Friday, 9 May 2014

Regression and autism continued (yet again)

I noticed a few weeks back that the topic of regression - developmental regression - with autism in mind resurfaced during a few media reports (see here and here). That last report by Jennifer Richler, who knows more than most about the research around regression and autism [1] particularly took my attention, and the implication that perhaps we need a little more investigation into this area with a focus on developmental trajectories and the small details which might reflect onset of the regressive phenotype(s) and indeed, any pre-regressive presentation. Whether also a history of developmental regression might affect age at diagnosis might be another question to be asked in light of the study findings from Mishaal and colleagues [2].
Journeys... @ Wikipedia 

It is therefore timely that the paper by Kern and colleagues [3] (open-access here) also appeared in my inbox recently talking about regression in relation to autism based on parental reports. The quote: "82 children (60.7%) were reported to have R[egressed]" was interesting because this seemed to be quite a high figure bearing in mind the participant group size (N=135).

My previous post on the topic of regression and autism highlighted the meta-analysis paper by Barger and colleagues [4] which at most set parent-reported regression in autism at around 40% of cases, bearing in mind how one goes about defining regression. Indeed, the recent paper by Goin-Kochel and colleagues [5] similarly found the rate to be around the 40% mark (36.9% overall) in their cohort of over 2000 children. Allowing for the assumption that rates of regression in cases of autism are a static entity and not subject to changes over time, the disparity between the figures is interesting.

I'm not on this occasion going to go through the Kern paper in excruciating detail because it is open-access. It is not altogether dissimilar from the earlier Richler paper in that parental report forms the crux of the observations and factors such as gastrointestinal (GI) issues were also included in the research mix. Where the two results separate is on a few main points: (a) Richler and colleagues included a control group; Kern et al did not, (b) Richler talks about: "no evidence that onset of autistic symptoms or of regression was related to measles-mumps-rubella vaccination"; Kern suggests: "The majority of parents reported that the regression was preceded by or was associated with vaccinations (57.3%) or another medically related event (11.0%)", and (c) Richler talks about children "who lost skills" had "more gastrointestinal symptoms than children with ASD and no regression"; Kern by contrast reports: "no significant relationship between the children’s age, gender, race, severity, or GI symptoms, and their membership in the D[elayed], DR [delayed and later regressed], or R[egressed] groups". I don't want to head too far into the discussions surrounding point (b) but will draw your attention to the paper by Woo and colleagues [6], who looking at data from the US VAERS (Vaccine Adverse Event Reporting System) observed that "The proportion of VAERS cases of autism with regression was greater than that reported in population-based studies, based on the subset of VAERS cases with medical record confirmation". I wonder if this might have something to do with the high rate of regression reported by Kerns et al also?

I was particularly interested in the differing results reported as a consequence of the presence of GI factors comorbid to core autism presentation with regression in mind. I note in the paper by Valicenti-McDermott and colleagues [7], they reported that "children with language regression more frequently exhibited an abnormal stool pattern" assuming that one equates abnormal stool pattern[s] as being the same as GI symptoms; well, functional GI symptoms at least. The paper from Mady Hornig and colleagues [8] (open-access here) adds to this sentiment with their observation that "Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD". All of this kinda puts a new slant on the recent papers confirming an over-representation of GI issues in cases of autism (see here).

I'm intrigued by the notion that combined regression and GI issues might be a distinguishing endophenotype (sub-group) in the growing plurality of autism. Autism research is still feeling its way through the concept of regression outside of something like Heller's syndrome / CDD (and anti-NMDA receptor encephalitis and other viral infections in mind) and how such reports fit into the grand scheme of how and why autism comes about. As per some recent chatter on the early [behavioural] identification of autism, regression occurring in cases of autism is also a potential fly in the ointment for establishing very early indicators of autism, further compounded by the start-stop that accompanies child development. And then there is the issue of racial differences in the reported rates of regression in autism... already covered by some media just to complicate matters further.

More to do methinks.

To close, although Europe is braced for that annual get-together that is the Eurovision Song Contest tomorrow (Saturday 10th May 2014) I'm not gonna post to any of the past or present songs. Instead, some very motivational lyrics from Kiss. Thank God.

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[1] Richler J. et al. Is there a 'regressive phenotype' of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA Study. J Autism Dev Disord. 2006 Apr;36(3):299-316.

[2] Mishaal RA. et al. Age of autism spectrum disorder diagnosis is associated with child's variables and parental experience. Res Autism Spect Disord. 2014; 8: 873-880.

[3] Kern JK. et al. Evaluation of regression in autism spectrum disorder based on parental reports. N Am J Med Sci. 2014 Jan;6(1):41-7.

[4] Barger BD. et al. Prevalence and onset of regression within autism spectrum disorders: a meta-analytic review. J Autism Dev Disord. 2013 Apr;43(4):817-28.

[5] Goin-Kochel R. et al. Developmental regression among children with autism spectrum disorder: Onset, duration, and effects on functional outcomes. Res Autism Spec Disord. 2014; 8: 890-898.

[6] Woo EJ. et al. Developmental regression and autism reported to the Vaccine Adverse Event Reporting System. Autism. 2007 Jul;11(4):301-10.

[7] Valicenti-McDermott MD. et al. Gastrointestinal symptoms in children with an autism spectrum disorder and language regression. Pediatr Neurol. 2008 Dec;39(6):392-8.

[8] Hornig M. et al. Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLoS One. 2008 Sep 4;3(9):e3140.

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ResearchBlogging.org Kern JK, Geier DA, & Geier MR (2014). Evaluation of regression in autism spectrum disorder based on parental reports. North American journal of medical sciences, 6 (1), 41-7 PMID: 24678477