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  • April 28, 2017
  • 03:04 AM
  • 32 views

Autism, pregnancy maternal immune activation and vitamin D?

by Paul Whiteley in Questioning Answers

Today's post is a bit of a mash-up, drawing on two articles quite recently published in the peer-reviewed science domain.The first is by Stephanie Vuillermot and colleagues [1] (open-access) suggesting that "early dietary supplementation with vitamin D may open new avenues for a successful attenuation or even prevention of neurodevelopmental disorders following maternal inflammation during pregnancy." These findings have also received some media attention (see here for example) and continues a research theme focused on vitamin D (the sunshine vitamin/hormone) and [some] autism (see here for example).The second paper is by Michael Lombardo and colleagues [2] (open-access) and also covers the topic of maternal immune activation (MIA) and its potential effects on offspring outcomes, concluding that: "MIA may confer increased risk for ASD [autism spectrum disorder] by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD."What are the connections between these papers? Well, obviously both deal with the concept of maternal immune activation (MIA) where infection, or possibly/rather 'inflammatory' responses to infection, during critical periods of pregnancy seem to be able to affect offspring developmental and other outcomes. This bearing in mind that pregnancy represents a time of 'reprogrammed immune function' such that the maternal immune system does not mount a response to the genetically dissimilar organism growing inside the body. Both papers model MIA in rodents (mice and rats respectively) given the ethics of undertaking such experimental studies in humans. Both studies concluded that (a) there is evidence that MIA is a real phenomenon and (b) bearing in mind rodents are not necessarily the same as humans (see here) (a shocker I know), MIA seems to invoke specific biochemical changes pertinent to the expression of genes *linked* to autism that are also potentially amenable to intervention.The Vuillermot findings in particular, offer some rather intriguing prospects for further study as a function of their conclusion that: "maternal VitD co-administration blocked the emergence of the ASD-relevant deficits in social interaction, stereotyped behavior, and emotional learning and memory." I appreciate that 'blocking the emergence' of autistic behaviours is not something that everyone is going to unanimously welcome (the implication being that every single autistic trait is somehow something to be eradicated). The idea however that aspects of even something like certain stereotyped behaviours under certain conditions and with certain intensity might 'set someone up' for the presentation of truly disabling conditions such as anxiety [3] (see here too) offers a degree of support for the idea of intervention targeting such behaviours in particular circumstances.But there is a potential research spanner in the works when it comes the idea that vitamin D might 'offset' some of the changes associated with exposure to MIA. The authors note: "VitD does not alter maternal or fetal inflammatory cytokine production." This statement was made on the basis that "prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains." Cytokines are those chemical messengers of the immune system. How then, you might ask? Well, back to the Lombardo paper and the possibility that vitamin D is not necessarily an 'anti-inflammatory' of choice under such circumstances but might - MIGHT - act on some of the mechanisms related to those genes expressed under MIA conditions. It's pretty well-known for example, that vitamin D does influence gene expression (see here for example) as our knowledge of the biological duties of the sunshine vitamin/hormone expand (see here). It is logical to assume that the next research step would be to see whether vitamin D administration *might* at certain times and under certain circumstances, affect the expression of those genes 'highly relevant to pathophysiology affecting ASD' under MIA conditions. This, in the context that maternal vitamin D levels during pregnancy again *might* have an important impact on the presentation of offspring autistic traits (see here).And since we're on the topic of vitamin D and autism (yet again), how about reading a new hypothesis paper on some potentially important connections [4]?----------[1] Vuillermot S. et al. Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation. Molecular Autism. 2017; 8: 9.[2] Lombardo MV. et al. Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder. Mol Psychiatr. 2017. Mar 21.[3] Bitsika V. & Sharpley CF. The association between parents' ratings of ASD symptoms and anxiety in a sample of high-functioning boys and adolescents with Autism Spectrum Disorder. Res Dev Disabil. 2017 Mar 1;63:38-45.[4] Gillberg C. et al. The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper. Autism Res. 2017. April 12.----------Vuillermot, S., Luan, W., Meyer, U., & Eyles, D. (2017). Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation Molecular Autism, 8 (1) DOI: 10.1186/s13229-017-0125-0Lombardo, M., Moon, H., Su, J., Palmer, T., Courchesne, E., & Pramparo, T. (2017). Maternal immune activation dysregulation of the fetal brain tran... Read more »

  • April 27, 2017
  • 08:49 AM
  • 42 views

Code Orange for the Bengal Tiger!

by Jente Ottenburghs in Evolutionary Stories

Genetic study highlights challenging conservation of the Bengal Tiger in India.... Read more »

  • April 27, 2017
  • 02:57 AM
  • 51 views

Is screen time a risk factor for ADHD?

