Insane Medicine, Chapter 4: The Manufacture of Autism Spectrum Disorders (ASD) (Part 2)

Editor’s Note: Over the next several months, Mad in America will publish a serialized version of Sami Timimi’s book, Insane Medicine. Part 1 of Chapter 4 was published last week. In Part 2, he discusses the lack of findings for any genetic or neurobiological basis for ASD, as well as the diagnostic criteria and testing for ASD. Each Monday, a new section of the book will be published, and all chapters will be archived here.

ASD genetics: Has the null hypothesis been disproven?
As previously discussed, the correct scientific stance is to assume that what we are characterising as autism or ASD does not exist as a natural category until we can demonstrate that this null hypothesis can’t be true. If we want to classify ASD as a genetically predetermined neuro-developmental disorder we have to demonstrate that the null hypothesis—that there are no specific genes or neurological abnormalities/differences—can’t be true.

The argument that autism is a strongly genetic condition rests primarily upon twin studies. I explained in the last chapter on ADHD why estimating genetic heritability using the twin method does not help you in distinguishing environmental from genetic causes. The only reliable way to establish the relevance of the genetic component is through molecular genetic studies, of which there is a growing database involving whole genome scans of thousands of children with the autism label.

No specific, characteristic, rare, common, or polygenetic genes for autism have been discovered, but not for want of looking. Various candidate genes, linkage studies, genome scans, and chromosome studies have all failed to produce and reliably replicate any particular genes associated specifically with autism. The more failures pile up, the more proponents of the genetic explanation paradigm start desperately talking about how autism genetics is “complex” and that there must be some sort of mysterious polygenetic interactions that accounts for the “missing heritability.”

The most likely explanation for this finding, or rather lack of finding— that there is no such thing as genes that cause autism—remains unmentionable.

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The continuing failure to identify specifics seems to have resulted in the majority of the human chromosome being identified as potentially harbouring autism genes, with major expert reviews typically concluding: “Many research teams have searched for genes that may be involved. They haven’t turned up any prime candidates yet, only dozens, maybe hundreds of bit players” (Hughes writing in 2012) and “With the advent of next generation sequencing techniques, the number of genes found that are associated with ASD is increasing to over 800 genes; consequently, it is becoming even more challenging to find unified explanations and functional associations between the genes involved” (Al-jawahiri and Milne writing in 2017).

The high ratio of males to females in ASD diagnoses also poses a problem for genetic theories. Genetic mechanisms need to account for this (such as autism being transmitted through the X chromosome), and thus far no molecular genetic studies have found an X or Y chromosome link.

Instead of facing up to the possibility that genes are not revealing themselves because they are not there, we are instead moving into an era where multiple research teams come together to create banks of “big data” in the hope that this can reveal tiny associations. It is hard to face the possibility that this mass of research money has led to a wasted endeavour, so instead they carry on getting the lion’s share of wasted research money because, “Sequencing technology quickly confirmed that the aetiology of ASD was multigenic and highly heterogeneous, with very few of the same pathogenic variants present in a significant percentage of afflicted individuals” (Rylaarsdam and Guemez-Gamboa, writing in 2019) and so “It may take many more decades of research before the scientific community has an accurate picture of how these modulators contribute to the aetiology of ASD. However, this understanding is critical for the development of effective therapies.”

Yes, keep throwing your research money at us. We’ve failed so far, but we need decades more of these failures to really know how badly we’ve failed, because we don’t understand the basic principles of scientific methodology. But hey, we’re scientists, we look like scientists, talk like scientists, so you should believe us.

Scientifically speaking, then, we have to assume that with regards to genetics, the cupboard is empty and the null hypothesis stands: There is no characteristic identifiable genetic abnormality/profile associated with ASD.

ASD brain imaging studies: Has the null hypothesis been disproven?
An important consideration to take into account in any analysis of neuroimaging profiles is that of “neuroplasticity.” This refers to the remarkable ability of the nervous system (particularly in children) to grow and change in response to environmental stimuli. The amazing plasticity of the human brain makes it difficult to determine precise cause and effect when individuals with different life experiences subsequently show what appear to be differences in neurological structure or functioning. This inconvenience makes it difficult for researchers to pin down behavioural features that children display as being caused by any neurological abnormalities or differences.

