Implications of Clinical and Anatomical Heterogeneity in Autism

Someone I follow on Twitter posted a study* that examined the brain anatomy of people with autistic disorder, Asperger’s Syndrome and neurotypical controls. Unfortunately, the journal in which this study was published, is not open access, so I was only able to read the abstract. The most interesting finding was that people diagnosed with autistic disorder had increased grey matter in the temporal and frontal lobes, which was not present in people with Asperger’s Syndrome. I asked the doctor who tweeted the study whether this was likely to relate only to differences in language, or to other skills as well. He replied that the brain abnormalities implicate differences in other functions as well, but he didn’t say which. Possibly this isn’t fully known or it wasn’t considered in this study, or he thought it was so obvious it didn’t warrant an explanation (within the limits of 140 characters). Maybe in that case I should be reading my neuropsychology textbook (which I will be taking a test on in a few weeks) more closely: I do know that both the frontal and temporal lobes are involved with many functions (including language), but they are both so complex that I wouldn’t know what a general finding about grey matter volume somewhere unspecified within these lobes says about cognitive functioning.

In any case, is this neuroanatomical finding an indication that autism and Asperger’s, which may be merged into autism spectrum disorder in DSM-V, are distinct after all? Not necessarily, if we’re taking the current DSM-IV criteria: these essentially only distinguish on the basis of early language development, while the neuroanatomical differences that were found, apparently indicate other functions are involved as well. Of course, the DSM-IV criteria mention other possible differences, for example in adaptive behavior, self-help skills and IQ. These are not mandatory, but if there were grounds to assume that these constituted medically distinghuisable autism subtypes, there is all the reason to actually create different diaagnostic subcategories for them: for example, one group of autistics who have, say, a language delay, low IQ and poor adaptive behavior, and another group (we might call them Asperger’s) who have none of these. If there were a neuroanatomical basis to distinguish these two groups, it would be all the better, since neuroimaging is much more objective than any psychological test. Note, however, that current diagnostic criteria do not make such a rigid distinction, and so far there is not enough evidence to support one, since too many people would be falling somewhere inbetween if the gap were too wide, but the differential diagnosis would make little sense (as in the current situation) if the distinction were too vague.

So what if neuoimaging, neuropsychology and/or psychiatry were eventually able to actually establish objectively different autism subtypes, according to which people could be classified on a mutually exclusive basis? Would they still all fall under the umbrella of autism, or would the spectrum shatter into what may be a dozen different disorders? I think that maybe it will be a little of both, with the disorders with a more homogenous presentation and known biomarkers, being broken off the spectrum (Rett Syndrome is already a current example of this) and the others remaining within the vague realm of the autism spectrum. Another possibility is of course that they’d all still be called “autism” when referring to the clinical feature, but people would distinguish different syndromes, such as what already happens with mental retardation syndromes.

Of course, this differentiation between neuroanatomical or genetic and behavioral subtypes of autism, will also have implications for treatment, prevention and cure, assuming that researchers aren’t going to listen to anti-cure advocates anytime soon. For example, imagine that there were autism subtypes for which a prenatal test existed so that people could abort an affected unborn child, others that could not be diagnosed prenatally but could be cured with some kind of drug, still others for which no cure existed but which responded favorably to a certain treatment, and yet others for which supportive interventions were still the only possibility. This would divide the autism/autistic community not just along ideological lines, but along medically objective lines. This would not mean, of course, that some types of autism are not autism after all. To use an analogy: some types of blindness may in the near future be cured through gene therapy, and for some others, a bionic eye might work. However, for my condition, no cure exists and one is very unlikely to emerge. Note, here, that the distinction is not based on the severity of our visual impairments, but on the genetic or anatomical cause of our eye condition. Likewise, it might well turn out that certain types of “severe” autism respond to a cure, but others do not, so that it isn’t like we can just invest all our money in finding a cure (which will probably turn out way more difficult than what certain lobby groups want us to believe) even if we only focused on “severe” autism, since supportive services will still be needed for some “severe” autistics. It is also quite likely that among those with curable types of autism, there will be “mild” cases, who are now kicked off the autism advocacy bandwagon for being too “high-functioning”. The only reason Asperger’s and autism are being distinguished for research purposes, after all, is that they have made it into diagnostically different categories within DSM-IV. DSM-V is likely to take care of that, so that researchers trying to establish neuroanatomically or genetically different autism subtypes, will have to distinguish their subgroups on the basis of clearly defined clinical charactertics, or have to acknowledge that one clinical presentation can have a neurologically or genetically heterogenous profile (and vice versa, of course).

* Toal F, Daly EM, Page L, Deeley Q, Hallahan B, Bloemen O, Cutter WJ, Brammer MJ, Curran S, Robertson D, Murphy C, Murphy KC, Murphy DG (2009). Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study. Psychol Med, 2009 Nov 6:1-11. [Epub ahead of print]