Year End Summary: 2021

This year was filled with both challenges and encouraging signs of progress. The world continues to cope with the many hardships associated with the COVID-19 pandemic, which have negatively impacted the community, including scientists who study autism. Families and individuals continue to show individualized and specialized needs, specifically those from racially and ethnically diverse communities, females and girls, and we continue to understand the specific needs of those groups. For example, the close of the year saw the publication of a report by the Lancet Commission, which formally introduces the concept of “profound autism” representing individuals with different support needs. New CDC data released in December also show that autism rates are rising while age at diagnosis is decreasing [1]. While this is not a comprehensive summary of every single autism discovery in 2021, here we summarize many significant autism discoveries and related news of the past year:

Listen to the 2021 Year End Summary here.

Lancet Commission Endorses Use of Term “Profound Autism”

On December 6, The Lancet published an extensive report from a global team of autism researchers and stakeholders. The report, titled “The Lancet Commission on the Future of Care and Clinical Research in Autism,” recognized that effective autism assessment and care require personalized, stepped-care approaches that meet an individual’s needs throughout their lives, and that greater investment is urgently needed to develop and refine practical interventions that can improve the lives of people with autism. The Commission also formally introduced the term “profound autism” to distinguish individuals who have high dependency needs and urged policymakers to focus on the unique needs of this group, which represents approximately 30% of people with autism [2]. The goal of this label is to recognize the uniqueness of these individuals and that their support needs and outcomes are different from those of others. There is also evidence that the underlying biology of those with “profound autism” is different [3-5].

Amy and Jonah Lutz

The term “profound autism” is intended to describe autistic people who are likely to need 24-hour support throughout their lives. The report states that useful categories like “profound autism” can bring attention to the different needs of different people. In fact, the goal of the new term “profound autism” is to equip parents, service providers and the public with the language necessary to ensure that each individual with autism receives the accommodations and interventions they need [2]. These can vary greatly. Some of those diagnosed with autism engage in destructive or self-injurious behavior. Some have intellectual disabilities; others are star students. Some are unable to perform basic tasks like brushing their teeth and getting dressed; others can live fully independent lives. Autism is a disorder in which no two diagnoses look the same, and terms like “profound autism” help distinguish needs

CDC Reports Autism Prevalence Continues to Rise

The CDC ADDM Network released updated autism prevalence data this year, announcing that one in 44 8-year-old children is diagnosed with autism [1]. This is an increase from the one in 54 number for 8-year-olds reported in March 2020. Using a slightly different but validated methodology from previous years [6], new CDC data confirm that autism prevalence and diagnoses have gone up steadily in the past five years. 

The CDC information makes it clear that we are getting better at diagnosing autism and identifying it earlier, which is encouraging because research has consistently shown the value of early intervention. However, more than 58% of children identified had intellectual disability or borderline intellectual disability. This cohort of children with profound autism warrants more attention from policymakers and service providers, as their needs are dramatically different from those with milder forms of autism. While the prevalence went up, the demographics across race, ethnicity and cognitive ability stayed pretty stable from the last prevalence estimate [1]. This information calls for further understanding of the nature of this rise beyond just diagnostic practices, including alerting pediatricians and supporting further and more expanded studies of gene x environment interactions [7]. One example would be the differential influence of toxic chemicals on cells with genetic mutations associated with autism, which revealed a susceptibility to toxic chemical exposures with cells with autism-related variation [8].

Reaching the Hard to Reach

Those from racially and ethnically diverse backgrounds have long been recognized as being diagnosed later, if at all. There are years and years of CDC data which show that while this trend is improving, it is still problematic in terms of equitable access to services. It also produces another problem that perpetuates the underdiagnosis and lack of access: not enough families from racially and ethnically diverse communities are being studied in research, which means most research findings apply to white communities, not the communities represented in the real world who need help [9]. A few studies this year specifically targeted those from either Hispanic [10] or Black and Hispanic families [11, 12]and found their needs were different or developed tools for their particular culture. However, in a commentary this year, researchers highlighted the need to engage diverse communities at the beginning of the research question, to ensure they have a voice at each step, and to possibly adapt the study question to their particular circumstances [9].

