The Autism studies/research thread

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Researchers at Rambam Medical Center in Haifa have identified a genetic mutation linked to a certain type of autism, developmental delays and movement disorders.

The mutation in the TBCB gene (Tubulin Folding Cofactor B), discovered by Dr. Sharon Bratman-Morag and Dr. Karin Weiss, is carried by one in 80 Ashkenazi Jews.

If both parents carry the gene, there is a 25 precent chance that their child could inherit the condition and show related symptoms.

The Health Ministry incorporated a screening test for the TBCB gene mutation as part of the national healthcare basket in November, making it accessible to all couples planning for pregnancy.

“The discovery can help families understand the risks to their pregnancies,” Bratman-Morg told The Times of Israel. “It also shows the increasing capabilities of genetic screening.”

What is autism spectrum disorder?
The causes of autism can be genetic. Israeli researchers, for example, have found gene mutations that might cause SHANK3 autism, a type of genetic autism that affects one million people worldwide. People with this autism may have delayed or absent speech, difficulties with social interaction, motor impairment and repetitive behaviors.

Environmental factors can also cause ASD. A study by Dr. Haitham Amal of the Hebrew University of Jerusalem found a link between nitric oxide, a compound in air pollution, and autism.

A recent study by Ben-Gurion University in the Negev, Clalit Healthcare and the Health Ministry found a significant increase in ASD in Israel, rising from 14,914 in 2017 to 32,222 in 2021.

This figure corresponds to significant increases in ASD around the world.

The Ashkenazi gene connection
Bratman-Morag, who is currently doing an internship in clinical genetics at Rambam, said that during her rotation at the Rambam Genetic Institute under Dr. Karin Weiss’s supervision six years ago, she and Weiss met a family of Ashkenazi Jewish origin.

Both of their children had mild cognitive impairment and ASD. They also had a movement disorder known medically as hereditary spastic paraparesis. This disorder affects the spinal cord and nerves, causing stiffness in the leg muscles and making walking and balancing difficult.

“We couldn’t find an explanation for their symptoms using regular genetic tests,” Bratman-Morag said.

The researchers used a special test that looks at the exome, a part of the DNA used for making proteins and where many genetic diseases originate.

“We found that both children had two copies of a faulty version of the TBCB gene,” she said. “We saw that both parents were carriers with one normal copy of the gene and one faulty copy.”

In a healthy body, the TBCB gene helps maintain a cell’s shape and supports its structure. However, mutations in the TBCB gene can disrupt how cells work in the brain, causing developmental and movement disorders.

“The TBCB gene had never been connected to any disease before,” Bratman-Morag said.

To understand further, the researchers teamed up with scientists at the Technion Faculty of Medicine.

At Prof. Daniel Kornitzer’s lab, the researchers used a yeast model. At Prof. Adi Salzberg’s lab, they used a fly model, in which they did gene editing using CRISPR, a tool that allows scientists to make precise changes in the structure of DNA.

Yeast and flies are often used in scientific experiments because they share some genetic similarities with humans.

“We also tested the two patients’ cells at Dr. Weiss’s lab,” Bratman-Morag said.

The experiments confirmed that the TBCB genetic mutation could lead to ASD and related disorders.

In non-Jewish populations, Bratman-Morag said, the occurrence of TBCB is 5:100,000.

In Ashkenazi Jews, the rate is 1:80. During their years of research, the researchers found eight more patients around the world with the same mutation.

“All of them are Ashkenazi Jews,” she said.

TBCB genetic testing in the national healthcare basket
In November, the Health Ministry began to include the TBCB gene testing in the national healthcare basket. It is accessible to all Israelis and not only Ashkenazi Jews.

“Nowadays in Israel, many people can’t really tell their exact origin,” she said. “This fact, and the fact that the cost of genetic tests is lower than previously, helped the ministry’s decision of one screening test for all.”

When two parents are carriers of the gene, Bratman-Morag said, “they have a one in four possibility of having a child with this syndrome.

Then, parents have options.

They can choose to have an abortion, she said, or to have in-vitro fertilization with genetic screening, in which only embryos without two abnormal copies of the TBCB gene are put into the uterus.

The third option is to keep the pregnancy, she said.

A year after the child is born, she said, parents will be able to see if their child has difficulty with motor development.

