Two distinct neurodevelopmental abnormalities that arise just weeks after the start of brain development have been associated with the emergence of autism spectrum disorder, according to a new Yale-led study in which researchers developed brain organoids from the stem cells of boys diagnosed with the disorder.

And, researchers say, the specific abnormalities seem to be dictated by the size of the child’s brain, a finding that could help doctors and researchers to diagnosis and treat autism in the future.

The findings were published Aug. 10 in the journal Nature Neuroscience.

“It’s amazing that children with the same symptoms end up with two distinct forms of altered neural networks,” said Dr. Flora Vaccarino, the Harris Professor in the Child Study Center at Yale School of Medicine and co-senior author of the paper.

Using stem cells collected from 13 boys diagnosed with autism — including eight boys with macrocephaly, a condition in which the head is enlarged — a Yale team created brain organoids (small, three-dimensional replicas of the developing brain) in a lab dish that mimic neuronal growth in the fetus. They then compared brain development of these affected children with their fathers. (Patients were recruited from clinician colleagues at the Yale Child Study Center, which conducts research, service, and training to improve understanding of health issues facing children and their families.)

The study was co-led by Alexandre Jourdon, Feinan Wu, and Jessica Mariani, all from Vaccarino’s lab at the Yale School of Medicine.

About 20% of autism cases involve individuals with macrocephaly, a condition in which a child’s head size is in the 90^th percentile or greater at birth. Among autism cases these tend to be more severe.

Intriguingly, the researchers found that children with autism and macrocephaly exhibited excessive growth of excitatory neurons compared with their fathers while organoids of other children with autism showed a deficit of the same type of neurons.

The ability to track the growth of specific types of neurons could help doctors diagnose autism, symptoms of which generally appear 18 to 24 months after birth, the authors say.

The findings may also help identify autism cases that might benefit from existing drugs designed to ameliorate symptoms of disorders marked by excessive excitatory neuron activity, such as epilepsy, Vaccarino said. Autism patients with macrocephaly might benefit from such drugs while those without enlarged brains may not, she said.

Creating biobanks of patient-derived stem cells could be essential to tailor therapeutics to specific individuals, or personalized medicine.

Infographic: Study calls for mental health support to reduce the risks of self-harm and suicide in autistic individuals CREDIT ICES

Autistic females (assigned sex at birth) have an 83% increased risk of self-harm leading to emergency healthcare relative to non-autistic people, according to a new study from ICES and the Centre for Addiction and Mental Health (CAMH).

Autistic males also had a 47% greater risk of self-harm events and had the highest incidence of suicide death compared to autistic females and non-autistic individuals.

The study, “Self-Harm Events and Suicide Deaths Among Autistic Individuals in Ontario, Canada,” was published today in JAMA Network Open and is the first in Canada to explore suicide rates and self-harm events in autistic versus non-autistic individuals factoring sex, sociodemographic and clinical risk factors.

“The presence of psychiatric illnesses substantially accounts for these increased risks,” says lead author Meng-Chuan Lai, staff psychiatrist and senior scientist at CAMH. “We know that many self-harm and suicide-related events could be prevented when people have access to tailored mental health supports and services, and this is crucial for autistic people.”

The study included cohorts of 379,630 and 334,690 individuals in Ontario, Canada to understand the incidence of self-harm events and suicide death, respectively. Autistic and non-autistic individuals were followed for self-harm events that resulted in emergency care (from 2005 to 2020) and death by suicide (from 1993 to 2018).

Study findings show:

• There were significantly more self-harm events leading to emergency healthcare in autistic compared to non-autistic people, across both males (47% increased risk) and females (83% increased risk), after adjusting for neighbourhood income and urban/rural status, intellectual disabilities, and psychiatric diagnoses.
• Although both autistic females and males showed higher incidence of suicide death than non-autistic females and males, these increased suicide death risks in both sexes were explained by the presence of psychiatric diagnoses.

“In my twenties, I accessed the emergency room a number of times seeking help for suicidal thoughts and ideations. During that time, I struggled with accessing mental health counselling and support in my city that didn’t have at least a six-month-long waiting list or were affordable, and I waited a over a year to access a psychiatrist,” says Megan Pilatzke, an advocate and autistic woman.

“This is a wake-up call,” says Yona Lunsky, Adjunct Scientist at ICES and Director of the Azrieli Adult Neurodevelopmental Centre at CAMH. “As mental health providers, we need to do more in terms of mental health promotion, and we have to work together with autistic people and their families to make sure that timely mental health supports are accessible, and adapted to meet their needs.”

”Autistic people are continually forced to mask and hide who we are to accommodate a world that generally does not accept our traits,” says Megan. “I want people to understand that autistic people are struggling because our needs are just not being met throughout society.”