by Paul Whiteley in Questioning Answers

The findings reported by Vivien Suchert and colleagues [1] observing that "screen time, but not other non-screen-based sedentary activities should be considered as being a risk factor for ADHD [attention-deficit hyperactivity disorder]" taps into long-running debates on whether our societal obsession with watching, clicking and swiping might not be 'a totally positive thing' when it comes to psychological development, health and wellbeing.Yes, I know this is a complicated area full of big personalities, sweeping generalisations, half-truths and soundbites (see here for example). But I talk about peer-reviewed science on this blog, and am dealing with presented evidence specifically looking at the issue of screen time and ADHD on this particular occasion.So, taking a not insignificant sample number of over 900 young adults aged 13-17 years old, researchers assessed various parameters in relation to "screen-based and non-screen-based sedentary behavior and ADHD symptoms." When I say 'assessed', immediately one potentially big issue stands out when it comes to measures of sedentary behaviour used in the study and the inclusion of the questionnaire method over and above the use of more objective measures such as physical activity monitors (see here). No mind, researchers analysed the collected data and determined a few key observations not least that: "Screen time was related to the total ADHD score (p < 0.001) as well as to the subscales inattention (p ≤ 0.016) and hyperactivity/impulsivity (p ≤ 0.008)." Further: "Sedentary time without screens was virtually not associated with ADHD."OK, to reiterate sweeping generalisations are not required on the basis of these results alone. There are a myriad of other methodological issues outside of just objective measures of sedentary behaviour that could skew the Suchert results and these should be taken into consideration. But set in the context that this is not the first time that screen use has been *corrrelated* with something like ADHD or ADHD-type behaviours [2] (or indeed the second time [3]) I'm minded to suggest that quite a more investigation is indicated. Of course, there are other factors to include in the research mix. The findings reported by Tong and colleagues [4] are potentially pertinent: "children with ADHD symptoms were likely to spend more time using a computer during school days; they were also more likely to eat while using a computer." This implies that ADHD or ADHD-type behaviours might predispose to increased screen time rather than the other way around. The relationship is likely to be complex.In terms of the potential 'hows and whys' of any connection between screen time and ADHD-type behaviours, well, there are already some clues. I'd perhaps suggest that the effects of screen time on sleep could be a good place to start given other peer-reviewed research clues [5]. The relationship between sleep and ADHD is a complicated one, but it is known that sleep interventions can [modestly] affect the presentation of some ADHD behaviours (see here). There are no doubt other research avenues worth looking into also.Should anyone act on the Suchert findings as they stand? Well, I don't do medical or clinical advice on this blog but I'm minded to suggest that some sensible advice provided by others might come into play: "No screens in the child’s bedroom. Pay attention to the content of the games, especially to violence. Set limits on screen time, and look for other ways to manage family interactions." With my 'what if' research hat on, I am also wondering whether the rise and rise of screens and screen time in the context of autism might also need some particular research examination, in light of the idea that autism and ADHD is not an unfamiliar diagnostic combination (see here)...To close, although perhaps most famous as a 'rat tickler', the passing away of Jaak Panksepp a few days back deserves mention given his notable ideas about autism and the influence they had and continue to have...----------[1] Suchert V. et al. Relationship between attention-deficit/hyperactivity disorder and sedentary behavior in adolescence: a cross-sectional study. Atten Defic Hyperact Disord. 2017 Apr 4.[2] Chan PA. & Rabinowitz T. A cross-sectional analysis of video games and attention deficit hyperactivity disorder symptoms in adolescents. Ann Gen Psychiatry. 2006 Oct 24;5:16.[3] Montagni I. et al. Association of screen time with self-perceived attention problems and hyperactivity levels in French students: a cross-sectional study. BMJ Open. 2016 Feb 26;6(2):e009089.[4] Tong L. et al. Attention-Deficit/Hyperactivity Disorder and Lifestyle-Related Behaviors in Children. PLoS One. 2016 Sep 22;11(9):e0163434.[5] Engelhardt CR. et al. Media use and sleep among boys with autism spectrum disorder, ADHD, or typical development. Pediatrics. 2013 Dec;132(6):1081-9.----------Suchert V, Pedersen A, Hanewinkel R, & Isensee B (2017). Relationship between attention-deficit/hyperactivity disorder and sedentary behavior in adolescence: a cross-sectional study. Attention deficit and hyperactivity disorders PMID: 28378132... Read more »

  • April 26, 2017
  • 03:02 AM
  • 75 views

Hornig, Lipkin and chronic fatigue syndrome again

by Paul Whiteley in Questioning Answers

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...----------[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.----------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... Read more »

  • April 25, 2017
  • 03:15 AM
  • 85 views

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

by Paul Whiteley in Questioning Answers

"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...----------[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.----------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... Read more »

  • April 24, 2017
  • 04:22 AM
  • 89 views

Promising mouse model for Ngly1 deficiency

by adam phillips in It Ain't Magic

A recent study of Ngly1 deficient mice used a secondary knockout to create double knockouts with symptoms similar to human NGLY1 deficiency.... Read more »

  • April 24, 2017
  • 03:05 AM
  • 92 views

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

by Paul Whiteley in Questioning Answers

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?----------[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.----------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... Read more »

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, 51-57. PMID: 28371743  

  • April 22, 2017
  • 06:14 AM
  • 122 views

Autistic adults as critical autism experts (with research caveats)

by Paul Whiteley in Questioning Answers

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

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. DOI: 10.3389/fpsyg.2017.00438  

  • April 21, 2017
  • 04:32 AM
  • 150 views

Parental exposures and risk of offspring autism: some curious details

by Paul Whiteley in Questioning Answers

"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...----------[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.----------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... Read more »

  • April 20, 2017
  • 05:19 AM
  • 150 views

DHM attenuates obesity-induced slow-twitch-fiber decrease via FLCN/FNIP1/AMPK pathway

by Joana Guedes in BHD Research Blog

Obesity is often associated with decreases in the proportion of skeletal muscle slow-twitch fibers and insulin sensitivity. Slow-twitch fibers are rich in mitochondria and utilize fatty acid oxidative phosphorylation for energy production. In their new study, Zhou et al. (2017) explore the role of the FLCN/FNIP1/AMPK signalling pathway in obesity-induced reductions in slow-twitch fibers and insulin sensitivity in skeletal muscle using high-fat-diet-induced (HFD) obese mice, ob/ob mutant mice, and palmitate-treated C2C12 myotubes. The authors also assess the effects of dihydromyricetin (DHM) on the obesity-induced decrease in slow-twitch fibers, and the molecular mechanisms responsible for this effect.... Read more »

  • April 20, 2017
  • 04:37 AM
  • 143 views

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

by Paul Whiteley in Questioning Answers

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...----------[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.----------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... Read more »

  • April 19, 2017
  • 04:31 AM
  • 165 views

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

by Paul Whiteley in Questioning Answers

"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...----------[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.----------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... Read more »

