Thursday, 10 August 2017

ADHD and law enforcement contact: not a straight-forward relationship

Several times on this blog I've talked about how a diagnosis of attention-deficit hyperactivity disorder (ADHD) seems to place the recipient at quite a bit of excess risk for various unfavourable outcomes (see here). I've tried hard not to make too many sweeping generalisations on this issue; mindful that behind every statistic in every peer-reviewed bit of science there are real people and real lives. But the data is becoming quite compelling on this matter...

The paper by Mark van der Maas and colleagues [1] makes an important contribution to the idea that the relationship between a diagnosis of ADHD and contact with law enforcement 'systems' is perhaps not as straight-forward as many might believe. Concluding that: "The observed connection between ADHD and criminality may be better understood through their shared relationships with indicators of poor social bonds", researchers suggest that social factors may very well come into play.

OK, based on a sample of over 5300 adults "representative of the general population of Ontario, Canada" researchers asked participants about their "self-reported arrest on criminal charges" history alongside examining ADHD-linked symptoms via the Adult Self Report Scale (ASRS-v1.1). They also interviewed/questioned about various social bonds - household size, education level, drug and substance abuse, etc.

They observed that: "screening positive for ADHD was twice as likely... and past use of medications for ADHD three times as likely... to be associated with ever having been arrested." But... when statistical modelling took into account the data on social bonds, things started to get a little more fuzzy. So: "In the best fitting statistical model, ever having been arrested was not associated with ADHD, but it was significantly associated with indicators of strong and weak social bonds." So things like anti-social behaviour, not progressing well in educational terms and substance use (abuse) might have some important influences on contact with law enforcement agencies. A shocker, I know.

I do have to point out a few important things about this research before anyone gets too immersed in the idea that ADHD is completely off the hook. First was the reliance on self-report when it comes to both ADHD signs and symptoms and also arrest record. The ASRS might very well be a nice rough-and-ready measure of ADHD symptoms but it is no substitute for a thorough assessment for a diagnosis of ADHD. Similarly, people may not always be completely truthful when it comes to their arrest record under several circumstances including research conditions...

Second is the concept of cause-and-effect. As easy as it is to say that ADHD was not itself linked to arrest record(s), it is important not to interpret the findings to say that there is 'no connection' between ADHD and 'having been arrested'. Minus sweeping generalisations, facets of ADHD - such as impulsivity and inattention - can and do perhaps account for some of the heightened risk for various types of offending behaviour [2]. It's fine to say that these facets of ADHD might be exacerbated under conditions of substance use/abuse for example, but one could easily then ask whether ADHD might have actually been involved in facilitating such substance use/abuse in the first place. Certainly, there is (peer-reviewed) evidence that a diagnosis of ADHD - if left untreated - may very well impact on educational outcomes for example [3] which could be one of several factors in determining other life choices.

The idea however that ADHD as a sole risk factor for adverse outcomes such as law enforcement contact does not exist in some sort of social vacuum is an important one to come from data such as that presented by van der Maas et al. It is perhaps the issue of 'vulnerability' that comes to the forefront, and how an ADHD diagnosis should perhaps be explored with that tenet in mind...

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[1] van der Maas M. et al. Examining the effect of social bonds on the relationship between ADHD and past arrest in a representative sample of adults. Crim Behav Ment Health. 2017 Jul 5.

[2] Berryessa CM. Attention, reward, and inhibition: symptomatic features of ADHD and issues for offenders in the criminal justice system. Atten Defic Hyperact Disord. 2017 Mar;9(1):5-10.

[3] Lu Y. et al. Association Between Medication Use and Performance on Higher Education Entrance Tests in Individuals With Attention-Deficit/Hyperactivity Disorder. JAMA Psychiatry. 2017 Jun 28.

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Wednesday, 9 August 2017

Methylphenidate + fatty acids for ADHD? Erm, we need more science...

I don't mind telling you that I was left a bit baffled by the results published by Mahbobeh Firouzkouhi Moghaddam and colleagues [1] (open-access available here) talking about the use of specific polyunsaturated fatty acids (PUFAs) as a sort of add-on to more traditional pharmacotherapy indicated for cases of attention-deficit hyperactivity disorder (ADHD). Baffled because science is supposed to be presented in such a way that methods and results are easy to read and intepret and hence replicate, and appropriate conclusions are supposed to be based on those results. Read on and I hope you'll see what I mean...

Based on the use of a randomised, placebo-controlled trial design, some 40 children (6-12 years of age) who obtained "the least score in an ADHD rating scale questionnaire, responding to the treatment based on least reduction of 25% of symptoms relative to the base state in ADHD scaling" were allocated to either a methylphenidate (MPH) + PUFA ("capsules containing 180mg EPA and 120 mg DHA") group or a MPH + placebo group. Participants were monitored quite regularly over 8 weeks of intervention via the ADHD rating scale adopted and "filled by the resident of psychiatry for patients of both groups." I say all that bearing in mind that I'm not exactly sure what specific ADHD rating scale was actually used during the study.

No mind, the results: "mean severity of symptoms before treatment in both groups of methylphenidate plus PUFA and placebo was the same, and severity of symptoms after treatment in the group under methylphenidate plus PUFA treatment had reduced much more compared to the placebo group, and major changes were observed in the subscale of predominantly attention deficit type." The authors were able to describe the types of symptom patterns presenting by participants in relation to ADHD type. Indeed, quite impressively: "Response to treatment (a reduction of at least 25% in the signs) in the group taking methylphenidate plus PUFA was 90% (18 patients) and in methylphenidate plus placebo group, it was 60% (12 patients)." They did also note side-effects in both groups; the most common in both groups (taking MPH) were sleep disorders and anorexia. For the PUFA group "just one case of burping" was recorded. Researchers concluded that further trials are needed to confirm/refute their findings.

Appreciating that these study results are presented in English but English is perhaps not the mother tongue of researchers, I can get past the slightly odd tone of the article text in places. I do still have an issue with not being able to find out which ADHD scale was used during the study; something that is important if someone wanted to try and independently replicate this study.

More than that, I have to say that I am also a little hesitant when it comes to the way the statistics and findings have been presented in this paper. My first reading of the results was that MPH + PUFA supplementation was superior to MPH + placebo based on the text presented in the article. A more detailed look at the findings revealed that this was not necessarily the case based on (a) looking at the comparisons across the various types of ADHD pre- and post-intervention groups (see Table 1 of the paper) and (b) comparing 'mean severity of symptoms after treatment' between the PUFA and placebo groups (Table 2). You will see that assuming a drop in ADHD scores denotes improvement in behaviour(s), Table 1 suggests that only those with the mixed/combined type of ADHD as a group showed a reduction in scores (9.4±8.39 vs. 0.6±1.20) between pre- and post-intervention with MPH + PUFAs. This was compared with two groups in the MPH + placebo arm of the trial: predominantly attention deficit and mixed type, where a reduction was noted. In all other scenarios, the group values actually increased. Bearing in mind the authors don't actually tell us how many people were included in those ADHD groups, I was a little surprised to see that the p-values remained highly significant for all ADHD types across both study arms. One can only deduce from these findings - those presented in Table 1 - that MPH + PUFA supplementation is at best, as good as MPH + placebo for a specific type of ADHD but at worst, potentially making MPH less effective in other types of ADHD.

