Showing posts with label identification. Show all posts
Showing posts with label identification. Show all posts

Tuesday, 31 October 2017

Colliding spectrums: autism and schizophrenia (meta-analysed)

Consider this post talking about the findings reported by Jorge Lugo Marín and colleagues [1] an extension of previous chatter on this blog about the possibility of overlapping spectrums when it comes to autism and schizophrenia (see here).

I appreciate that there is some 'history' when it comes to moves to separate autism and schizophrenia [2] but the evidence being produced more recently perhaps questions whether the historical 'eagerness' to compartmentalise the labels as separate and independent was more of a socio-political thing over and above a true reflection of the state of any relationship (see here and see here for examples). Indeed, when [peer-reviewed] science for example, starts talking about a possible 'subtype of autism linked to psychosis' (see here) you know that the connections are perhaps not to be under-estimated...

Lugo Marín et al report results following a meta-analysis of the relevant peer-reviewed science done on this topic. Ten papers fulfilled their inclusion criteria. They report that: "The pooled prevalence of SSD [schizophrenia spectrum disorder] in the total ASD [autism spectrum disorder] sample was close to 6%, pointing to a high co-occurrence of the two conditions." Further, that more research is required about the specific hows-and-whys of SSD or symptoms of SSD appearing alongside [some] autism (and vice-versa) and onward, the possibility of preferential screening and intervention.

I've thought about the relationship between autism and schizophrenia quite a bit over the years. Not only because in my own area of research interest - gluten- and casein-free diets and autism - there is history linking autism and schizophrenia (see here) but also because the relationship down the years seemingly plays into the stigmatisation of a label i.e. move autism 'away' from schizophrenia because of the perceived 'dangerousness' connotations attached to schizophrenia for example (see here for a more recent example of this in action [3]). On that point, the evidence is getting clearer that whilst the diagnosis of schizophrenia (plus other factors) is by no means preventative of 'dangerous' acts being committed, people diagnosed with the condition are seemingly far more likely to be victims of something like crime than perpetrators (see here). Sounds familiar doesn't it?

Then also there is the 'identity' perspective to consider when talking about autism and schizophrenia in the same breath. Schizophrenia is considered to be a mental health issue; autism by contrast is primarily viewed as a developmental condition, which, although increasing the risk of developing a mental health issue (see here for example), is not itself described as such per se. I say this acknowledging that support for schizophrenia as being a 'neurodevelopmental disorder' is also growing [4] as words like 'prodrome' become more frequently discussed. Also important in this context, are the possible effects of certain comorbidity being 'over-represented' in cases of autism potentially also impacting on the subsequent risk of a diagnosis of schizophrenia (see here).

Keeping the theme of 'identity' going when discussing autism and schizophrenia, there is another angle to consider in terms of 'ownership' of the labels and perceptions around such a concept. I speak of the movement towards use of terms like 'autistic person' over 'person with autism' preferentially considered by some (see here) and how such a move is seemingly at odds with identity in terms of schizophrenia. The term 'schizophrenic' is considered unsuitable in this day and age (see here - "A person is not the sum total of the symptoms") alongside other 'label-first' terms such as 'manic depressive' and 'psychotic' for example. You can perhaps see how labelling someone as 'autistic' whilst at the same time labelling them has 'having schizophrenia' under circumstances where the two spectrums collide, presents a quandary when it comes to language and identity and perhaps serves to reiterate the gulf between the labels/conditions in terms of perceived stigma for example.

What we can say on the back of the Lugo Marín findings is that, in these days of ESSENCE (see here) and RDoC (see here) the possible reunification of the autism and schizophrenia spectrums in specific cases, should not be seen as something detrimental to either label and could provide some important insights into the genetic and biological nature of both spectrums (see here). I have my views about where the two spectrums might meet on a biological level [5] but no doubt there will be lots of other intersections too. Indeed, once again harking back to the [sadly forgotten] writings of Mildred Creak and colleagues and their "9 key features of ‘schizophrenic syndrome in childhood’", their description is uncannily pertinent to large parts of the autism spectrum when taking into account inclusion of diagnostic items such as "abnormal perceptual experience", "distortion in motility patterns" and "acute, excessive and seemingly illogical anxiety" and the often pronounced effects that such symptoms can have on quality of life.



To close, a picture relevant to today...

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[1] Lugo Marín J. et al. Prevalence of Schizophrenia Spectrum Disorders in Average-IQ Adults with Autism Spectrum Disorders: A Meta-analysis. J Autism Dev Disord. 2017 Oct 4.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.

[3] Sasson NJ. & Morrison KE. First impressions of adults with autism improve with diagnostic disclosure and increased autism knowledge of peers. Autism. 2017 Oct 1:1362361317729526.

[4] Owen MJ. et al. Neurodevelopmental hypothesis of schizophrenia. The British Journal of Psychiatry. 2011;198(3):173-175.