“Our healthcare system should take a two-pronged approach to support autistic people,” says Lai: “Enhancing access to mental health services, and autism-informed accommodations for those services. For example, we can support autistic individuals who come into the healthcare settings by offering calming spaces, providing maximal predictability possible, understanding their communication styles and preferences, meeting their sensory needs, and supporting them if they wish to come accompanied by a person they trust.”

The CAMH Azrieli Adult Neurodevelopmental Centre offers resources and tools aimed at individuals, their families, and clinicians to support the mental health of autistic people.

One limitation of the study is that the number of autistic individuals may be underestimated, because individuals who had yet to receive a formal diagnosis, or whose diagnosis was made by private practice psychologists may not have been included. Autistic people could have been miscategorized in the non-autistic group, which would have underestimated suicide-related outcomes in the autistic group. Finally, many self-harm events are not captured by health records, as individuals may not visit the emergency department for health care in these situations.

The July 2023 National Autism Indicators Report examines changes in access and disruptions to healthcare services for autistic children and adults during the beginning of the COVID-19 pandemic. Policy Impact Project at A.J. Drexel Autism Institute

The COVID-19 pandemic and mitigation measures changed how people accessed health care services and engaged in their communities. Access to appropriate services and accommodations help autistic individuals in maintaining employment, pursuing education, caring for their health and establishing independence. Because autistic people often have greater health care needs than non-autistic peers, the pandemic-related changes in access to health care may have been an extra burden on their health and, ultimately, quality of life, according to the latest National Autism Indicators Report, issued by Drexel University’s A.J. Drexel Autism Institute. 

Researchers at Autism Institute’s Policy and Analytics Center examined changes in access and disruptions to health care services for autistic children and adults during the beginning of the COVID-19 pandemic. These findings will inform better evidence-based practices for future public health emergencies to improve policies and programs for autistic individuals.

“The COVID-19 pandemic was an unprecedented public health emergency, and the impacts were far reaching,” said Jessica Rast, PhD, research scientist at the Autism Institute and lead author of the report. “Our hope is that we can learn from this pandemic response, so we can improve systems of care for autistic people, for all people. While such improvements would help in future times of crisis, we hope they can be implemented in times of less turmoil to improve care overall.”

Rast and her co-authors noted that changes in access to services result in long-term consequences, which can be dire for autistic people.

“This is an equity issue. If the people who need more care can’t access it, we’re disadvantaging a whole population,” said Rast. “And unfortunately, the people who are disadvantaged in other ways, such as Black autistic people, saw more disruptions in care during the COVID-19 pandemic.”

The research team examined various data sources from before and after the start of the COVID-19 pandemic, including health care claims and administrative records; the availability of services for autistic children based on caregiver reports from the National Survey of Children’s Health; national emergency hospitalization records through the National Emergency Department Sample; hospital admissions data via the National Inpatient Sample; and service use among autistic adult patients in records from Kaiser Permanente Northern California. The data sources cover various populations from nationally representative pictures of autistic children and adults to other sources that covered specific, but still diverse, populations.  

The research team found autistic adults, ages 45 and older, had higher rates of visits to the emergency department and hospitalizations for COVID-19 compared to non-autistic adults and autistic children and younger adults (younger than 44). The significant increase in hospital visits among older autistic adults – compared to other older adults – demonstrates the need for improved public health care policies to maintain usual health care services for individuals during a public health emergency.

For younger autistic people access to care – including well-child visits, dental care, emergency department visits and inpatient hospitalizations – decreased during the COVID-19 pandemic. Black and Hispanic autistic children experienced larger decreases compared to white children. Virtual health care became an important avenue for care during the COVID-19 pandemic. About half of autistic children had a virtual or telehealth care visit in 2021, as did non-autistic children with special health care needs. Just over one-third of autistic children missed or delayed a well visit because of the COVID-19 pandemic. 

There were also policy changes at the beginning of the COVID-19 pandemic to increase access to health care. However, enrollment in public health insurance – like Medicaid – among autistic children remained about the same as before the pandemic. Although, there were differences in insurance coverage by race and ethnicity among autistic children – with an increase of Black non-Hispanic autistic children being covered by public health insurance in 2021, compared to before the COVID-19 pandemic.

“The changes in health policy during the COVID-19 pandemic, including increased Medicaid and Children’s Health Insurance Program (CHIP) enrollment and continuous coverage requirements, played a crucial role in safeguarding the health insurance and access to healthcare for autistic individuals,” said Kaitlin Koffer Miller, DrPH, director of the Policy Impact Project at the Autism Institute and co-author of the report. “These policies helped mitigate negative impacts, ensuring uninterrupted health care services and reducing the uninsured rates across the U.S. While the expiration of the continuous coverage requirement through Medicaid raises concerns, the overall improvements highlight the importance of inclusive health policies for the well-being of autistic individuals.”

