"Autism prevalence in China is comparable to Western prevalence" But is it really?

I was intrigued by the findings reported by Xiang Sun and colleagues [1] whose paper is the source material for the quote heading this brief post: "Autism prevalence in China is comparable to Western prevalence."

Intrigued because the idea that the prevalence of autism - in school-aged children - hovers around 1 in 100 (1%) in the Western world is still being banded around, even when data is being produced suggesting that rates are actually increasing well beyond the 1% mark in recent times (see here and see here).

Don't get me wrong, I am impressed with the Sun paper and the significant efforts and work that went into their study to look at "autism prevalence (mainstream and special schools) in Jilin City, and mainstream school autism prevalence in Jiamusi and Shenzhen cities" in China. Impressed because of the numbers involved, the 3-stage process undertaken (screening, clinical assessment, research diagnostic assessment) as part of the study and also because the data adds to a growing volume of other studies looking at autism in China (see here and see here for examples) and nearby areas (see here).

I'm not going to bore you with any more of my musings on this paper and issue. Suffice to say that the 1% statistic is old and increasingly out of touch with the current reality of autism in many, many different nations...

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[1] Sun X. et al. Autism prevalence in China is comparable to Western prevalence. Molecular Autism. 2019; 10: 7.

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The prevalence of autism in China meta-analysed

"Based on diagnostic criteria the pooled prevalence of ASDs [autism spectrum disorder] was 39.23 per 10,000... specifically, the prevalence of autism was 10.18 per 10,000."

That was the conclusion reached by Fei Wang and colleagues [1] following their "comprehensive meta-analysis of the pooled prevalence of ASDs in China" based on data from 44 studies comprising about 2.3 million people aged below 18 years of age. Relying on data published from database inception up to February 2017, authors trawled the peer-reviewed scientific domain  - "PubMed, EMBASE, PsycINFO, China National Knowledge Infrastructure, Chinese biomedical literature service system (SinoMed) and Wan Fang" - looking for pertinent articles regarding the epidemiology of autism in China. Their results covered "30 provinces/ municipalities/ autonomous regions in China" and were in the most part conducted in the 21st century. A few studies (n=7) were rated as being of 'high methodological quality' with the remaining meeting guidance for 'moderate quality'.

Accepting that diagnosis via DSM or ICD was not the only inclusion criteria - also including "screening tools [such as the Clancy Autism Behavior Scale (CABS), Children Autism Spectrum Test (CAST) and Checklist for Autism in Toddlers (CHAT)]" - the collected figures arrived at 0.39% and 0.01% for ASD and autism are quite a bit lower than we're typically used to seeing. Take for examples, the most recent stats from the US CDC on [estimated] ASD prevalence (see here) talking about 1.7% of 8-year olds diagnosed with autism or the data from Northern Ireland (see here) (2.9% of school-aged children), and you can see quite a stark difference. Only when Wang took into account the prevalence of ASD solely based on those studies utilising screening tools does the figure of 429.07 per 10,000 equating to 4.29% look anything like the data from those other countries.

What could all this mean? Well, we do have to be a little careful not to read too much into these collected statistics. As per another paper [2] published at roughly the same time as the Wang paper, there may be various factors - 'challenges' - influencing the particular status of autism screening and case ascertainment in China that might need consideration. As far as I can see, there is for example, no national screening guidance for autism covering all of China, so "inconsistencies in screening and diagnostic procedures... and discrepancies between diagnostic criteria" are going to be potentially significant variables. Indeed, other studies have pointed to a 'high prevalence rate of suspected autism' in some parts of China (see here) which is directly contrary to the Wang findings. Alongside other potentially important factors such as 'willingness' to screen for autism and socioeconomic factors influencing 'ability' to screen for autism, and the picture that emerges is a complicated one.

But... one also has to entertain the possibility that the prevalence of autism in China *might* be different to other countries around the globe. I've kinda touched upon this quite recently (see here). I don't want to speculate too much about why this might be at this point, but some combination of genes and elements of environment could be relevant (see here) with lots more science to be done...