Then to the data showing "comparison between the mean severity of symptoms in the intervention and control groups after the treatment" (Table 2). Here again, the picture is one of no real [statistical] difference between MPH alone and MPH + PUFA supplementation after 8 weeks of intervention based on the group scores and the p-values produced. Yes, you could say that MPH + PUFA seems to show some equivalence to MPH + placebo, but then the question 'why take a PUFA supplement?' comes to the surface. And please also, none of that 'almost significant' stuff based on a p-value of 0.18 for example particularly in light of other discussions...

"This study shows that PUFA is an efficient nutrient to treat ADHD and it can be used to treat patients." I'm not so sure that this sentence is completely compatible with the study findings as they are presented; both in the text of the results and the table data. Don't get me wrong, more than most I would love to see fatty acids finding their place with at least some people presenting either with a diagnosis of ADHD or significant features of ADHD (see here and see here for examples) also on the back of some very recent peer-reviewed findings [2]. The trouble is that I don't think these are necessarily the results to show that...

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[1] Moghaddam MF. et al. Effectiveness of methylphenidate and PUFA for the treatment of patients with ADHD: A double-blinded randomized clinical trial. Electron Physician. 2017 May 25;9(5):4412-4418.

[2] Chang JC. et al. Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies. Neuropsychopharmacology. 2017 Jul 25.

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Tuesday, 8 August 2017

Toxoplasma infection may be a risk factor for manifestation of psychotic-like symptoms

It's been a while since I last talked about Toxoplasma gondii on this blog (see here). All the initial research excitement from a few years back on how T. gondii exposure might correlate with various psychiatric symptoms/conditions seems to have been toned down in recent times. Still, I continue to be fascinated with the idea that at least for some, exposure to T. gondii might be more than just a somatic thing...

The findings reported by Lindgren and colleagues [1] illustrate how my interest in the gondii remains justified as per their conclusion: "Toxoplasma infection may be a risk factor for manifestation of psychotic-like symptoms." Based on data from Finland - "Health 2000, a large cross-sectional health survey of the Finnish general population aged 30 and above" - the authorship team included on the Lindgren paper contain some names familiar to the T. gondii research scene: namely Faith Dickerson and Robert Yolken.

So, the presence of lifetime psychotic-like symptoms via "section G of the Composite International Diagnostic Interview, Munich version (M-CIDI)" were analysed alongside seropositivity to Toxoplasma "defined as a cutoff of 50IU/ml of IgG antibodies" in nearly 6000 participants. Various other potentially interfering variables - "age, gender, education, region of residence, cat ownership, and C-reactive protein measuring inflammation" - were also thrown into the statistical mix. Cat ownership by the way, refers to the [disputed] research hypothesis that some cats might be unwitting hosts for the gondii with potential onward implications for owners (see here).

Results: "T. gondii seropositivity was significantly associated with clinically relevant psychotic-like symptoms... and with the number of psychotic-like symptoms." That being said, presenting with an immune profile suggestive of some contact with T. gondii did not show any significant connection with diagnosed conditions with a psychotic element to them such as schizophrenia. The authors however, felt confident enough to say that psychotic symptoms might not be totally unrelated to T. gondii exposure.

Accepting that there may be various reasons why someone might present with clinically-relevant psychotic-like symptoms [2] I find good reason to continue with the research agenda looking at T. gondii exposure and human behaviour on the basis of results such as those from Lindgren. The spectrum of labels - behavioural/psychiatric - potentially *associated* with T. gondii exposure is not to be sniffed at [3]. Even if only a proportion of cases are found to be *associated* with gondii exposure, there are treatments readily available (see here) to manage the infection. Whether such intervention(s) might also provide some relief of psychiatric symptoms alongside, is something too that needs more investigation...

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[1] Lindgren M. et al. The association between toxoplasma and the psychosis continuum in a general population setting. Schizophr Res. 2017 Jul 12. pii: S0920-9964(17)30391-2.

[2] Cosgrave J. et al. The interaction between subclinical psychotic experiences, insomnia and objective measures of sleep. Schizophr Res. 2017 Jul 12. pii: S0920-9964(17)30397-3.

[3] de Barros JL. et al. Is there any association between Toxoplasma gondii infection and bipolar disorder? A systematic review and meta-analysis. J Affect Disord. 2017 Feb;209:59-65.

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Monday, 7 August 2017

Not everyone referred for an autism assessment will 'meet diagnostic criteria'

I want to introduce the findings reported by Isaac Smith and colleagues [1] to you today, and some important points related to the assessment and diagnosis of autism or autism spectrum disorder (ASD).

Looking at a cohort of youth "referred for psychological evaluations at an outpatient clinic", some 70 young adults were categorised according to their referral status (for autism or not) and outcome status (autistic or not). Authors reported on a few important things:

"Approximately half of cases referred for suspected ASD did not meet diagnostic criteria." Yes, the final numbers were quite small but this is an important finding. Minus too many sweeping generalisations, I find myself looking at that sentence again in the context of some recent social media discussions about self-diagnosis and autism (see here). Once again, minus important issues such as identity, emotions and/or politics, I find evidence that there is no substitute for a thorough professional assessment when autism is suspected. Yes, there is always the fear that self-observations might not necessarily be accurate ones [2] but...

Then: "Youth neither referred for nor diagnosed with ASD demonstrated lower anxiety than those who were referred and diagnosed." On the basis of that last sentence acknowledging that anxiety is often a frequent issue associated with autism (see here) I am, yet again, wondering whether we've been too harsh on the writings of people such as Mildred Creak and colleagues [2] for example, and their examination of the cross-over between autism and 'schizophrenic syndrome in childhood'. No, I'm not saying that autism is schizophrenia or vice-versa (despite the potential for some overlap), but their '9 key features' seems to cover quite a bit more of the essence of autism than perhaps other widely used triadic/dyadic descriptions including: e.g. "abnormal perceptual experience... acute, excessive and seemingly illogical anxiety... distortion in motility patterns." That last point on 'motility patterns' adds to the interest in how movement issues and allied presentations might also be a core feature of autism (see here).

Finally: "Comorbidity was high in all groups, including those referred primarily for ASD assessment, underscoring the importance of comprehensive assessment regardless of specificity of the referral." Comorbidity, whether behavioural/psychiatric or somatic, is a key feature of autism. The days of autism independently existing in some sort of diagnostic vacuum are becoming a distant memory (see here). More than that, the Smith findings in this area provide some exquisite evidence for the concept of ESSENCE - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - championed by the likes of Prof Gillberg and colleagues. The idea being that even with the label of autism outside of the equation, other developmental/behavioural/psychiatric labels/issues will often [variably] overlap (see here).

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[1] Smith IC. et al. The Under- and Over-Identification of Autism: Factors Associated With Diagnostic Referral. J Clin Child Adolesc Psychol. 2017 Jul 17:1-7.

