Wednesday, 23 January 2019

"Further studies are required to understand links between ASD, ADHD, and gender identity..."

The findings reported by Ada Cheung and colleagues [1] provide the blogging fodder today, and specifically the observation that: "depression was prevalent in 55.7%, anxiety in 40.4%, ASD [autism spectrum disorder] in 4.8% and ADHD [attention-deficit hyperactivity disorder] in 4.3%" in an Australian adult transgender cohort.

The aim of the Cheung study was to "assess referral numbers and describe the sociodemographic and clinical characteristics"of their cohort, with specific reference to the prevalence of ADHD and/or ASD (autism). The autism 'connection' (and why I'm blogging about this research) follows quite a bit of other research suggesting that gender identity issues and/or reassignment behaviours *might* be over-represented when it comes to a diagnosis of autism (see here and see here and see here for examples). I stressed the word *might* because, so far, there is still some doubt about whether autism / autistic features is / are the more important variable above other comorbid features or comorbidity (see here). I'll also come to the idea of whether 4.8% is actually 'over-represented' or not when it comes to the autism [prevalence] numbers game shortly...

Based on data for quite a large number of individuals (N=540), researchers arrived at those pretty standout figures for various psychiatric and behavioural comorbidity being present. They use the words 'not surprisingly' when it came to the depression and/or anxiety prevalence stats garnered, and how "discrimination and difficulties accessing gender-affirming treatments" may be a contributory factor. I'd also draw your attention to the finding that: "Despite relatively high levels of education, unemployment rates of 21.3% were high in this relatively young cohort, four-fold higher than the Australian general population unemployment rate of 5–6%" as another possibility to (partly) account for some of those psychiatric features / diagnoses being reported on (see here).

So, 4.8% of the cohort with ASD. Is this a particularly high figure? Well, it depends. The authors rely on data from the Australian Bureau of Statistics (2015) which listed 0.7% as the "Australian population prevalence" of autism or ASD. I've not been able to find much more in the way of published estimates of adult autism specifically in Australia but would perhaps hazard a guess that 0.7% is likely to be an underestimate of the true autism rate on the basis of other population data for example (see here). Bear also in mind that Cheung et al also relied on "consecutive consultations between 1st January 2011 and 31st December 2016" so covered quite a long period of time period over which referral data was collected.

The Cheung study also ventures into some of the possible hows-and-whys of autism (and ADHD) being potentially over-represented among their transgender cohort. I'm not going to head too much into what these might be here because the long-and-short of it is that we don't know about possible overlapping genetics for example (although autism genes aren't necessarily just genes for autism) or even whether non-genetic factors might be at work: "it has been suggested that endocrine disruptors such as prenatal exposure to phthalates or antidepressants may be an explanation for the increase of ADHD and ASD and relationship with gender variance" (authors words not mine). Likewise whether the presence of autism or autistic traits means that someone is more or less likely to be 'socially conforming' is something that cannot be confirmed or denied in relation to gender variance at the present time.

All I will say is that more research is indicated in this area. Preferential screening for a range of developmental / behavioural / psychiatric issues is probably also implied as and when someone clinically presents for gender-related issues, in order to ensure that the care they receive is tailored specifically to them.

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[1] Cheung AS. et al. Sociodemographic and Clinical Characteristics of Transgender Adults in Australia. Transgend Health. 2018 Dec 26;3(1):229-238.

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Tuesday, 22 January 2019

"no good evidence that time in front of a screen is "toxic" to health"

BBC News January 4 2019
Quite a few days back the BBC here in Blighty ran the headline "Worry less about children's screen use, parents told" as part of their coverage of the paper by Neza Stiglic & Russell Viner [1]. This paper - "a systematic review of reviews" no less - set out to "systematically examine the evidence of harms and benefits relating to time spent on screens for children and young people’s (CYP) health and well-being, to inform policy."

Informing policy is just what the Stiglic/Viner paper did (see here), as the Royal College of Paediatrics & Child Health (RCPCH) concluded that: "Many of the apparent connections between screen time and adverse effects may be mediated by lost opportunities for positive activities (socialising, exercise, sleep) that are displaced by screen time" but parents shouldn't necessarily get too stressed if their offspring find some enjoyment in their computer/tablet and/or phone in amongst their busy lives. Indeed it was refreshing to see that children and young peoples' voices were being heard on the potential benefits of screen time, with comments such as: "Gives you knowledge" and "Provides you with more opportunities to reach a wider community." All those hours of watching You Tubers fooling around or building whatever on Roblox or similar platforms can actually be intermixed with something approaching gaining knowledge; i.e. learning. Who knew!