In that case, “they can give the child physiotherapy at an early age and help them develop,” Bratman-Morag said.

The illness “causes them difficulties with walking, but they can learn to live with that,” she said.

To this end, a team of researchers from the United States of America has developed an advanced screening model to identify toddlers with autism from underserved areas. Their model holds the potential for accessible diagnosis for toddlers from culturally and linguistically diverse backgrounds.

However, there is a lack of valid ASD screening measures, particularly among the under-resourced and culturally and linguistically diverse (CLD) communities. Physical barriers like distance, combined with social and cultural barrier, often delay in screening, negatively impacting the neurodevelopment of toddlers. Researchers are now focusing on the development of tools that can help in early diagnosis, along with training the primary care (PC) and early intervention (EI) providers.

Advancing research, a team of researchers led by Dr. Roula Choueiri from the Kennedy Krieger Institute, USA, developed a new, interactive screening model called the Rapid Interactive Screening Test for Autism in Toddlers (RITA-T). The developed model offers precise and quick diagnosis for kids between the age of 18 to 36 months. It can help PC and EI providers in the diagnosis of high-risk toddlers and help family members with important information and referrals. This study, published in Pediatric Investigation on September 27, 2024, explores the potential of RITA-T to improve early identification of high-risk toddlers from underserved areas. Explaining more about the study, Dr. Choueiri says, “For our study, we compared the demographic and socioeconomic traits of two groups of toddlers diagnosed with ASD. One group underwent the RITA-T screening and the other did not.”

Over the course of a 14-month long study, the team trained EI providers and assisted PC providers in implementing the RITA-T model in their practice. PC providers used the RITA-T alongside the standard Modified Checklist for Autism in Toddlers, revised with follow-up (MCHAT-R/F). These cases were then recommended to specific urban tertiary care centers called the Autism-R diagnosis clinic. For the group that did not perform RITA-T screening, the MCHAT-R score and a parent-completed questionnaire were necessary and these patients were recommended to standard Autism-S clinic.

In both the groups, toddlers underwent 90-minute diagnostic evaluations conducted at these centers by neurodevelopmental pediatricians or neurology nurse practitioners. The team of researchers then assessed demographic and socioeconomic factors, including gender, race, ethnicity, travel time, and wait times for diagnosis. Some statistical tests were performed to compare the data collected from the two groups.

The findings revealed interesting insights into the demographic and socioeconomic characteristics. While the gender and age of the toddlers belonging to both the groups were similar, there was a significant difference in travel time and wait time. Toddlers in the RITA-T group traveled longer distances for their evaluations but shorter wait times from referral to appointment.

The study also considered the Area of Deprivation Index (ADI), which combines socioeconomic indicators like income, education, employment, housing, and transportation, to identify areas with high levels of deprivation. The ADI score for toddlers referred to through the RITA-T system was high, indicating that they come from neighborhoods with deprived socioeconomic conditions. Additionally, households in the RITA-T group had lower incomes compared to the non-RITA-T group.

These findings support the success of the RITA-T screening approach. Since the PC questionnaire was not mandatory for RITA-T-based screening, the diagnosis became easily-accessible for families, who are not conversant with English as a language. It also allowed screening of patients staying further away from urban centers. Maria DeMeo, a pediatric nurse practitioner at Boston Children’s Hospital and a member of the research team, mentions, “More patient referrals during the study period may have resulted from the RITA-T method’s ability to streamline and expedite the entire screening process.”

While these findings are significant, this observational study included more patients screened via RITA-T model, which led to comparison between two unbalanced group sizes. Also, the data regarding the race and ethnicity of the patients was not very clear. However, the participating EI and PC practitioners agreed that using the RITA-T model and integrating it into their programs was easy. Sharing his concluding thoughts with us, Dr. Choueiri says, “The model definitely improves wait time and access to diagnostic services. It also reduces the burden of excessive paperwork, making it easier for family members.”

A new study published in the Journal of Attention Disorders has revealed key factors linked to maladaptive daydreaming in neurodivergent adults. Emotional dysregulation, internalized stigma, escapism, and self-esteem emerged as significant predictors, varying across individuals with autism spectrum disorder, ADHD, and both diagnoses. These findings offer insights into how neurodivergent individuals use vivid daydreaming as a coping mechanism for emotional and social challenges.

