Anti-psychotics for non-psychotic issues

A bit of a lazy post for you today with lots of quotes based on the findings reported by Ragnar Nesvåg and colleagues [1] asking some important questions about 'off-label' use of antipsychotics.

Drawing on population-based data from Norway concerning "which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0–18-year-old boys and girls" the conclusions drawn make for some interesting reading.

So: "In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010." I found this to be quite a reassuring figure insofar as antipsychotic use not to be at 'epidemic proportions' or at least not as high as other psychoactive meds.

Next: "The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users." These data are a little more worrying. Granted, certain antipsychotics have received license elsewhere in the world when it comes to aspects of labels such as autism (see here) but importantly, this doesn't yet include the 'core symptoms' of autism, or at least not here in Blighty (see here). This hasn't however seemingly stopped many from receiving such prescriptions it seems (see here).

Finally: "These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls." Accepting that diagnoses and labels are sometimes not the starting point for the use of antipsychotic medication (physicians normally treat symptoms not labels) and that there is often significant overlap between various psychiatric and behavioural diagnoses, these findings are challenging. Not least because although very good at treating symptoms experienced b y many people, antipsychotics are not without their side effects (see here and see here for example).

The implication from the Nesvåg data is that antipsychotic use may be very much moving outside of the realms of just treating psychosis...

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[1] Nesvåg R. et al. Mental disorder diagnoses among children and adolescents who use antipsychotic drugs. European Neuropsychopharmacology. 2016. July 21.

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Nesvåg, R., Hartz, I., Bramness, J., Hjellvik, V., Handal, M., & Skurtveit, S. (2016). Mental disorder diagnoses among children and adolescents who use antipsychotic drugs European Neuropsychopharmacology DOI: 10.1016/j.euroneuro.2016.07.001

Induced labour and autism (again)

"In this nationwide sample of live births we observed no association between induction of labor and offspring ASD [autism spectrum disorder] within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor."

So said the findings reported by Anna Sara Oberg and colleagues [1] supposedly providing some reassurance to mums-to-be and other groups around the likelihood of offspring autism when birth or labour has to be induced. Based on the analysis of one of those oh-so important Scandinavian health registries, researchers followed all the live births recorded in Sweden between 1992 and 2005 looking for signs that labour was induced. As per some media discussion of the study: "Methods to induce labor include rupturing of membranes, mechanical or pharmacological ripening of the cervix, and administration of oxytocin, either used alone or in combination." They also followed the cohort, numbering above a million offspring, looking for recorded diagnoses of ASD in children and, taking into account "a wide range of measured confounders" examined whether induced labour might elevate the risk of offspring ASD.

The headlines suggesting 'no link' between induced labour and offspring autism don't however actually tell the full story of these findings. When taking into account the full cohort - "1 362 950 births"- there did seem to be a slight increased risk of offspring autism associated with labour induction. This association persisted "after adjustment for measured potential confounders" albeit to an even lesser degree. The 'no link' headlines seemed to have focused on further analysis where siblings, one who was induced, one who was not, were compared with regards to autism rates: "thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD."

I've talked about labour induction and autism risk before on this blog (see here) based on findings [2] that Oberg et al were knowledgeable about and that had reported something of an increased risk based on the analysis of over half a million births in a part of the United States. Personally, I do think there is a little more to see in this area than has hitherto been uncovered. The reasons for induction is something to focus on as per the observations that issues such as pre-eclampsia and gestational diabetes are mentioned and the body of research linking such factors to offspring autism risk (see here and see here for examples). That induction also might mean use of oxytocin (the cuddle hormone!) is something else that perhaps require further investigations too. Without trying to scaremonger, I do wonder whether further thought might be needed based on the findings reported by Leffa and colleagues [3] with oxytocin in mind.

The take-away message: induced labour is pretty unlikely to 'cause' offspring autism but beware of sweeping generalisations and media headlines...

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[1] Oberg AS. et al. Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders. JAMA Pediatr. 2016. 25 July.

