Wednesday, 26 April 2017

Hornig, Lipkin and chronic fatigue syndrome again

Drs Mady Hornig and Ian Lipkin once again provide some fodder for this blog, continuing one of their important research themes on how chronic fatigue syndrome (CFS) (sometimes also referred to as myalgic encephalomyelitis, ME) might show some important immune-related issues [1].

This research tag-team and the teams of dedicated scientists who surround them are making some real progress with regards to the idea that ME/CFS is a physical condition (not psychosomatic and not 'biopsychosocial') with some readily identifiable biological features potentially accompanying cases. Of course we're not there just yet when it comes to a biological test for ME/CFS but science has at least started down that particular research path...

With accompanying media attention in tow (see here), the focus of the most recent results were on how disease sub-types might be important to CFS and specifically, how: "Immune signatures in the central nervous system of ME/CFS patients with atypical features may be distinct from those with more typical clinical presentations."

Authors described how cerebrospinal fluid (CSF) samples from "32 ME/CFS cases with classical features and presentations and 27 ME/CFS cases with atypical features or clinical presentations" were included for analysis. On what basis was 'typical' and 'atypical' described? Well: "The ‘classical’ (C-ME/CFS) group had acute onset of disease marked by a prodrome consistent with infection; ‘atypical’ (A-ME/CFS) ME/CFS patients met full diagnostic criteria for ME/CFS at onset of their illness, but had a less standard onset of ME/CFS and/or developed other disorders after illness onset of ME/CFS." Interestingly one person included in the A-ME/CFS group was described as having Gulf-War Illness (another important condition talked about on this blog).

The results: various cytokines (chemical messengers of the immune system) were assayed for and with some nifty statistical 'corrections' authors reported some potentially important differences between the groups. So: "We found discrete differences in immune signatures of the CNS in ME/CFS subjects with atypical presentations that included sparse inter-cytokine networks and lower levels of two inflammatory mediators, the Th17 cytokine, IL17A, and the IFNγ- and TLR4-induced chemokine, CXCL9." All-in-all results suggested a "less robust CNS immune activation in A-ME/CFS."

Much more research is required in this area for sure. But these results are interesting and pertinent to the idea that within the heterogeneity (where have a I heard that before?) of CFS/ME, there may be quite a few phenotypes and subgroups that might be readily separable with a little biological research effort. Does this therefore mean when we talk about the pluralisation of lots of labels (the autisms, the schizophrenias, the depressions, etc), we might also one day called it 'the chronic fatigue syndromes'? Well, I've kinda speculated about this before in the peer-reviewed domain...

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[1] Hornig M. et al. Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations. Transl Psychiatry. 2017 Apr 4;7(4):e1080.

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ResearchBlogging.org Hornig M, Gottschalk CG, Eddy ML, Che X, Ukaigwe JE, Peterson DL, & Lipkin WI (2017). Immune network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome with atypical and classical presentations. Translational psychiatry, 7 (4) PMID: 28375204

Tuesday, 25 April 2017

Who'd have thunk it: physical activity inversely associated with BMI and body fat percentage

"In this sample of middle-aged adults, drawn from the general population, physical activity was inversely associated with BMI [body mass index] and body fat percentage. For people with the same BMI, those who were more active had a lower body fat percentage."

Those were the conclusions made by Kathryn Bradbury and colleagues [1] (open-access) drawing on data derived from "cross-sectional analysis of participants recruited into UK Biobank in 2006–2010." Said results continue a research theme where physical activity figures in the aforementioned dataset.

So: "119 230 men and 140 578 women aged 40–69 years, with complete physical activity information, and without a self-reported long-term illness, disability or infirmity" were included for study - not an under-powered study by any means. Height and weight of participants were measured by trained staff "using standardised techniques." Physical activity estimates were gathered via self-report; specifically the use of 'touchscreens' as information gatherers regarding "walking, moderate physical activity and vigorous physical activity" and how often in a typical week participants "did each of the activities for 10 min or more" then onward for how many minutes during a day. Such data was number-crunched to provide something called "excess metabolic equivalent (MET)-hours/week of physical activity during work and leisure time." The authors also report on some efforts to off-set the potential unreliability of self-reported physical activity and several other variables (whether occupation involved primarily sitting or standing, tobacco smoking status, alcohol consumption, etc) were also thrown into the statistical mixer.

