Wednesday, 17 January 2018

Sleep duration and ADHD: a correlation across the years?

"Longer sleep duration (>10 hours per day) was associated with a lower ADHD [attention-deficit hyperactivity disorder] symptom score" was one of the findings reported by Gabriela Peralta and colleagues [1].

They sought to examine whether a particular set of activities (sleeping, physical activity, television watching, etc) might show some *correlation* to "(1) attention-deficit/hyperactivity disorder (ADHD) symptoms and (2) behavior problems, both assessed at 7 years, in ADHD-free children at baseline."

Drawing on a not-insignificant number of children participants (N=817) who were part of a research birth cohort previously discussed on this blog (see here and see here), authors relied on parental report via the Conners' Parent Rating Scales and the Strengths and Difficulties Questionnaire to ascertain ADHD and 'behaviour problem' scores respectively. This was carried out when the child was aged around 7 years old. A few years earlier - when the child was around 4 years old - parents had previously reported on a few other variables: "the time that their children spent sleeping, watching TV, engaging in cognitively stimulating activities, and engaging in physical activity." The two sets of data were married together for analysis.

Results: it's probably not escaped your notice that (a) parental report is a mainstay of the Peralta data and (b) data for a child at 4 years old and then again at 7 years old represents quite a large time frame during which lots can (and does) happen. With those factors firmly in mind, researchers provided some frequency data on activities at 4 years old. They then added in the data taken at 7 years old where that finding on longer sleep duration (at 4 years) seemed to be linked to lower ADHD scores (at 7 years) came from. Further: "Longer time spent in cognitively stimulating activities (>1 hours per day) was associated with lower scores of both ADHD symptoms... and behavior problems" and also rather interestingly: "Time spent watching TV and engaging in physical activity were not associated with either outcomes."

The quite fuzzy picture emerging from this data - with appropriate caveats - is that sleep and 'keeping the mind active' might be important factors when it comes to the presentation of something like ADHD (symptoms) and other 'behaviour problems' in childhood. The sleep side of things is particularly topical at the moment, given some research chatter about how a sleep intervention might be something to consider for at least some (diagnosed) cases of ADHD (see here). There are also seemingly lots of benefits from ensuring a regular bedtime routine for young children; assuming that is, that poor sleeping patterns are not an early marker for possible ADHD?

The whole 'cognitively stimulating activities' bit is slightly more fluffy in terms of what constitutes such activities and any relationship with ADHD or behavioural issues. I say this on the basis that whilst reading and writing for a 4-year old is likely to be cognitively stimulating, so are lots of other activities such as exploring nature for example or even spending time on the dreaded computer/tablet devices (depending on what activities are being done). Even time spent in front of the gogglebox could be considered cognitively stimulating if they're watching Blue Planet for example, and not just a re-run of Peppa Pig (sorry Peppa). And on the topic of television viewing or at least screen time in the context of ADHD risk, other data have suggested something *correlatively* different from the Peralta findings (see here) just to complicate matters further.

To close, it's been a while but here is some music... Elvin Bishop and a track brought back to life by the Guardians...

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[1] Peralta GP. et al. Sleeping, TV, Cognitively Stimulating Activities, Physical Activity, and ADHD Symptom Incidence in Children: A Prospective Study. J Dev Behav Pediatr. 2017 Dec 18.

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Tuesday, 16 January 2018

Vitamin D and autism... another double-take?

A quick-ish post today as I bring the results published by Dong and colleagues [1] to your attention and the [translated] observation that: "Serum 25-hydroxyvitamin D level in children with ASD [autism spectrum disorder] is obviously lower than that in the healthy control group, and there are negative correlations between vitamin D levels and core symptoms of ASD." 'Obviously' eh?

It's another study from China (see here) and yet again I find myself correcting language as per the authors' use of the term 'healthy control group' when describing not-autism. In much the same way that the word 'neurotypical' is a bit of a nonsense, so the insinuation that a diagnosis of of autism automatically means 'not healthy' is far too broad a sweeping generalisation.

Anyhow, vitamin D and autism was the name of the research game for these authors; something not altogether new and novel for at least some of the authorship group (see here and see here for examples). Indeed, my use of the term 'another double-take' in the title of this post refers to the observation that this group have really gone to town with their clinical trial registered research project in this area (see here for example).

"Serum vitamin D level in ASD children was significantly lower than that of the control group... and the between-group percentage difference of normal, insufficient and deficient levels of vitamin D was statistically significant." Bearing in mind that vitamin D levels were checked using a gold-standard technique (liquid chromatography-mass spectrometry, LC-MS), I'm inclined to accept these results as they stand. I'm not saying that other methods of vitamin D analysis are all bunk, but rather that LC-MS is a mighty powerful method for sample analysis with vitamin D in mind.

