Sunday, 24 November 2013

A bottom-up approach to autism research?

If anything else, the recent discussions on the principles of RDoC - Research Domain Criteria (see here) - being applied to psychiatry have prompted many to question whether our current diagnostic labels are actually fit for purpose when it comes to answering the big research questions of how and why.

Bottoms up? @ Wikipedia 
RDoC, for those of you who might not know, is described by the US National Institute of Mental Health (NIMH) as an attempt to: "define basic dimensions of functioning (such as fear circuitry or working memory) to be studied across multiple units of analysis, from genes to neural circuits to behaviors, cutting across disorders as traditionally defined".

In other words, by all means use the DSM or ICD as your diagnostic key, but don't necessarily expect the genes (and epigenetics), biochemistry and brain / body physiology to also fit neatly into those categories that you diagnose with. The proof for this disparity is laid out in front of us all as labels such as autism or schizophrenia or ADHD remain in the most part a mystery when it comes to aetiology, common biological signatures (including replicative work) and consequently generalised intervention options to improve quality of life and functioning.

Even before RDoC I, like quite a few others, often thought that the reliance on something like the label of autism or autism spectrum as a research starting point offered little when it came to autism science. In a previous post, I did talk about the possibility of overcoming this issue as per the discussions on focusing on phenotypes - smaller subgroups on the autism spectrum - characterised by something like response to intervention for example (see here). Indeed, my recent droning on the area of dietary intervention for autism (see here) exemplified how such a shift in focus might yet yield some testable results.

Enter then another modified example of this approach with the paper by Lisa Unwin and colleagues* (open-access version here) and their discussions on a bottom-up approach to autism research. I admit that I was always going to be interested in this paper because of (a) the presence of Andrew Whitehouse on the authorship list (see previous posts here and here) and (b) mention of the 'autisms' over the more 'unitary' label of autism (see here).

As Unwin et al describe, the bottom-up approach used in the paper refers to "known aetiological risk factors, and whether individuals exposed to these risk factors have a more homogenous phenotype". In this case, low birth weight and independently maternal use of SSRIs during pregnancy (see here) were the starting points and then "examining the homogeneity within the groups based on medical complaints such as sleep problems and gastrointestinal complaints in addition to core features of ASD such as social behavior, language characteristics, and severity". Actually on the point of anti-depressant use during pregnancy and autism risk, I'm minded to bring in other, more recent evidence that suggests risk may have been over-inflated?

The first part of the Unwin paper looked at those children with an ASD where maternal SSRI use was reported during pregnancy and suggested that "children with ASD whose mothers took SSRIs during pregnancy were significantly more likely to experience gastrointestinal complaints during childhood" compared with no maternal SSRI history. The second study included in the paper examined children with ASD with a low birth weight compared against those with a normal range birth weight. They suggested "greater sleep disturbances" to be present in the former group.

Whilst the participant numbers included in this paper were low and the results are crying out for replication, I find this approach to be a breath of fresh air when it comes to autism research. Not only because of the realisation that there may be different phenotypes within the autism spectrum as a function of suggested risk factors - of which there may several (see here and here for example) - but also because the authors expanded their horizons outside of just looking at the core behavioural symptoms associated with autism. Indeed the focus on bowel issues (see here) and sleep issues (see here) reflect how frequently these variables crop up and how, for some people, they can so significantly affect quality of life.

There are some other nuggets of research gold to come out of this paper which are worthy of comment. So, "it seems reasonable that environmental factors may be related to the expression of non-core ASD symptoms among these children rather than to any variance in core symptomatology". In other words, autism might actually be greater than the sum of its triadic (sorry dyadic) parts. As per my chatter about the 'autisms' previously, the authors also note: "A key question facing the field is whether the long-held view that autism is a unitary disorder with a single causal pathway is correct, or whether autism may best be conceptualized as an umbrella term for a collection of behavioral disorders resulting from a range of causal pathways, analogous to cerebral palsy". Not surprisingly the authors conclude that the plural autism might be "a more accurate representation".

Tom Insel of the NIMH is quoted along similar lines with his phrase: "Clearly autism is many disorders". I'd have to say that I agree and that 'range' of conditions falling under the autism umbrella seems to be growing all the time.

Music maestro.... Common People by Pulp?


* Unwin LM. et al. A "bottom-up" approach to aetiological research in autism spectrum disorders. Front Hum Neurosci. 2013 Sep 19;7:606. doi: 10.3389/fnhum.2013.00606.

---------- Unwin LM, Maybery MT, Wray JA, Whitehouse AJ. (2013). A "bottom-up" approach to aetiological research in autism spectrum disorders. Front Hum Neurosci. DOI: 10.3389/fnhum.2013.00606