[2] Lewis LF. A Mixed Methods Study of Barriers to Formal Diagnosis of Autism Spectrum Disorder in Adults. J Autism Dev Disord. 2017 Aug;47(8):2410-2424.

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

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Saturday, 5 August 2017

Pre-pregnancy weight and risk of offspring ADHD

"Compared to normal weight mothers, the risk of having a child with ADHD [attention-deficit hyperactivity disorder] was significantly increased if the mother was overweight..., obese... or severely obese."

So said the findings reported by Andersen and colleagues [1] examining data from some 80,000 mother and child pairs "participating in the Danish National Birth Cohort (DNBC)." The name of the research game was to look-see whether maternal weight before pregnancy might be an important factor when it comes to offspring developmental and behavioural outcomes specifically with ADHD and/or autism in mind.

The results showing a possible relationship between maternal pre-pregnancy weight and ADHD were to some extent mirrored in relation to offspring autism albeit not showing the 'dose trend' of hazard ratios - overweight, obese, severely obese - noted in relation  to ADHD. Indeed authors noted that: "Regarding ASD [autism spectrum disorder], an increased risk was observed in underweight... and obese... mothers" illustrating a less confident pattern of possible association.

This is not the first time that this topic has been discussed on this blog (see here). One still has to be a little careful with such 'observational' research so as not to assume that only pre-pregnancy maternal weight is a risk factor for offspring ADHD or anything else. I'm also minded to suggest that the continued use of the body mass index (BMI) statistic is not without difficulties. That and the fact that we're also no further forward when it comes to talking about possible mechanisms behind any association given the myriad of effects that excess weight can potentially cause to mother and any children to be (see here).

What we can however take from this and other independent data [2] is that the physical health of mothers (and fathers) might be quite important to offspring even when the prospect of children is still a twinkle in the eyes of parents. We're all constantly being told to eat well, exercise regularly and cut out or cut back on certain things to achieve optimal health and wellbeing. This and other research if true, suggest that heeding such advice might have inter-generational implications too, for lots of different reasons [3]...

Music to close, and sorry Your Majesty, but some of my brood find the alternative 'God Save the Queen' much more entertaining than the original...

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[1] Andersen CH. et al. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur Child Adolesc Psychiatry. 2017 Jul 15.

[2] Van Lieshout RJ. et al. Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review. Obes Rev. 2011 May;12(5):e548-59.

[3] Jensen ET. et al. The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm. J Pediatrics. 2017. March 21.

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Friday, 4 August 2017

Is current guidance for the management of CFS/ME in England fit for purpose?

"This multi-centre study in the NHS has shown that CFS/ME [chronic fatigue syndrome/myalgic encephalomyelitis] is a long term condition that persists for the majority of adult patients even after receiving specialist treatment."

So said the study results published by Simon Collin & Esther Crawley [1] (open-access) providing important information on some 400 patients diagnosed with CFS/ME who were in receipt of "NHS specialist CFS/ME services in England." Said specialist services, we are told, follow "guidance provided by the National Institute for Health & Care Excellence (NICE), including specific guidelines for diagnosis, specialist care, and ongoing management, with an overall patient-centred approach to treatment."

In case you've not followed the link to the NICE guidance covering CFS/ME, specialist care here in England generally describes various elements including the use of cognitive behavioural therapy (CBT) and/or graded exercise therapy (GET) based on the PACE trial results [2] and findings from other studies. Yes, the same PACE trial that 'continues to give' when it comes to arguments/debates (delete as appropriate) in CFS/ME circles (see here); see also the end of this post for more links to more recent happenings.

The Collin/Crawley research looked at several groups - newly referred and former patients - who attended one of eleven CFS/ME specialist services and who completed various questionnaires concerning the presentation  of fatigue, physical function and other aspects like mood and pain. Importantly: "They were also asked “Do you think that you are still suffering from CFS/ME?”" at follow-up either some 1 year after their initial clinical assessment or in some cases, 2-5 years later.

Results: "50–65% experienced little or no change in their condition 1–5 years after accessing a specialist service and 10–20% reported a deterioration, up to 30% of patients reported very much or much better health (and the majority of those who experienced little or no change had improved slightly)."

There are a few ways you could look at such results. You could say that specialist CFS/ME services are doing a fairly good job for approximately a third of patients who use them based on the figures reported. The authors do note some variability between the services that were included for analysis and given also that CFS/ME probably includes various 'sub-groups' under its banner, I'm not surprised therefore that there were potential best-responders and non-responders to the intervention(s) put in place.

The other way you could look at these data is with slightly less enthusiasm. Upwards of about two-thirds of patients surveyed saw no real difference to their symptoms long-term even after accessing such specialist services. More worryingly, a significant minority ("10-20%") reported deterioration; assuming this deterioration was in part or whole linked to their receipt of said specialist services, this is potentially in direct contravention of the tenet: first do no harm. These percentages - cumulatively up to 70%+ of patients - suggesting that specialist treatment might not necessarily be fit for purpose, need also to be analysed in the context of the costs associated with such specialist provisions in these days of rationing in many other parts of the NHS (see here for an example).

There is another detail included in the Collin/Crawley paper that requires comment: "Comparison with previous literature." The authors specifically focus in on the results for CBT and GET described in the PACE trial. They note: "The proportions of PACE trial participants (in the CBT and GET arms) who rated their overall health as very much or much better at 12 and 31 months were 41% and 42–48%, respectively, compared with 28% and 30% in our study (at 12 months and 2–5 years)." The authors suggest that differences in the number/intensity of sessions provided in the PACE trial and in 'real-life' might be one variable to account for the disparity reported on but I think we have to be a little bit careful here before saying specialist services either 'aren't doing it right' or 'aren't providing enough of a service'. There is for example, a debate currently rumbling on whether the recovery statistics subsequently produced from the PACE trial were entirely representative of the data produced (see here and see here for discussion on the authors reply). Minus any sweeping generalisations but in that context, I think one has to consider that there may be simpler answers to the disparity between studies: in a real-life context, CBT and GET are not as good an intervention for CFS/ME as some people might think. Indeed, it's potentially relevant that the US CDC has omitted CBT and GET from their current guidance for CFS/ME (see here) on top of similar changes to other guidance on this topic (see here). I know there may be some push-back to the idea that CBT and GET may not be the most suitable methods for 'treating' CFS/ME but nonetheless...

The Collin/Crawley paper provides a good snapshot of what patients themselves are saying about the current methods of treating/managing CFS/ME here in England. The picture the data paints is one of quite a bit more to do when it comes to how we care for some of the most ill people in society (see here for the quality of life comparisons). The focus on CBT for example, and the idea that those with the condition perhaps just need 'a change of attitude' towards their illness, is seemingly not working as well as some might wish. Although GET has shown some signs of efficacy for some with CFS/ME (see here), the sweeping generalisation that such an intervention is suitable for all with CFS/ME is also not borne out by the data and indeed, could potentially be quite damaging to some.  And patients are now saying that in the peer-reviewed science arena as well as on other forums too. Indeed, I again draw your attention to a quote from the opinion piece by Jonathan Edwards [3]: "If they [people with CFS/ME] are still ill, presumably these approaches have failed and the priority is to find something more effective." Who would disagree with such a sentiment?