Results: well, who'd have thunk it? Those reporting higher levels of physical activity (via questionnaire responses) tended to have a lower BMI and a lower body fat percentage. They were also likely to eat more fruit and vegetables that those with low levels of physical activity. Diet, occupation type and education level did not however seem to affect the primary findings.

Accepting again that self-reported physical activity is not a great substitute for more objective measures and that BMI, whilst a good rough-and-ready indication of weight status, tends not to differentiate between fat and muscle, these are important results. They imply that far from not being able to outrun a bad diet (see here) physical activity still has an important place in maintaining a sensible weight and thus reducing the risk of a myriad of adverse health outcomes. Added to other findings indicating that we all really need to move quite a bit more (see here), the message seems to be that the human body was made for moving so move it. And the latest figures on obesity and physical activity highlight the challenges being faced in this area.

And so to close,  a song to help with that 'move it' sentiment...

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[1] Bradbury KE. et al. Association between physical activity and body fat percentage, with adjustment for BMI: a large cross-sectional analysis of UK Biobank. BMJ Open 2017; 7: e011843.

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ResearchBlogging.org Bradbury, K., Guo, W., Cairns, B., Armstrong, M., & Key, T. (2017). Association between physical activity and body fat percentage, with adjustment for BMI: a large cross-sectional analysis of UK Biobank BMJ Open, 7 (3) DOI: 10.1136/bmjopen-2016-011843

Monday, 24 April 2017

Sensory issues in adult ADHD controlling for autistic symptoms...

I was intrigued to read the paper by Bijlenga and colleagues [1] reporting on "the prevalence of sensory hyper- and hyposensitivity among adults with ADHD [attention-deficit hyperactivity disorder], controlling for autistic symptoms."

The authors concluded that among their cohort of over 100 adults diagnosed with ADHD, both sensory hyper- and hyposensitivity symptoms as described by response to the Adolescent/Adult Sensory Profile-NL (AASP-NL), were over-represented compared with population norm data. Interestingly, authors also took a snapshot of 'autistic symptoms' based on responses to the Autism-spectrum Quotient (AQ) and reported that: "Adults with ADHD had more autistic symptoms" but: "Sensory hypo- and hypersensitivity were both related to an increased ADHD score, even showing a dose-response relationship, but not to any autistic symptom or comorbid disorder."

My intrigue stems from a few implications of such findings, with the requirement for much more study. First is the quite important overlap between autism and ADHD (see here) confirmed symptom-wise in the Bijlenga paper. Second is the idea that, within this cohort at least, adults with ADHD may variably present with sensory issues. Third, assuming that the AQ 'does what it says on the tin' with regards to screening for autistic symptoms (see here), the lack of a notable connection between autistic symptoms and sensory sensitivities in the context of adult ADHD might have some important implications related to my first point when autism and ADHD appear simultaneously. Indeed it poses the question: are sensory issues, now noted in specific relation to autism via at least one diagnostic schedule (see here) actually 'a core part of all autism' or perhaps a feature of something else for some?

Reiterating that more research is required (not least more formal screening for autism over and above the use of AQ or related screening schedules) that last point/question might actually make more sense than many people might first realise. If, for example, we take the view that autism rarely exists in some sort of diagnostic vacuum (see here and see here) and that science and clinical practice really needs to be more proactive when it comes to an autism diagnosis being a starting point not the finishing line (see here), it's not beyond the realms of possibility that sensory issues for some might have been spuriously linked to autism when in fact other comorbid labels/symptoms better account for their presentation. This not only has implications for screening/diagnosis but also management of said sensory symptoms, as per other reports talking about the use of stimulant medication indicated for ADHD 'affecting' aspects of odour sensitivities for example [2]. By saying that I'm not making any sweeping judgements about pharmacotherapy for ADHD treating sensory issues present alongside autism, merely that new avenues might open up.

