Concepts of Autism, Quasi-Autisms and Autisms?

Author: Dick Sobsey

This post discusses three ways of conceptualizing autism. While the distinction among these three ways of thinking about autism may seem like a purely theoretical issue, each of these conceptual models has powerful implications for the way that we study and treat autism.

Model 1: Autism versus Quasi-Autisms, conditions that share some features of “real” or primary autism, but are distinct from autism as a primary condition.

Model 2: Primary and Secondary Autism views autism as single phenomenon that can be caused by various other conditions or may be exist independently as aprimary condition.

Model 3: Multiple Autisms as a set of separate distinct syndromes that share certain common characteristics in their clinical presentation.

Ever since Swiss psychologist Eugen Bleuler first used the term autism to describe a subgroup of individuals with schizophrenia, the notion of autism has been a highly fluid concept. In the 1940s, Kanner used the term “autism’ to describe a developmentally diverse group of children with significant deficits in social behavior, while Asperger used the term "autistic psychopathy" to describe a cognitively higher functioning group of individuals with similar difficulties. Since that time, definitions and diagnostic criteria have continually evolved. One of the factors influencing our concept of autism has been the identification of numerous syndromes that appear to share characteristics with autism. These include Angelman syndrome, FOXG1 syndrome, fragile-X syndrome, Landau-Kleffner syndrome, Rett syndrome, tuberous sclerosis, and Williams syndrome, among others.

The autism-versus-quasi-autism model was predominant for many years. When it was discovered that many individuals who had been previously diagnosed with autism had fragile-X or Rett syndrome or some other more specific condition, it was typically assumed that these conditions were similar to autism but distinct from it. This model was commonly expressed as an understanding that these other conditions were part of the autism spectrum but not actually autism. Since there was no equally definitive way of diagnosing autism, the concept of autism was at least in part an exclusive definition, defined as much by what it was not as by what it was. It was defined to some extent by behavior but also defined as not a long list of other conditions even if individuals with these conditions met the behavioral criteria.

This model was gradually eroded as more and more specific conditions were identified among individuals with autism. With the advent of new genetic testing techniques that could detect deletions and duplications within genes. This model became more and more cumbersome as dozens of new syndromes were diagnosed. The concepts of primary and secondary autism began to replace those of autism and quasi-autistic “autism spectrum” conditions.

This concept was partially reflected in the controversial diagnostic criteria for autism that appeared in the DSM-V, which recognized that autism could be secondary to other conditions. Nevertheless, this only recognized that some cases autism could be attributed to specific syndromes, and did not address whether those cases which could not be more specifically diagnosed should be considered to be primary autism, or merely might be the result of various other specific conditions that have yet to be discovered and diagnosed.

Since this MECP2 duplication syndrome was first identified in 2005 and diagnosis requires advanced genetic testing many, probably most have been diagnosed as autistic before the specific syndrome was identified. Ramocki and colleagues (2011) <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861792/ > characterize the relationship as follows:

Taken together, our data suggest that MECP2 duplication syndrome is another cause of syndromic autism in males.

This conceptualization views autism as phenomenon that can be caused by MECP2 duplication syndrome and presumably any number of other causes. The notion of syndromic autism, autism associated with a constellation of other symptoms (whether or not these comprise an identified syndrome, however, leaves open the question of whether autism can exist as a primary condition or it is always secondary to other conditions known or unknown.

With the advent of advanced diagnostic testing, such as genetic microarray analysis, more and more specific genetic conditions associated with autism have been identified. Increasingly, this has led to researchers and clinicians adopting a somewhat different model of autisms < https://www.scientificamerican.com/article/autisms-a-more-appropriate-te.... In this model, autisms are viewed as a collection of conditions that produce a set of more or less similar autistic symptoms. Although this model has been primarily promoted by geneticists, this conceptualization has much broader implications for research and intervention.

