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New Technologies, New Data, New Solutions

This year’s progress in autism research includes promising findings, clarifications, explanations, and the uncovering of new avenues of inquiry. The focus is now on personalized medicine: finding the right treatment for the right person at the right time through targeted interventions. Advances in technology and genetic testing are opening new avenues for therapeutics, rapid drug testing, and improved differentiation of subgroups of autism.

Listen to the 2024 Year End Summary here.

The Value of Genetic Testing

With the improvement of genetic testing techniques, identifying genes contributing to an autism diagnosis is becoming increasingly precise. Currently, a genetic cause of autism can be pinpointed in around 20% of cases (1). While guidelines vary slightly, most professional organizations associated with autism recommend genetic testing for affected families (2). Testing can aid our understanding of autism symptoms as well as provides therapeutic options for individuals with a diagnosis (3). One example of progress in autism treatment involves Rett Syndrome, a developmental disorder that includes many autistic features. Last year, the FDA approved the drug trofinetide for Rett Syndrome, which affects growth factor signaling. This year, the long-term efficacy of trofinetide was demonstrated (4).

A promising new tool revealed this year is the use of brain organoids to identify and develop more personalized gene therapies for individuals with rare genetic syndromes. For instance, Timothy Syndrome is characterized by autism and heartbeat irregularities. Utilizing cells derived from individuals with Timothy Syndrome, researchers in the Pasca lab at Stanford University developed a targeted gene therapy that corrected deficits in cell migration and electrical signaling—a significant step toward personalized clinical therapy (5). This advancement provides hope not just for Timothy Syndrome but for many rare genetic disorders associated with autism. Although these genetic variants are rare, therapies developed for specific cases have the potential for broader applications.

In addition to using derived brain organoids, which are grown in a dish, scientists are also studying the actual brain tissue of deceased individuals with autism. For example, the Geschwind Lab at UCLA, via the Autism BrainNet program, has studied gene activities directly in the brain. They found that genes controlling neuronal function, migration, cell-to-cell signaling, and neuronal communication are downregulated, while those controlling immune system activation are upregulated (6). These findings, initially observed in blood samples, have now been validated in brain tissue. Researchers have also identified changes in gene expression across different brain cell types organized into distinct networks (7). These discoveries show that, even after decades of research, new basic science findings continue to reshape our understanding of autism (8).

Advances in Measuring Outcomes

Progress was made this year in addressing a persistent challenge in behavioral studies: how to measure outcomes effectively. A new tool, the Brief Observation of Social Communication Change (BOSCC), was developed to assess the efficacy of different therapies, moving beyond traditional diagnostic measures that were not designed for this purpose (9). The BOSCC has been used across various studies to demonstrate the benefits of early intervention (9). Remote assessments, adapted during COVID-19, also showed validity in measuring social attention in rare genetic syndromes associated with autism, with potential for broader application (10-12).

Research also focused on utilizing existing instruments to measure clinically-significant change, bridging the gap between laboratory results and real-life impact. While not as high-profile as medication or therapy, these methodological advances are crucial for ensuring the success of treatment trials (13,14).

Environmental Factors: What Remains to Be Explored?

Understanding which environmental factors contribute to autism remains a formidable challenge. This year, several studies provided new data, clarified previous findings, and examined novel factors. For instance, while prenatal infections and immune challenges are still considered risk factors for autism, additional studies suggest that these relationships may be moderated by genetics or shared familial factors (15,16). Concerns about COVID-19 infection during pregnancy being linked to an autism diagnosis inn those children were alleviated by two studies showing no association between maternal COVID-19 and autism in offspring (17). Similarly, neither cannabis use during pregnancy (18) nor prenatal diet (19) was linked to an autism diagnosis. Increased screen time was associated with preschool autism traits and lower developmental scores (20,21), furthering the long-held belief that multiple genetic and environmental factors may contribute to an autism diagnosis rather than one single factor being the cause.

One potential mechanism linking environmental factors such as immune challenges or antiepileptic drugs to autism risk involves the timing of brain cell activation during early development (22). Disruptions in these processes may hinder proper brain development, a theory increasingly supported by research into neurodevelopmental disorders.

Recurrence Rates

Decades of evidence show that individuals with a family history of autism are at higher risk of diagnosis compared to the general population. High-risk groups include those born prematurely (23) or with rare genetic disorders associated with autism. The Baby Siblings Research Consortium (BSRC) updated recurrence risk statistics for families with one autistic child. While the general population risk is 1 in 36, younger siblings face a risk of 1 in 5 (24). Following children to school age, the numbers are higher (25). Furthermore, the risk increases for families with multiple autistic children in the family. Interestingly, recurrence risk is higher when the older sibling is female, suggesting a protective effect in some females that may be outweighed by genetic liability in others (24,26).

Additional data from Denmark’s health registries revealed that individuals with extended family histories of autism or psychiatric disorders, such as bipolar disorder and schizophrenia, have an increased likelihood of autism diagnoses (27). Longitudinal studies, like the Autism Science Foundation’s Next Gen Sibs Project, continue to explore these familial relationships over time.

The Enduring Question: How Many People Have Autism?

Each year, families, researchers, and public health officials ask, “How many people have autism?” The CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network estimates the prevalence every two years. The latest report calculated a rate of 1 in 36 for eight-year-olds. This year, a study using a large healthcare database confirmed rising prevalence rates, an increase in adult diagnoses, and a growing recognition of autism in females, although females remain underdiagnosed compared to males (28,29). Late-diagnosed individuals often exhibit a different autism phenotype, characterized by symptoms that allow for more social camouflaging (30,31).

The Spectrum Within Autism

Autism manifests in a wide range of presentations. Some individuals, described as having “profound autism,” exhibit severe intellectual disabilities, limited language, and require constant supervision. These individuals also display higher rates of aggression, self-injury, and stereotyped behaviors, often due to their inability to communicate distress (32-36). Research increasingly shows that biologically, individuals with profound autism differ significantly from those with non-profound autism. For example, brain imaging studies reveal that individuals with profound autism exhibit distinct brain structures and functions, including widespread brain overgrowth (37,38). The differentiation between non-profound and profound autism can sometimes be made quickly (39,40) and is based on features like adaptive abilities, motor skills, language, and cognitive abilities (38).

Families of individuals with profound autism face unique challenges related to stigma, accommodation, and access to support. Despite progress in public awareness, societal perceptions often marginalize those with severe disabilities. Experts like Drexel University’s Dr. Giacomo Vivanti advocate for embracing the complexity and nuance of autism, acknowledging that the experiences of those with profound autism differ substantially from others on the spectrum (41).

Insights into Language Development

Severe language deficits are common in individuals with profound autism, but language and communication challenges are widespread across the spectrum. While language impairments are no longer part of the DSM5 criteria, they are critical in understanding the nature of autism. This year, research identified genetic links, such as neurexin family genes, that affect language abilities (42). Studies also showed that minimally verbal individuals often have better receptive language skills than expressive skills, emphasizing the importance of tailored language development strategies (43). Parent language input and social skills also play critical roles in shaping language outcomes (44).

Gender Differences in Autism

Large studies highlight significant gender differences in autism. Males show higher heritability rates and are more frequently diagnosed, while females with autism are more likely to have intellectual disabilities (26). Biological differences may contribute to these disparities, including gene expression and neural connectivity (45-48). Understanding these differences is crucial for addressing issues such as the higher rates of suicide and anxiety observed in autistic females (49-51).

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