The Stiglic/Viner review paper drew on data from 13 reviews reporting "associations between time on screens (screentime; any type) and any health/well-being outcome in CYP [children and young people]." All was not however completely rosy when the reviews were boiled down to a consensus, as we are told that authors found "moderately strong evidence for associations between screentime and greater obesity/adiposity and higher depressive symptoms" and "moderate evidence for an association between screentime and higher energy intake, less healthy diet quality and poorer quality of life." I don't think anyone should really be surprised that more screen time *might* mean an increased tendency towards being overweight or obese. If one subscribes to the idea that energy in - energy out is at least partially related to being overweight or being obese [2] it stands to reason that unless people are running around whilst using their tablets or phones, there is likely to be less 'energy out'.

As for the 'higher depressive symptoms', well let's just say that this is something else that is no stranger to the debate about screen time, as other recent research has similarly observed (see here). Whether it is the actual use of tablets, phones and/or television or the type of material being accessed [3] *correlating* with depression is a question that needs further investigation. I might add that the scenario of when screen time turns into an addiction also needs to be discussed in this context (see here), bearing in mind the limitations of observational studies in relation to discerning cause-and-effect.

Also: "There is weak evidence for association of screentime with behaviour problems, anxiety, hyperactivity and inattention, poorer self-esteem and poorer psychosocial health in young children." Bearing in mind that 'weak evidence' does not mean 'no evidence', this part of the Stiglic/Viner review paper is also important. It means that sweeping conclusions that screen time is somehow playing a major role in the rise of behaviour problems in children (young and old) are not yet necessarily backed up by the scientific evidence. Indeed, as per other topics on this blog, I'd advance the position that certain facets of screen time may actually be advantageous to quite a few children and young people (see here) who are perhaps not for example, the social butterflies that other children are.

The Stiglic/Viner review and subsequent RCPCH advice does not say that screen time for children is risk-free. It does not say that parents shouldn't be continually asking questions about how long their children spend using screens and/or what material they are accessing. It does however mean that, on the basis of the currently available evidence, parents shouldn't get too stressed about moderate screen use in their offspring. Balance things out with the odd physically active inclined hobby or two (avoiding any tiger parenting notions) by all means, but don't stress too much about their swiping. See the potential positives as well as the potential negatives of screen use, and remember that screen time is an inevitable part of growing up these days...

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[1] Stiglic N. & Viner RM. Effects of screentime on the health and well-being of children and adolescents: a systematic review of reviews. BMJ Open. 2019;9:e023191.

[2] Malhotra A. et al. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br J Sports Med 2015;49:967-968.

[3] Kelly Y. et al. Social Media Use and Adolescent Mental Health: Findings From the UK Millennium Cohort Study. EClinical Med. 2019. Jan 4.

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Monday, 21 January 2019

Hyperemesis gravidarum exposure as a risk factor for autism?

Hyperemesis gravidarum mentioned in the title of this post refers to "prolonged and severe nausea and vomiting" during pregnancy alongside other symptoms. It's thought to affect only a relatively small percentage of pregnant women despite vomiting and nausea being pretty common throughout many pregnancies. Indeed, hyperemesis gravidarum (HG) is much more than just nausea and vomiting.

The findings reported by Marlena Fejzo and colleagues [1] looked at the "neurodevelopmental outcomes of 267 children delivered by 177 mothers with HG were compared to neurodevelopmental outcomes from 93 children delivered by 60 unaffected mothers." The study was undertaken on the basis that previous published research from this study group [2] had identified "neurodevelopmental delay" as a possible *correlate* tied to HG exposure during pregnancy. That being said, on that last occasion researchers also described finding "no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder" in their cohort.

This time around: "Similar to at age 8, the children (now 12) exposed in utero to HG had over 3-fold increase in odds of neurodevelopmental disorders including attention, anxiety, sensory, sleep difficulty, and social development delay/social anxiety." With a longer follow-up period, researchers also reversed their 'no evidence for increased risk' sentiments with regards to a diagnosis of autism in their cohort. So: "there was also a significant increase in Autism Spectrum Disorder (ASD), reported in 22/267 (8%) of children exposed to HG in utero and no unexposed children."

Let me be clear on this: these latest results on their own don't necessarily mean that HG *causes* offspring autism. Although 8% of the HG exposed group reporting autism or ASD seems quite high, it has to be seen in light of an increasing (estimated) prevalence of autism more generally (see here and see here). I'd also suggest that as with many other pregnancy/gestational factors put forward as potentially influencing offspring autism risk, one needs to be mindful of the issues involved in teasing out which is the important variable from potentially many (see here and see here).