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[1] Wang F. et al. The prevalence of autism spectrum disorders in China: a comprehensive meta-analysis. Int J Biol Sci. 2018 May 12;14(7):717-725.

[2] Pang Y. et al. Challenges of case identification and diagnosis of Autism Spectrum Disorders in China: A critical review of procedures, assessment, and diagnostic criteria. Research in Autism Spectrum Disorders. 2018; 53: 53-66.

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"given that 81.6% of the children diagnosed with ASD had IQs below 40"

The quote titling this post - "given that 81.6% of the children diagnosed with ASD [autism spectrum disorder] had IQs below 40" - was part and parcel of the findings published by Zhijuan Jin and colleagues [1] who set about estimating the prevalence of autism or ASD among children resident in Shanghai, China.

This is not the first time that research groups have set out to determine the estimated prevalence of autism at a city / region / countrywide level in China [2], but does, I think, mark the first time that said prevalence estimates have been based on the DSM-5 description of autism (well, almost the first time [3]).

Looking at a population of some 75,000 children resident in Shanghai and aged between 3-12 years old, details of a two-stage project are described this time around. Parents and teachers completed the Social Communication Questionnaire to identify those children who might be 'at-risk' for autism/ASD. Those who were picked up as being 'at risk', were then subject to some rather more comprehensive assessment based on the use of DSM-5, of which just over 200 children were "identified as ASD cases." The estimated prevalence figure arrived at was 8.3 per 10,000 although the authors suspect that this is an underestimate...

But then back to that opening quote, and a quite a notable percentage of children diagnosed with autism who also presented with a low IQ classification. Bearing in mind the fact that there are differences in IQ ranges across different instruments, an IQ rating of 40 or below (age-adjusted) typically indicates quite a significant cognitive impairment or delay and is one facet of the diagnosis of learning (intellectual) disability. The observation from Jin et al that over 80% of their cohort could potentially be defined as such provides some important data on the combination of autism and learning disability (LD).

On previous blogging occasions when the topic of autism and LD has been discussed, the question of how prevalent is LD in autism has been a difficult one. On some occasions, the data has suggested that around 35% of children with autism have LD on the basis of IQ scores (see here). On other occasions, a figure nearer 70% has been implied (see here). The Jin data suggest that in their cohort, 70% may actually be quite a conservative estimate.

I would like to see more study on this topic. I'd like to know whether, seemingly like other ethnic groups, learning disability + autism is the more typical presentation when it comes to autism in Chinese children and how this plays out as children age into adulthood. I'd like to know whether the distinction between autism and social (pragmatic) communication disorder (SCD) noted in the DSM-5 exerted any effect on the Jin data. I'd like to know quite a bit more on this rather interesting area of investigation...

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[1] Jin Z. et al. Prevalence of DSM-5 Autism Spectrum Disorder Among School-Based Children Aged 3-12 Years in Shanghai, China. J Autism Dev Disord. 2018 Feb 16.

[2] Sun X. et al. Prevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis. Mol Autism. 2013 Apr 9;4(1):7.

[3] Jiang L. et al. Epidemiological investigation on autism spectrum disorders among preschool children in Shanghai. Zhonghua Liu Xing Bing Xue Za Zhi. 2015 Dec;36(12):1365-8.

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The epidemiology of suspected autism in Shenzhen, China

I read with interest the paper by Weikang Yang and colleagues [1] (open-access) talking about "a high prevalence rate of suspected autism in children" in Longhua District, Shenzhen (China).

Detailing results based on the administration of the Autism Behavior Checklist (ABC) to some 15,000 children - "with a response rate of 91.2 %" - authors describe how approximately 2.6% of participants scored higher than 67 on the ABC and thus "had a high probability of autism" and a further 611 children (4%) scored between 53-67 and "had questionable autism". Boys, we are also told, "were more likely to develop autism when compared with their female counterparts" and certain familial factors correlated with screening outcomes.