[2] Gregory SG. et al. Association of autism with induced or augmented childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) databases. JAMA Pediatr. 2013 Oct;167(10):959-66.

[3] Leffa DD. et al. DNA damage after chronic oxytocin administration in rats: a safety yellow light? Metab Brain Dis. 2016 Aug 3.

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Oberg, A., D’Onofrio, B., Rickert, M., Hernandez-Diaz, S., Ecker, J., Almqvist, C., Larsson, H., Lichtenstein, P., & Bateman, B. (2016). Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders JAMA Pediatrics DOI: 10.1001/jamapediatrics.2016.0965

No association between [current] mycotoxin exposure and autism

Although research stories stating a link (an association if you will) between condition A and factor X make for interesting reading, not all science is so blessed with such news-worthy findings. That's not to say that 'negative findings' are any less important than the 'hey, we found this...' studies, just that they don't perhaps tend to grab the headlines as much as those finding something.

In saying all that I'm standing up for negative findings today and some rather interesting science reported by Jennifer Duringer and colleagues [1] (open-access available here) on the lack of any significant relationship between current urinary mycotoxin content and their cohort of 25 young people diagnosed with an autism spectrum disorder (ASD).

Just in case you didn't already know, mycotoxin refers to "“natural” environmental contaminants, defined as secondary metabolites produced by fungi that reside in our food supply and on every surface in our environment." There are various types of mycotoxins (lots!) that occur as a consequence of various exposure patterns including fungi/moulds growing on foods or being present in our environment. Generally speaking, mycotoxins are something to be avoided (being careful with any sweeping generalisations there).

Duringer et al started their research journey on the basis that weather conditions pertinent to mycotoxin production have been linked to autism (see here) and some small-scale study that "suggested that individual exposure to mold increased the severity of neurophysiological abnormalities seen in autistic children" [2]. I know that furrowed brows will ensue when one talks about precipitation correlating with autism as per 'other correlations' but that was the basis for their study and should so be respected.

The technology used to test participants' urine sample for any presence of mycotoxin is not to be sniffed at as yet again (see here) tandem mass spectrometry steps up to the analytical plate. Some 87 mycotoxins were assayed for based on some previously published work and some important details such as the fact that urine samples were run in triplicate (even six times if you count the fact that each replicate was run in positive and negative ion modes) are included as part of the study protocol.

Results: given the fact that the cohort consisted of 25 young people with autism and 29 age-matched controls, one has to be a little cautious about making too many sweeping generalisations. What we can say is this: 20% of the participants with autism (5/25) came up with a 'positive' sample defined as 'any mycotoxin' being present. This contrasted with 14% of controls (4/29). The amounts detected were low; in some cases very close to or below the limit of quantitation where suitable standards could be obtained and used as comparators. When pooled together, those 9 participants with a positive sample were compared with the participants with a negative result to see if any potential correlates might show statistical significance. They didn't.

There are caveats to this work outside of the small participant group included for study. The authors highlight a particularly important one insofar as their focus on young adults "well after the in utero or infant-toddler exposure window when ASD develops and is diagnosed." In other words, the burden of current exposure to mycotoxins with autism in mind is probably low but that does not mean that "exposure windows" at other times might not exert an important effect. Indeed, other authors have speculated on other correlates [2] linked to the science of epigenetics for example, as perhaps being another area ripe for further study. This should be added to the list.

For now however, we can only base conclusions on the available (peer-reviewed) evidence...

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[1] Duringer J. et al. No Association between Mycotoxin Exposure and Autism: A Pilot Case-Control Study in School-Aged Children. Toxins (Basel). 2016 Jul 20;8(7). pii: E224.

[2] Mezzelani A. et al. Ochratoxin A as possible factor trigging autism and its male prevalence via epigenetic mechanism. Nutr Neurosci. 2016;19(1):43-6.

