlers seem to develop slightly faster than males in terms of their language ability and their social ability and how well they perform daily living skills — adaptive things for a two-year-old,” said Pierce. “Typically developing females are accelerated in their development relative to males.”

Pierce says the findings for autistic children of no clinical differences between males and females at the time of first onset of autism lead to two possible conclusions.

“One is that previous studies that report sex differences are wrong, perhaps due to small sample size, sampling bias, limited study measures, or other methodological issues,” she said. “An alternative conclusion is that sex differences do not exist at the time of first onset, but instead emerge slowly at later ages, driven by psychosocial factors like socialization or differences in biology that may unfold across development.”

To examine this alternative possibility, a high-quality, large-scale study that tracks autistic children from toddlerhood through school age and beyond would be required, according to Pierce.

Autism is highly heritable, and Pierce says the findings have implications for understanding the development of the condition, enhancing early detection, and improving early intervention. Because the study found that toddlers with autism clustered into scientifically robust subtypes within the autism spectrum rather than by sex, she thinks it may be preferable to focus on these differences instead when seeking to understand clinical heterogeneity and the most appropriate interventions for each subtype, for example.

“ If you can improve a toddler's language and communication at the youngest ages possible, then they're going to get their needs met better, and they're going to be able to contribute to society more effectively, because they can do whatever it is that they love to do,” said Pierce. “It's really about having every child reach their full potential.”

The study was funded, in part, by National Institutes of Mental Health

Autism spectrum disorder (ASD) is linked to a fourfold increased risk for early-onset Parkinson’s disease (PD), results from the largest, population-based cohort study of its kind to date showed.

The findings indicated “that there can be shared biological drivers behind ASD and Parkinson’s disease,” study investigator, Weiyao Yin, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, said in a release.

“One hypothesis is that the brain’s dopamine system is affected in both cases, since the neurotransmitter dopamine plays an important part in social behavior and motion control,” Yin added.

The study was published online on May 27 in JAMA Neurology.

A Plausible Link
Recent research pointed to a plausible biological link between ASD and PD. However, large, longitudinal studies investigating the risk for PD following an ASD diagnosis are scarce, the researchers noted.

Our study is the first population-based study, to our knowledge, using prospectively collected data, longitudinal design, and life-course approach to strengthen the inference,” they wrote.

PD, defined as a first-ever diagnosis of PD or other idiopathic or degenerative parkinsonian disorders, was identified in 438 individuals without ASD (0.02%; 1.3 cases per 100,000 person-years) and in 24 individuals with ASD (0.05%; 3.9 cases per 100,000 person-years), corresponding to a relative risk (RR) of 4.43.

Depression and antidepressant use were present in 46.7% of individuals with ASD, and antipsychotic use, which can cause Parkinson-like symptoms, was present in 31.5%.

A study published in 2023 revealed there's a difference in how children with autism or ADHD clear the common plastic compound bisphenol A (BPA), compared to neurotypical children.
Researchers from Rowan University and Rutgers University in the US looked at three groups of children: 66 with autism, 46 with ADHD, and 37 neurotypical kids. In particular, they analyzed the process of glucuronidation, a chemical process the body uses to clear out toxins within the blood through urine.

They found that kids with ASD and ADHD couldn't clear out BPA and another similar compound called diethylhexyl phthalate (DEHP) with as much efficiency as other kids, potentially leading to longer exposure to their toxic effects.
"Detoxification of these two plasticizers is compromised in children with ASD and ADHD," wrote the researchers in their published paper. "Consequently, their tissues are more exposed to these two plasticizers."

It was only in the case of BPA that the difference was statistically significant though: the efficiency was reduced by about 11 percent for kids with ASD and 17 percent for kids with ADHD, compared with the control group of children.

The researchers think that gene mutations in certain individuals mean that BPA can't be cleared as well as it needs to be, which means the substance sticks around in the body. That potentially could cause damage in terms of neuron development and operation.