To close, and related to today's post, has the dust settled yet regarding that special issue about the PACE trial published in the Journal of Health Psychology? I would say not...

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[1] Collin SM. & Crawley E. Specialist treatment of chronic fatigue syndrome/ME: a cohort study among adult patients in England. BMC Health Services Research. 2017; 17: 488.

[2] White PD. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36.

[3] Edwards J. PACE team response shows a disregard for the principles of science. 2017. J Health Psychology. March 28.

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Thursday, 3 August 2017

The pharmacological and non-pharmacological treatment of paediatric ADHD

The findings - "systematic review with network meta-analyses" - reported by Ferrán Catalá-López and colleagues [1] (open-access available here) on the topic of treating attention-deficit hyperactivity disorder (ADHD) were expected [2].

Looking at the available peer-reviewed science comparing "the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents" authors identified nearly 200 randomised trials looking at various intervention options. With data from over 26,000 people diagnosed with ADHD to examine, they applied some nifty statistical analyses leading to various conclusions on the basis of their categorisations of the various interventions analysed: "pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity)."

First: "behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo." I don't think this is a particularly novel finding given the intervention options typically indicated for ADHD (see here).

Then: "Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants." This is important insofar as any notion that use of pharmacotherapy alone is going to 'tackle' ADHD. It also suggests that parents, teachers and significant others have a role to play in managing the symptoms of childhood ADHD as per various examples (see here).

Also: "Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed." It should be no surprise to anyone that there is a cost-benefit balance to be struck when it comes to pharmacotherapy for ADHD or anything else. Medicines always have the potential for side-effects. The lack however, of 'serious adverse events' noted by Catalá-López et al is reassuring and adds to other reviews (see here) highlighting a role for regular monitoring and good medicines management with specific regards to medicines indicated for ADHD.

Finally: "There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine." I don't disagree with these findings but do find it a little 'odd' that other systematic reviews/meta-analyses of something like dietary interventions and/or use of fatty acids for ADHD have come to slightly different conclusions (see here and see here respectively). I don't doubt that there are going to be some subtle differences in what studies were included for further analysis and the interpretation of findings, but 'lack of evidence' is, in my mind at least, perhaps not an entirely accurate viewpoint. Indeed, a more recent paper is a further case in point [3].

"An open and honest discussion with parents and older children about uncertainties of available treatments and the balance between benefits, costs, and potential harms should be established before starting treatment." I think a sentence like this should be added to every article trying to arrive at a coherent statement for many different behavioural and psychiatric labels. It tells us that whilst scientific progress is being made when it comes to the important management of ADHD (see here), there typically is no one-size-fits-all 'silver bullet' that will vanquish all of the challenging symptoms of ADHD and onward improve current and future quality of life. Added to the idea that a multi-pronged approach to managing ADHD is typically better than any one single intervention option, and the Catalá-López article might turn out to be something rather important for many different people with various degrees of interest in ADHD and beyond.

Music: and when Mars Attacks...

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[1] Catalá-López F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017 Jul 12;12(7):e0180355.

[2] Catalá-López F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: protocol for a systematic review and network meta-analysis of randomized controlled trials. Systematic Reviews. 2015;4:19.

[3] Chang JC. et al. Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies. Neuropsychopharmacology. 2017 Jul 25.

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Wednesday, 2 August 2017

Fidget spinners: "their alleged benefits remain scientifically unfounded"

Fidget spinners, those spinning toys that have taken the world by storm in recent months, are great little things. My brood have several and, at least for the first few days of getting them, were constantly spinning them on their fingers or any other suitable surface. A welcome - if temporary - distraction from the tablets, phones, games consoles et al that pervade their lives.

Some of the claims however, that have been made about fidget spinners are not so great. Namely that these toys might have some almost magical qualities in 'eliminating anxiety' in relation to various diagnostic labels such as attention-deficit hyperactivity disorder (ADHD) or autism. The paper by Rachel Schecter and colleagues [1] confirms however that as things currently stand: "their alleged benefits remain scientifically unfounded."

Accepting that the research literature on the use of fidget spinners is, at the moment, pretty much nil, Schecter et al provide a little peer-reviewed clarity on the various claims being made around fidget spinners and conditions like ADHD and autism. They suggest that because  "fidget spinners and other self-regulatory occupational therapy toys have yet to be subjected to rigorous scientific research" any medicinal claims around them should really be reserved until appropriate scientific evidence emerges. Further that such toys may represent "potential choking hazards" so medical professionals (and I assume parents and caregivers also) need to be mindful. Such findings follow other opinions from members of this authorship group on other modern day trends and fads [2].

I don't want to undermine the popularity and usefulness of something like fidget spinners as a toy. I can remember the hacky sack sharing a similarly popular position when I was a kid; albeit not accompanied by any psychobabble explanations of improved this-or-that accompanying such use. I neither want to totally poo-poo the idea that for some at least, fidget spinners *might* offer some relief for something like stress under certain circumstances. But what I will continue to take exception to is the way that loose words about a toy having some medicinal qualities for one or more groups can seemingly fill the marketing airways without rigorous scientific evidence to back them up...

To close, vicars... careful when you go to the pub.

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[1] Schecter RA. et al. Fidget spinners: Purported benefits, adverse effects and accepted alternatives. Curr Opin Pediatr. 2017 Jul 7.

[2] Serino M. et al. Pokémon Go and augmented virtual reality games: a cautionary commentary for parents and pediatricians. Curr Opin Pediatr. 2016 Oct;28(5):673-7.

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Tuesday, 1 August 2017

Stepping into big data: who in the world walks the most each day?

With some journalistic flair, the BBC headline titled: 'Do you live in the world's least active country?'' caught my eye recently, discussing the findings reported by Tim Althoff and colleagues [1] (the first edition of their headline mentioned 'laziest' over 'least active'!)

The name of the research game was to analyse captured data on some "68 million days of minute-by-minute step recordings from 717, 527 anonymized users of the Argus smartphone application developed by Azumio." Said data spanned over 100 countries around the world, although researchers chose to zoom in on 46 countries where at least 1000 people had downloaded the app.

Results suggested that there were some quite considerable differences in steps per day according to the country data analysed and also variables such as gender/sex. Participants in Hong Kong for example, irrespective of gender, were top of the walking chart clocking up an average of 6800 steps per day. At the opposite end of the steps per day spectrum, those in Indonesia averaged just 3500 steps per day. The average number of steps per day across all the data analysed was round about the 5000 mark. There are some other potentially important snippets of information also included in the Althoff paper - the concept of 'activity inequality' - but I'm gonna stick with the steps per day data on this occasion.