Bearing in mind little details such as the fact that the ABC was administered to parents and that authors "only used ABC which is a screening tool to detect cases" to reach those 'high probability' and 'questionable' diagnoses of autism, these are interesting findings. That a total of 6.6% of children in this particular part of China may have "suspected autism" represents quite a leap compared with other estimates of prevalence [2] in this part of the world. Even recent data using other screening instruments such as the Childhood Autism Spectrum Test (CAST) among other things on a paediatric population based in China only came up with a estimated figure of 119 per 10,000 (1.19%) [3].

I'm willing to accept that there are issues with screening instruments used in the context of autism (see here) and so one has to be quite careful about extrapolating from their results. The authors mention the word 'overestimate' in their text; although I might also add that their sole reliance on "mainstream middle-class kindergartens" excluding "many diagnosed cases [who] may be attending special schools" means we should be cautious about discarding their findings outright.

In light of what is continuing to emerge in terms of the 'autism numbers game' in other parts of the world I'll be interested to see how this pans out in China too, bearing in mind that autism might not be the only diagnosis/label 'on the up' in China...

Music to close, and if you have half an hour or so free, how about remembering Pierre Boulez?

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[1] Yang W. et al. Epidemiological investigation of suspected autism in children and implications for healthcare system: a mainstream kindergarten-based population study in Longhua District, Shenzhen. BMC Pediatr. 2015 Dec 15;15(1):207.

[2] Wan Y. et al. Prevalence of autism spectrum disorders among children in China: a systematic review. Shanghai Arch Psychiatry. 2013 Apr;25(2):70-80.

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Yang W, Xia H, Wen G, Liu L, Fu X, Lu J, & Li H (2015). Epidemiological investigation of suspected autism in children and implications for healthcare system: a mainstream kindergarten-based population study in Longhua District, Shenzhen. BMC pediatrics, 15 (1) PMID: 26667375

Prevalence of schizophrenia in China up: was Dohan (partially) right?

"The prevalence of schizophrenia in China has more than doubled between 1990 and 2010, with rates being particularly high in the most developed areas of modern China."

So said the study results from Chan and colleagues [1] reviewing the collected peer-reviewed "epidemiological studies of schizophrenia in mainland China published between 1990 and 2010."

Taking into account data from 42 eligible trials covering some "2 284 957 persons, with 10 506 diagnosed with schizophrenia" researchers applied some statistical wizardry "to estimate the probability of case of schizophrenia ("prevalence") by type of residency in different years."

The figures make for interesting read as the estimated lifetime prevalence rate of schizophrenia steadily rose between 1990, 2000 and 2010. Further: "In 1990 there were 3.09 (2.87-3.32) million people in China affected with schizophrenia during their lifetime. The number of cases rose to 7.16 (6.57-7.75) million in 2010, a 132% increase, while the total population increased by 18%." As per my opening sentence, area of residence in terms of industrialisation and urbanisation also seemed to exert something of an effect. I might add that this data also seems to have appeared in another publication [2] (open-access).

I have no doubt that the reasons behind the increase in cases of schizophrenia in China are likely to be numerous and complex. To say that there may be just one factor universally contributing to every case of schizophrenia in China would be a fool-hardy thing to state in these days of plural labels (including 'the schizophrenias') and multi-factorial explanations of how someone arrives at such a diagnosis. That screening and assessment facilities have no doubt changed over the course of 20 years in China is also worth mentioning.

I do however want to forward one idea that perhaps requires a little bit more investigation as potentially being pertinent to the increase in prevalence rates: food, and specifically, the idea that gluten consumption may have played a role as per the ideas of the late Curt Dohan. Quite a good overview of 'Dohan's hypothesis' can be read here by Dr Emily Deans from the Evolutionary Psychiatry blog. He basically suggested that where grain (and milk) consumption were rare, so schizophrenia tended to be rare. Conversely, where populations started to take on board grain (and milk) as a staple food, so admission rates for schizophrenia increased. Dohan produced quite a few papers discussing this hypothesis including this one [3] including the idea that foods containing gluten and casein can produce exorphins akin to certain opiates.

