What do "Self-Identified Persons With Autism" tweet about?

"This study aims to explore the feasibility of using the Web-based social media platform Twitter to detect psychological and behavioral characteristics of self-identified persons with ASD [autism spectrum disorder]."

That was the study aim described by Yulin Hswen and colleagues [1] demonstrating that everyone's various musings on social media platforms like Twitter are fair game for lots of different people and different uses (see here) including that of research purposes. As if to prove the point, authors also mention that: "This study was considered exempt from ethical review because only publicly available Web-based data collected from the Twitter platform were analyzed."

Researchers reported that "152 self-identified users with ASD and 182 randomly selected control users from March 22, 2012 to July 20, 2017" were the lucky (unsuspecting) participants of their study. Said participants were also chosen "from users who consented on Twitter to disclose their data publicly (ie, no privacy settings were selected by users) and are completely public." Various hashtags were used to identify said users (participants) including the #actuallyautistic tag, as researchers mention how their study was "the first study to identify ASD users through Twitter." Hmmm...

So what did researchers do? They examined the content of tweets. They examined tweets in relation to "the emotions of fear, anxiety, and paranoia" on the basis that previous investigations have "identified these emotions as key differentiating emotions of persons with ASD compared with matched populations without an ASD diagnosis." I'm not too sure that such sweeping generalisations are pertinent to everyone on the autism spectrum but there you go...

That's not all, as we are told that "the presence of OCD-related tweets" was also included for analysis. OCD refers to obsessive compulsive disorder, and the reasoning behind this was "to understand whether these symptoms are present among Twitter users with ASD and whether the presence or absence of digital obsessive-compulsive symptoms could assist in reducing misdiagnoses of ASD." There is the potential for overlap between autism and OCD (see here for example) so this makes sense. A few other parameters were also included for study including what time people tweet at.

Results: people (both autistic / with autism and not autistic) tweet quite a lot. I don't think anyone should be surprised at this (certainly I'm not). Onward: "Users with ASD posted a greater number of tweets compared with control users for all 3 emotions" under investigation. When they added up the total number of tweets from the groups mentioning the words fear, anxiety and paranoia, "Twitter users with ASD posted a higher number of tweets compared with control users."

Also: "Users with ASD posted a higher number of tweets compared with control users for 4 OCD-related keyword categories—fixate,... count,... excessive,.. and concern." That being said, for 8 other 'OCD-related keywords' such as 'obsess' and 'worry' there was no statistical difference between the groups. I'm not exactly sure what the word 'freak' also included in the OCD-related keywords had to do with OCD or anything else. But ho-hum.

So what was the net result of all this? To tell you the truth, I honestly don't know for sure. OK, some people who 'self-identify as autistic' seem to tweet certain words more frequently, but does this actually mean anything? Does the content of their tweets really reflect their emotional or other state? And is there anything like 'an autistic tweet' or 'pattern of tweets'? I'm inclined to say probably not despite the findings reported by Hswen et al. We're some way of from diagnosing autism or anything else by social media content in case you're wondering.

Caveats? Well, lots. The use of 'self-identifying' as a proxy for 'actually diagnosed' and the problems associated with that is a standout issue. Even the authors acknowledge that: "There is a possibility, however, that there are some who might have self-diagnosed themselves as having ASD without a clinical consultation, and we, therefore, cannot verify the clinical diagnosis of ASD in our study population." Er, yeah, this is an issue. And once again I'm going to post some science - peer-reviewed science - on why formal diagnosis trumps self-diagnosis every single time (see here and see here for examples). Also: "Twitter users who self-identify as having ASD may not be representative of the general population of individuals with ASD." Another big yes from me, on the basis that (a) large swathes of the population, whether diagnosed with autism or not, are not all that keen on using social media, and (b) autism is a label that covers a huge amount of heterogeneity in terms of the population it covers, meaning that some people can't access things like Twitter in the same way as others can. It's highly unlikely that one would be able to say that any group of Twitter users are representative of any group in 'the real world' and that includes those diagnosed with autism. I'd even argue that talk about an 'autistic community' on something like Twitter or anything else is a misnomer given the huge heterogeneity in functioning, views and opinions that is present across the autism spectrum (see here).

And since we're on the topic of Twitter data being mined and researched, the paper by Giorgianna Passerello and colleagues [2] continues the theme...

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[1] Hswen Y. et al. Using Twitter to Detect Psychological Characteristics of Self-Identified Persons With Autism Spectrum Disorder: A Feasibility Study. JMIR Mhealth Uhealth. 2019 Feb 12;7(2):e12264.

[2] Passerello GL. et al. Using Twitter to assess attitudes to schizophrenia and psychosis. BJPsych Bull. 2019 Feb 20:1-9.