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Duringer J, Fombonne E, & Craig M (2016). No Association between Mycotoxin Exposure and Autism: A Pilot Case-Control Study in School-Aged Children. Toxins, 8 (7) PMID: 27447670

Anxiety spreads across various psychiatric labels

"Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe."

So said the findings reported by Karpov and colleagues [1] who sought to put some further research flesh on to the bones of the idea that clinically relevant anxiety symptoms might not be unstrange bedfellows with a variety of other psychiatric labels.

Based on the analysis of various patient groups included in the "Helsinki University Psychiatric Consortium Study" for the presence of anxiety symptoms (as measured by the Overall Anxiety Severity and Impairment Scale (OASIS)) researchers reported that approaching half of their cohort variously diagnosed with "schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188)" reported as 'severe or extreme' their anxiety. Drilling down further into their data, authors concluded that said anxiety symptoms correlated with "high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders."

Accepting that it is not necessarily new news that clinically relevant psychiatric signs and symptoms might extend beyond the handy diagnostic boxes that we currently use as part of our labelling system, I'd like to think there is another important feature of this 'interconnectedness'. The idea for example, that 'tackling' seemingly secondary issues such as anxiety might impact on more primary diagnosis is something that I'm keen to see extended in the research literature. There are various example of this being suggested/done with regards to other labels (see here for example) and indeed, how from a quality of life aspect, dealing with the very obvious disruption that chronic anxiety would bring, might be a target over and above intervention for other, more primary diagnoses...

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[1] Karpov B. et al. Anxiety symptoms in a major mood and schizophrenia spectrum disorders. Eur Psychiatry. 2016 Jul 19;37:1-7.

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Karpov, B., Joffe, G., Aaltonen, K., Suvisaari, J., Baryshnikov, I., Näätänen, P., Koivisto, M., Melartin, T., Oksanen, J., Suominen, K., Heikkinen, M., Paunio, T., & Isometsä, E. (2016). Anxiety symptoms in a major mood and schizophrenia spectrum disorders European Psychiatry, 37, 1-7 DOI: 10.1016/j.eurpsy.2016.04.007

On staff training in the UK autism services sector

I tread carefully in discussing the findings reported by Karola Dillenburger and colleagues [1] (open-access) on the question of "knowledge and training with regards to autism" received by "health, social care, and education staff who work within the statutory autism services sector in the UK." The observation that "an acute lack of autism-specific training that has detrimental impacts" was apparent is a worrying sign indeed.

Although not intimately involved in the autism services sector, I do have some knowledge of the provision of education and other services for people on the autism spectrum as a consequence of my employer. Although perhaps having a biased opinion, I can testify to the benefits of good teaching and service provision with caring staff - 'friends' as I think most people would like to call them - making a real difference to people's lives and prospects. But as many people might remember, not every service provision is seemingly so inclined...

With the aim of surveying both professionals and service users to elucidate "the lived experience of those who use, and those who are tasked with providing, autism services" researchers gathered data via various different tools and sources pertinent to ascertaining the knowledge and training of autism among providers and service users views on staff training.

Results: well, I guess the term 'must try harder' is probably the best overview that Dillenburger et al give based on their cohort made up of nearly 800 professionals "from health, social care, and education" and a significantly smaller group of people with autism and their families. A couple of sentences kinda sum up the state of things: "A total of n = 175 health and social care (HCS) professionals responded to an open question about their future autism training needs, with only a very small minority (n = 12) having no suggestions or being happy with the training that had received. The vast majority (n = 163) felt that more training was needed." In other words, quite a bit more needs to be done for the carers and educators of those with autism to aid their caring and educating roles and said training should perhaps be on-going.

A few other points are worth mentioning too. So: "The survey showed that nearly half of the professional participants knew someone with autism personally." Acknowledging the old saying that is 'if you've met one person with autism, you've met one person with autism' and how sweeping generalisations are not required, the authors go on to say: "This makes a farce of brief 1–2 h autism awareness-raising sessions directed towards professionals who work in the autism field." Ouch, is the word that springs to mind.