A few times before on this blog I've talked about steps per day and walking patterns (see here and see here for examples) and what they might mean for health and wellbeing. Being partial to wearing an actigraph day-to-day, I see walking as part of the my own exercise regime and am a fan of things like the 10,000 steps a day challenge. Not least that as well as aiding in maintaining good physical health, there may be various other benefits from walking as part of a consistent exercise regime. Accepting that there may be various reasons why people don't walk perhaps as much as they should - health issues, age, environment and 'walkability' of the environment, etc - I am a little disappointed with the observations emerging from the Althoff paper insofar as how sedentary many people worldwide seemed to be. Yes, the current data was based on an app and so may have a degree of error in terms of it's recording capability (including whether a phone was carried with a person throughout the day or when engaging in other physical activities) but the average steps being counted per day seem to be quite a bit lower than many experts are advising for maintaining optimal health.

And because walking is [typically] free and can be undertaken by most people, I'd personally like to see a bigger push from Governments and the like to get more people back into walking...

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[1] Althoff T. et al. Large-scale physical activity data reveal worldwide activity inequality. Nature. 2017. 10 July.

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Monday, 31 July 2017

Placental inflammation and autism?

The placenta. Quite an important part of the nine months that makes us; an organ exquisitely evolved to provide oxygen and nutrition to the developing embryo/foetus as well as removing various un-necessaries. Without it we wouldn't even be...

A recent paper by Jennifer Straughen and colleagues [1] suggests that when it comes to the placenta and it's important functions during gestation, there may be some interesting data pertinent to at least some cases of autism spectrum disorder (ASD). Indeed the authors note: "Histologic evidence of placental inflammation and maternal vascular malperfusion pathology are associated with ASD."

Based on identifying some 55 persons diagnosed with ASD and nearly 200 matched controls, researchers analysed findings based on placentas "reviewed as part of routine care." Although not particularly au-fait with the inner workings of the placenta, I understand that various 'issues' were screened for and some interesting observations made. Words like 'acute placental inflammation' and 'maternal vascular malperfusion pathology' are banded around; many of which seemed to be more frequently associated with a subsequent diagnosis of ASD. In short, there seemed to be quite a bit more going on with those placentas from mums of children with autism compared with the not-autism controls.

This is important work. I've talked about the placenta and offspring autism previously a few times on this blog (see here and see here for examples). Allied to the rather sweeping idea that autism 'begins in-utero' and there is a case to be made for further inspection of organs like the placenta [2] when it comes to at least some cases of offspring autism - some, but not all. Indeed, it is perhaps timely that other independent papers [3] remind us of the work of the late Paul Patterson et al and the concept of maternal immune activation (MIA) and how the required reprogramming of the maternal immune system during pregnancy might very much rely on optimal placental function to keep the developing child safe and sound...

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[1] Straughen JK. et al. The association between placental histopathology and autism spectrum disorder. Placenta. 2017. July 8.

[2] Schroeder DI. et al. Placental methylome analysis from a prospective autism study. Mol Autism. 2016 Dec 15;7:51.

[3] Bilbo SD. et al. Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders. Experimental Neurology. 2017. July 8.

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Saturday, 29 July 2017

Various childhood psychiatric disorders may be risk factors for later substance abuse

"Childhood ADHD [attention-deficit hyperactivity disorder], ODD [oppositional defiant disorder], CD [conduct disorder], and depression increase the risk of developing substance-related disorders."

So concluded the results of the meta-analysis published by Annabeth Groenman and colleagues [1] surveying the peer-reviewed research literature between 1986 and 2016. Drawing on data from nearly 40 studies covering over three quarters of a million people that "included 22,029 participants with ADHD, 434 participants with ODD or CD, 1,433 participants with anxiety disorder, and 2,451 participants with depression" researchers looked at the risk in relation to "later alcohol-, nicotine-, or drug-related disorders or substance use disorders (SUDs)."

The level of risk identified concerning childhood psychiatric disorders and later substance abuse were not by any means borderline. Risk for SUD, substance use disorder, was particularly marked for all diagnoses and confirms the authors' conclusions about their findings that "emphasize the need for early detection and intervention to prevent debilitating substance-related disorders in later life." I say that, bearing in mind that one other diagnosis or set of diagnoses - anxiety disorder - did not seem to be related to later risk of substance-related disorder ("although the findings are highly heterogeneous").

As part of a growing pattern of research exploring the risk of future adversity associated with a diagnosis of something like ADHD or CD (see here) I share the author's sentiments that 'early detection' and 'intervention' are worthwhile ventures when it comes to such diagnoses. If one also assumes that ADHD and/or CD in particular, might also increase the risk for future psychopathology (see here), the case becomes even stronger to try and intervene early and improve future quality of life for both the individual and also on a more societal level. Guidance on this topic already exists [2].

But there are other factors to consider with such research. SUD reflects a complicated set of conditions in terms of how-and-why people arrive at such a diagnosis. Factors such as the role of peers and social issues such as poverty and homelessness [3] can all influence risk of SUD as can a variety of other variables that need to be taken on board. Whilst zooming in on individuals is a big part of the strategy to minimise any excess adverse risk of SUD in relation to ADHD, CD, ODD or depression, it should not be the only focus.

Finally, allied to the Groenman results, I might also draw your attention to those published by Clarissa Bauer-Staeb and colleagues [4] talking about how "substance misuse history conveys the greatest risk in all BBV [blood-borne viruses]" in relation to those diagnosed with a severe mental illness as a further undesirable outcome potentially stemming from certain substance abuses. And with it, yet more action is required...

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[1] Groenman AP. et al. Childhood Psychiatric Disorders as Risk Factor for Subsequent Substance Abuse: A Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2017 Jul;56(7):556-569.

[2] Harstad E. et al. Attention-Deficit/Hyperactivity Disorder and Substance Abuse. Pediatrics. 2014; 134:

[3] Tompsett CJ. et al. Peer Substance Use and Homelessness Predicting Substance Abuse from Adolescence Through Early Adulthood. American journal of community psychology. 2013;51(0):520-529.

[4] Bauer-Staeb C. et al. Prevalence and risk factors for HIV, hepatitis B, and hepatitis C in people with severe mental illness: a total population study of Sweden. Lancet Psychiatry. 2017 Jul 4. pii: S2215-0366(17)30253-5.

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Friday, 28 July 2017

'Somali autism': a phenotype?

"Results lend support to previous studies that found higher rates of ASD [autism spectrum disorder] intellectual disability in children of immigrants from low human resource index countries compared to other groups."

So said the findings reported by Amy Esler and colleagues [1] continuing an important research theme looking at how race/ethnicity might have some important 'effects' on the presentation of autism (see here). Although I've titled this post 'Somali autism' I don't necessarily want anyone to assume that I'm just zooming in on Somalia and that every Somali child who has been diagnosed with autism is somehow the same as each other either in autistic presentation terms or any of the comorbidity that inevitably surrounds autism. Autism is an extremely heterogeneous diagnosis with an often very individual and complicated clinical presentation.

I'm not going to dwell too much on this topic because I've covered it a few times before on this blog (see here and see here). Suffice to say that Esler et al follow the trend suggesting that "children from the Somali diaspora" seem more likely to present with autism + learning (intellectual) disability based on their study cohort. They also observed that: "Few differences were found in the presence of specific symptoms and behaviors across groups once IQ was controlled" meaning that the presence of intellectual/learning disability seemed to be the important variable.