[5] Prata J. et al. Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation. 2017 Sep 4;14(1):179.

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Monday, 24 February 2014

The [universal] early identification of autism or not?

As I might have already intimated, whilst I'm all in favour of the very early identification of autism and the potential effects this might bring to a child in terms of something like benefiting from early intervention, I'm not overly enthused by the collected evidence which has been amassed so far in this area despite some promising data.
Under my umbrellas @ Wikipedia 

Most people with some knowledge of autism will know that it is an extremely heterogeneous condition, with presentation also seemingly tied up with the risk of various other comorbidity appearing alongside. That autism also seems to include an element of regression for quite few on the spectrum, means that the holy grail that is very early red flags hinting at the earliest manifestation(s) of autism is going to be a difficult universal concept to find. Also complicated by various other factors including ethnicity, issues around the possible stability of symptoms in the early years and the possibility of plural autisms. Oh and healthcare providers can, on occasion, be barriers themselves too (see here).

Two papers recently caught my eye on this topic, coming to quite different conclusions.

The first paper by Samango-Sprouse and colleagues* based on an impressive participant number (N=1024) reported that their "study demonstrates an efficient means to identify infants at risk for autism spectrum disorder by 9 months of age and serves to alert primary care providers of infants who are vulnerable for autism spectrum disorder before symptoms are discernible by clinical judgment of primary care providers, parental concerns, or by screening questionnaires". They arrived at this conclusion on the basis of "abrupt head circumference acceleration and the absence of head tilt reflex by 9 months were used to identify infants at risk for autism spectrum disorder". So, with some more work to do, looking at head size and the head tilt reflex might be something to watch for in subsequent publications.

The second paper by Stenberg and colleagues** including an authorship list of the great and good of autism research (including Drs Hornig and Lipkin) came to a rather different conclusion based on the behavioural identification of children aged 18 months as likely having autism: "results imply that it might not be possible to detect all children with ASD at this age". Their participant size was even more impressive.

Of course I am kinda looking at apples and pears in comparing these two findings. The Samango-Sprouse study looking at something rather more physiological than behavioural, as compared to the Stenberg findings which was putting the M-CHAT (Modified Checklist for Autism in Toddlers) screening tool through it's paces based to a large part on the MoBa cohort. Again, with ear to the autism research ground, some people might remember that M-CHAT (itself a revision of the CHAT) has gone through even more adaptation fairly recently with the Diana Robins paper*** talking about M-CHAT-R/F (see here for more details). One therefore wonders if the Stenberg findings are already out-of-date even before they were published?

Insofar as the issue of rapid head circumference acceleration being potentially linked to the development of autism, well, we know the topic of head size and autism is a complicated one (see this previous post). I'm also thinking back to the work that came out the MIND Institute a couple of years back, which suggested that brain enlargement in relation to autism might show some link to the issue of regression (see here) at least for some types of autism. Quite how this data (if reproduced) would impact on the Samango-Sprouse findings is still unclear.

Don't get me wrong, the issue of early red flags potentially pointing to autism is a very, very important area of autism research. Every once in a while one hears about some ground-breaking research that a new marker for autism is on the horizon - see Jon Brock's post one example of this a few months back - but more often than not, nothing further comes of such research. What perhaps I would like to see more of in this area are a few things:

  • some better appreciation for 'the autisms' over the singular concept of autism (and different developmental profiles / red flags potentially being present across different sub-groups?),
  • greater amalgamation of various sources of information, behavioural and physiological, to see if looking at overt signs and symptoms together with something like head growth charts, might actually yield more real-world effects in combination. Although seemingly forgotten, the issue of airway anatomy and autism (no, really) might also be something to include here alongside other early markers that have been previously suggested.

Oh, and remember that at least one of the diagnostic schedules to denote autism or not has recently gone through a bit of a change, so one waits to see how this might affect all this early identification talk too.

Music to close. Having seen the Lego Movie not-so-long ago with some of my brood, I can very much recommend it for all ages. And just remember: everything is awesome...

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* Samango-Sprouse CA. et al. Identification of infants at risk for autism spectrum disorder and developmental language delay prior to 12 months. Autism. 2014 Feb 18.

** Stenberg N. et al. Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample. Paediatr Perinat Epidemiol. 2014 Feb 18.

*** Robins DL. et al. Validation of the modified checklist for Autism in toddlers, revised with follow-up (M-CHAT-R/F). Pediatrics. 2014 Jan;133(1):37-45.

