Year End Summary: 2020

by Alycia Halladay, PhD, Chief Science Officer and The Scientific Advisory Board of ASF

Listen to the 2020 Year End Summary here.

The COVID-19 pandemic

The COVID-19 pandemic upended the lives of families around the world, but autism families were dealt an even harsher hand.  Autism families rely on frequent in-person therapies such as speech, occupational therapy and applied behavioral analysis. Most often, these services are provided in schools or clinics; the pandemic has disrupted or eliminated treatment in both settings, resulting in further isolation of people with ASD and their families^1,2. This isolation manifests as increased screen time, reduced exercise and decreased social interaction. In addition, comorbidities have heightened the risk of COVID hospitalization, a fear that weighs heavily on the minds of autism parents^3,4.  

Surveys of families affected with ASD link high stress levels to the strain of constant care of individuals with ASD and concerns about the person with ASD becoming ill³.   These concerns increase with severity of ASD symptoms.  According to caregivers, those who lost access to school-based services are the most affected.  Fear of exposure to COVID-19 discouraged families from taking needed respite care or eliminated it as a possibility.  While concerns about the health of the person with ASD generate the greatest stress, financial concerns and worries about the health of all family members³ greatly compound it. In fact, compared to neurotypical children and adolescents, those with autism have a higher rate of emotional problems and conduct problems and showed reduced sociability during the shutdown⁵.

One of the hardest hit populations may be those with profound autism, severe behaviors and intellectual disabilities. A survey of families with children with rare genetic forms of ASD (who typically show more severe behaviors) reveals that almost half of those surveyed lost school-provided academic services and not all were able to re-access them via telehealth.  However, of those who lost medical services, about 50% were able receive services via telehealth, and many hoped to continue telehealth after the pandemic had resolved⁶.  Things were especially dire for families mid-shutdown, and these families should be followed up to see what accommodations worked and which did not.

1 in 54

In the midst of the pandemic, the CDC released data that showed a small increase in the prevalence of autism in 8 year olds⁷. Some of this change might be attributed to a rise in recognized prevalence of ASD in black children, which has been historically low due to under ascertainment.  A similar trend was also seen in 4 year olds in non-white racial and ethnic groups⁸. While less disparity in recognition and diagnosis in non-white children is good news, the increase in prevalence of ASD in children of color is a call to action for communities to ensure access to care for all children. Another CDC analysis using the ADDM methodology showed that 25% of kids noted to have ASD using record review are not actually diagnosed with ASD; half of those were not receiving any services⁹.  What is causing this increase in prevalence?  Certainly, better surveillance is one factor, but there is increasing evidence that genetic and environmental interactions may be contributing to an ASD diagnoisis^10,11.

Black Lives Matter

With the murder of George Floyd earlier this year, racial tensions in the United States engendered an international re-awakening and re-ignited awareness of racism and systemic discrimination.  This is true in many areas of sociology and psychology and autism is no exception.  While the gap in diagnosis between black and white children is narrowing, it still persists.  There is a higher risk for non-white children to be missed and not receive an appropriate diagnosis⁹.  The diagnostic experiences of black children was documented in an in-depth analysis of families who are involved with the AGRE database.  Their age of diagnosis is higher as compared to white children, despite the age of parent concern being similar.  The delay is not due to lack of insurance or presence of intellectual disability, the latter usually lowers the age of diagnosis due to more recognizable symptoms¹².  This significant delay in formal diagnosis robs non-white children of the opportunity for early intervention. A systematic review summarizing decades worth of research also highlighted fewer opportunities for access to care, a higher proportion of unmet service needs and less access to specialized medical, educational and community services for children of color, when compared to white families¹³.  Not surprisingly, African-American parents also have documented higher levels of parenting stress compared to white families¹⁴.   

Late this year, a study reported that a visually-based screening tool for Hispanic families (and potentially others) worked better in that population than traditional tools¹⁵.  Other systematic changes need to occur in autism research to create greater diversity, including recruiting more diverse scientists and physicians into autism treatment and research, and developing and maintaining programs to keep them working with families with ASD¹⁶.

Earlier detection and diagnosis 

The year 2020 saw renewed efforts to find innovative approaches to improve diagnosis for all children. Most of these studies took place with infants with a high probability of diagnosis because they have diagnosed older siblings. Several have demonstrated the promise of EEG – electroencephalography – as a way to find biomarkers that predict autism and reveal further understanding of how the brains of infants and toddlers work.  For example, new studies found that toddlers who show late signs of ASD have lower levels of electrical communication in the frontal and middle parts of the brain^17,18.  Differences in infant brain activity, as well as particular electrical signals, also serve to predict learning ability and later markers of intelligence in ASD^19,20.  In addition, assessing certain measures in persons with autism (proband) may help predict the probability of autism or the severity of its symptoms in younger siblings, specifically adaptive behavior, communication and language²¹.  Also, early observations of how babies look at and respond to their mothers and how they match expressions and respond to mothers’ voices are an indicator of ASD risk.  These markers could be used as targets to improve language and communication^21-23.