A final quick glance at some of the other peer-reviewed literature on the topic of sensory issues and ADHD reveals that there is some history in this area [3]. Said sensory issues have also been *linked* to some of the other behavioural facets noted in cases of ADHD [4]. Perhaps, in light of such data, it is time for ADHD - whether in symptoms or in label - to be taken into account when sensory issues are discussed in the context of autism in the science literature and in clinical practice?

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[1] Bijlenga D. et al. Atypical sensory profiles as core features of adult ADHD, irrespective of autistic symptoms. Eur Psychiatry. 2017 Feb 21;43:51-57.

[2] Romanos M. et al. Improved odor sensitivity in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2008 Dec 1;64(11):938-40.

[3] Clince M. et al. Comparing and Exploring the Sensory Processing Patterns of Higher Education Students With Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. Am J Occup Ther. 2016 Mar-Apr;70(2):7002250010p1-9.

[4] Shimizu VT. et al. Sensory processing abilities of children with ADHD. Braz J Phys Ther. 2014 Jul-Aug;18(4):343-52.

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ResearchBlogging.org Bijlenga D, Tjon-Ka-Jie JY, Schuijers F, & Kooij JJ (2017). Atypical sensory profiles as core features of adult ADHD, irrespective of autistic symptoms. European psychiatry : the journal of the Association of European Psychiatrists, 43, 51-57 PMID: 28371743

Saturday, 22 April 2017

Autistic adults as critical autism experts (with research caveats)

"Findings suggest that autistic adults should be considered autism experts and involved as partners in autism research."

That was the conclusion reached in the paper by Kristen Gillespie-Lynch and colleagues [1] (open-access) reporting on the results of an online survey assessing "autism knowledge and stigma among 636 adults with varied relationships to autism, including autistic people and nuclear family members." Among the various groups of people who contributed to the survey, several viewpoints emerged. The message primarily however was that: "autistic people are autism experts through their lived experiences." I don't think many people would quibble with such findings.

A few other details emerged from the Gillespie-Lynch study that merit discussion. Many participants showed a "reduced tendency to view autism through a deficit-defined medical model compared with non-autistic people." This is perhaps not an unexpected finding given the history of applying the medical model to autism and the rise and rise of the neurodiversity movement that "challenges the medical model" in particular respect over the question of deficit vs. difference and implications thereof. Although the medical model provides the means to identify and diagnose autism or autism spectrum disorder (ASD) (on the basis of deficits), it's not unexpected that for some, once those tasks have been completed, the 'treatment' side of the model is not necessarily a top priority; or at least not as important as addressing the various inequalities that seem to stem from a diagnosis. That being said, I do agree with the authors sentiments that: "the neurodiversity movement and the medical model overlap in recognizing that supports are needed to ameliorate challenges associated with autism." Those challenges are variable and person-dependent but include the effects of both core and peripheral signs and symptoms and the various over-represented comorbidities that seem to follow a diagnosis of autism (see here). I would, at this point, also caution on using the words 'biopsychosocial model' in the context of autism as the authors have included in their discussions, given what it has meant for other labels (see here) and the potential 'psychologising' of some important medical symptoms.

I added the words 'with research caveats' to the title of this post to ensure that such a positive message about autism and the autism spectrum is not just given a 'free pass' when it comes to scrutiny of the scientific method, the way the study was carried out and the applicability of the results to the entire autism spectrum. This was an online survey not a face-to-face piece of research (other related research has similarly used such a method and on more than one occasion) and the authors acknowledge that they: "did not verify diagnosis of participants who self-identified as autistic" for example. Given what we are beginning to see when it comes to some of the 'self-screening' instruments out there regarding possible autism or not (see here), I'm always a little cautious that self-diagnosis / self-identification does not necessarily mean [eventual] clinician-diagnosed autism and how important this is when it comes to correctly ascertaining the wants and wishes of those diagnosed as being on the spectrum.

On the point about the representativeness of this research, the authors also note: "Findings may not generalize to autistic participants who lack the verbal and computer skills needed to complete the survey." Yet another example it seems of this important issue.