Rast and Koffer Miller highlighted recommendations from the report, including having health care providers ensure equitable and high-quality access on virtual platforms.

“This can include creating physical and virtual environments that provide individuals the opportunity to request accommodations and are sensory-friendly,” said Koffer Miller. “Additionally, providers can use communication strategies that cater to diverse communication preferences. This may include using visual aids, written instructions, or plain language to enhance understanding and ensuring any online platforms are user-friendly and accessible for individuals with diverse sensory and cognitive profiles. Organizations like the ASERT Collaborative have been beacons of information, providing accessible resources focused on COVID-19 that could be a model for health care providers.”  

They also note that health care policies should continue to support telehealth and virtual care options for mental health services, including easing portability restrictions and expanding coverage. The report showed there were no substantial changes in mental health care early in the COVID-19 pandemic, but just under half of autistic children received mental health care before and during the pandemic. According to the researchers, about 10% had unmet needs for mental health care in 2019 and 2021.  

By supporting telehealth and virtual care, individuals on the autism spectrum and other neurodivergent populations can benefit from increased accessibility and convenience, the report suggests.

Most mothers who took prescription antiseizure medications during pregnancy can breathe a sigh of relief: A new study published today in Lancet Neurology found that young children who were exposed to commonly-prescribed medications in utero do not have worse neurodevelopmental outcomes than children of healthy women.  

Commonly used antiseizure medications such as lamotrigine and levetiracetam are generally considered effective and safe, especially compared to many first-generation epilepsy treatments that carried profound risks to the unborn child. But while epilepsy may no longer be the reason that prevents someone from starting a family, there is still not enough information about how drugs taken by the mother affect maternal and child outcomes after delivery.  

The new study provides reassurance to patients and offers guidance to neurologists who are faced with a challenge of maintaining fragile balance between prescribing drug dosages that suppress mother’s seizures but carry no increased risks of neurological complications for the baby. 

“A blanket saying that all antiseizure medications are bad is overly simplistic and doesn’t make sense biologically,” said senior author Page Pennell, M.D., professor and chair of neurology at the University of Pittsburgh. “Being able to say that no, taking these medications will not put their future child at a greater risk of autism or learning disabilities, has a huge impact for women with epilepsy who are considering pregnancy.”  

Epilepsy is a neurological disorder of abnormal electrical activity in the brain that affects over one million American women of childbearing age. With its sudden and debilitating seizures and limited number of medications, which caused significant risks to the developing fetus, the condition was considered incompatible with pregnancy for much of the 20th century, though that landscape is gradually changing.  

The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study was launched two decades ago with the goal of delivering high-quality information about how antiseizure medications affect both the mother and the child. The prospective observational study recruited women who were treated for epilepsy at twenty medical centers across the United States and followed them and their babies over the course of pregnancy and several years postpartum. 

Previous research that has come out from the study highlighted the need to carefully monitor and adjust the dosage of antiseizure medications to achieve adequate control of seizures without compromising the health of the fetus. The new study focused on determining whether exposure to these drugs causes long-term neurodevelopmental effects that negatively affect the child. 

To assess the effects of fetal exposure to medications, children at the age of three years old were tested for their vocabulary and verbal comprehension skills as well as ability to describe simple pictures. Children of women with epilepsy were as good at verbally describing simple objects and pictures as children of women without epilepsy. Their ability to understand language was also comparable to children of the same age who were born to women without epilepsy, highlighting that both lamotrigine and levetiracetam pose low risks for negatively affecting cognitive outcomes.  

In a secondary analysis researchers found that a high dosage of levetiracetam in the third trimester of pregnancy was correlated with adverse neurodevelopmental effects on the baby and recommend especially careful monitoring of blood levels of this drug and thoughtful dosing strategies. Researchers point out, however, that additional research is needed to determine if the same holds true for other antiseizure medications that are less common.  

Screening for mood and anxiety disorders is another important factor that clinicians must consider. As part of the study researchers observed that increased maternal anxiety and, to a lower degree, depression has negative effect on newborns.   

“The findings provide valuable information for women with epilepsy, but there is still much to do as we don’t know the risks for most antiseizure medications,” said lead author and one of several principal investigators of the study Kimford Meador, M.D., professor of neurology at Stanford University. 

“For many years, prescribers did not have good information on cognitive outcomes of children exposed in utero to more recently approved antiseizure medicines,” said Adam Hartman, M.D., program director in the NINDS Division of Clinical Research and NINDS project scientist for MONEAD. “This study represents another important step in advancing our knowledge; however, there is more confirmatory work to be done, particularly for the secondary outcomes.”