I've always been interested in this work given my research affinity to the idea that certain foods might have some important 'effects' on certain behaviours or diagnostic labels covering certain behaviours [4]. That ideas about gluten and casein potentially being important to 'some' autism [5] have generally emerged from the discussions in schizophrenia perhaps highlights how central Dohan has been given also the tangled history that schizophrenia and autism have at times shared.

In recent times, there has been more interest in Dohan's hypothesis and the idea that some people diagnosed with schizophrenia (or on the schizophrenia spectrum) may demonstrate specific genetic and biological issues associated with gluten and casein. I've blogged about it a few times including the idea of immunological gluten 'sensitivity' in schizophrenia (see here and see here), a possible role for food and gastrointestinal (GI) inflammation in cases (see here) allied to a possible role for milk antibodies in relation to potentially predicting the development of schizophrenia (see here). All of this set in the context of some growing interest in food and nutrition within psychiatry (see here). Such research has met with some criticism down the years but more and more the peer-reviewed evidence is highlighting how things like immune function and the concept of inflammation do seem to be important to various psychiatric labels.

Some of the elements discussed by Dohan and others seem to make sense in the context of schizophrenia and China. The idea of "rates being particularly high in the most developed areas of modern China" might imply that food and the types of food eaten in more developed areas may be slightly different from those in less developed (more traditional) areas of the country. In the context of milk consumption and given the important biology associated with milk consumption in China (quite a high proportion of the population are deemed lactose intolerant), one might also envisage some connection.

I'm not saying that a complex condition like schizophrenia is all down to food within the data coming out of China. What I am saying is that one might entertain the idea that as part of suite of potentially important variables, what someone is eating may have some bearing on their psychiatric health and wellbeing and hence potentially be amenable to change...

Music: Descendents - Everything Sucks. Dedicated to Kylo Ren and, as one of my brood observed when watching the latest Star Wars film, the fact that he is rather an angry man throughout. I'd like to think in subsequent films we might see a 'lighter' side to ole' Ben...

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[1] Chan KY. et al. Prevalence of schizophrenia in China between 1990 and 2010. J Glob Health. 2015 Jun;5(1):010410.

[2] Chan KY. et al. Urbanization and the prevalence of schizophrenia in China between 1990 and 2010. World Psychiatry. 2015;14(2):251-252.

[3] Dohan FC. Genetic hypothesis of idiopathic schizophrenia: its exorphin connection. Schizophr Bull. 1988;14(4):489-94.

[4] Whiteley P. et al. Gluten- and casein-free dietary intervention for autism spectrum conditions. Front Hum Neurosci. 2013 Jan 4;6:344.

[5] Whiteley P. Nutritional management of (some) autism: a case for gluten- and casein-free diets?  Proc Nutr Soc. 2015 Aug;74(3):202-7.

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Chan KY, Zhao FF, Meng S, Demaio AR, Reed C, Theodoratou E, Campbell H, Wang W, Rudan I, & Global Health Epidemiology Reference Group (GHERG) (2015). Prevalence of schizophrenia in China between 1990 and 2010. Journal of global health, 5 (1) PMID: 26649171

Amino acids and autism in China

Many happy returns @ Paul Whiteley

Questioning Answers is 2 years old today (19th February 2013). Happy Birthday to 'me', or should that be 'it'?

Still a relative newcomer to the blogosphere but still churning out posts on all things autism research and beyond. Just in case you thought that I did actually bake a cake for the occasion, I didn't. But if I had have done (and yes a man can make a cake), it would have looked like the cake shown alongside. So please loyal readers, take an imaginary bite and enjoy.

To task. I've had hold of the short paper by Wen-Jun Tu and colleagues* (open-access) for a few weeks/months but have only now have got round to posting about it. It continues some familiar themes on this blog on (a) the focus on the -omics and application of technologies like mass spectrometry to autism and (b) amino acids revealing some really quite interesting differences in cases of autism vs. not-autism, as they are doing in conditions like schizophrenia and chronic fatigue syndrome also. A bit out of left field but I was also interested to read the paper by Shingyoji et al on plasma amino acid profiles potentially predicting lung cancer too. Wow, these guys get around.