Also: "service user interviews identified the lack of adequate staff training, inadequate services, and lack of support for individuals with autism and their caregivers and saw that this potentially contributed adversely to their mental health issues." I don't think I need to expand on this any further aside from suggesting that these issues when combined with a lack of resources and tightening budgets do not exactly make for a great portrait of how society helps some of its most vulnerable members.

And finally, the authors don't mince their words when it comes to the effects of a lack of appropriate autism-specific training et al: "Findings reported here show that in a culture where a lack of apposite training is the norm, those who attend minimal ‘autism training’ are regarded as ‘autism experts’ in the eyes of others who know even less. Dangerously, they may even become the trainers for the next generation. In reality, they are the one-eyed wo/man in ‘the land of the blind'."

What more can I say?

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[1] Dillenburger K. et al. Staff Training in Autism: The One-Eyed Wo/Man…. Int J Environ Res Public Health. 2016 Jul 16;13(7). pii: E716.

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Dillenburger K, McKerr L, Jordan JA, & Keenan M (2016). Staff Training in Autism: The One-Eyed Wo/Man…. International journal of environmental research and public health, 13 (7) PMID: 27438846

The (surprising) rate of ADHD in Taiwan

The idea that use of the diagnostic label called attention-deficit hyperactivity disorder (ADHD) is on the increase, and pretty significantly so, is quite common-place these days (see here). Appreciating that not everyone is convinced that the increase is necessarily genuine (see here) I would like to discuss some interesting data coming out of the 'big data' country that is Taiwan in the form of the findings reported by Wang and colleagues [1].

As regular readers might already know, Taiwan is the producer of quite a lot of big data findings in recent years as a function of the implementation of the National Health Insurance Research Database (NHIRD) some of which have been covered before on this blog (see here for example). This time around Wang et al set about exploring "trends in ADHD diagnosis in youths and the proportion of those receiving medication, with the aim of determining whether ADHD is overdiagnosed and overmedicated in Taiwan."

With a participant number approaching 150,000 diagnosed with ADHD between 2000 and 2011 - young people below 18 years of age - researchers calculated figures for ADHD each year between 2000 and 2011. They also looked at some details around medication history for cases during each year based on "those with at least one record of pharmacotherapy (immediate-release methylphenidate, osmotic controlled-release formulation of methylphenidate, and atomoxetine)."

Results: very interestingly the prevalence rates of ADHD for 2000 and in 2011 were not as dissimilar as you might first think (0.1% vs 1.2% respectively). The authors also point out that their prevalence rates are at odds with other work: "The rate of ADHD diagnosis was far lower than the prevalence rate (7.5%) identified in a previous community study using face-to-face interviews." They did observe some differences in rates of ADHD according to age where rates seemed to be higher as age increased - those aged between 7-12 years old or 13-18 years had a higher rate of ADHD compared with those 6 years and under. They also noted that medication use was 'more probable' as children got older and indeed, that medication use generally was on the rise.

These are important data. Yes, one could argue that the results might only be relevant to Taiwan and not necessarily generalisable to other parts of the world but you could say that about any piece of research based on one population. The NHIRD has strengths; many of them outside of just being rather large and including some 99% of the population and I've generally taken to believing findings from it as and when they emerge. So when the authors conclude that their findings are "not consistent with a systematic public opinion about overdiagnosis or overmedication of ADHD in Taiwan" I'm generally inclined to go with them.

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[1] Wang LJ. et al. Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011. Epidemiol Psychiatr Sci. 2016 Jul 20:1-11.

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Wang, L., Lee, S., Yuan, S., Yang, C., Yang, K., Huang, T., Chou, W., Chou, M., Lee, M., Lee, T., & Shyu, Y. (2016). Prevalence rates of youths diagnosed with and medicated for ADHD in a nationwide survey in Taiwan from 2000 to 2011 Epidemiology and Psychiatric Sciences, 1-11 DOI: 10.1017/S2045796016000500