Donielle Johsnon with her family

Unfortunately, not all of the challenges facing underserved communities are the same. For example, those who are minimally verbal and have intellectual disabilities are left out of research for logistical reasons, or, in many cases, the intellectual and verbal abilities of individuals with more profound autism are not reported at all [13]. Those with intellectual disability are usually recognized more often, but there were only four intervention studies published in PubMed in 2021 that specifically included a group of autistic people with intellectual disability.  

Understanding Autism in Females 

While females with ASD have not typically been placed in the “underdiagnosed” category, they certainly are a group that has been underserved by scientific research. Because of the 4:1 difference in prevalence for males to females, autism research studies typically include four times fewer females, which means findings are not generalizable to females [14-17].

In the last year, there have been several studies showing that the challenges faced by autistic females are different from those facing autistic males. For example, a phenomenon called “passing as autistic” (otherwise known as masking) — where someone with autism tries to hide their symptoms to pass in social situations — was found to be elevated in females [18, 19]. Comorbidities like epilepsy have been shown to be higher in females [20], and baseline brain activity in autistic youth is different based on biological sex [16]. While the female brain is clearly different from the male brain, even in autism, the lack of females included in research has also significantly impaired our understanding of brain differences between males and females with ASD for more personalized support [21].

Because of the disparity in diagnosis between males and females, there are very few studies that can examine the effects of sex and gender on diagnosis, making consistent findings across sex/gender almost impossible, but it has been done [22]. What has been learned is that the striatum (and genes controlling striatal development) may play a role in autism symptoms in females. This has not been identified as an area of interest in males [23]. Research also shows that females have a higher burden of variants in the oxytocin receptor gene, which affect them differently than males with ASD [15], and differential links between brain activity and autism features [16], supporting something called the “female protective effect.” This protective effect might be genetic or might occur through the estrogen pathway [24, 25]. Finally, while the entire autism community has a higher than expected rate of gender dysphoria, it seems to affect girls more than boys [26]. Behavioral features are also slightly different, which complicates diagnosis [17]. Together, these results demonstrate that scientific findings, including use of biomarkers for diagnosis, which are seen in males may be different than those seen in females. Scientists need to ensure that enough females are recruited into research studies and better understand the difference between females and males to ensure that scientific findings generalize to care in the community.

The Pandemic Is Still Causing Problems

Almost two years into the pandemic, scientists are still working to understand the long-term effects on people with autism. Studies focused on increases in challenging behaviors and loneliness in autistic youth and adults [27, 28], and also on understanding the mental health challenges due to prolonged social distancing guidelines, including multiple waves of lockdowns [29-32]. Additionally, studies show that families with autism are disproportionately affected by job losses and food insecurity [33, 34]. And while telehealth-based diagnosis and services are becoming more common as a result of social distancing, families of younger children who need direct behavioral supports remain the least satisfied [35, 36], a trend continuing from 2020 [37]. The challenges associated with the pandemic are not limited to those with a diagnosis and their families. Scientists who dedicate their lives to help those on the spectrum have struggled with some of the same issues that families with autism have [38], including mental health and childcare challenges. This compounds the problem of developing scientific discoveries and delivering them to the community.

New Technologies for Diagnosis and Treatment

With the pandemic came the use of remote and virtual technologies, not just to identify and diagnose autism, but also to provide supports and services. As the pandemic continues, researchers are studying what works and what doesn’t, especially in families who say that they found telehealth more accessible and beneficial [35]. Remote assessments have changed the nature of how autism is diagnosed, with scientists emphasizing the need for use of good clinical judgment rather than reliance on singular instruments [39]. Telehealth assessments have meant that diagnosis is now more accessible to those in remote areas who are traditionally underdiagnosed. Another bright spot is that the pandemic has allowed children to be observed remotely in their home environment, which may significantly enhance the ability of clinicians to observe early markers of autism [39, 40]. New technologies that enable videotaping via remote camera — for later review by clinicians — are also gaining traction. Recently, Cognoa received FDA marketing authorization for its new remote videotaping tool, CanvasDx. Duke University also published data a tool that plays different movies and visual scenes on an iPad and allows clinicians to determine the likelihood of an autism diagnosis by examining where the children looked in the scene [41], as past research has shown that children with autism are more likely to look at objects and less likely to look at social stimuli. In both cases, these recordings, together with standard early screening methods, can be analyzed to help facilitate diagnosis. A 2021 review found these mobile digital technologies to be promising in diagnosis [42].