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ResearchBlogging.org Samango-Sprouse CA, Stapleton EJ, Aliabadi F, Graw R, Vickers R, Haskell K, Sadeghin T, Jameson R, Parmele CL, & Gropman AL (2014). Identification of infants at risk for autism spectrum disorder and developmental language delay prior to 12 months. Autism : the international journal of research and practice PMID: 24550549



ResearchBlogging.org Stenberg N, Bresnahan M, Gunnes N, Hirtz D, Hornig M, Lie KK, Lipkin WI, Lord C, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Surén P, Susser E, Svendsen BK, von Tetzchner S, Oyen AS, & Stoltenberg C. (2014). Identifying Children with Autism Spectrum Disorder at 18 Months in a General Population Sample Paediatr Perinat Epidemiol. DOI: 10.1111/ppe.12114

Monday, 29 April 2013

Autism and the folding placenta

Men don't generally talk about placentas it has to be said. But today, in the name of blogging, I'm going to.

I'm going to start by telling you how the placenta really is a marvel of biological engineering. An absolutely vital part of our existence in-utero that nourishes us and protects us during our earliest days living in the amniotic sac. Little wonder that whole nations have come to revere the placenta as mother, sibling even doubles of ourselves (see here). Although I have to say I do draw the line at placenta pate.
 Folding time @ Wikipedia  

The reason for all this appreciation of the placenta follows the publication of a paper by Cheryl Walker and colleagues* who, as part of the MARBLES initiative (don't you just love these acronyms), reported that looking for trophoblast inclusions (TIs) in the placenta "could serve as a predictor for children at elevated risk for autism spectrum disorder (ASD)".

Trophoblasts by the way, are a specialised group of cells which play an important role in processes like embryo implantation. Trophoblast inclusions are abnormal cell cluster which form, "a distinctive microscopic placental morphological abnormality" linked to tissue folding described by some of the same authors in earlier work in this area**.

In the most recent paper, the authors detail the blinded examination of 117 placentas (used of course) from "at-risk" siblings of children already diagnosed with an autism spectrum disorder (ASD) compared with 100 control specimens for the frequency of TIs. Whereas control placentas had no more than 4 TIs, the at-risk sibling placentas "had an eight-fold increased odds of having two or more TIs" according to accompanying press.

Prediction values, as in blinded prediction of those at-risk siblings compared to controls were reported according to the number of TIs identified. In other accompanying press literature on this study, a figure of 90%+ accuracy is reported "to identify without prior knowledge which of the placentas came from the younger sibling of a child with autism, and which from another study participant who did not have autism in the family".  This however was offset by corresponding issues with sensitivity. The implication for this work being that examining placentas might yield either important information about the subsequent risk of a child developing autism or an ASD and/or lead to new clues about the prenatal environment linked to cases of autism.

I highlighted the previous paper by some of the authors in this area and note how in that study they were actually looking at archived placental tissue from those who were subsequently diagnosed with ASD (n=13). Indeed in that study, TIs were reported as present in 5 of the 13 samples from participants with ASD (38%) compared with 8 of 61 controls (13%). You can perhaps see from these figures that we are probably not talking about an all-or-nothing relationship when it comes to TIs 'predicting' autism or not.

There's no doubt that the Walker results are interesting and potentially informative if reproducible bearing in mind I'm still a little unclear on the hows and whys of TIs and autism risk. Sure, the authors speculate that this might be part and parcel of some of the genetic landscape of autism, given the link between TIs and chromosomal disorders***, but that might not be the whole story**** (thanks Natasa) and with some interesting knock-on effects***** (open-access). Please note I am not making links between any specific infection, autism and TIs at this point.

I'm very interested in this whole area of pregnancy and gestation as perhaps being critical times for autism, sorry the autisms; recognising that this area of investigation might not cover every case of autism - think regression for example. I'm minded also to take you back to the Barker hypothesis (see this post) and think whether or not one might extrapolate some of the work on placental functioning****** to overlap with autism risk? Just thinking out loud as others eminently more qualified than I already have.

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* Walker CK. et al. Trophoblast inclusions are significantly increased in the placentas of children in families at risk for autism. Biol Psychiatry. April 2013.

** Anderson GM. et al. Placental trophoblast inclusions in autism spectrum disorder. Biol Psychiatry. 2007; 61: 487-491.

*** Kliman HJ. Structural abnormalities in the placenta. BMC Pregnancy and Childbirth. 2012; 12(Suppl 1): A3.

**** Banks J. et al. Chlamydia trachomatis infection of mouse trophoblasts. Infection & Immunity. 1982; 38: 368-370.

***** de la Torre E. et al. Chlamydia trachomatis infection modulates trophoblast cytokine/chemokine production. J Immunol. 2009; 182: 3735–3745.

****** Henrikson T. & Clausen T. The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstetricia et Gynecologica Scandinavica. 2008; 81: 112–114.

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ResearchBlogging.org Walker, C., Anderson, K., Milano, K., Ye, S., Tancredi, D., Pessah, I., Hertz-Picciotto, I., & Kliman, H. (2013). Trophoblast Inclusions Are Significantly Increased in the Placentas of Children in Families at Risk for Autism Biological Psychiatry DOI: 10.1016/j.biopsych.2013.03.006