There are some important extensions required to this area of study. Not least is the idea that genetic and/or biological variables could eventually be studied and compared with other racial/ethnic groupings with autism in mind. I'm minded also to mention that in amongst such 'where next' research, the potential role of something like vitamin D might be explored, given the [growing] interest in this vitamin/hormone with autism in mind (see here for example). As well as looking at differing sun exposure patterns (particularly mother and child exposure patterns) in those moving to less sunnier climates, the genetic machinery of making vitamin D might also figure in any future investigations too (see here).

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[1] Esler AN. et al. Phenotypic Characteristics of Autism Spectrum Disorder in a Diverse Sample of Somali and Other Children. J Autism Dev Disord. 2017 Jul 8.

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Thursday, 27 July 2017

Early pregnancy vitamin D levels and later offspring 'behavioral difficulties'?

Drawing on data derived from the Rhea mother-child cohort based in Crete, Greece, the findings reported by Vasiliki Daraki and colleagues [1] provide some food for thought; specifically the observation that "high maternal vitamin D levels in early pregnancy may protect against [offspring] behavioral difficulties, especially ADHD [attention-deficit hyperactivity disorder]-like symptoms at preschool age."

Including nearly 500 mother-child pairs, researchers set about looking at whether pregnancy levels of vitamin D - "serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks)" - correlated with cognitive functions and/or behavioural 'difficulties' in offspring at 4 years of age.

Results: as per the headline titling this post, there did seem to be some potentially important *associations* between maternal pregnancy levels of vitamin D and offspring outcomes. So: "children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity-impulsivity symptoms... and 40% decreased number of total ADHD-like symptoms... at 4 years of age, compared to children of women in the low 25(OH) D tertile (<38.4 nmol/l), after adjustment for several confounders." Investigations looking at pregnancy vitamin D levels and various cognitive functions of offspring children revealed nothing too significant.

Of course you would be right to point out that this was a study pitting one variable - pregnancy vitamin D levels - against a multitude of different offspring cognitive/behavioural outcomes some four years later. It's not entirely inconceivable that despite 'adjustment for several confounders' the authors might be in error in linking vitamin D to offspring outcomes and that some (more than one?) other variable(s) might account for the results. I should also point out that Greece is not exactly sunshine deficient; sunshine being a primary pathway pertinent to the biological synthesis of vitamin D.

But this is not the first time that pregnancy vitamin D levels have been *associated* with offspring ADHD or ADHD-like behaviours (see here) and I doubt it will be the last. Added to work looking at the possibility of an *association* between pregnancy vitamin D levels and offspring risk of autism (see here for example), bearing in mind autism and ADHD are not totally unconnected, there is an interesting theme developing on this topic. Perhaps Government (English at least) policy on recommending vitamin D supplementation for large swathes of the population (see here) may have a multitude of onward effects outside of just reducing the risk of bone manifestations of vitamin D deficiency/insufficiency?

And just before you go, even ALSPAC has something further to say on this matter [2]...

To close, 'Are you Tony Stank?'

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[1] Daraki V. et al. High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother-child cohort, Crete, Greece. Eur Child Adolesc Psychiatry. 2017 Jul 6.

[2] Darling AL. et al. Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomes in childhood: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Br J Nutr. 2017 Jul 12:1-11.

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Wednesday, 26 July 2017

Open label study of probiotics and autism

"We concluded that probiotics have beneficial effects on both behavioral and GI [gastrointestinal] manifestations of ASD [autism spectrum disorder]."

So said the study results published by Sanaa Shaaban and colleagues [1] detailing observations from their "prospective, open-label study" following some 30 children diagnosed with an autism spectrum disorder (ASD) before and after 3 months of probiotic usage. The study details were posted in a clinical trials repository (see here) and note how various measurements were taken as participants took a preparation containing "100 × 106 colony forming units of three probiotic strains; Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacteria longum."

Including some notable authors on the paper who are seemingly not adverse to [scientifically] examining some of the more non-traditional interventions put forward with autism in mind (see here and see here), researchers caution about their latest findings. So: "this study is a single center with a small number of patients and a great deal of additional wide-scale randomized controlled trials are needed to critically confirm the efficacy of probiotics in ASD." Yes, indeed; blinding for example, is a rather important part of the scientific process and other studies 'in progress' have adopted such factors (see here). Set against a growing tide of research suggesting that those trillions of wee beasties that inhabit our deepest, darkest recesses (the gut microbiome) might have more than a passing connection to some autism - some aspects of autism - this area of study is crying out for quite a bit more attention (see here also) not least on hows-and-whys (see here). The way that someone might potentially 'impact' on the gut microbiome in a probiotic sense is also potentially important (see here).

I have only one further point to make about the Shaaban results in relation to the observations that behavioural signs and symptoms (as assessed by the ATEC) seemed to show a relationship with GI symptoms following probiotic use. I'm wondering whether this potential tie-up might learn something from work looking at probiotic use in something like irritable bowel syndrome (IBS) (see here) and onward what happens to psychiatric issues that are seemingly over-represented in cases of IBS (see here). I say that on the basis that bowel issues seem to be most definitely over-represented when it comes to a diagnosis of autism (see here) and the whole 'gut-brain axis' thing continues -across decades - to persist with autism in mind (see here)...

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[1] Shaaban SY. et al. The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutr Neurosci. 2017 Jul 7:1-6.

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Tuesday, 25 July 2017

"a leaky gut may play a critical role in the development of age-related inflammation and frailty"

The quote heading this post is taken from the findings reported by Yanfei Qi and colleagues [1] who set out to investigate whether "an aging-associated leaky gut is linked to the age-related inflammation and frailty."

'Leaky gut' is still something of a contentious claim in medical and scientific circles despite some increasing evidence to say that it is a real phenomenon and potentially relevant to several conditions (see here) including some parts of the autism spectrum (see here). Although leaky gut is perhaps a slight misnomer - we all have leaky guts to some degree - the more accurate term 'intestinal hyperpermeability' suggests that for several different reasons, parts of the gastrointestinal (GI) tract may, at times or more chronically, be slightly more permeable that they typically should be. This in turn means that the contents of the GI tract - food derivatives, gut bacteria, etc - might be more readily exposed to parts of the body that they really shouldn't be and onward, potentially pathogenic.

Qi et al carried out some important analysis on two cohorts of differing ages (18-30 years old vs. 70 years and over) with regards to serum samples provided by participants. Markers of immune function, specifically inflammatory related compounds (e.g. tumour necrosis factor (TNF)-α and interleukin (IL)-6)) were assayed for, alongside levels of zonulin "a marker for leaky gut". Zonulin is something that I've covered quite recently on this blog in relation to autism research (see here). This biological data gathered by Qi and colleagues was also complemented by physiological measures such as "strength of plantar flexor muscles and number of steps taken per day."

Results: serum concentrations of zonulin were quite a bit - 22% - higher in the older participants compared to younger ones. Researchers also reported that levels of "high-mobility group box protein (HMGB1, a nuclear protein triggering inflammation)" were elevated in the older participants group too. They observed that zonulin levels also seemed to tie into concentrations of TNF-α and IL-6 (albeit not necessarily impressively). Zonulin levels also showed a potentially important *relationship* with "habitual physical activity" (those 'steps per day' data that was collected). The conclusion: "Serum zonulin was associated with both systemic inflammation and 2 key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty."