Understanding heritability is also key to predicting an autism diagnosis. Early this year, a scientific analysis examined sperm of fathers with kids with ASD and the presence of de-novo mutations.  These de-novo mutations appear in the person with ASD but not in the blood of either parent and therefore the origin of these mutations is elusive.  A significant proportion of fathers with kids with de-novo mutations and autism had mutations in their sperm, but not their blood.  This is called a somatic mutation because it is not found in all tissues of the body²⁴.  While still in early days, these findings suggest a pre-conception marker for autism probability may potentially be found in sperm²⁴.  It’s also important to note that not all of the de-novo mutations could be found in fathers’ sperm.  

The largest analysis of genes associated with autism published this year not only identified 102 genes that significantly contributed to autism risk, but also noted that some are associated with neurodevelopmental disorders in general, including intellectual disability, while others were specific to ASD²⁵.  A separate commentary pointed out that across publications in ASD genetics, there are very few, if any genes, specific to autism²⁶. Many families have asked why genetic analysis is necessary since genes are biologically innate and cannot be changed.  A recent analysis found that 12% of autism cases resulted from a pathogenic gene found upon genetic testing.  Families that have children with genetic mutations often join together for support and advocacy and may receive opportunities to participate in clinical trials that target their specific genetic mutation²⁷.   

A newer area of scientific genome study involves not DNA, but epigenomes, which are chemical modifications to DNA that serve to turn genes on and off.  Cord blood obtained from infants who develop autism has a different methylation profile than that of those who do not develop ASD²⁸, suggesting epigenetic assays that measure modifications of DNA should be utilized to understand the probability of a diagnosis as well, especially in specific phenotypes²⁹.  It is also becoming clearer that those with a strong genetic familial influence may show different risk factors than those with no family history.  For example, the influence of paternal age and gestational obesity and metabolic disorders on likelihood of having a child with ASD differs based on family history^30,31.

Heritability in ASD also includes non-genetic factors, including exposures of parents and grandparents.  A preliminary analysis showed a slightly increased likelihood of ASD in frequent marijuana users³², possibly through changes in sperm, but that clearly does not explain all of the causes of ASD.  In addition, low neonatal vasopressin levels were predictive of an ASD diagnosis in a small cohort.  Other environmental factors known to be associated with ASD, such as air pollution, were studied in animal models.  For example, the offspring of pregnant mice placed near roadway pollution exposures in California were found to have neurodevelopmental delays and social communication deficits³³, further demonstrating the need to reduce air pollution to improve the health of children worldwide.  The first study of the heritability of ASD across generations was explored this year, using subjects from the Swedish National Registry. In this study, researchers determined an elevated rate of autism in children of siblings with ASD.  This is the first study to document the rate of ASD across generations, although more work needs to be done to understand this “next generation”³³.  Research along these lines has also shown differences in brain function in undiagnosed females with a family history of ASD, which may be passed on to later generations³⁴.

Skin cells may lead to new options

The brain is the most important organ to study in ASD, but unfortunately not enough brain tissue exists for all new exciting and potentially revolutionizing scientific studies.  That’s why it is important to learn about the Autism BrainNet which works to make sure families understand why brain tissue donation is so important.  However, hanks to work by scientists across the world in different fields of research, ASD scientists can now use cells from different parts of the body, and, by adding chemicals and conducting genetic manipulations, turn those cells into brain cells to be studied. These initial cells can come from blood, teeth, the nose, or skin³⁵.  Because they are “induced” into becoming brain cells, they are called iPSCs or “induced pluripotent stem cells”. Although they aren’t true brain cells, they can be used to understand the brains of people with ASD, both with and without known genetic mutations, in the hopes of developing more targeted interventions.  In fact, as more and more of the cells grow together, they connect, attach and grow in ways that have the shape of “mini-brains”³⁶.  These cells are now being used in experimental settings to understand how the brain connects, and to screen different compounds for treatment^37,38.

Sex and Gender Differences

Sex differences in the way autism features and symptoms present have traditionally been hard to measure – the M/F disparity in diagnosis itself means that fewer females participate in research studies.  There has been concern that diagnostic instruments may be biased and not pick up as many girls as boys.  However by using a collection of databases across the world with over 9,000 people included, controlling for age and cognitive ability , scientists found that the standard screening and diagnostic instruments are not biased towards boys compared to girls^39,40. Looking at particular age ranges, boys do seem to have more frequent restrictive and repetitive behavior earlier than their female counterparts, with girls showing more of these behaviors in adolescence³⁹.  

Another theory that might better illuminate the disparity in diagnosis is the idea that females may be protected against an autism diagnosis by genetic, environmental or other factors, or multiple factors working together.  Several studies, including the largest one published this year²⁵, confirm that females carry more genetic mutations across the genome compared to males. This suggests that females can tolerate more genetic mutations than males without showing symptoms⁴¹, supporting the hypothesis of the “female protective effect.”