But... further investigation is indicated in this area. Indeed, I hark back to the findings reported by Andrew Whitehouse and colleagues [3] who observed a "strong, positive association between increasing frequency and severity of NVP [nausea and vomiting during pregnancy] and ASD severity in offspring." No, not necessarily HG, but an implication that some of the overt features of HG might hold some *connection* to offspring autism risk for whatever reasons...

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[1] Fejzo M. et al. Analysis of neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum reveals increased reporting of autism spectrum disorder. Reprod Toxicol. 2018 Dec 27. pii: S0890-6238(18)30558-6.

[2] Fejzo MS. et al. Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 2015 Jun;189:79-84.

[3] Whitehouse AJO. et al. Symptom severity in autism spectrum disorder is related to the frequency and severity of nausea and vomiting during pregnancy: a retrospective case-control study. Mol Autism. 2018 Jun 19;9:37.

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Saturday, 19 January 2019

"maternal obesity and overweight were significantly associated with [offspring] increased ASD risk"

The title heading up this brief post - "maternal obesity and overweight were significantly associated with [offspring] increased ASD [autism spectrum disorder] risk" - comes from the results published by Xian-Yang Lei and colleagues [1].

Under systematic review and meta-analysis conditions, researchers basically found what many people had suspected for quite a while, insofar as maternal weight, before or during pregnancy, being a 'risk factor' for an offspring diagnosis of autism or ASD. They arrived at their conclusion based on "13 eligible studies for meta-analysis (involving 943,293 children and 30,337 cases)" which collectively found that "both maternal obesity... and maternal overweight... were significantly associated with ASD, while maternal underweight was not associated with ASD." Researchers also looked at paternal weight as a possible risk factor for offspring autism but found no statistical association between paternal obesity, overweight or underweight based on the available data (limited to only three studies).

Mindful of the potential for 'stigma' to set in with such investigation, and likewise being careful not to generalise too much from such findings, the Lei results point to both the requirement for more research in this area and a possible 'intervention' route towards reducing the risk of offspring autism: "pre-pregnancy weight control is suggested." I've covered this topic numerous times on this blog (see here and see here and see here for examples) and have concluded that whilst correlation is not the same as causation and that pre- and peri-pregnancy weight is often intricately tied into other features of the condition known as metabolic syndrome, immune function and in particular inflammation, are perhaps important areas for further assessment. Research should perhaps head in that direction, and see what further crops up...

And as if to further prove the point [2]...

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[1] Lei XY. et al. Association between parental body mass index and autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2018 Nov 23.

[2] Windham GC. et al. Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain in Relation to Autism Spectrum Disorder and other Developmental Disorders in Offspring. Autism Res. 2018 Dec 21.

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Friday, 18 January 2019

"Treatment-resistant depression: consider autism"

The brief letter by Michael White [1] talking about how: "Clinicians need to be mindful of the possibility of undiagnosed autism in all patients with TRD [treatment-resistant depression]" was a bit of an eye-opener. White who lists "has an adult son with autism" on the 'competing interests' section of his publication, offers an interesting perspective in relation to TRD (described as those "who do not respond adequately to a course of appropriate antidepressant medication within a certain time").

The letter from White is brief but covers quite a few important issues including (a) the observation that autism rarely exists in a diagnostic vacuum when it comes to psychiatric and/or behavioural labels (see here) and (b) the quandary of whether depression occurring alongside autism is a 'comorbidity' or something rather more 'core' to at least some autism (see here). That last point in particular is an important one given how many times depression has cropped up in the peer-reviewed research literature with autism in mind and onward whether certain typically indicated interventions for depression are actually cutting the clinical mustard where autism is mentioned (see here).

I am slightly cautious not to go 'all in' with the idea that every case of TRD is just undiagnosed autism. There are multiple other potentially important things to consider where depression - treatment resistant or not - presents (see here and see here for examples) over and above a diagnosis of autism or the presentation of clinically significant autistic features. But there could be some merit in physicians at least thinking about undiagnosed autism as and when TRD presents...

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[1] White MJ. Treatment-resistant depression: consider autism. Br J Gen Pract. 2019 Jan;69(678):14.

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Thursday, 17 January 2019

An easily testable blood metabolic profile associated with ASD diagnosis?

"The present study supports early recognition of a distinctive metabolic profile in DBS [dried blood spots] whose distinguishing features suggest a reduced flux through the mitochondrial fatty acid β-oxidation pathway and provides insight into concealed molecular mechanisms determining ASD [autism spectrum disorder]."