This is interesting stuff. It kinda accords with other independent data suggesting that generally speaking, gut barrier function does not necessarily have to deteriorate with age, but under certain circumstances such as age + inflammation, there might be effects to had [2]. Certain classes of medication might also show some involvement in this process too [3]. Although by no means a universal connection, I was interested in these results in the context of autism. Specifically how those Esnafoglu et al findings [4] reporting on 'significantly higher' serum zonulin levels in their cohort with autism, might also tie into reports of inflammatory markers being elevated in at least a subgroup of those on the autism spectrum (see here for example). I'd like to see the Qi study replicated with quite a few different labels and subgroups within labels...

In relation to the suggestion that serum zonulin levels negatively correlated with habitual physical activity (steps per day), again, there is a whole other research agenda to be [cautiously] followed. It's already known that certain patterns of exercise can affect (increase) intestinal permeability [5] although the specifics still require quite a bit more investigation (hint: exercising for 2 hours plus at a time is probably not great for gut function). As with everything in life, there is a balance to be struck between too little and too much of a good thing...

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[1] Qi Y. et al. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging. J Am Med Dir Assoc. 2017 Jul 1. pii: S1525-8610(17)30297-9.

[2] Valentini L. et al. Small intestinal permeability in older adults. Physiol Rep. 2014 Apr 22;2(4):e00281.

[3] Meier J. & Sturm A. The intestinal epithelial barrier: does it become impaired with age? Dig Dis. 2009;27(3):240-5.

[4] Esnafoglu E. et al. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. J Pediatr. 2017 May 11. pii: S0022-3476(17)30487-0.

[5] Costa RJS. et al. Systematic review: exercise-induced gastrointestinal syndrome-implications for health and intestinal disease. Aliment Pharmacol Ther. 2017 Aug;46(3):246-265.

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Monday, 24 July 2017

On DSM-5, Asperger syndrome and 'level of support'

It wasn't so much the findings reported by Garrido and colleagues [1] that took my attention, but rather their use of a particular sentence: "We have equated diagnosis of Asperger syndrome with ASD-level 1 of support" in the context of the DSM-5 guidance for diagnosing an autism spectrum disorder.

For those who might not know, the two main documents for diagnosing autism or autism spectrum disorder (ASD) are the ICD and DSM schedules. Both are currently under/have recently been the subject of revision (ICD-11 and DSM-5 respectively) and both have played a significant role in relation to various aspects around autism (see here for example).

The quite recently revised DSM-5 description of autism (see here) has been the source of quite a lot of discussion. Not only that the latest description might have some quite important effects on the numbers of people potentially being diagnosed with autism or ASD (see here) but also that this revision did away with the diagnostic sub-categories included in previous DSM versions; notably the diagnosis of Asperger syndrome. There were mechanisms built into the DSM-5 such that those already diagnosed with Asperger syndrome (AS) would not lose out in terms of 'identity' but as the DSM-5 becomes more readily used (and also assuming ICD-11 allies with DSM-5 as anticipated), the specific diagnosis of AS is likely to be consumed by the broader ASD label in the longer term. Other authors have talked about the hows-and-whys of this issue in more informed detail than I ever could (see here although I think the authors needs to spellcheck 'Asperger' in some places).

With that rather long introduction in mind, I want to go back to that 'ASD-level 1 support' labelling of AS in the Garrido paper. DSM-5 criteria for autism, sorry ASD, does provide the diagnosing team with an option to place the recipient of a diagnosis on a scale of severity ranging from 'requiring support' to 'requiring very substantial support' shown as levels 1-3 respectively. The assumption is that money and resources will be attached at varying degrees based on the support level indicated. The level 1 support option applied to AS presumes that the dyad of symptoms - social affect and restricted, repetitive behaviours - does impact on day-to-day functioning but issues such as the consistent and complex use of language as a communicative strategy for example, puts their support requirements below say those with 'marked' or 'severe' deficits in verbal and nonverbal social communication skills. Fair enough. When however it comes to the repetitive behaviour side of things in terms of severity, level 1 support basically acknowledges that inflexible behaviour "causes significant interference with functioning in one or more contexts" but importantly, does not use words like 'distress' as it does in level 2 and 3 descriptions.

I may just be focusing too much on details here, but it strikes me that the sweeping assumption made by Garrido et al reveals a broader issue with level of support shown in DSM-5. Although there is not a great deal of peer-reviewed research out there on the severity/support level components to the DSM-5 ASD diagnosis, the work that is there tends to suggest a degree of 'fuzziness' both in the pattern of skills/deficits displayed in relation to autism and onward how clinicians might define decisions on support level [2]. What seems to be inferred with the level of support criteria offered in DSM-5 is that those with a current diagnosis of AS as a group - this diagnosis then changing to ASD - will seemingly never hit criteria for levels 2 or 3 on the basis of the language and communicative skills they possess. I say this with the understanding that I'm not precisely sure whether the individual components of the dyad - social affect and restricted, repetitive behaviours - are separately graded in terms of level of support needed in DSM-5 or just condensed into one severity level for all the diagnostic components combined. Garrido and colleagues imply that one severity level is likely going to be the rule.

There is another issue that needs comment, on whether at least some cases of AS actually meet the operational criteria of DSM-5 ASD over and above the new categorisation of social (pragmatic) communication disorder (SCD) (see here). I can see this being a contentious point. SCD as the name suggests, focuses on 'the social use of verbal and nonverbal communication' and how 'deficits result in functional limitations in effective communication, social participation, social relationships, academic achievement, or occupational performance, individually or in combination'. Previous data has suggested that something approaching 10% of cases of AS - redefined as ASD in DSM-5 - might not actually meet DSM-5 criteria for ASD but might hit diagnostic thresholds for SCD [3]. As I've asked before on this blog, what level of support are those with SCD likely to get? and what are the implications for 'membership' of the autism spectrum for those diagnosed with SCD? are questions that still need answering.

I have been a little pedantic in this post but do want to convey the message that even with the redefinition of AS into ASD, the DSM-5 severity/level of support descriptions are in need of a lot more experimental study to see how they work in real-life [4]. Indeed, further longitudinal studies on how DSM-5 diagnosis and severity 'grading' translate into money, resources and services offered and received and onward outcomes for those diagnosed, should really be in the planning stages as we speak...

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[1] Garrido D. et al. Communicative and social-adaptive profile in children with autism spectrum disorder: a new approach based on the DSM-5 criteria. Rev Neurol. 2017 Jul 16;65(2):49-56.

[2] Weitlauf AS. et al. Brief Report: DSM-5 “Levels of Support:” A Comment on Discrepant Conceptualizations of Severity in ASD. Journal of autism and developmental disorders. 2014;44(2):471-476.

[3] Kim YS. et al. A comparison of DSM-IV pervasive developmental disorder and DSM-5 autism spectrum disorder prevalence in an epidemiologic sample. J Am Acad Child Adolesc Psychiatry. 2014 May;53(5):500-8.