I have to say that I'm also a little disheartened that yet again an important group that was once very firmly on the autism spectrum aren't really given the credit they deserve according to the Gillespie-Lynch findings: "Autistic participants were more likely to recognize that most children cannot outgrow autism." The 'optimal outcome' children and adults it seems, still represent one of the most maligned groups associated with the autism spectrum (assuming that optimal outcome occurring in up to 9% of the autism population is not an insignificant figure). This despite the fact that even the diagnostic stability of the most 'high-functioning' cases of autism can wobble it seems (see here) even into adulthood. One of the premier experts on autism also seems to agree according to some recent media (see here). I often wonder if the seeming lack of acceptance of this group/feature might have something to do with the 'identity' side of autism and the idea that within the vast heterogeneity of autism (or the plural autisms if you prefer) the use of 'them and us descriptions' like 'neurotypical' are perhaps not as binary or long-lasting as many would believe or want to believe?

Within the context of [approximate] phrases such as 'if you've met one person with autism, you've met one autistic person' there is caution in over-generalising these latest results but they are nonetheless important. I think it would be rather fitting to end with a few choice phrases from the Gillespe-Lynch paper: "As many of our survey respondents indicated, each person, regardless of whether or not they are autistic, is unique" and: "Some autistic people seek out factual knowledge about autism while others believe that they can only be experts in their own particular form of autism." Either way, the insights provided by people on the autism spectrum (all parts of the autism spectrum and indeed, across the age ranges) should be valued, and where possible, incorporated into research and practice.

And one voice from the autism spectrum carries some rather sensible messages...

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[1] Gillespie-Lynch K. et al. Whose Expertise Is It? Evidence for Autistic Adults as Critical Autism Experts. Front. Psychol. 2017. March 28.

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ResearchBlogging.org Gillespie-Lynch, K., Kapp, S., Brooks, P., Pickens, J., & Schwartzman, B. (2017). Whose Expertise Is It? Evidence for Autistic Adults as Critical Autism Experts Frontiers in Psychology, 8 DOI: 10.3389/fpsyg.2017.00438

Friday, 21 April 2017

Parental exposures and risk of offspring autism: some curious details

"Overall, our results were consistent with no positive association between parental asthmagen exposure and ASD [autism spectrum disorder] in the children."

So said the findings reported by Alison Singer and colleagues [1] (open-access) continuing a research theme from this group [2] looking at whether "parental workplace exposures to risk factors for asthma (“asthmagens”)" might have relevance to offspring risk for autism.

Based on data derived from some of those oh-so-important Scandinavian research registries (this one based in Denmark), researchers initially looked at some 12,000 cases (where autism was mentioned in medical records) compared with over 48,000 controls (not autism) to ascertain whether parental work exposures might play some role in autism risk. This numbers were eventually boiled down somewhat.

Despite the opening line to the post, there were some curious details to emerge from the collected analyses. So: "We observed an inverse association between any maternal occupational asthmagen exposure and ASD in the children." Researchers reported that maternal occupational exposure actually seemed to be protective against the development of offspring autism according to their findings. They note that this finding was "largely explained by latex exposures" on the basis of linking occupational codes "to an asthma-specific job exposure matrix (JEM)." In other words, they didn't specifically look at latex exposure in every single case but rather relied on the probability that a particular occupation would entail this or other exposure.

A few other curious details also emerged: "Some paternal occupational asthmagen categories were positively associated with ASD, including bioaerosols..., pharmaceutical drugs (manufacturing or extensive handling)..., and metals." The authors tend to talk down these findings as per the suggestion that: "Some of these associations could be chance findings resulting from multiple comparisons or could reflect bias, such as unmeasured confounding" but I would perhaps be a little more cautious about rejecting them outright. Indeed the authors note on one point in relation to maternal exposures: "While adjustment for unmeasured confounding could bring the association to the null, the confounding would need to be implausibly strong to mask a positive association."

I've covered the topic of parental (occupational) exposures and offspring autism risk before on this blog (see here) alongside associated research (see here). The current take-away message from quite a bit of this research is that there may be target classes of compounds to 'look out for' when it comes to offspring autism risk, but as of yet there is no smoking gun. One also needs to read such research in the context of the myriad of 'associations' that have been made with offspring autism risk down the years (see here for example) and how genes and environment might mix in relation to the plural autisms. Cumulative effects are more likely over single factors.