Further: "There were negative correlations between serum vitamin D level in ASD children and total ABC [Autism Behavior Checklistscore or ABC subscale scores (body behavior, self-care, language and social interaction). There were negative correlations between serum vitamin D level in ASD children and total CARS [Childhood Autism Rating Scalescore and CARS subscale scores (imitation, nonverbal communication and general impression). There were negative correlations between serum vitamin D level in ASD children and SRS [Social Responsiveness Scale] behavior subscale or ATEC [Autism Treatment Evaluation Checklistsocial interaction subscale." In short, vitamin D  levels seemed to *correlate* with quite a few behavioural results, although I'm slightly less inclined to read too much into such findings given the relatively small participant group included for study and the 'snaphot' study methodology.

But yet again, this is another example illustrating that vitamin D metabolism should very much be a part of any assessment when it comes to autism (see here and see here)...

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[1] Dong HY. et al. Correlation between serum 25-hydroxyvitamin D level and core symptoms of autism spectrum disorder in children. Zhonghua Er Ke Za Zhi. 2017 Dec 2;55(12):916-919.

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Monday, 15 January 2018

"Meningitis is a significant risk factor for developing ADHD later in childhood"

The quote heading this post comes from the results published by Hadžić and colleagues [1] who sought to "examine the frequency of ADHD [attention-deficit hyperactivity disorderin children who had had bacterial meningitis."

Bacterial meningitis by the way, reflects meningitis brought about by one of a number of bacteria (e.g. meningococcal, pneumococcal, TB, Group B Streptococcal, Hib) with treatment via timely use of antibiotics.

Comparing 60 children who "had had meningitis in the first year of their lives" with 60 control children who did not have meningitis, researchers looked at the frequency of ADHD - "assessed through the structural clinical interviews with parents according to the criteria set in DSM-IV." They observed that over 60% (37/60) of those with a history of meningitis had reported behaviours consistent with a diagnosis of ADHD compared with only 5% (3/60) of controls.

I might question the use of parental interviews outside that of the actual assessment of children as being one variable that puts the Hadžić results at something of a disadvantage. But, and it is an important 'but', this is not the first time that ADHD or behaviours that characterise ADHD have been talked about in the context of meningitis. Indeed, tuberculous meningitis (TBM) has been mentioned in the context of ADHD before [2] and on more than one research occasion [3] (albeit by the same research group).

The mechanisms / modes of action? Well, we're still left to speculate. Meningitis involves inflammation of the membranes (meninges) that protect the brain and spinal cord. The after-effects for some can involve brain damage but also a variety of other adverse outcomes have also been noted including issues such as epilepsy and/or seizure disorder. It's not inconceivable that one or more of these adverse effects *could* impact on the presentation of something like ADHD or at least, ADHD-related behaviours. Further research needs to be conducted on what follows from something like bacterial (and viral) meningitis in terms of 'brain symptoms' and onward what this might mean for risk of ADHD.

What this latest research does illustrate quite well is that, much like the debates in autism circles, not every single person diagnosed with ADHD or those presenting with clinically-relevant ADHD symptoms does so through some inborn process. Infection - or response/after-effects of infection - can seemingly play quite a big role for some; bearing in mind also that other, various types of infection, have been previously implicated in relation to ADHD (see here and see here) outside of just meningitis.

And whilst on the topic of infection potentially being related to *some* neurodevelopmental diagnoses, I note some conversations on social media have tried to (once again) poo-poo the idea that autism, or a diagnosis of autism, might not be a lifelong issue for some people. 'Masking' of autism is the new, universal idea emerging, which whilst important, probably doesn't cover every case of autism symptoms dissipating [4] (see here for my take)...

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[1] Hadzic E. et al. Is Bacterial Meningitis a Risk Factor for Developing Attention Deficit Hyperactivity Disorder. Isr J Psychiatry Relat Sci. 2017;54(2):54-57.

[2] Wait JW. & Schoeman JF. Behaviour profiles after tuberculous meningitis. J Trop Pediatr. 2010 Jun;56(3):166-71.

[3] Wait JW. et al. Tuberculosis meningitis and attention deficit hyperactivity disorder in children. J Trop Pediatr. 2002 Oct;48(5):294-9.

[4] Hacohen Y. et al. N-methyl-d-aspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression. Developmental Medicine & Child Neurology. 2016; 58: 1092-1094.