  • April 18, 2017
  • 04:21 AM
  • 186 views

"Asthma was associated with increased risk for schizophrenia"

by Paul Whiteley in Questioning Answers

'Big data' Taiwan is once again the topic of a post on this blog as the results published by Wei-Chen Wang and colleagues [1] (open-access available here) receive an airing, specifically that: "Asthma was associated with increased risk for schizophrenia."There are some common themes attached to these findings. Taiwan is already a research-favourite place on this blog as a result of their use of the National Health Insurance Research Database (NHIRD) for various research purposes. I can't name all the occasions I've talked about research from Taiwan based on the NHIRD but a few of them can be seen here and here. Another commonality of this latest research from Wang et al is the idea that physical illness with a substantial immune system component to it *might* show an important connection to a behavioural/psychiatric disorder. Asthma and related atopic diseases has been mentioned on a few other occasions (see here and see here). Hold those thoughts for now...This time around Wang and colleagues "aimed to investigate the association between asthma, corticosteroid use, and schizophrenia." Comparing 'measures of schizophrenia' in some 25,000 participants diagnosed with asthma and 50,000 without asthma over 7 years, and adjusting for various potentially confounding variables - "sex, age, residence, socioeconomic status, corticosteroid use, outpatient and emergency room visit frequency, Charlson comorbidity index, and total length of hospital stays days for any disorder" - the results were interesting. Not least that "asthma was associated with significantly greater hazard ratio for incident schizophrenia." Researchers also noted that various other confounding variables also showed a relationship with schizophrenia such as rural residence, poor general health and lower economic status. "Corticosteroid use was not associated with increased risk for schizophrenia" we are also told.Whilst interesting, the results do not say that everyone with asthma is at risk of developing schizophrenia. Not even close. The rates of schizophrenia identified in the Wang study were also quite low overall despite the large starting populations studied: "Of the total 75,069 subjects, 238 were diagnosed with schizophrenia during the study period: 100 (0.40%) of subjects were in the asthma cohort and 138 (0.28%) in the non-asthma cohort."But, set within the context of other independent datasets [2] observing "the existence of an association between atopic disorders in general and asthma in particular and the risk of developing schizophrenia" there is cause for further investigation into any association. Not least that Wang et al describe their results in the context that: "a convergent disturbance in the immune-inflammatory system may contribute to the pathoetiology of asthma and schizophrenia." Y'know, all that talk that among the [plural] schizophrenias, one or two phenotypes might, to some quite large extent, be linked to immune function or dysfunction. Well, it's not as if we haven't got some quite reliable research clues already (see here). There may also be some subsequent discussions on the requirement for enhanced screening for something like schizophrenia as and when a diagnosis of asthma (or other atopic disease) is diagnosed as per other data (see here).Finally, going back to the previous research occasions when asthma has been *correlated* with labels such as attention-deficit hyperactivity disorder (ADHD) and even autism, I'm wondering whether there could be wider links present when it comes to immune-related conditions and behavioural presentations. It's pretty well known that various behavioural/developmental/psychiatric labels tend to 'club together' (see here and see here for examples). There is also a growing realisation that alongside overlapping genetics and biology when it comes to such labels, the days of autism genes for example, just being genes for autism are beginning to drift off (see here); something probably relevant to conditions such as ADHD and schizophrenia too. So, could it be that immune system related conditions such as asthma and atopic disease, might have lots and lots of implications in relation to many developmental/behavioural/psychiatric labels? Even more intriguing, are there clues to possible intervention avenues too? (with no medical or clinical advice given or intended).We await further investigations...----------[1] Wang WC. et al. Asthma, corticosteroid use and schizophrenia: A nationwide population-based study in Taiwan. PLoS One. 2017 Mar 28;12(3):e0173063.[2] Pedersen MS. et al. Schizophrenia in patients with atopic disorders with particular emphasis on asthma: a Danish population-based study. Schizophr Res. 2012 Jun;138(1):58-62.----------Wang WC, Lu ML, Chen VC, Ng MH, Huang KY, Hsieh MH, Hsieh MJ, McIntyre RS, Lee Y, & Lee CT (2017). Asthma, corticosteroid use and schizophrenia: A nationwide population-based study in Taiwan. PloS one, 12 (3) PMID: 28350822... Read more »

Wang WC, Lu ML, Chen VC, Ng MH, Huang KY, Hsieh MH, Hsieh MJ, McIntyre RS, Lee Y, & Lee CT. (2017) Asthma, corticosteroid use and schizophrenia: A nationwide population-based study in Taiwan. PloS one, 12(3). PMID: 28350822  