Insofar as the current Singer results, I do feel that the authors might have been a little premature in making the sweeping claims that they have on the basis of their findings: "this large population-based case-control study does not suggest a positive measurable association between parental occupational asthmagen exposure and ASD." I say this in the context that 'asthmagen' exposure could be incurred via several routes (see here). I don't doubt that the correlations/findings reported by Singer could be 'due to chance', but until such claims can be independently verified in direct study (see here for one idea) and perhaps tested in animal models for example, they should really just report what they found without fear, favour or complication...

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[1] Singer AB. et al. Parental exposures to occupational asthmagens and risk of autism spectrum disorder in a Danish population-based case-control study. Environmental Health. 2017 16: 31.

[2] Singer AB. et al. Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum Disorder in the Study to Explore Early Development. J Autism Dev Disord. 2016 Nov;46(11):3458-3468.

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ResearchBlogging.org Singer, A., Burstyn, I., Thygesen, M., Mortensen, P., Fallin, M., & Schendel, D. (2017). Parental exposures to occupational asthmagens and risk of autism spectrum disorder in a Danish population-based case-control study Environmental Health, 16 (1) DOI: 10.1186/s12940-017-0230-8

Thursday, 20 April 2017

"a gradual decline in recorded diagnoses of CFS/ME since 2001"?

The quote forming the title of today's post comes from the paper by Simon Collin and colleagues [1] (open-access available here) who, based on analysis of the UK "Clinical Practice Research Datalink (CPRD), formerly known as the General Practice Research Database (GPRD)" set out to look at the "Incidence of CFS/ME [chronic fatigue syndrome/ myalgic encephalomyelitis], FM [fibromyalgia], post-viral fatigue syndrome (PVFS), and asthenia/debility." I say incidence but that last sentence should really read as  'recorded incidence'.

Searching the research database between January 2001 and December 2013, researchers looked at the [recorded] incidence (that's incidence not prevalence) of the various fatigue-related conditions/labels recorded by participating GP (general practice) surgeries.

Recorded diagnoses of CFS/ME showed a soft but noticeable decline over the period of study: "Annual incidence of CFS/ME decreased from 17.5 [per 100,000 people] in 2001 to 12.6 in 2013." A similar decline was also noted in respect of PVFS and asthenia/debility. When however it came to FM, there was an overall increase in cases between 2001 and 2013 (albeit characterised by peaks and troughs in recorded diagnoses across specific years).

Some other important data were also reported on. So: "All diagnoses showed strong evidence of variation by age and sex" and estimated socio-economic status (SES). Further: "Incidence rates of CFS/ME were 2.4-fold higher among women... with peak incidence in the 40–49 years age group." Women were also more likely to be over-represented in relation to a diagnosis of FM too.

This is potentially important data. It suggests that at least among participating GP practices in the CPRD, recorded diagnoses of CFS/ME seem to be going down. The caveats however mentioned by the researchers do need to be highlighted, not least that they "examined recorded data rather than actual incidence, i.e. we are describing incidence rates of GPs’ recording of diagnostic codes" and "diagnoses were not independently validated." In other words, this is data based on "GPs enter[ing] medical diagnoses and symptoms as Read codes." I might also add in another quote from the authors too: "In 2005, 48% of GPs in one English region did not feel confident about making a diagnosis of CFS/ME, and 28% did not recognise CFS/ME as a legitimate illness." A bit of an issue by all accounts if one would like to get accurate data on incidence or prevalence.

I also have a to raise a point in relation to this latest data and how it compares with other data produced by the same research group (see here). Keeping in mind that incidence is not the same as prevalence, I bring back to your attention the findings reported by Collin and colleagues [2] on another occasion suggesting that nearly 2% of 16-year olds in the ALSPAC cohort were affected by CFS. More work needs to be done when it comes to official monitoring of the numbers of cases of CFS/ME (and FM) outside of just reliance on GP practice recordings in order to get a true picture of numbers of cases. Of course, there is another possible explanation for the fall in recorded diagnoses: GPs are increasingly understanding that some of the symptoms included under the banner of CFS/ME overlap with various other conditions/labels too...