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Saturday, 13 January 2018

Bowel issues over-represented in autism (and perhaps linked to some behaviours)

"Make it so Mr WORF"
Once again(!) more evidence emerges from the peer-reviewed science domain highlighting how functional gastrointestinal (GI) issues such as constipation and diarrhoea are very much over-represented when it comes to a diagnosis of autism (see here). The study providing the data this time was by Zhu and colleagues [1] and was carried out in China; thus illustrating how such bowel issues cross countries and ethnicity when it comes to autism.

There's little novelty in their findings that all-manner of functional bowel condition were more frequently present in their cohort of over 320 children diagnosed with an autism spectrum disorder (ASD) compared with some 200 not-autism controls. The authors' observation that almost 50% of their sample of children diagnosed with autism presented with at least one bowel issue is not as surprising in research-terms as it perhaps once might have been.

What is perhaps interesting is the growing focus on how such bowel issues may *correlate* with behaviour noted in children with autism, as per the results of other independent findings (see here). To quote from Zhu et al: "Compared with ASD children without GID [gastrointestinal disorders] (n=166), the ASD children with GID (n=162) got higher scores in the "Body and Object Use" of ABC [Autism Behavior Checklistscale... and had more emotional problems. Moreover, the score of behavior problems questionnaire was higher in the ASD children with GID." This is not necessarily new news to many people (particularly to parents and caregivers) but should be a topic that is given more research and clinical consideration among professionals.

More needs to be done in this area, not least on:

  • improving the ways of detecting and reporting on functional bowel issues in the context of autism (see here),
  • ensuring that questions about bowel function are asked during autism assessments and exams,
  • moving away from over-simple 'psychological' assumptions/explanations to potentially account for bowel issues in relation to autism (see here) without appropriate gastroenterological referral (also including ridding ourselves of the old-saying 'it's part of their autism'),
  • ensuring that appropriate gastroenterological resources are available and timely referral is present (particularly for paediatric resources),
  • following guidance that is out there in the peer-reviewed domain on screening and treating bowel issues in the context of autism (see here),
  • not being afraid to look for signs of more serious bowel pathology as and when functional bowel symptoms are present (see here) and,
  • embracing the idea that gut and brain might not be completely separate and independent in the context of autism and beyond (see here). 


'Nuff said I think.

But just before you go, some other study results [2] for you to mull over with regards to the question: what is the 'normal range' of bowel movements? Answer: anything from 3 a day to 3 a week apparently.

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[1] Zhu J. et al. Association between behavioral problems and gastrointestinal disorders among children with autism spectrum disorder. Zhonghua Er Ke Za Zhi. 2017 Dec 2;55(12):905-910.

[2] Mitsuhashi S. et al. Characterizing Normal Bowel Frequency and Consistency in a Representative Sample of Adults in the United States (NHANES). Am J Gastroenterol. 2018 Jan;113(1):115-123.

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Friday, 12 January 2018

Allergic disease and ADHD yet again...

Although words like 'first' and 'largest' were used in the paper by Chia-Feng Yang and colleagues [1] (open-access available here) observing that "AD [atopic dermatitis] and asthma with allergic sensitization are associated with ADHD [attention-deficit hyperactivity disorder] in children", I'm minded to be a little cautious with such 'we're the first/best' assertions.

Cautious because, on quite a few peer-reviewed research occasions (see here for example), a possible *link* between various allergic disease and ADHD has already been noted; even potentially extending to studies talking about how treatment for allergic disease might on some occasions also impact on presented ADHD symptoms (see here) (with no medical advice given or intended).

Yang et al relied on data from a research favourite country, Taiwan, derived from an initiative called the Childhood Environment and Allergic diseases Study (CEAS). The clue is in the name of the initiative in terms of what they were looking for/at, as per other publications derived from the initiative [2]. From the 3200-odd participants eligible for participation, researchers relied on data from over 2700 children. Questions about allergic disease history were asked to parents of said participants, alongside other 'environmental' factors such as family income, tobacco exposure and breastfeeding history. I note also a question about 'incensing at home' is also included relating to the use of burning incense typically linked to religious practices in certain cultures.

When it came to a diagnosis of ADHD, it's not entirely clear about how this was ascertained but it looks like diagnosis was given by a clinician: "The conditions of disease in children were confirmed by board-certified child psychiatrists or pediatric neurologists, according to the clinical evaluation." I should also mention that participants also received skin prick tests (SPTs) covering a range of potential allergens: "house dust mites (HDMs mix, including Der p, Der f, Der m, and Blot allergens), cockroaches, dog dander, milk, egg, and crab allergens" as way of defining allergic sensitisation.