  • April 17, 2017
  • 03:00 PM
  • 200 views

The continuing trials and tribulations of PACE

by Paul Whiteley in Questioning Answers

I honestly hadn't intended talking about the PACE trial - "pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation" in relation to chronic fatigue syndrome (CFS) - quite so much on this blog. Others have done it so much better than I ever could.My interest however keeps being piqued in relation to the results originally produced suggesting that: "CBT [cognitive behaviour therapy] and GET [graded exercise therapy] can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome" and the subsequent myriad of voices quite unanimously suggesting that one perhaps needs to be a little careful with such sweeping generalisations (see here).OK, for anyone new to this topic, below are a few of the previous occasions that it has been discussed on this blog in chronological order:Chronic Fatigue Syndrome and various factors (2014) (see here)Chronic fatigue syndrome and the detrimental application of the 'biopsychosocial model' (2016) (see here)PACE-gate! (2016) (see here)PACE trial recovery data and chronic fatigue syndrome (2017) (see here)PACE trial recovery data and chronic fatigue syndrome - a reply (2017) (see here)I want to add a few more 'science references' to this issue because some important things are being discussed in the peer-reviewed domain, in the context that CBT and GET at the moment, are considered 'best practice' here in the UK and beyond when it comes to CFS. That may change in future times (see here) as it has in other parts of the world (see here) but that's where we are at the time of writing. I might add that the addition of new references to this post is a rather more descriptive thing minus too much additional commentary from me, and that the views represented are those of the authors. I wrote this post on 9 April 2017 so it is accurate up to that point.OK, starting with the editorial from Keith Geraghty [1] mentioned in that PACE-gate! post, we have an authors reply to some of the points raised [2]. The main crux of the reply is to correct "misunderstandings and misrepresentations of the PACE trial." Next up was a paper by Leonard Jason [3] (someone with quite an impressive research track record when it comes to CFS) and some comments on the pacing intervention (adaptive pacing therapy, APT) used and "patient selection ambiguity." This is a particularly interesting paper because APT - "based on the envelope theory of chronic fatigue syndrome" where the symptoms of CFS are "not reversible by changes in behaviour" - did not hit the 'research spot' according to the original PACE trial results.I want to next include the paper by Luis Nacul and colleagues [4] into proceedings, and a role for "selection bias and disease misclassification" when it comes to studies on CFS (and myalgic encephalomyelitis, ME). To quote from them: "When studies using the broad Oxford criteria... were excluded, a virtual disappearance of effect for graded exercise therapy (GET), cognitive behaviour therapy (CBT) and other psychological therapies recommended by the NICE guidelines (National Institute for Health and Care Excellence.. was revealed." Guess which criteria (among the many available) were used in the original trial?Onward. The paper by Steven Lubet [5] titled: 'Investigator bias and the PACE trial' sets out quite an 'accusation' in that: "the PACE investigators “impartiality might reasonably be questioned”." This is a theme that crops up again shortly. The paper by Tom Kindlon [6] asked whether graded exercise in particular, could be thought of as 'safe and risk-free'? I set this question within the context that the original PACE trial did find that: "Non-serious adverse events were common" and GET did seem to produce the largest number of 'serious adverse effects' in number if not in participants.Nearly there. Next up is the paper from Carolyn Wishire [7] who, when talking about "lively discussion", reports on various potential forms of bias in behavioural intervention studies using the PACE study as a kind of template. This author was the lead on the recent peer-reviewed commentary (open-access) re-analysing the 'recovery' data subsequently published in relation to the PACE trial. Then, we have the paper by Jonathan Edwards [8] who notes that the PACE trial represents a lesson in how research design needs to develop further when it comes to science in general. To quote: "The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed." And finally Charles Shepherd [9] provides further commentary on the PACE trial and a call for independent review.And rest.There is quite a lot to take in from those various publications and I don't doubt that this is not the last we are going to hear about the PACE trial. Allied to articles such as this one describing how: "Physicians used to dismiss the disease as psychosomatic" (past tense) it certainly would not out of place to suggest that there are still questions that need to be answered about the design and results obtained from the PACE trial and their applicability to the (very) wide CFS/ME population. To quote again from the paper by Edwards [8]: "If they are still ill [those diagnosed with CFS/ME], presumably these approaches have failed and the priority is to find something more effective." Wise words indeed.To close, it's here... the first glimpse of The Last Jedi.----------[1] Geraghty KJ. ‘PACE-Gate’: When clinical trial evidence meets open data access. J Health Psychology. 2016. Nov 1.[2] White PD. et al. Response to the editorial by Dr Geraghty. J Health Psychology. 2017. Jan 24.[3] Jason LA. The PACE trial missteps on pacing and patient selection. J Health Psychology. 2017. Feb 1.[4] Nacul L. et al. How have selection bias and disease ... Read more »

White, P., Chalder, T., Sharpe, M., Angus, B., Baber, H., Bavinton, J., Burgess, M., Clark, L., Cox, D., DeCesare, J.... (2017) Response to the editorial by Dr Geraghty. Journal of Health Psychology, 2147483647. DOI: 10.1177/1359105316688953  

  • April 13, 2017
  • 04:40 AM
  • 232 views

Video Interaction for Promoting Positive Parenting in autism: yes but not quite...

by Paul Whiteley in Questioning Answers

"Video feedback may help babies ‘at risk of autism’" went one write-up of the study results published by Jonathan Green and colleagues [1] (open-access available here). Continuing a theme of kids at risk of autism potentially 'avoiding' an autism diagnosis (see here) following the use of "a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting)" there is some degree of optimism from these latest results together with a pinch of 'not-so-fast'...Including data from some 54 families - "28 intervention, 26 nonintervention" - researchers reported on the effects of interventions vs. no intervention on various aspects of functioning primarily the "severity of autism prodromal symptoms." Prodromal means early symptoms and is more readily associated with other labels/conditions. The authors reported that results were not completely cut-and-dried in terms of effect(s) of intervention on diagnostic outcome for example (i.e. there were "no intervention effects on diagnostic outcome") but potentially something to see when it comes to the 'severity' of autism prodromal symptoms and "parent-dyad social communication." The authors also noted that measures of communication and language did show something of a trend towards some benefit observed in the intervention group, but did not yield any significant difference when comparing intervention with no intervention over the quite long study period (39 months). This contrasts with their previous results [2] possibly indicating something rather more adverse when it came to intervention and aspects of language/communication. I might also draw your attention to the fact that from a bank of some 84 families invited to join the study, just over half actually agreed or fulfilled the criteria for joining.I know this is an area of research that people really want to see work. Alongside other early intervention research in relation to autism (see here for example), the idea that some small adjustments to early interactions might affect the presentation of autism still enjoys quite a lot of support in various quarters. The thing is that these and other results whilst suggesting that things like 'parental responsiveness' can improve as a result of intervention(s), have so far shown that important outcomes for young children are far less impressive. This is something evident across quite a lot of the research literature in this area even when meta-analysed (see here including some chatter about effect sizes).I'm not suggesting that we everyone just 'gives up' when it comes to early interventions like the one described by Green and colleagues. I do however think science and clinical practice needs to be a little more focused on things like potential best-responders to such interventions (as it does for many other aspects of autism science) and not so focused on creating grand media headlines. I might also throw in the idea that study design is something that needs to be improved particularly in light of other recent findings [3] talking about how "placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual" (guess what many studies in this area use as their comparator?) Accepting that variables such as the plural autisms (see here) are inevitably going to affect results from such studies, I'm minded to suggest that quite a few more resources need to be committed to looking at the possible 'hows and whys' of autism coming about before any talk about early parent-mediated intervention becoming widespread. So, questions like whether screening for inborn errors of metabolism in relation to autism (see here) could be a good first step as part of the mantra 'diagnosis is a starting point not the finishing line' and then taking things from there...----------[1] Green J. et al. Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years. J Child Psychol Psychiatry. 2017 Apr 10.[2] Green J. et al. Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial. Lancet Psychiatry. 2015. Jan 22.[3] Jones RM. et al. Placebo-like response in absence of treatment in children with Autism. Autism Res. 2017. 12 April.----------Green J, Pickles A, Pasco G, Bedford R, Wan MW, Elsabbagh M, Slonims V, Gliga T, Jones EJ, Cheung CH, Charman T, Johnson MH, & British Autism Study of Infant Siblings (BASIS) Team. (2017). Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years. Journal of child psychology and psychiatry, and allied disciplines PMID: 28393350... Read more »