So said the findings reported by Rita Barone and colleagues [1] including some notable names on the authorship list with some previous interest in acyl-carnitines and autism (see here), one important source of discussions in the Barone study.

Some basics from the Barone study: "A targeted panel of 45 ASD analytes including acyl-carnitines and amino acids extracted from DBS was examined in 83 children with ASD... and 79 matched, neurotypical (NT) control children." Autism was confirmed as autism in the 83 autistic children, also including the application of some important exclusionary criteria such as a "positive history for mitochondrial disease or known medical conditions including autoimmune disease and inflammatory bowel diseases (IBD)/celiac disease." I was also happy to see that researchers screened for 'possible autism' in their control participants too: "The Social Communication Questionnaire was used to screen and exclude autism in TD [typically developing] children."

Although the Barone study was a study predominantly analysing dried blood spot samples (a sample medium that has always been slightly under-utilised in research circles), researchers did also look at urine and blood samples obtained during the course of their study. They reported some interesting observations as a consequence of analysis; notably that: "Twenty-five out of 40 studied [autistic] subjects (62.5%) had significantly decreased blood Vitamin D3 levels with normal Ca/P ratio." Decreased vitamin D levels are no stranger to autism (see here and see here).

Insofar as the 'ASD analytes' results, we are told that 8 acyl-carnitines were significantly increased in the autism group compared to the control (not autism) group. I'm not going to bore you with the specific details but suffice to say the list of compounds was pretty robust and "confirm the same, unique pattern of acyl-carnitine profile" as noted in other studies with other groups. Researchers also mention how one particular amino acid - citrulline - was also significantly increased in the autism group compared to controls. They talk about how: "Blood citrulline level is considered a biomarker of gastrointestinal mucosal surface and enterocyte integrity" among other things and could have some implications for that and other 'effects'.

And then something else: "The present study confirms that patients with ASD may show a distinct metabolic profile, demonstrating that this can be used to identify a subset of ASD patients with respect to TD at younger ages." I'm always a little bit wary of studies talking about biomarkers and autism (see here for another example) but the important use of the word 'subset' denoting how autism is a label covering significant heterogeneity makes me feel a little easier about such sentiments (see here and see here) albeit with much more study being required.

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[1] Barone R. et al. A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses. Front Psychiatry. 2018 Dec 7;9:636.

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Wednesday, 16 January 2019

Subclinical autistic traits affecting adolescent sleep patterns?

There was something rather intriguing about the results published by Liisa Salmela and colleagues [1] (open-access available here) observing that: "Elevated levels of autistic traits were significantly associated with shorter weekday sleep duration" in a cohort of adolescents from Helsinki in Finland. The fact that researchers also concluded that "autistic traits remained an independent predictor of short sleep duration when comorbid psychiatric symptoms were controlled for" added to the intrigue.

I was impressed with some elements of the Salmela study; notably the use of actigraphy as an objective measure of sleep accompanying self-report data derived from the Pittsburgh Sleep Quality Index (PSQI). The fact that actigraphs were worn "continuously for an average of 8.36 nights (SD = 1.76; range 4–17)" also meant that researchers had access to quite a bit of data from their 150+ participant study group when it came to activity cycles covering sleep.

What was the measure of autistic traits used I hear you ask? Well, we are told that: "Autistic traits were assessed using the Autism Spectrum Quotient (AQ)" which is an OK measure I suppose, although not without some shortcomings in terms of what is being specifically measured (see here). I should also mention that for the most part, the Salmela study was a study of non-autistic adolescents (two participants were reported to have "scored at or above the clinical cut-off score of 32" on the AQ).

"Continuous autistic traits significantly predicted weekday total sleep time" and "having elevated autistic traits as measured by AQ (Autism Spectrum Quotient) increased the risk for short sleep duration." Mindful that correlation is not necessarily the same as causation, details were important to the Salmela findings as we are also told that (a) as a group, boys tended to score higher on the AQ and (b) again as a group "boys had significantly shorter weekday total sleep time" than girls. It's perhaps no surprise therefore that: "Sex had a statistically significant main effect (p = 0.032) on total sleep time."

Next question: why? Why should autistic traits potentially "increase the risk for short sleep duration in a general adolescent population"? Is there something about the presentation of autistic traits that affects sleep either through psychological/cognitive processes or more physiological processes? Well, those are questions that still need answering. And alongside we seem to have yet another example where core autistic features may very well impact on so-called comorbid issues to add to the collection (see here and see here). This also has potential implications for intervention too...

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[1] Salmela L. et al. Autistic traits and sleep in typically developing adolescents. Sleep Med. 2018 Oct 29;54:164-171.

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