Anyhow. I say it is a short paper but actually the Tu paper is a letter, and although there is relatively little novelty in just looking at amino acid chemistry in autism - what's up and what's down - these days, it does look at autism in quite a different ethnic population (Chinese) compared to quite a lot of the other papers in this area.

Indeed China, as well as emerging as a world superpower albeit with some peculiarities, is also starting to put quite a bit more effort into autism as per papers like this one from McCabe** with the very interesting title: Bamboo shoots after the rain... (hence the cute picture of the baby panda shown below looking so inquiring).

The net findings reported by Tu and colleagues reflect a few things:

• Based on quite a small participant group of children diagnosed with DSM-IV autism (n=20) compared with asymptomatic controls (n=20), there were some very distinguishing plasma amino acid results found.
• Tandem mass spectrometry was the main analytical method for determining amino acids complemented by immunoassay for detecting circulating neurotransmitters such as plasma dopamine.
• Levels of some amino acids were significantly elevated (lysine, glutamate - glutamic acid and homocysteine); others were depressed (tryptophan, tyrosine, glutamine) in the autism group compared with controls.



Ailuropoda melanoleuca @ Wikipedia  

• When it came to the level of significance, the biggest group differences were in the elevated levels of leucine (p=0.000 apparently), higher homocysteine (same p-value again) and elevated plasma dopamine (ditto on the p-value).

Of course I don't really need to say too much about these findings that have not already been said. Glutamate and glutamine are already on the autism research radar for quite a few reasons; same goes for homocysteine and it's link into things like methylation and the folate metabolic pathway. Tryptophan is a potentially important one bearing in mind its metabolism into things like melatonin among other things. Leucine? Well think branched chain amino acids and that rather interesting study by Novarino and colleagues*** (see this post) in relation to autism, and one cannot help but wonder if there might be some overlap.

Interestingly, one of my papers on the gluten- and casein-free (GFCF) diet (open-access) gets a mention in the text, with the authors seemingly worried about how their results might be further worsened if and when a GFCF diet is instigated following on from some similar suggestion by Arnold and colleagues****. Indeed this is an issue which has more recently been discussed in the meta-analysis by Sharp and colleagues*****. I'm minded to respond that rather than worry about how things could 'get any worse', a closer inspection of why they have the results they have and indeed, dealing with what they actually found, might be a good starting point, accepting the study by Jim Adams and colleagues (see this post) on what might be achieved by micronutrient supplementation. That and the fact that they reference gastrointestinal (GI) issues as potentially being involved with their results which begs the question: why not try and 'sort out' the GI issues or least one of them?

From the ethnicity point of view, the Tu study is an important one given the overlap between their observations and what has been found in other more Western populations allowing for the genetic, environmental and epigenetic differences that one might envisage and the eternal question of whether autism is presented the same worldwide. Such research actually makes a really good case for doing a little bit more cross-collaborative work among different peoples in different countries with autism, based not just on genetics as seems to have been the case so far, but also more functional biochemistry too.

Because this blog is the big 2 now, and given the association between this age and the word 'terrible', a song which I always thought best encapuslates a toddler tantrum from Nirvana (sorry about the language). Toodle pip.

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* Tu WJ. et al. Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism. J Clin Biochem Nutr. 2012; 51: 248-249.

** McCabe H. Bamboo shoots after the rain: Development and challenges of autism intervention in China. Autism. November 2012.

*** Novarino G. et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 2012; 338: 394-397.

**** Arnold GL. et al. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003; 33: 449-454.

***** Sharp WG. et al. Feeding Problems and Nutrient Intake in Children with Autism Spectrum Disorders: A Meta-analysis and Comprehensive Review of the Literature. J Autism Dev Disord. February 2013.

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Tu WJ, Chen H, & He J (2012). Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism. Journal of clinical biochemistry and nutrition, 51 (3), 248-9 PMID: 23170055