Green J, Pickles A, Pasco G, Bedford R, Wan MW, Elsabbagh M, Slonims V, Gliga T, Jones EJ, Cheung CH.... (2017) Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years. Journal of child psychology and psychiatry, and allied disciplines. PMID: 28393350  

  • April 12, 2017
  • 10:59 AM
  • 247 views

Flyfocals: Vision and Vectors Help Hunting Robber Flies

by Melissa Chernick in Science Storiented

Image credit: Thomas ShahanRobber flies (Asilidae family) are not your typical house flies. They are small, predatory insects that feed on a vast array of other arthropods. While they are small in size (10 times smaller than a dragonfly), these guys are serious hunters. For example, Mallophora omboides is known as the “Florida bee killer” for its taste for honey bees. Other robber flies hunt down wasps, dragonflies, spiders, or grasshoppers, just to name a few. Perhaps almost as impressive as the types of prey is how they are subdued. Typically, robber flies will perch out in an open sunny place and wait, seizing their prey in flight and injecting it with neurotoxic or proteolytic enzymes that both immobilizes it and liquefies its insides.A recent study in Current Biology took a closer look at the robber fly’s “aerial attack strategy.” The authors focused on the genus Holcocephala, a group native to the Americas. Let’s start by going over something you know about but probably never realized had an actual term: constant bearing angle (CBA) strategy. Initially, I tried to describe this just using text, but it is really best visualized with the help of a supplemental graphic from the paper.Figure S1 from Wardill et al. (2017). Diagram showing how the constant bearing angle strategy (CBA) and proportional navigation can be used to intercept targets. It looks like an eye, but you are actually looking down on the "Human" and seeing the top of the head (black) and shoulders (white). Visualize this: You are walking along and ahead of you a ball is rolling along the ground from your left. But you decide that you want to get to the ball before it would intercept your path. If you want to catch the ball you can’t run straight for where you see it or it will have rolled past that spot before you get there. If you want to intercept that ball while it is still on your left, you will technically have to turn to backward, changing your “bearing angle.” You must anticipate where it will be and run in a straight line to that spot. This line is a “parallel range vector.” There are several of these vectors, depending on when you choose to change course.The study considered whether the flies were using this CBA strategy to catch their prey. To do this, the researchers went out to a field and hung up a big white sheet as a backdrop for their high-speed video cameras. Next, they set up their “fly teaser,” a custom made plastic frame that housed a stepper motor and several pulleys to move taut fishing line. This allowed for precise, computer controlled movements of the beads they attached to the fishing line. When a robber fly perched on a blade of grass in their study area, they “teased” it with a bead (a.k.a. dummy prey item for the fly). They included several variations including bead size and direction. They recorded the fly with two synchronized cameras running at 1000 fps to get a 3D view of the attack. For each attack video, they analyzed the frame at which the flies started to take off and until it began a terminal deceleration on final approach of the target. Then: measure, measure, measure, math, math, math.They found that the flies were fairly consistent with the CBA model. If they decelerated or reversed the bead during the attack, the robber flies compensated, actively keeping the range vectors parallel. One unexpected finding occurred in cases where the bead moved in front of the fly and it took off with a head-on collision course. They found that the fly still intercepted the bead while flying at a backward angle, meaning that the latter part of its trajectory was distinctly curved. When they took a closer look, the found the results to reflect a “lock-on” process “during which the fly has a new heading and the speed is fixed to a value slightly higher than that of the prey.” This lock-on strategy has not been described in any other flying animal. The flies were able to compensate for unexpected changes in the target’s velocity and uncertainties in the location, size, and speed of the target.Adapted from paper's graphical abstractThis type of hunting relies very heavily on vision. So each robber fly was captured for later, high detailed analysis of the head and eyes. It is important to remember that insects have compound eyes. Repeating units (the ommatidia, which have hexagonal faces called facets) that make up the eyes function as separate receptors that, when put together, assemble view of the environment. The researchers measured several parts and angles within the eyes, and once again math, math, math. This revealed the ommatidia in the front, center portion of each eye (colored red in the picture) to be nearly double the size of those in other areas, have extended focal lengths and smaller receptors. This means that the flies can reduce diffraction, focus incident light, and optimize resolution in this area. This results in a frontal fovea, or area within the eye that provides greater visual acuity than the rest of the eye. Sort of like the embedded lens of bifocal glasses; while that is an incredibly simplified way to look at it, it tells you a lot about how the flies might strategize prey capture. Also, they could be judging distance using stereopsis. This is when they use both eyes in combination to depth and 3D structure. The authors sum things up nicely, so I'll leave it in their words: "[It is kind of amazing the] accurate performance that a miniature brain can achieve in highly demanding sensorimotor tasks."Interested in more details? Here’s a video summary put together by the researchers: ... Read more »

