Four Autism Subtypes

Princeton University announced a study and subsequent paper in Nature Genetics about four distinct autism subtypes.  I missed it at the time.  I don't follow things as assiduously as I used to. 

It is gratifying to see something I predicted start to come to pass. Because autism shows clear symptoms and collections of symptoms, it has long been known that there is a strong biological component. Family studies and genetic evidence show that it is in fact largely heritable.  But it has been elusive - expected symptoms are simply not there sometimes, and some co-occurring conditions are frequent enough to make one wonder if an individual presentation is some variant of OCD or ADHD, or how the clear depressive/anxiety symptoms fit into the explanation.  For this reason I started saying a decade ago that there must be subtypes clouding the picture. I didn't have the knowledge to do more than wave my hands at what those subtypes might be, but there was clearly something that had more OCD elements and something that had more impairment of theory of mind/inability to consider alternative explanations. Common symptoms like demand avoidance have a variety of presentations, sometimes are not present, and sometimes are found just as strongly in people who have not a hint of autism elsewhere. That should suggest it is a useless category, but it isn't. When you work with patients it is prominent and you develop techniques for working around them.  (Unfortunately, these techniques do not work on theoretically higher-functioning people like your supervisor.)

Though I conceded that there was a spectrum to the condition, I thought it was not only a spectrum. The idea of a wheel/pie chart of symptoms, and the older multipolar theories still had explanatory power for me. The most serious cases, which require significant intervention and resemble what we have always called autism, or in Europe, Asperger's Syndrome were not only more severe, but somehow qualitatively different, as if some further thing was broken - yet not always the same thing. The Princeton study identifies a reason for two of the categories having more serious presentations: de novo mutations for one and rare variants for the other. De novo mutations usually have little effect, though more often negative. Changing your genetic programming at one tiny location usually just gets overrun by redundancy effects in development.  However, just the wrong change at just the wrong place can be catastrophic. The effect for rare variants is similar but usually milder. The parent who passed it to you and all those before who passed it to them survived and had fertile young, after all. 

The team also found that autism subtypes differ in the timing of genetic disruptions’ effects on brain development. Genes switch on and off at specific times, guiding different stages of development. While much of the genetic impact of autism was thought to occur before birth, in the Social and Behavioral Challenges subtype — which typically has substantial social and psychiatric challenges, no developmental delays, and a later diagnosis — mutations were found in genes that become active later in childhood. This suggests that, for these children, the biological mechanisms of autism may emerge after birth, aligning with their later clinical presentation. 

This also made immediate sense to me. In other psychiatric conditions symptoms do not always show at birth. They may activate under the hormonal influences of puberty and proceed slowly. Late-onset paranoid schizophrenia comes on so gradually that symptoms are not clear until the late thirties or beyond.  We can sometimes retrospectively see that the illness was present in the early 30s, some few quirks that no one thought much about at the time. In such patients, development was normal for a considerable time, and many cognitive systems are entirely intact. That this is also true for autism adds up. 

 The team also found that autism subtypes differ in the timing of genetic disruptions’ effects on brain development. Genes switch on and off at specific times, guiding different stages of development. While much of the genetic impact of autism was thought to occur before birth, in the Social and Behavioral Challenges subtype — which typically has substantial social and psychiatric challenges, no developmental delays, and a later diagnosis — mutations were found in genes that become active later in childhood. This suggests that, for these children, the biological mechanisms of autism may emerge after birth, aligning with their later clinical presentation.