Beyond just supporting diagnosis, mobile technology may be used to improve cognitive and social skills across the lifespan [43]. A recent systematic review indicated that these mobile interventions were particularly helpful in targeting practical skills [43, 44]. They can also be used to predict responses to stressful situations and abnormal sensory arousal [45]. Finally, robots and videogames on devices are showing promise in helping kids with autism develop social skills [46, 47]. While these technologies may have benefits beyond the pandemic and can alleviate some of the burden of traveling to multiple appointments, they will not replace the need for children to be diagnosed and/or receive therapy from trained, in-person clinicians [39, 48].

Intervention Before Diagnosis

A few years ago, scientists in the UK began studying the possibility of promoting skills in parents as a way to mitigate autism symptoms in infants [49]. By working with parents in their home and promoting social and communication skills through activities like reading and play, autism severity scores improved. This year, a group in Australia conducted its own randomized controlled study starting at 9-12 months — before a diagnosis can be made — to provide support to parents and offer video feedback on supporting language and social development in their infants. This study showed that support of infant social and communication skills measured at one year led to a reduction of autism severity scores at 24 months, with these improvements being maintained long after the end of the intervention period [50]. Factors like caregiver interaction and adjusting the environment to promote learning in these toddlers are key ingredients to changing developmental trajectory [51, 52]. New tools are also allowing earlier and earlier detection of markers of ASD, with some evidence that it can be done as early as 12 months of age [53]. These findings represent the potential benefits of decades worth of early detection work and operationalize a methodology for parents to learn to promote social and communication skills in their infants.

However, the need for earlier detection and diagnosis of autism remains a priority within autism research and the autism community. This year, researchers identified changes in the grey matter (cell bodies) and white matter (the neuron branches) in children as young as 12 months of age [54] who go on to be diagnosed with autism. Changes in brain activity, while not a diagnostic marker, can be seen in infants as young as 3 months of age [55] and can prove helpful in diagnosis at 6 months [56]. In addition, some behavioral signs can also trigger preemptive intervention. Groups led by UC Davis demonstrated both declining gaze to faces, which was replicated in two different cohorts [57], and unusual inspection of objects at 9 months, which predicts reduced social engagement at 12 months in those who later develop an autism diagnosis [58]. In addition, vocalizations (or intents to communicate) were lower in children as young as 12 months [59]. Together, while not diagnostic, some of these early markers and signs can facilitate entry into preemptive interventions, which can produce skills in caregivers and infants that change the developmental trajectory. Finally, there is an erroneous perception that parents believe that all of autism is “bad” and needs to “be eliminated.” In fact, when they were specifically asked, parents identified characteristics like love, kindness, humor, humanity and resilience that they value and appreciate in their children [60].

Autism and Aging

There has traditionally been a lack of understanding as to what happens to autistic adults as they enter their golden years. This year, Drexel University utilized Medicaid data to examine the risk of dementia in those with autism and found that those with ASD were 2.6 times more likely to be diagnosed with dementia compared to the general population [61]. This has profound impacts on planning for elderly relatives with ASD and developing interventions that may stunt the development of dementia in this population.