Since they carry a higher level of risk factors, why the lower rate of diagnosis in females?  One study using a cohort of younger siblings of individuals with ASD examined hormone levels at birth.  While there were no differences overall, younger infant siblings with an older sister with ASD had a stronger relationship between many hormones found at birth and autism symptoms⁴².  This effect has also been seen in other studies, and is suggestive of a differential role of genetic and environmental influences in siblings of females compared to males.  More research is obviously needed.   While they may explain male and female differences in the expression of features, these subtle differences, like improved sociability and camouflaging in females, do not count for the disparities in diagnosis between males and females⁴³.   

Cognitive and Verbal Abilities:

There has been great debate over the importance of language and cognitive abilities in people with ASD, as it may influence access to services. There is now more evidence that those with low cognitive ability or minimal language may constitute a subgroup of those with ASD that need a different approach.  The patterns of brain activity in people with ASD with minimal verbal ability^44,45 and heritability in those with decreased cognitive ability is, in fact, different than those with normal language function and ASD⁴⁶.

How you define a good outcome and how a family perceives “success” depends significantly on cognitive ability.  Families of those with lower cognitive ability consider a good outcome to be possessing adaptive skills above that of an 8-year-old, participating in activities outside of the home and engaging with social contacts outside of the family.  Those with a higher cognitive ability define a good outcome as being employed (if they want to be), living independently and having at least one true friend.  Things that influence good outcome in this group are fewer mental health problems and measures of happiness⁴⁷. Mental health issues, like anxiety, present very differently across people with differing IQs and while several studies have linked higher IQ to higher levels of anxiety^48,49, it may be that measures of anxiety are not sufficient in those with intellectual disability⁴⁷.  

Anxiety and Sleep 

Families and individuals with ASD describe anxiety as one of the most serious problems facing people with autism.  Anxiety occurs in as high as 80% of people with normal to high IQ, but it’s unclear what the prevalence is in those with lower IQ⁴⁸.  Cognitive Behavioral Therapy (CBT) has long been used as a treatment for anxiety symptoms, including in people with autism, but it may not be appropriate for those with lower IQs. While a large Cochrane review of CBT shows a mild level of improvement across studies⁵⁰, more recent studies show larger improvements in community care settings⁵¹, and in young children and adolescents^52,53.  These  may be particularly helpful for those with comorbid ADHD and anxiety in ASD⁵⁴.

Sleep is also often highly disrupted in people with autism.  This year, a study reported that the growth of the hippocampus in infancy is different in those with ASD and sleep issues compared to those without sleep issues⁵⁵.   This is the first study to show a specific biomarker for later sleep difficulties in infants – paving the way to more effective sleep therapies. 

New Interventions and Telehealth

As new autism genes are identified (thanks to larger sample sizes and new sequencing techniques) scientists are moving quickly to create animal models with these mutations in order to understand the functions of the genes and ultimately, develop targeted interventions.  The goal of these treatments is a reversal of any impairments in behavioral features of ASD like social interaction or vocalizations.  These models can also show changes in brain structure or connection between neurons, which may also be altered by a treatment.  In one model system, the target of intervention was the tau protein, which is also responsible for Alzheimer’s Disease.  Knocking down tau alleviated symptoms of ASD in young mice⁵⁴, and could possibly reduce cognitive declines in people with ASD and dementia. In another autism mouse model that knocks out the neuroligin protein, scientists found that a new cancer drug reversed neurobiological and behavioral symptoms associated with autism⁵⁶.  This compound could move to clinical trials in the coming years. 

Studies of pandemic-induced telehealth-based interventions are just starting to emerge. One method of telehealth called ECHO, has been used by autism researchers for years, and recent studies show that it is effective in helping train other doctors and disseminate knowledge.  ECHO stands for “Extension for Community Healthcare Outcomes” and has been used to help train care providers to treat everything from blood disorders to diabetes to opiate addiction all over the world.  A group of researchers is working to determine its efficacy in helping physicians treat families with ASD.  An experimental study showed that it improved pediatrician knowledge⁵⁷, which led to higher screening rate⁵⁸. 

Other methods of autism screening are also being used via telehealth, including the Systematic Observation of Red Flags, a screening instrument that involves observation of home video clips⁵⁹.  Even biological measures, such as attention to social scenes, have been adapted for online use⁶⁰.  Successfully implementing valid online screening tools is critical during the pandemic when many clinics are closed, and will also be useful after the pandemic to ease the burden on families of having to travel to a clinic for assessment⁶¹.

2020 was a year like no other, in that families and scientists were forced to pivot rapidly and adjust to the harsh realities of COVID-19, but scientific progress continued, and many of the new adaptations have opened new avenues to improve diagnosis, screening, and service delivery for people with ASD.  Instead of returning to normal, scientists will take what was useful and helpful via telehealth as well as new technologies developed during this time.  Now, scientists will move on to continue helping families mid- and post-pandemic building on what was learned and having a better sense of how to be prepared.help their other family members and themselves.

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