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"NMDAR-antibody encephalitis might best be described as a mixed mood-psychosis syndrome"

Every once in a while a paper comes along with the potential to 'really shift opinions'. I'm gonna place the publication by Adam Al-Diwani and colleagues [1] in that category, and their (pre-registered) systematic review around the topic of N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis.

NMDAR-antibody encephalitis reflects a condition characterised by the immune system failing to identify self as self. For whatever reason, the immune system starts treating specific cells of the body as 'enemy' and mounts an immune attack against them. This results in the formation of specific antibodies - "against the NR1 subunit of the NMDA receptor" [2] - also typically resulting in "psychiatric features before progressing to seizures, a complex movement disorder, autonomic dysfunction, and hypoventilation." The book and film 'Brain on Fire' is about as good an education as you might need on the personal costs and effects of NMDAR-antibody encephalitis.

As Al-Diwani et al mention, things are getting rather interesting for NMDAR-antibody encephalitis in psychiatric circles. Awareness of the condition is growing, albeit with further 'flesh on the bones' required in terms of clinical features to look out for which could accompany the biological testing for the condition. Researchers sought to do just that: "the psychopathology of NMDAR-antibody encephalitis needs to be clearly defined to encourage accurate clinical identification and prompt treatment."

They trawled the peer-reviewed scientific literature looking for mention of NMDAR-antibody encephalitis, and eventually settled on over 300 records describing 1100 people in total. Over 460 of those people were identified with "definite NMDAR-antibody encephalitis according to consensus criteria" and their psychiatric features were examined. "The authors extracted 50 lower-level psychiatric features reported in these 464 patients, defined their frequency, and grouped them into eight higher-level features." Further comparisons were made leading to them assessing "whether individual patients were best described by one or by several psychiatric diagnoses" used as comparators.

Various features were potentially important: "The most common higher-level features were behaviour (316 [68%]), psychosis (310 [67%]), mood (219 [47%]), catatonia (137 [30%]), and sleep disturbance (97 [21%]), and these features frequently coexisted in individual patients." Various interesting graphs and figures are presented by the authors to illustrate their findings. The end result was the description of NMDAR-antibody encephalitis as "polymorphic and not to respect traditional psychiatric classifications." That being said, the notion of a "mixed mood-psychosis syndrome" represents as good a description as any based on the Al-Diwani findings.

Other details? "Overall, the age and sex distribution centred around young women, and the frequency of cases was greatly reduced after 40 years of age." Important information there about a potentially vulnerable group. Also: "139 (30%) of 464 cases were associated with ovarian teratoma, seven (2%) with previous herpes simplex virus encephalitis, and 24 (5%) with pregnancy." Ovarian teratoma is described as a rare cancer categorised as a 'germ cell tumour'. The *link* between ovarian teratoma and NMDAR-antibody encephalitis is something that has been of interest for a few years [3] and perhaps provides a clue for further investigation.

I do stand by my 'game-changer' type comment of the Al-Diwani paper. There is of course more to do in this area (including examining a curious link between NMDAR-antibody encephalitis and 'an autistic-like regression' in some children which is becoming all the more prominent in the research literature [4]). Putting all the various features identified by the authors into a useful set of diagnostic criteria is also a next step...

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[1] Al-Diwani A. et al. he psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. The Lancet Psychiatry. 2019. Feb 11.

[2] Finke C. A transdiagnostic pattern of psychiatric symptoms in autoimmune encephalitis. The Lancet Psychiatry. 2019. Feb 11.

[3] Acién P. et al. Ovarian teratoma-associated anti-NMDAR encephalitis: a systematic review of reported cases. Orphanet J Rare Dis. 2014;9:157.

[4] Khundakji Y. et al. Anti-NMDA receptor encephalitis in a toddler: A diagnostic challenge. International Journal of Pediatrics and Adolescent Medicine. 2018; 5: 75-77.

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"parental asthma was associated with slightly elevated risk of ASD in offspring"

The paper by Tong Gong and colleagues [1] provides the blogging fodder today and the finding that "parental asthma was associated with slightly elevated risk of ASD [autism spectrum disorder] in offspring."

As unusual as it might sound to some people that a condition primarily affecting the lungs *might* show a connection to a developmental diagnosis in offspring, this is not the first time that asthma and autism has been talked about on this blog (see here and see here). Granted, much of that previous peer-reviewed research has been looking at the possible *connection* between asthma and autism diagnosed in the same person (albeit not necessarily always describing a link). But there is some research history connecting the two labels. Indeed, one of the primary comorbidities that can follow a diagnosis of autism - attention-deficit hyperactivity disorder (ADHD) - seems to have an even stronger *association* with asthma (see here).