Understanding the Role of Genetics in Autism 

Traditionally, genetic variation association with autism has been bucketed as “rare” mutations and “common” mutations. Rare mutations on genes typically lead to deleterious effects such as seizures or intellectual disability [62]. Sometimes, like in the case of BRCA (breast cancer gene), they can be fatal. Common mutations are seen in lots of people, not just those with autism, but the human body can tolerate many common mutations with no major effects. However, if the genetic variant is found in an autism risk gene, for example, then it can dispose someone to an autism diagnosis [62]. Mutations found in autism risk genes — including those associated with cell adhesion, neuron-glia interactions and synapse formation — are most likely to be common variants involved in autism [3].

This year, sequencing of more than 800 people with an autism diagnosis revealed that 27% had evidence of a rare genetic mutation, mostly in one of the 102 genes identified in 2020 as being relevant for ASD [3, 63]. Presence of a mutation of one of these genes also results in a distinct set of behavioral features early in life that is different from those without a rare mutation [64]. Interestingly, instead of advancing the traditional “rare vs. common variation debate,” scientists this year learned that even in those who have a rare genetic mutation, there is also a high burden of common variation [63]. Scientists found that both rare and common genetic risks contribute to autism susceptibility, and that the dual risks may increase the likelihood of an autism diagnosis [63]. These findings make things complicated for genetic counselors who need to assess all the factors and communicate to families whether or not a particular rare variant is causative. In addition, sequencing technologies are revealing more and more genes that are relevant to ASD but incredibly rare; in fact, they are likely to be part of a multi-factorial cause of individual cases of ASD [65]. Finally, we’ve learned that common variation influences not only core autism symptoms, but also psychiatric comorbidities [66].

Studying Rare Genetic Syndromes Opens the Door to New Therapeutics

The use of induced pluripotent stem cells, or iPSCs, to study the brain on a cellular level has so far been focused on rare genetic diseases associated with autism, like Dup15q syndrome, CNTNAP2 and CDKL5 disorder. However, while the genetic targets may be more specific than in idiopathic autism, there are also converging mechanisms of disrupted connectivity in the brain that make these single gene disorders useful in understanding the neurobiology of ASD [67-71].

In addition to some shared (and some distinct) neurobiology across autism with a known genetic cause, there is overlap on the basic neurobiology level in terms of cortical thickness [72] and G-protein-coupled-receptors across different psychiatric disorders, including autism [73]. Some of these rare genetic syndromes have been responsive to targeted gene therapy, which opens up the door for them to be used in idiopathic autism if proven safe and effective in large groups of people with neurodevelopmental disorders.

Remember Glial Cells? They May Play a Bigger Role Than We Thought.

One brain cell type that is experiencing renewed interest in autism is glial cells, particularly with regard to sex differences in ASD. Glial cells are found in the brain, but they do not communicate with each other. Rather, they provide insulation to neurons that do communicate via electrical impulses. Traditionally, because they were not thought to be communication cells, they were not considered critical for study. But recent evidence has shown that there may be different subtypes of autism defined by the upregulation of genes that control glial cells [74]. Gene expression in these microglia may also contribute to differences in brain structure [75]. In addition, the direct study of brain tissue has shown that in certain layers of the cortex, astrocytes — a type of glial cell — are decreased [76]. Taken together, the dysregulation of glial cells may contribute to different cell processes, brain structure, functional changes and psychiatric syndromes associated with autism.

What Can We Do to Improve Outcomes of Those with Autism?

New research shared this year focused on improving outcomes. First, we learned that the presence of a brother or sister not on the autism spectrum improves adaptive behavior across the lifespan for those with an autism diagnosis [77]. On the other hand, parental stress in early life and early adverse events can make outcomes worse [78].