An analogous situation that may help illustrate why this is important, might be headaches. Headache can be caused by a great variety of different conditions (e.g., sinus infections, head trauma, brain tumor, hangover, stress). Some headaches are categorized as primary headaches because they are not the result of some other primary condition. If we group them all together, we may find that it is difficult to find a useful treatment. If we group them according to their primary causes, we have a much better chance of finding a successful treatment. For example, antibiotics may be effective in treating sinus-infection headaches but unlikely to be beneficial to others.

As research moves forward toward treating some of the syndromes associated with autism, the potential implication of conceptualizing them as separate autisms becomes clear. For example, both Rett syndrome and MECP2 duplication syndrome produce autistic behavior, and each of these has been shown to be reversible under laboratory conditions. However, the causes and potential treatments for these two syndromes are polar opposites. Rett syndrome is caused by underactivity of the MECP2 gene and potential treatments attempt to increase this activity, but MECP2 duplication syndrome is caused by overactivity of the same gene and potential treatments attempt to decrease this activity. While these are extreme examples, this may help to explain why so may attempts to find the cause or the appropriate treatment for autism seem to evaporate. If the collection of individuals we categorize as autistic is actually a heterogenous group there may be no single approach to understanding or treating them. To go a step further, as many articulate advocates for individuals with autism suggest, some people diagnosed with autism may just need to left alone and accepted as they are, while other may have real medical conditions and could benefit from treatment.

This issue of how we conceptualize autism can also affect research on autism. For example early in 2016, the highly respected scientific journal Nature published a report suggesting that researchers had created the first primate model for human autism. These “autistic primates” were cynomolgus monkeys genetically modified with an extra copy the MECP2 gene to have MECP2 duplication syndrome. If we conceptualize autism as a single condition with various causes, these primates may be a reasonable model for all autism. If we consider each of the many syndromes now associated with autism as a separate condition, these primates are unlikely to be a reasonable model for more than a tiny subgroup. If we only consider primary autism as genuine, these are “quasi-autistic” monkeys and do not represent primary autism.

While much of the emerging medical and scientific information moves us toward conceptualizing autisms as a basket of related conditions, there has also been a strong practical argument made against fragmenting autism into a collection of separate conditions. Perhaps the strongest of these is simply that in spite of the now long list of conditions that produce autistic (or autistic-like) behavior, the largest number of individuals diagnosed with autism have no more specific diagnosis. Whether this will change in the future remains uncertain at this time.

It might also be argued that in spite even polar differences among these specific autism syndromes there is still a useful common core. Going back to the polar opposite Rett and MECP2 duplication syndromes, for example, one might ask how could such polar opposites producing similar symptoms be seen as showing a common core of autism. Here is one idea. Both underactivity and overactivity of MECP2 reduce the responsiveness of epigenetic coding, the process by which our social environment (as well as our physical and biological environment) modifies our DNA. If we theorize autism as an epigenetic condition resulting from an inability of the affected individual to modify his or her DNA to the gestational and postnatal environment, it just might allow us to avoid the apparent conceptual fragmentation. While Rett and MECP2 duplication syndrome are an extreme example of polar opposites producing similar effects, many other disorders (e.g., Angelman syndrome, fragile-X syndrome) associated with autism also are now recognized as epigenetic disorders. Of course, this idea that all autism could be an epigenetic phenomenon remains untested, and like so many dozens other theories of autism, it too may be destined for the scrapheap.

It has also been pragmatically argued that treating autism as one condition has resulted in social and political gains including major service and funding advantages. These might be lost through fragmentation into numerous smaller groups.

There is really no consensus on how we conceptualize autism. The trend seems to be moving toward thinking of autism as the clinical presentation of a large collection of other disorders, but that trend may change. For now at least, we have three competing ways of thinking about autism:

Autism as a single primary condition that exists along with numerous distinctly, separate “quasi-autistic” conditions that share some attributes with primary autism, but are not really autism.
Autism that can be a primary condition or that may be secondary to some other recognized or unknown condition.
Autisms as a group of (recognized and unrecognized) conditions that produce similar behavioral characteristics.

Concepts of Autism, Quasi-Autisms and Autisms?

Author: Dick Sobsey

Territorial Acknowledgement