Gong et al set out to investigate a few important issues: "the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to β2-agonists, other asthma medications and offspring ASD." It would be difficult to describe the Gong study as 'underpowered' given that their use of those fabulous Scandinavian population registries - this time in Sweden - covering "all children (N=1,579,263) born in Sweden 1992-2007." From the total population, researchers identified some 22,000 children diagnosed with an ASD. They looked at their exposure to "parental asthma or prenatal asthma medications" and compared the data with other populations (not diagnosed with autism) including various degrees of siblings and extended family members.

As per the title of this post, a possible *association* was revealed between parental medical history of asthma and offspring risk of a diagnosis of ASD. Asthma in either parent seemed to show a connection, but maternal asthma showed the stronger connection. Also: "The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings... full-cousins... and half-cousins." This suggests that familial factors were not 'confounding' factors. Another detail is important to mention: "Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD." This is an important detail. It mirrors the findings reported in the paper by Su and colleagues [2] looking at another Scandinavian cohort, and their conclusion: "children born to women who used β2AA [β2-adrenoreceptor agonist] during pregnancy have an increased risk of ASDs in later life" with the caveat that risk of offspring autism was "more likely due to underlying maternal diseases rather than the exposure to β2AA itself."

Implications? Well, several. Not least that more study is required looking at the biological and genetic links between autism and asthma. Y'know, something along the lines of the fact that 'autism genes are probably not just genes for autism' (see here) and how autism has been previously studied in the context of lung architecture too (see here).

What else? How about examining the possibility of some shared biological mechanisms also at work? Perhaps start with inflammation for example [3] and work through other potential immune-related issues as well (see here). And how about also thinking about the possibility of shared 'exposure' events being potentially important? Asthma is a condition affecting the lungs. Something like air pollution is therefore a prime suspect when it comes to the development and continuation of the condition. Likewise, air pollution is no stranger to the autism peer-reviewed research landscape (see here for example). Is it possible that air pollution might be implicated in asthma and autism?

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[1] Gong T. et al. Parental asthma and risk of autism spectrum disorder in offspring: a population and family based case-control study. Clin Exp Allergy. 2019 Feb 11.

[2] Su X. et al. Prenatal exposure to β2-adrenoreceptor agonists and the risk of autism spectrum disorders in offspring. Pharmacoepidemiol Drug Saf. 2017 Jul;26(7):812-818.

[3] Murdoch JR. & Lloyd CM. Chronic inflammation and asthma. Mutat Res. 2010;690(1-2):24-39.

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Madeleine Portwood: a pioneer

A short post today to celebrate the life and mark the passing of a friend and pioneer: Madeleine Portwood who died a few days ago (February 2019) after a long illness.

Madeleine was so much more than her Educational Psychologist title conveyed. She was a trailblazer; writing several books on the topic of dyspraxia (also known as developmental coordination disorder). She was a researcher. And she also wasn't afraid to court the odd bit of controversy either (see here).

I had the pleasure of working alongside Madeleine on several occasions; most recently on a study that we're just data analysing at the moment. She was always the seasoned professional, with a no-nonsense approach to everything she turned her hand to and a dry humour accompanying her intellect. She wasn't afraid to voice an opinion, and for that and many other reasons she was always held in high esteem by many.

My condolences go to her family and friends. She will be missed.

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Melatonin pathway dysregulation driving melatonin issues associated with autism?

The paper published by Anna Maruani and colleagues [1] provides the blogging fodder today and the observation that: "melatonin variations in ASD [autism spectrum disorder] could be mainly driven by melatonin pathway dysregulation."

Melatonin has been part-and-parcel of the autism research landscape for many, many years (see here). Most people with some knowledge of melatonin will probably know of its connection to the sleep-wake cycle and the reasoning behind the use of supplemental melatonin to [hopefully] improve sleep in some people and groups of people (see here). Indeed, for some of those diagnosed as being on the autism spectrum who present with often significant sleep-related problems (see here for example), the clinical use of melatonin has been nothing short of miraculous for some when it comes to improving several parameters of sleep [2]. But melatonin is also quite the molecular handyperson too (see here) outside of just the sleep-wake cycle...

As to the precise reason(s) why melatonin appears to be an issue for 'some autism', science so far has been pretty short on firm conclusions. The Maruani study set out to try and cast some further light on the hows-and-whys around melatonin, specifically looking at both measured levels of melatonin in plasma and also pineal gland volume (PGV), on the basis that the pineal gland produces melatonin. Researchers report estimated measurement of PGV "with magnetic resonance imaging (MRI) with a voxel-based volumetric measurement method" in "78 individuals with ASD, 90 unaffected relatives and 47 controls."