Maladaptive daydreaming is a condition in which individuals engage in excessive, vivid, and immersive fantasies that interfere with their ability to function in daily life. Unlike ordinary daydreaming, which is often brief and inconsequential, maladaptive daydreaming is characterized by a loss of control, where individuals feel compelled to spend hours absorbed in their imagined worlds. This behavior frequently disrupts important activities, such as work or relationships, and can cause significant distress.

Maladaptive daydreaming is a relatively new and understudied area of research, although it is gaining more recognition among researchers and the general population, especially online,” said study author Anna Pyszkowska of the University of Silesia in Katowice.

“There is some research about maladaptive daydreaming and its correlations with autistic or ADHD traits, but no study has investigated these aspects simultaneously. We wanted to see if there are significant differences in maladaptive daydreaming rates in these populations. Additionally, we wanted to examine whether individuals on the autism spectrum, with ADHD, or with AuDHD vary in how they experience maladaptive daydreaming, including whether there are different predictors.”

The researchers conducted their study by recruiting participants who had been formally diagnosed with autism spectrum disorder, ADHD, or both conditions. Participants were primarily recruited online through neurodivergent advocacy groups and mental health clinics in Poland. The sample included 139 individuals with ADHD, 74 with autism, and 80 with both diagnoses.

The study found that maladaptive daydreaming was similarly prevalent across all three groups, with 37% to 46% of participants meeting the criteria. However, the key factors contributing to the condition varied among the groups.

Emotional dysregulation emerged as a significant predictor of maladaptive daydreaming, particularly for individuals with autism. Difficulties in identifying and managing emotions were strongly linked to excessive daydreaming in this group, suggesting that daydreaming may serve as a coping mechanism for emotional challenges.

contrast, among participants with ADHD, only certain aspects of emotional dysregulation, such as difficulty accepting emotional responses, predicted maladaptive daydreaming. This finding indicates that the role of emotional dysregulation differs based on the neurodevelopmental condition.

Escapism, particularly self-suppression escapism, was another consistent predictor of maladaptive daydreaming across all groups. This supports the idea that maladaptive daydreaming functions as a way to avoid negative emotions or difficult realities.

Internalized stigma, including feelings of alienation and social withdrawal due to societal judgment, was strongly associated with maladaptive daydreaming, especially among individuals with autism. These findings highlight the social and emotional burdens faced by neurodivergent individuals, which may drive them to retreat into fantasy worlds.

In terms of self-esteem, low self-competence was linked to maladaptive daydreaming in individuals with autism, while higher self-liking predicted lower levels of daydreaming in participants with ADHD.

Interestingly, while ADHD symptoms were more strongly associated with maladaptive daydreaming than autistic traits, individuals with both diagnoses displayed unique patterns. These participants exhibited higher levels of emotional dysregulation, internalized stigma, and self-suppression escapism compared to those with only ADHD or autism. This suggests that the interplay of symptoms from both conditions exacerbates the factors contributing to maladaptive daydreaming.

“The key takeaway is that maladaptive daydreaming is, in fact, associated with attention and emotion dysregulations, and can also be considered as one’s way of escaping from an unpleasant reality,” Pyszkowska told PsyPost. “The latter is additionally important in the neuroatypical population as they often experience stigma and discrimination that may lead to internalized stigma: a situation when you accept and internalize negative stereotypes about yourself and apply them to your own self-perception.”


“Our research showed that the more internalized stigma and dysregulation you experience, the more you want to escape from this reality into your daydreams. Interestingly, there were differences in predictions of maladaptive daydreaming in our three populations studied which showed that it is important to investigate these topics in complex ways.”

However, as with all research, there are some limitations. The sample size was relatively small, especially for the autism-only group, and participants were recruited online, which may have introduced bias. “The sample in this study may be biased as the invitation informed participants that the study was investigating daydreaming in the neurodivergent population,” Pyszkowska noted. “This may have led to the overrepresentation of maladaptive daydreamers, as the topic attracted their attention.”

Future research could address these limitations by including larger and more diverse samples. Further investigation into the content and functions of daydreaming, particularly how it varies across neurodivergent populations, would also provide deeper insights. Exploring potential interventions, such as emotion regulation training or stigma reduction programs, could help individuals manage maladaptive daydreaming more effectively.