Research continues to show that, especially in the early years, parents and caregivers can play a critical and life-changing role in their child’s development. For young children, Naturalistic Developmental Behavioral Interventions (NDBIs), which are child-led and utilize behavioral principles delivered in the home, are most helpful [79, 80] and now may be delivered via telehealth [81]. One good thing to come out of the pandemic is the availability of remote access to video series, including but not limited to the Autism Navigator, which can help parents identify early signs and deliver these interventions to their young children from home [82]. The literature on the efficacy of these NDBIs grows greater every year.  However, not everyone has access to early interventions or even expert clinicians. To address the disparities seen across the world and across different comorbidities and other individual factors, the Lancet Commission report called for a stepped-care and personalized health model for interventions [2]. This includes provisions not just for individual and family factors, but also for accessibility and cost. These recommendations on how different groups approach care are essential to obtain a more specialized approach to helping families and individuals on the spectrum lead happy, healthy and successful lives. Unfortunately, some promising therapeutics like oxytocin failed to meet the cut of significantly helping those with ASD [83].  Other organ systems besides the brain, including the gastrointestinal system, continue to be investigated to help alleviate co-occurring medical conditions.  Many families turn to things like probiotics to help with issues like constipation and diarrhea, however, new evidence suggests that the microbiome is more influenced by diet than autism itself [84] calling into question the validity of probiotic use for GI problems.

In Memoriam

Sadly, the autism community lost three scientists this year who have made enormous contributions to the field and changed the way people think about autism. Sir Michael Rutter, known as the Father of Child Psychiatry, a professor at the Institute of Psychiatry at Kings College London, was one of the most influential psychiatric scientists of the past 50 years. He was one of the first researchers to study autism, publishing a study of autistic twins in 1977. He helped dispel the myth that parenting styles influenced an autism diagnosis and brought scientific rigor to understanding autism. He helped develop the two gold standard tools for diagnosis: the ADI-R and the ADOS. His commitment to helping children and families was not limited to autism, however; he helped families with a number of psychiatric conditions and behavioral issues.

Li-Ching Lee, who served as the Associate Director for Global Autism at the Wendy Klag Center of Johns Hopkins School of Public Health, was one of the reasons why autism is recognized as a global condition. She focused her research on identifying and helping families with autism across the world, calling it a “human rights issue” when the needs of families in under-resourced countries were ignored. She also worked tirelessly to understand autism in the US, working closely with the CDC to understand who and where people were being diagnosed and how they could be helped. Beyond being an amazing scientist, her fellow students have called her an amazing friend, mentor and teacher who went above and beyond to help her students be successful while helping families.

Finally, George C. Wagner of Rutgers University was one of the first behavioral neuroscientists to try to develop a behavioral model of ASD in rodents at a time when scientists were starting to try to understand how to recapitulate the features in model systems. His work helped define how autism should be studied in animals, and how it overlapped or was different than other psychiatric disorders. He based his models on the core features rather than particular behaviors, including delay of skill development, plateauing of skills and possible regression of skills. This helped fundamentally change the field of animal models of ASD. Many of his students (including ASF CSO Alycia Halladay) went on to help families with ASD following training.

All three of these amazing scientists will be remembered not just for their contributions to science, but for their training of early career researchers who continue to make an impact.

The Last Word

Over the last 40 years, autism has moved from a categorial (yes/no) diagnosis to a dimensional diagnosis [85], taking into account the complexity and differences of features across the lifespan. While there may be core features of ASD that are common across the spectrum, people with autism, just like people without autism, are all different and need to be recognized as such [2, 86].  

While this summary captures what happened in 2021, we urge you to read more about how science has changed the way families with autism have been perceived, treated and helped over the past 40 years. The Journal of Autism and Developmental Disorderspublished a series that you can look through here, and Dr. Giacomo Vivanti shared his long-term perspective on the November 14 ASF podcast here: In fact, one of the best ways to keep up with changes in autism science is to subscribe to the ASF podcast on Spotify, Apple Podcasts or Google Podcasts.

You can make a difference

These research findings and important discoveries were thanks to the thousands of families and autistic individuals who participated in research studies over the past few years. As you can read from this report, your contributions make an impact. There are other research opportunities and as we continue to live in the pandemic, many more of them are available in your own home with interaction with professionals to support you. You can read more about them here. Finally, there are ways to learn about credible science outside social media, which also includes SpectrumNews and the Autism BrainNet. Just signing up for more information on the Autism BrainNet gets you regular information about what the brains of autistic people look like and how they are different from those without a diagnosis.


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