[4] Burns CO. & Matson JL. An evaluation of the clinical application of the DSM-5 for the diagnosis of Autism Spectrum Disorder. Expert Rev Neurother. 2017 Jul 5.

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Saturday, 22 July 2017

"medical disorders in children with ASD and ADHD appear to be widespread"

The quote titling this brief post is taken from the results of the systematic review undertaken by Jet Muskens and colleagues [1] (open-access) who surveyed the peer-reviewed science literature "on medical comorbidity in the two major developmental disorders autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)."

Continuing an important theme (see here), the authors concluded that various categories of conditions - "immunology, neurology and gastroenterology" - are over-represented in relation to autism and ADHD and that "future studies should not only focus on psychiatric symptoms, but provide a broader evaluation of medical disorders" when it comes to those labels.

Minus too much chatter, I was impressed to see that many of the research articles covered on this blog down the years had made it into the Muskens review. So, the likes of Harumi Jyonouchi gets a well-deserved mention (see here and see here) and the focus on how the immune system might be doing so much more than just protecting us from the odd pathogen or two. The authors also bring in some of the very convincing scientific evidence that various gastrointestinal (GI) issues are over-represented in relation to autism (see here). There's even mention of how useful that Taiwanese research database has been down the years to autism and ADHD research (see here).

What's more to say? Well, preferential screening for various medical conditions in the context of an autism diagnosis yet again, receives more support. As does the idea that when a medical diagnosis is received by a person diagnosed on the autism spectrum, that medical diagnosis deserves the same healthcare management and/or treatment as it does in the context of not-autism save any further health inequalities potentially appearing (see here). The days for example of 'blaming autism' for every single physical complaint are also to be consigned to the historical dustbin. And with it, recognition that concepts such as ESSENCE or 'autism plus' (see here and see here) really need to include the somatic as well as the behavioural/psychiatric...

Whilst welcoming the Muskens review, it's important to note that others have already 'primed' for the importance of medical comorbidity in relation to a diagnosis of autism...

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[1] Muskens JB. et al. Medical comorbidities in children and adolescents with autism spectrum disorders and attention deficit hyperactivity disorders: a systematic review. European Child & Adolescent Psychiatry. 2017. July 3.

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Friday, 21 July 2017

Antidepressants during pregnancy and autism in offspring (with care)

There are a few topic areas in the quite vast autism research landscape that consistently seem to keep cropping up. The possibility of some kind of *association* between pregnancy antidepressant use and risk of offspring autism is one of those areas (see here) as the results published by Dheeraj Rai and colleagues [1] (open-access) are presented for your attention. I would also draw your attention to an accompanying editorial discussing the Rai findings (see here).

So: "To help to improve the understanding of the association between antidepressant use during pregnancy and autism in offspring, we applied a range of... causal analytical methods on data from a large total population cohort in Stockholm County" was the starting point, as once again one of those very useful Scandinavian registries provided the source study material (indeed, Rai et al are seemingly experts in their analysis of such resources). The added bonus to the Rai study was their attempt to 'unravel' any association between gestational antidepressant exposure and autism from the reason why such medication was being taken in the first place: maternal psychiatric health issues (and whether this variable may in fact account, at least in part, for any association that has previously been identified).

From a starting population approaching three-quarters of a million people, researchers eventually settled on looking at over 250,000 children under 17 years of age (but over 4 years of age "in whom a diagnosis of autism might be less reliable") who were born to over 150,000 mothers. The vast majority of children (239,943 of 254,610) had no history of exposure to antidepressants during pregnancy. The remaining participants were divided up into two groups: one where there was documentation leading to the assumption of exposure to pregnancy antidepressants (n=3342) and one where there was an indication for such exposure ("mothers with a psychiatric disorder") but no recorded use of antidepressants during pregnancy (n=12,325). Researchers summed up how many children were diagnosed with an autism spectrum disorder (ASD) in each group and applied some statistical modelling.

Results: I think it's important to first highlight a statistic that seems to have been missed by many covering the Rai findings: "Of the 238 943 cohort children for whom there was no record of maternal history of psychiatric disorder or antidepressant use during pregnancy, 4889 had autism (2.1%)." That's 2.1% with a diagnosis of autism or ASD; quite a far cry from the 1% [estimate] statistic from just a few years back (at least here in Blighty).

Then: "Exposure to antidepressants during pregnancy was associated with a higher odds of a diagnosis of autism in offspring than exposure to a maternal psychiatric disorder without antidepressants." The authors caution that: "the absolute risk was small, and 4.1% of children exposed to antidepressants in utero had autism compared with 2.9% of those with a maternal history of psychiatric disorder." Further when looking at those children diagnosed with ASD in the groups, authors observed that "autism without intellectual disability" seemed to be over-represented; something also picked up in previous findings from authors on this current paper [2].

Alongside various opinions on these findings (see here for example), the authors caution about the possible meaning of their results. One obviously has to be quite careful when discussing such data to ensure that an important class of medicines is not unduly vilified. No medicine is however without potential side-effects and appropriate clinical decisions and good medicines management [2] is key, particularly when pregnancy is included as variable. The authors talk, for example, about how "if a causal link were robustly established, and if no pregnant women took antidepressants during pregnancy, only 2% of autism cases in this population would be prevented." Alongside they [importantly] mention that antidepressant use during pregnancy is not typically just a 'choice' but rather being clinically indicated: depression does not simply disappear when a woman is pregnant. Interestingly too, they mention about how their data "suggest that there is an increased background risk of autism in children of women with psychiatric conditions, regardless of antidepressant treatment." This follows a trend in other areas of psychiatry (see here for example).

Yet again, the call is further research in this area and, quite a few more investigations into the possible hows-and-whys of any association (with medication use and/or maternal psychiatric presentation) is made. I might also suggest that taking into account other childhood conditions such as attention-deficit hyperactivity disorder (ADHD), potentially over-represented when it comes to a diagnosis of autism or ASD, could be another important step forward in light of other preliminary *associations* being made with pregnancy medication history in mind (see here). This also includes looking at any issues associated with timing of potential exposure and/or dose ("Because of small numbers, we were not able to assess trimester specific or dose response effects.").

Insofar as the suggestion that autism without intellectual (learning) disability might be an important phenotype when it comes to any association, subsequent research in this area seemingly fits in well with increasingly vocal calls [4] to stop using the generic label of autism as a research starting point (see here). Allied to suggestions for more 'bottom-up' research with autism in mind (see here), also coincidentally mentioning "maternal SSRI use during pregnancy" in the context of autism [5], a future research agenda is seemingly emerging. I might also point out that certain sensitivities need to be kept in mind on the basis of suggestions that an 'environmental exposure' might, in whole or part, be *associated* with a particular type(s) of autism.

All such work - present and future - however needs to be done/presented with care, understanding and minus scaremongering, so as not to unduly alarm pregnant mothers, their families or indeed, the physicians providing their care at such a critical time...

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[1] Rai D. et al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ. 2017; 358: j2811.

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