Wardill, T., Fabian, S., Pettigrew, A., Stavenga, D., Nordström, K., & Gonzalez-Bellido, P. (2017) A Novel Interception Strategy in a Miniature Robber Fly with Extreme Visual Acuity. Current Biology, 27(6), 854-859. DOI: 10.1016/j.cub.2017.01.050  

  • April 12, 2017
  • 04:39 AM
  • 244 views

On a 'bidirectional relationship' between depression and autoimmune disorders

by Paul Whiteley in Questioning Answers

"We replicated the finding that autoimmune disorders are frequently comorbid with depression, using a longitudinal national birth cohort and self-report data, which is increasingly used in the study of depression."So said the findings reported by Jack Euesden and colleagues [1] (open-access) adding further to a growing peer-reviewed literature base [2] citing a 'connection' between immune function/dysfunction and the presentation of psychiatric/behavioural features (see here). And yes, their results did seem to add to other work more generally on the overlapping presence of autoimmune disorders and something like mood disorder (see here) and specifically with certain autoimmune parameters in mind (see here).Drawing on data from the National Child Development Study (NCDS), an initiative based here in Blighty that "comprised of all children born in England, Scotland and Wales, in one week of 1958", researchers posed various questions to participants. These included querying them about their medical histories in respect of "23 autoimmune disorders" and questioning around "three self-report measures of depression onset" at various stages of the 1958 participant cohort. These were self-report measures but alongside, researchers also accessed data from blood samples with respect to genetic analyses.Results: based on data from over 8100 participants, approximately 4% of the sample "reported ever being diagnosed with an autoimmune disorder." Alongside, some 1500 participants (18%) reported "ever experiencing depression" (i.e. were described as 'positive' for the measures of depression used during the study). When looking at the data combined, researchers concluded that there was significant 'comorbidity' between the self-reports of depression and the self-reports of autoimmune disease. As per the title of this post, the nature of the relationship was bi-directional in that: "Autoimmune disorder onset associated with increased subsequent hazard of depression onset" and "depression increased subsequent hazard of autoimmune disorder onset."Keeping in mind that self-report whilst a good rough-and-ready measure is not exactly the same as analysis of medical records when it comes to confirming any diagnosis nor that depression screens are the same as face-to-face diagnosis for something like clinical depression, there are some important implications raised from this and other related work. Analysis of 'shared pathways' between something like depression and autoimmune disease (bearing in mind, both terms cover quite a lot of clinical area) is perhaps something to consider. We're already beginning to realise that something like 'autism genes are not just genes for autism' and no doubt such a sentiment extends to other behavioural/psychiatric labels too. I note the authors also head down the [previously trodden] path suggesting that immune-based treatments might serve more than one purpose when it comes to the correlation between depression and autoimmune disease (see here). Keeping also in mind that autoimmune disease basically reflects a loss of immune tolerance to self, one wonders how deep the rabbit hole might go. If we take one specific autoimmune condition, coeliac disease, where the primary treatment is the use of a gluten-free diet, does this mean that such a diet might be useful for some types of depression too (see here)?There are still lots of questions still to be asked/answered with regards to the 'connection' between depression and autoimmune disease. But research such as this from Euesden et al represents further realisation that the immune system seems to be doing quite a bit more than just protecting us from the odd pathogen...----------[1] Euesden J. et al. A bidirectional relationship between depression and the autoimmune disorders – New perspectives from the National Child Development Study. PLoS ONE. 2017; 12(3): e0173015.[2] Andersson NW. et al. Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study. Psychol Med. 2015 Dec;45(16):3559-69.----------Euesden J, Danese A, Lewis CM, & Maughan B (2017). A bidirectional relationship between depression and the autoimmune disorders - New perspectives from the National Child Development Study. PloS one, 12 (3) PMID: 28264010... Read more »

  • April 11, 2017
  • 10:22 AM
  • 268 views

Risking Limb for Life? (A Guest Post)