Results: there was a "strong positive association between ADHD and allergic sensitization as diagnosed by positive SPTs." In other words, despite finding a fairly low level of ADHD in their sample (1%), those who 'reacted' to one or more of the allergens tested for via the skin prick test seemed to be at some increased risk of ADHD. Such an enhanced risk spanned both those presenting with "AD with allergic sensitization and asthma with allergic sensitization."

The authors provide some further results and details on the possible hows-and-whys of their results. Obviously the immune system figures quite strongly given what for example, they were testing for with the SPT and their focus on AD and asthma. The word 'inflammation' also figures quite heavily. I note too that the authors reiterate previous suggestions that: "Control of allergens exposure might be a critical factor influencing the development of ADHD."

There is a further scheme of work to follow in this area, not just dealing with mechanisms but also in relation to 'treating' allergies also potentially 'treating' [some] ADHD. I say this on the basis that other independent research has observed that before reaching for the antihistamine as a potential ADHD-modifier, there may actually be a connection between early antihistamine exposure and the development of ADHD [3] (albeit with potential confounders) to keep in mind. Other work also supporting a link between ADHD and atopic disease [4] provides some other 'clues' that may require further investigation; not least "cow's milk intolerance", which ties into similar findings (see here) and could also be one route from which ADHD heightens the risk of subsequent future psychiatric disorder (see here) in light of other 'milk' associations (see here).

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[1] Yang CF. et al. Association between allergic diseases, allergic sensitization and attention-deficit/hyperactivity disorder in children: A large-scale, population-based study. J Chin Med Assoc. 2017 Nov 24. pii: S1726-4901(17)30304-0.

[2] Wang IJ. et al. Allergens, air pollutants, and childhood allergic diseases. Int J Hyg Environ Health. 2016 Jan;219(1):66-71.

[3] Schmitt J. et al. Increased attention-deficit/hyperactivity symptoms in atopic dermatitis are associated with history of antihistamine use. Allergy. 2017 Oct 4.

[4] Hak E. et al. Association of childhood attention-deficit/hyperactivity disorder with atopic diseases and skin infections? A matched case-control study using the General Practice Research Database. Ann Allergy Asthma Immunol. 2013 Aug;111(2):102-106.e2.

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Thursday, 11 January 2018

ICF core sets for autism: "third in a series of four empirical studies"

Peer-reviewed discussions on the International Classification of Functioning, Disability and Health (ICF) core sets for autism have appeared a couple of times before on this blog (see here and see here). The idea behind developing the ICF core sets - a World Health Organisation (WHO) initiative - is to build up a kind of framework for describing and organising information on functioning and disability across various diagnoses.

Autism has been in the ICF sights for a few years now. The hope is that science and clinical practice can start to get closer to the many abilities and disabilities that seem to derive from a diagnosis and offer more evidence-based 'clues' of where and when support needs to be targeted. Also perhaps potentially providing some good evidence for just how heterogeneous the autism spectrum really is...

Bearing in mind the previous research occasions where the development of the ICF core sets for autism have been discussed from a systematic review and 'experts' perspective, the paper by Soheil Mahdi and colleagues [1] adds a third tier to proceedings: "to describe functioning in ASD (as operationalized by the ICF) derived from the perspectives of diagnosed individuals, family members, and professionals." This is an important part of the ICF development schedule, in that it gave an important voice to those people who are themselves autistic and their family members. All of this set in light of a growing 'debate' on who speaks for who(m) in the context of autism (see here) and how talking more to those on the autism spectrum about their experience of autism might be a rather good idea (see here) (bearing in mind that not everyone can or does make their voice heard in such conversations - see here).

So, drawing on discussions - "focus groups and semi-structured interviews" - with some 19 stakeholder groups, the authors report how 'meaningful concepts' talked about by stakeholders were linked to the draft ICF categories already present. Various talking points emerged; some mirroring what has been previously observed: "Positive aspects of ASD [autism spectrum disorder] included honesty, attention to detail, and memory". Others, not exactly aligning with other discussions by other groups: "Body structures were sparsely mentioned by the participants."

The outcome was however pretty much the same as the other ICF development occasions: "The experiences provided by international stakeholders support the need to understand individuals with ASD in a broader perspective, extending beyond diagnostic criteria into many areas of functioning and environmental domains." The core triad/dyad of symptoms it seems, is only the starting point when it comes to what autism looks like and means. A shocker indeed!