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[1] Collin SM. et al. Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study. J R Soc Med. 2017 Jan 1:141076817702530.

[2] Collin SM. et al. Chronic Fatigue Syndrome at Age 16 Years. Pediatrics. 2016 Feb;137(2):e20153434.

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ResearchBlogging.org Collin SM, Bakken IJ, Nazareth I, Crawley E, & White PD (2017). Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study. Journal of the Royal Society of Medicine PMID: 28358988

Wednesday, 19 April 2017

Allergy and ADHD meta-analysed and guess what...

"Reports of frequent manifestation of allergic diseases in children with attention deficit hyperactivity disorder (ADHD) have been the subject of mounting clinical interest."

OK, go on.

"The objective of this study was to compile and assess available studies on the association between ADHD and allergic diseases in children."

And your findings... "children with ADHD are more likely to have asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis than their counterparts. Interventions including strategies for managing allergies in children with ADHD would be beneficial."

So said the systematic review and meta-analysis published by Celine Miyazaki and colleagues [1] (open-access) who provide quite a good 'where we're at' update when it comes to a potentially important intersection between a developmental condition (ADHD) and a series of somatic, immune-based conditions (allergy).

Regular readers of this blog might already know that I have a blogging interest in all-things immune system and behaviour (see here for example). Indeed, acknowledging that the immune system may be doing so much more than protecting us from the multitude of viral, bacterial and other insults we face each day is gaining some real [peer-reviewed] scientific momentum.

Boiling down the peer-reviewed literature to five studies meeting the meta-analysis criteria laid out by authors, cumulatively including some 60,000 research participants (including data derived from that wonderful Taiwanese research registry that I keep going on about), researchers set to work on the examining the various findings. Nearly 8,000 of the 61,811 children included for study were diagnosed with ADHD and various allergic diseases were 'examined' in the context of the ADHD label or without the label. The results were as mentioned in the first paragraph.

When it came to looking at which specific allergic disease diagnoses were most strongly linked to ADHD a familiar theme emerged: "children with ADHD have an 80% increased odds of asthma compared with children without ADHD." I'm beginning to lose track of the number of times I've covered this association down the blogging years (see here and see here and see here). Indeed, these results add to other reviews on this topic [2] previously covered on this blog (see here).

The nature of the association? Well, more studies are still required. The authors talk about some work looking at possible overlapping genetic issues with autoimmunity in mind, and that is probably going to be quite important. More than that however is the idea that other less-genetic factors might also play a role. Y'know how social factors such as poverty might figure (see here) for example. I'm also minded to bring in the possibility of an 'association' between food allergy and behavioural symptoms (see here) in light of other work. Such a connection might also implicate all-manner of other bodily systems including the [hyped-up] field of microbiomics for example. Suffice to say that connections are likely to be complex and potentially numerous.

The other implication from the Miyazaki results is another thing I've been going on about for some years on this blog: preferential screening. Y'know, when a diagnosis of asthma for example, is received, how about screening for ADHD and related developmental issues? Or, the other way around, screen for allergic diseases when a diagnosis of ADHD is received? And then there's the intervention angle, and some potentially useful data from both other developmental/behavioural diagnoses and allergy symptoms (see here) and some rather more direct evidence (see here)?

To close, my brood have just discovered Little Britain and the laughter has gone on and on and on...

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[1] Miyazaki C. et al. Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis. BMC Psychiatry. 2017; 17: 120.

[2] Schans JV. et al. Association of atopic diseases and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses. Neurosci Biobehav Rev. 2017 Mar;74(Pt A):139-148.

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ResearchBlogging.org Miyazaki, C., Koyama, M., Ota, E., Swa, T., Mlunde, L., Amiya, R., Tachibana, Y., Yamamoto-Hanada, K., & Mori, R. (2017). Allergic diseases in children with attention deficit hyperactivity disorder: a systematic review and meta-analysis BMC Psychiatry, 17 (1) DOI: 10.1186/s12888-017-1281-7