by Miss Behavior in The Scorpion and the Frog

By Matthew Whitley Imagine you are walking alone in parking lot, when suddenly somebody grabs you by the arm and flashes a knife, demanding your money. Do you A) scream for help, B) try to wrestle the knife away, or C) remove your arm from your shoulder and make a break for it? Disarming your assailant may seem preferable to dis-arming yourself, but for a lizard option C is a likely response. A lizard tail left behind. Image by Metatron at Wikimedia Commons.You likely have heard before that many lizards can break off their tail when trying to make an escape. This ability is called caudal autotomy; autotomy meaning the ability to shed a limb, and caudal simply being a fancy word for tail. Of course, losing a limb is no simple procedure, and lizards possess many specialized features to make caudal autotomy possible. There are two main kinds of caudal autotomy in lizards: intervertebral and intravertebral. Intervertebral refers to when the tail breaks between vertebrae, and is considered the simpler and more primitive form. Intravertebral, on the other hand, involves some more complex features. The word intravertebral refers to fracture planes found in the middle of each vertebra in the middle of the lizard’s tail. At these fracture planes, the bone can easily snap in half. This snapping of bone is performed by the lizard itself—when its tail is caught, muscles surrounding the bone just above where its tail is held squeeze tight until the bone breaks. After the bone breaks, the rest of the tail follows: the skin stretches and breaks, muscles detach, any remaining tissue divides, and—POP—the tail falls off! After snapping your arm off to run from an attacker, you would probably just bleed out in your retreat, but lizards have that covered. In their tails, lizards have sphincters (rings of muscle) along their arteries—vessels that normally carry blood to the tail. When the tail is detached, these sphincters tighten to prevent blood from gushing out. Additionally, their veins, which normally bring blood back from the tail, have valves that prevent blood from flowing backwards, similar to the valves in your heart. And while the lizard makes its escape, the dislocated tail jerks and twitches, which distracts the lizard’s assailant. The tail owes its spastic actions to fast, glycolytic muscles, a variety of muscle that can act quickly and with a lot of force, but wears out quickly. After our reptilian friend has made its daring escape, it has a new problem—it has no tail. A lizard without its tail is at a disadvantage, just as you would be without your arm. Lizards rely on their tails for several functions, including movement, nutrient storage, and social and sexual behaviors. Fortunately, lizards that exercise caudal autotomy can actually re-grow their tails, a process which itself is highly complex. In lieu of a lengthy explanation of another amazing phenomenon, I’ll share this tidbit: to regain lost nutrients and help recover, some lizards have been known to go back and eat their lost tail! So when you tear off your arm to escape a mugger, don’t forget to return to the scene of the crime to self-cannibalize…or maybe just buy some pepper spray beforehand. Here you can see that the lizard is caught by the tail, pops it off and runs away, and the tail is left twitching.Works CitedBateman, P., & Fleming, P. (2009). To cut a long tail short: a review of lizard caudal autotomy studies carried out over the last 20 years Journal of Zoology, 277 (1), 1-14 DOI: 10.1111/j.1469-7998.2008.00484.xClause, A., & Capaldi, E. (2006). Caudal autotomy and regeneration in lizards Journal of Experimental Zoology Part A: Comparative Experimental Biology, 305A (12), 965-973 DOI: 10.1002/jez.a.346Gilbert, E., Payne, S., & Vickaryous, M. (2013). The Anatomy and Histology of Caudal Autotomy and Regeneration in Lizards Physiological and Biochemical Zoology, 86 (6), 631-644 DOI: 10.1086/673889 ... Read more »

Clause, A., & Capaldi, E. (2006) Caudal autotomy and regeneration in lizards. Journal of Experimental Zoology Part A: Comparative Experimental Biology, 305A(12), 965-973. DOI: 10.1002/jez.a.346  

Gilbert, E., Payne, S., & Vickaryous, M. (2013) The Anatomy and Histology of Caudal Autotomy and Regeneration in Lizards. Physiological and Biochemical Zoology, 86(6), 631-644. DOI: 10.1086/673889  

  • April 11, 2017
  • 09:00 AM
  • 258 views

Looking for clues for past life on Mars

by EE Giorgi in CHIMERAS

NASA's Curiosity Mars. Credits: NASA/JPL-Caltech/MSSSOn August 6, 2012, the NASA Curiosity rover landed on Mars at the base of Mount Sharp, a mountain the size of Kilimanjaro (~19,000 feet) in the middle of Gale Crater. Nina Lanza, space scientist at the Los Alamos National Laboratory, remembers the day well. As part of the team that built ChemCam, one of the ten instruments on the rover, she spent three months at the Jet Propulsion Laboratory in California, living on “Mars time” to follow Curiosity’s first “steps.” ChemCam stands for “chemistry camera” and comprises a laser-induced breakdown spectroscopy (LIBS) instrument and a Remote Micro Imager (RMI). It was built at the Los Alamos National Laboratory in collaboration with the French space agency CNES. Nina Lanza and postdoctoral fellow Patrick Gasda are two of the Los Alamos scientists who work on the instrument. “We get to shoot a laser on Mars for a living,” Lanza says, grinning.And the laser on ChemCam is extremely powerful. When focused on a target, it vaporizes a small amount of material by heating Martian rocks to a temperature that’s roughly equivalent to that of the surface of the sun. “When we fire at a nearby target,” Gasda explains, “the elements get excited and, as they come down from that excited state, they emit light.”By looking at the light emitted by the target, scientists can analyze the composition of rocks and soils on Mars. Previous Mars missions have found ice in the near-surface at high latitudes, begging the question: was there ever water on other parts of Mars at some point? And if there was—does that mean there could have been life, too?With the very first laser shots from ChemCam, the answer was a definitive yes. “ChemCam discovered that all Martian dust is hydrated,” Lanza explains. “Given how dusty Mars is, this means that water is everywhere on the planet. We also found evidence that water was flowing in Mars’s past.” “Gale Crater was filled with water,” Gasda adds. “From the sequence of sedimentary rocks we know of flowing streams in the crater that converged to a large body of still water that likely lasted for millions of years.”“Curiosity gave us a picture of Gale Crater as an extremely habitable system,” Lanza continues. “We know that on Earth systems like this, with long-lasting neutral pH waters, would definitely support life.”But how do you go about finding evidence for life? You search for clues, in other words, unique markers that identify biological activity.“A potential marker could be manganese minerals,” Lanza says. In 2016 Curiosity found rocks rich in manganese-oxides at a location called Kimberley. “Manganese deposits in the terrestrial geological record mark the shift to higher concentrations of atmospheric oxygen due to the emergence of photosynthesis. This means that there could have been more oxygen in the Martian atmosphere in the past.” Water. Oxygen. What about other building blocks of life? How do we look for those?“Nucleic and amino acids have been found in space,” Gasda tells me. “However, ribose—the ‘R’ in RNA, one of the first building blocks of life—and other sugars have never been found in space because they are too unstable. In order to have life, you need molecules that stabilize these sugars in water. Borates are particularly promising molecules for stabilizing sugars [1].”Boron is highly soluble in water. In 2013 researchers from the University of Hawaii found boron in a meteorite from Mars [2]. That’s when Gasda became interested in this quest. “Once we knew that Gale Crater had once hosted a large body of water, it was natural to search for boron in those sediments.” ChemCam did indeed find boron on Mars in 2016. Together with the manganese oxides, this is still not sufficient evidence for life on Mars, but it shows that some of the raw ingredients were present. The scientists are primed to keep looking. Curiosity has been on Mars almost five years (or 1660 sols), and its data is helping researchers fine-tune the instruments for the next Mars rover, provisionally named Mars 2020, to be launched in July 2020. “We need to look for biosignatures,” Lanza says. “And we may not find them. But if we don’t, to me, the most striking question would be: what if there were indeed all the ingredients for life on Mars, yet life never happened? What made Earth so unique that life could happen here but nowhere else?”Gasda nods. “And if we are indeed unique, shouldn’t this make us feel more special, and make us more cautious about the way we treat our planet and our biodiversity?” I mention the current political climate, with the planned budget cuts to scientific research, and the appalling denial of any intervention to curb global warming. “These cuts to basic research are disheartening,” Lanza says. “People often think of NASA research as esoteric and out of touch. And yet almost everyone has GPS technology on their smart phones today, something we owe to space research. Take the electron as another example. I’m sure people in the nineteenth century found J. J. Thomson’s research on the electron to be highly academic, with few practical applications. Yet without his discovery we wouldn’t have electricity, and our lives today would be fundamentally different.” “The best measure for progress,” Lanza concludes, “is when you can’t imagine the knowledge you are going to gain. Let the science surprise you.” Nina Lanza is a staff scientist, and Patrick Gasda is a postdoctoral research fellow, both in the Space and Remote Sensing group at the Los Alamos National Laboratory. They are both on the science team for the Curiosity Mars rover mission. The opinions expressed here are their own and not their employer’s. Both will be speaking at the March for Science in Santa Fe, New Mexico, on April 22nd. [1] Ricardo, A. (2004). Borate Minerals Stabilize Ribose Science, 303 (5655), 196-196 DOI: 10.1126/science.1092464[2] Stephenson, J., Hallis, L., Nagashima, K., & Freeland, S. (2013). Boron Enrichment in Martian Clay PLoS ONE, 8 (6) DOI: 10.1371/journal.pone.0064624... Read more »