I await more on this topic, and perhaps, mentioning how the ICF core sets for autism might also *correlate* with other important research streams such as that related to quality of life [2].

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[1] Mahdi S. et al. An international qualitative study of functioning in autism spectrum disorder using the World Health Organization international classification of functioning, disability and health framework. Autism Res. 2017 Dec 11.

[2] Lin LY. & Huang PC. Quality of life and its related factors for adults with autism spectrum disorder. Disabil Rehabil. 2017 Dec 11:1-8.

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Wednesday, 10 January 2018

Probiotics are "a good choice in remission of inflammatory bowel diseases" (says review)

The systematic review and meta-analysis published by Mahboube Ganji-Arjenaki & Mahmoud Rafieian-Kopaei [1] provides the blogging fodder today, on the topic of  "the efficacy of probiotics in attaining clinical response on patients with various types of IBD [inflammatory bowel disease]."

Probiotics, in case you've not heard, include a range of bacterial and yeast species thought to have some sort of health benefit by acting on the multitude of microorganisms that call us (predominantly our digestive tract) home. Inflammatory bowel disease (IBD) typically means one of two conditions: ulcerative colitis (UC) and/or Crohn's disease (CD). Both IBD conditions involve inflammation of parts of the gastrointestinal (GI) tract, in which many of those previously discussed microorganisms reside in. Putting the two concepts together - probiotics and IBD - and it stands to reason that they might have some [variable] interaction with one and another.

The authors surveyed the current peer-reviewed science literature on the topic of probiotics 'for' IBD, grouped the results together and set about trying to come up with some summary statements based on the statistical results obtained. Bearing in mind that the term 'probiotic' includes quite a few different bacterial/yeast species, both alone and in combination, they came up with a few take-home messages.

First: "Probiotics are beneficial in IBD, especially the combination ones in UC." Given what traditional treatment options are currently available for UC (see here), the idea that popping a few pills, most of which are readily available without a doctor's prescription, containing bacteria and/or yeasts must represent a rather good deal for those diagnosed with UC. I say this minus any medical or clinical advice from me: please, consult you medical physician before making any such changes.

Second: I note that two particular 'preparations' are mentioned in the review text: Saccharomyces boulardii and VSL#3. Both of these products (yes, I know S. boulardii is a strain of yeast) have had previous airtime on this blog for various different reasons (see here and see here for examples). Both of them also have some pretty good evidence when it comes to other bowel-related conditions and states as told again by the all-powerful meta-analysis/systematic review (see here).

Finally I note that the safety profile of these preparations seemed to be pretty good based on the trial data included for study. That's not to say that they are completely side-effect free [2] (particularly in the context of the use of immunosuppressants for potentially treating UC for example) but their risk profile seems at least to be on a par with more traditional pharmacotherapies.

What's more to say? Well, just before I finish I do want to try and relate some of the Ganji-Arjenaki - Rafieian-Kopaei findings back to the core material of this blog: autism. I say this with some cautions but: (a) science has told us a few times that inflammatory bowel disease does seem to be over-represented when it comes to a diagnosis of autism (see here), and (b) discussions should be turning to 'what can we do to help' when it comes to IBD accompanying autism, given that presentation might be slightly less 'mainstream' in such cases [2] (see here for my take on this study). I've also already touched upon the study by Grossi et al [3] (see here) talking about how a probiotic formulation seemed to affect both gut and behaviour in a case report and what that could mean for [some] others diagnosed with an autism spectrum disorder (ASD). Such findings asks science to do a lot more to see if a dual diagnoses of autism and IBD represents an important target for probiotics as an extension to work on autism and more 'functional' bowel complaints either already completed or still underway (see here and see here).

And bear in mind that outside of any gut-brain notions specifically with IBD and autism in mind (see here), there is evidence to suggest that effective medical treatment of IBD might generally extend to quite a few domains [4] which I daresay are just an important in the context of autism as they are to not-autism...

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[1] Ganji-Arjenaki M. & Rafieian-Kopaei M. Probiotics are a good choice in remission of inflammatory bowel diseases: A meta analysis and systematic review. J Cell Physiol. 2018 Mar;233(3):2091-2103.

[2] Lee M. et al. Association of Autism Spectrum Disorders and Inflammatory Bowel Disease. J Autism Dev Disord. 2017 Nov 23.

[3] Grossi E. et al. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Medical Case Reports. 2016;4:2050313X16666231.

[4] Mählmann L. et al. Psychological wellbeing and physical activity in children and adolescents with inflammatory bowel disease compared to healthy controls. BMC Gastroenterology 2017; 17: 160.

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