Their results were interesting: "We first found that both early morning melatonin level and PGV were lower in patients compared to controls." Those early morning melatonin levels - "collected between 8:30 and 10:30 a.m." - were measured using "a radioimmunoassay" method looking at plasma samples. As well as lower plasma melatonin being described in the autism group compared with the other groups, researchers also observed that: "Relatives displayed to a lesser extent a reduced level of melatonin compared to controls, but that did not reach significance z = 0.88, p = 0.38)." Potentially also interesting.

Further: "Analysis revealed that the volume of the pineal gland was lower in patients than in controls, and lower in relatives than in controls." Some additional statistical modelling led however to the conclusion that: "PGV acted as a modest contributor to the melatonin deficit observed in ASD." In other words, as per the title of this post "melatonin variations in ASD could be mainly driven by melatonin pathway dysregulation" over and above just the physical volume of the part of the brain charged with producing melatonin.

Mention of 'melatonin pathway dysregulation' in the Maruani results got me thinking about previous study results discussed on this blog (see here). The results from Pagan and colleagues [3] provided some pretty valuable insights into the biochemistry of melatonin and some of the 'in-betweener' compounds involved in it's formation. Specifically: "a disruption of the serotonin-NAS [N-acetylserotonin] -melatonin pathway in ASD." Add in other research (see here) talking about low levels of one of the metabolites of melatonin being noted in parents, and there's a case for looking further at the biochemistry of melatonin synthesis in relation to autism over and above just volumes of brain structures. Indeed, how about beginning with examinations of the starting material for melatonin - the amino acid tryptophan - and see where this might take us (see here and see here).

Oh, and it appears that the pineal gland is probably not the only place that melatonin is synthesised [4]. Perhaps further investigation in this area might also want to look at "the enterochromaffin (EC) cells throughout the gut" for example, and their potential role/effect with melatonin (and its precursors) and autism in mind...

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[1] Maruani A. et al. Morning Plasma Melatonin Differences in Autism: Beyond the Impact of Pineal Gland Volume. Front. Psychiatry. 2019. Feb 6.

[2] Maras A. et al. Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. J Child Adolesc Psychopharmacol. 2018 Oct 11.

[3] Pagan C. et al. The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders. Transl Psychiatry. 2014 Nov 11;4:e479.

[4] Chen CQ. et al. Distribution, function and physiological role of melatonin in the lower gut. World J Gastroenterol. 2011;17(34):3888-98.

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"An estimated 7.7 million children in the United States (16.5 percent) have at least one mental health disorder"

The press release carrying the quote titling this post - "An estimated 7.7 million children in the United States (16.5 percent) have at least one mental health disorder" - concerns the findings reported by Daniel Whitney & Mark Peterson [1]. Their research letter discussed findings (from the United States) "providing recent national and state-level estimates of the prevalence of treatable mental health disorders and mental health care use in children."

Based on data derived from the 2016 National Survey of Children’s Health (NCSH), a "nationally representative, parent-proxy survey of US children younger than 18 years" that has been mentioned more than once on this blog (see here and see here), researchers present some important data. Including information from over 46 million children (now that's what I call a decent sample size) various trends were observed, notably that almost one in seven children and young adults were reported to have a mental health condition. Such conditions covered "depression, anxiety problems, or attention-deficit/hyperactivity disorder" and by present, I mean that parents responded in the positive to the question: "Has a doctor or other health care provider EVER told you that this child has” a mental health disorder?"

Another detail was also mentioned in the Whitney & Peterson paper: "half of the estimated 7.7 million US children with a treatable mental health disorder did not receive needed treatment from a mental health professional." This was based on responses to the question: "DURING THE PAST 12 MONTHS, has this child received any treatment or counseling from a mental health professional? Mental health professionals include psychiatrists, psychologists, psychiatric nurses, and clinical social workers." Other media on the Whitney / Peterson paper have picked up on this trend (see here) and the possible whys-and-wherefores.

The primary weakness of the NCSH - "parent-proxy survey" - is more than compensated for by the huge participant numbers included for study. The figures arrived at also follow a trend seemingly present across many nations (see here and see here and see here) suggesting that significant numbers of young people are experiencing mental health disorder. We can quibble about the reasons for the increase but there is no mistaking the fact that something is going on. And it's seemingly affecting millions of children and young people around the world...

And as if to prove the point further [2] the startling findings from Gräf et al: "School performance was available for 1462 children (51% boys, mean age 7.3 years). Of these, 41% had signs of at least one MHP [mental health problem]."

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[1] Whitney DG. & Peterson MD. US National and State-Level Prevalence of Mental Health Disorders and Disparities of Mental Health Care Use in Children. JAMA Pediatrics. 2019. Feb 11.

[2] Gräf C. et al. Mental health problems and school performance in first graders: results of the prospective cohort study ikidS. European Child & Adolescent Psychiatry. 2019. Feb 26.

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