I’ve previously written a post to complain about the behavioural assays that are used in research with mouse models of autism.  I’m seriously concerned that these tests just aren’t tapping into autistic behaviours, and that autistic development might be so complex and social in nature that animals like mice can’t really simulate it.  I therefore suggested that autism research with mouse models might be better limited to the molecular level.

I think it’s possible to broaden this criticism a little.  I’ve also argued that autism is a social construction and that it doesn’t really have clear biological underpinnings.  In this sense, we can see a clear contrast between autism and something like Fragile X Syndrome, which has a clear genetic cause, or anxiety, which has a clear functional/evolutionary purpose.  Both anxiety and Fragile X are associated with clear, albeit somewhat heterogeneous, biological processes; biological heterogeneity in autism is far greater.

This heterogeneity makes it difficult for us to develop a core theory or model of autism.  There are many different interpretations of what “autism” is.  One longstanding idea is that autism is probably related to a cognitive style that makes it harder to integrate lots of information in real-world contexts, or, to put things differently, that makes it easier to focus on details.  In 1989, Uta Frith (1989/2003) proposed the weak central coherence theory of autism, which has been subsequently modified (Frith & Happé, 2006).  Other variants on this basic approach include the enhanced perceptual functioning theory (Mottron et al., 2006) and context blindness theory (Vermeulen, 2012).  More recently, various Bayesian and predictive theories have been proposed (Lawson et al., 2014; Qian & Lipkin, 2011; Pellicano & Burr, 2012; Sinha et al., 2014), and variants on these approaches are emerging (e.g., Kavelis et al., 2018).  While I don’t mean to say that all of these theories are the same – there are some very important differences, but to save time, I don’t want to get into them – we can probably be justified in grouping them together as representing one extremely broad way of conceptualizing the core cognitive characteristics of autism.

However, there isn’t a consensus that autism falls somewhere within the range defined by these integrative/coherence/local processing models, broad as that range is.  On the contrary, scholars have often suggested that the major underlying factor in autism is social-cognitive.  Theory of mind has been brought forward as a possible “core deficit” (Baron-Cohen et al., 1985), although there are good reasons to doubt this.  A later refinement suggests that autism is characterized by strong systemizing and weak “empathizing,” representing an “extreme male brain” (Baron-Cohen, 2002), and while this account is somewhat simplistic and popularized, and while I fear it reinforces stereotypes and stigmas, it has gained a great deal of attention.

Yet another approach is the intense world theory, which suggests that autistic people are hyper-reactive to the world (Markram & Markram, 2010).  This is related to the idea of an excitation-inhibition imbalance in autism (Rubenstein & Merzenich, 2003).

Other scholars emphasize social experience, suggesting that young autistic children are less motivated to initiate social contact with others (Chevallier et al., 2012; Mundy, 1995).  The ensuing lack of opportunities for social learning and practice could then have cascading effects on development.  While this approach might be seen as risking the stereotyping of autistic people and risking the distraction of our attention away from the painful isolation of those autistic people who are rejected by others, it is difficult to ignore empirical evidence of reduced social orientations and joint attention in some young autistics (see, e.g., Osterling & Dawson, 1994).

Thus, we do see many competing models of autism.  While we can probably rule out some of these ideas, like the notion that an extreme male brain causes autism, others here are more compelling, and it is difficult to choose a single one.  The simplest explanation for our failure to find a single cognitive theory of autism is probably that no single core theory of autism is possible.  Autism is a social construction, and a heterogeneous range of symptom outcomes fall within our socially-constructed category of autism.  It’s extremely unlikely that the same processes have resulted in all of these outcomes.

Now, how does this relate to animal models?  Well, if we can’t agree on a model of autism, how can we agree on an animal model of autism?  If we can’t agree on the features we are trying to model, how can we then develop models?

Worse, many of these models have unclear neurobiological underpinnings.  We can model excitation-inhibition balances, but how does one translate context blindness into a neurobiological manipulation that can be implemented as an animal model?  Even for specific theories, we have something of an overdetermination problem: there might be more than one neurobiological way of producing a cognitive/behavioural outcome, and thus multiple different ways of developing an animal model, even though not all of these ways may result in “correct” models of many autistic people.  And then, as I argued before, we have the problem that assessing some behavioural outcomes may be difficult or impossible in animal models, so how would we even know if the model results in the desired outcome?

This does not necessarily make animal models useless, and I do think they animal models can have some uses in the autism field, but I think it does raise questions about whether we can truly describe anything as an animal model of autism.

Author Note, Nov. 27, 2019:

I’m starting to see more animal models looking at sensory behaviour, and I have to say I see nothing inherently wrong with this.  A known genetic variant associated with autism could be modelled in an animal and one could look at whether this animal displays atypical behaviours in response to sensory stimuli.  That being said, the sensory systems of some animals are quite different from those of humans, so there is some need for caution in this area.  Furthermore, one could also examine sensory-related behaviours in humans with the genetic variants, and perhaps the humans might be able to describe something about their sensory experiences as well.  Thus, it seems as though the animal models might chiefly be useful insofar as they would allow for additional exploration of the molecular and neurobiological mechanisms underlying the behavioural sensory responses, in addition to other advantages such as the ability to more rapidly explore longitudinal trajectories.

References

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