We see this neuroplasticity at play in all sorts of ways, from the ability that children have to compensate over time for brain injuries, to the findings that London cab drivers have larger volumes than almost anyone else of brain areas that are highly involved in navigating and spatial awareness. Thus, any brain differences found could be the result of environmental factors affecting brain development (like psychological trauma), differences in the rates that maturation takes place (for example, we know that on average girls develop a little faster than boys) and variations resulting from other features in the research subjects (for example, their intellectual ability).

It means that we can’t assume any differences we find are the result of a pre-existing biological problem. After all, the brain is the body organ whose function is that of enabling the organism to adapt to the environment. It would be surprising if the brain was not influenced by the experiences the organism has.

However, the biggest problem for autism studies, as with ADHD, comes from the lack of consistently replicated findings. This consistent inconsistency plagues research in this area. For example, some studies focussing on an area of the brain called the “cerebellum” have documented an increase in cerebellar volume among children diagnosed with an ASD, while others have found smaller than average cerebellar volumes; yet others have reported no significant differences between children with ASD and non-ASD subjects.

Similarly, studies on another area called the “amygdala” have been widely inconsistent, including some studies that found significant differences in volume and others that found no differences. This is the picture that emerges from this research. With clockwork regularity, a team of researchers announce their latest finding: “We have found that the connections between the two halves of the brain are smaller in autism, suggesting ASD is a disorder of brain connectivity,” and this then goes round the world media, but then we never hear of the subsequent research teams who can’t replicate these findings.

This shambolic, confused, and contradictory reality of autism brain research was brought home to me when I participated in a debate about autism with a colleague at an academic event in March 2017. We each had to put forward papers supporting our view. The colleague I was debating with, who believes that autism is a “known” disorder of the nervous system and that with sufficient research we will discover its neurological basis, put forward three papers to support his position. They were:

“The emerging picture of autism spectrum disorder: Genetics and pathology,” a 2015 paper by Chen and colleagues. This paper proposes that research points to a primary role in ASD for the limbic system and cerebellum.
“Neuroimaging in autism spectrum disorder: Brain structure and function across the lifespan,” a 2015 paper by Ecker and colleagues. This paper focuses on frontal and temporal lobes and the cerebral cortex as the primary sites of interest in causing ASD.
“Autistic spectrum disorders: A review of clinical features, theories and diagnosis,” a 2015 paper by Fakhoury. This paper plumps for the primary issue in ASD being the balance of excitatory and inhibitory synapses.
It’s a complete mess. No common theme emerged from these three “state of the art” research reviews. There is little overlap in their favoured theories. None of the papers properly discussed the effects of environment or possible other factors (like levels of intellectual impairment in the research samples) on the results.

Theories come and go, and no one has a clue really what, how, or where this apparent neurodevelopmental abnormality or difference is. It is a swirling cauldron of self-proclaimed scientists that cannot face up to a scary reality—that their science hasn’t met the basics required of the scientific method. Most seem unprepared to state the obvious—that the null hypothesis stands and their research maybe heading down one blind alley after another into a cacophony of dead ends.

Finally, some researchers are waking up to the idea that maybe they will not find anything. A 2016 paper entitled “ASD validity,” which includes the renowned autism researcher Professor Christopher Gillberg amongst its authors, concludes, “The findings reviewed indicate that the ASD diagnosis lacks biological and construct validity,” and they recommend disbanding the ASD diagnoses as a basis for research. Sadly, they go on to suggest a broader neurodevelopmental construct instead. None of this evidence (or rather lack of it) seems to have the slightest dent in the continuing expansion in the numbers receiving ASD labels or in the assumption that there exists a natural thing called autism.

Here too then, as far as the science is concerned, the cupboard is also empty. No one has come near to finding a characteristic abnormality, and as a result there is no biological marker or brain scan used to diagnose autism. The null hypothesis stands—there is no characteristic brain abnormality associated with ASD.

What is autism anyway?
ASD did not develop out of any scientific discovery, and it has been created and popularised through social and political drivers.

We should not be surprised by the lack of progress in discovering the biological foundations. We don’t really know how to make a useable and exclusive definition of a case. If our definition of a case includes a wide variety of features that ar