Ricardo, A. (2004) Borate Minerals Stabilize Ribose. Science, 303(5655), 196-196. DOI: 10.1126/science.1092464  

Stephenson, J., Hallis, L., Nagashima, K., & Freeland, S. (2013) Boron Enrichment in Martian Clay. PLoS ONE, 8(6). DOI: 10.1371/journal.pone.0064624  

  • April 11, 2017
  • 04:02 AM
  • 222 views

Risk of death by injury and autism

by Paul Whiteley in Questioning Answers

"Individuals with autism appear to be at substantially heightened risk for death from injury."That was the research bottom line published by Joseph Guan & Guohua Li [1] from Columbia University Medical Center, who trawled the accumulated data included in the US National Vital Statistics System screening death certificates issued between 1999 and 2014. Of the approximate 32 million death certificates issued, researchers found that some 1300 people diagnosed as on the autism spectrum had their death recorded and recorded with mention alongside the word 'autism'.A few details about those 1367 deaths among those with autism compared with the not-autism population have captured media headlines (see here) not least the finding that: "The mean age at death for individuals with autism was 36.2 years (SD = 20.9 years), compared with 72.0 years (SD = 19.2 years) for the general population." This data tallies with other reports on premature mortality in relation to autism (see here) and also in respect of some of the over-represented comorbidity that accompanies the label such as learning (intellectual) disability (see here). I might also forward the idea that another over-represented comorbidity - attention-deficit hyperactivity disorder (ADHD) - appearing alongside autism (see here) might also have some relevance when it specifically comes to injury risk too (see here). Researchers noted that around a quarter of deaths recorded for those with autism were attributed to injury - quite a bit more than compared to those general population death stats - and that suffocation, asphyxiation and drowning made up a considerable portion of those deaths following injury.OK a step back is required here. This data does not mean that those diagnosed on the autism spectrum have a life expectancy of 36.2 years (plus or minus 20 years or so). I know it might seem a little obvious to make such a statement but I do want to make that point clear. The data did find that premature mortality due to injury and non-injury does seem to 'hit younger' when it comes to autism (bear in mind also that the majority of recorded deaths where autism was mentioned were not caused as a result of injury).Appreciating that some people have voiced their concern about these and other aspects of the Guan/Li paper (see here) I have to say that I'm slightly more focused on the pattern of death by injury reported over above whether the data is truly representative of the autistic population at large or not. Death by drowning is sadly something all too familiar when it comes to autism, particularly when taken in the context of the wandering/elopement data (see here). Yes, for some, autism, the presentation of autism and autism+, can be a life-limiting diagnosis. I know that last sentence does not make for great PR but readers should look at it in the context of other important peer-reviewed information too (see here and see here).So, what can be done to improve life prospects for those on the autism spectrum?  Well, outside of moves to reduce the multitude of health inequalities that seem to coincide with receipt of a diagnosis of autism (see here and see here for examples), there are some practical solutions. Lessons about water safety and learning to swim represent a first course of action [2] and something that may have various other beneficial effects in terms of physical fitness (another issue that pervades the autism research literature). I appreciate that some children (and adults) might be a little nervous around water but with a bit of creative thinking (i.e. making swimming fun and not just about learning to do lengths of the pool) I don't doubt that learning such a life-saving skill can be made much more palatable. In the age where cinemas and theatres have 'autism-friendly' screenings, surely autism-friendly swimming sessions can't be too far behind?In relation to reducing other potential causes of death such as suffocation and asphyxia, there may be other things to consider. I'm assuming that food and eating patterns may be something to be looked at when it comes to problems such as choking. This means education about eating small morsels of food and the importance of properly chewing food before swallowing so reducing the frequency of food packing for example. This might also have implications as and when medication is taken orally (via the mouth) and little details such as ensuring that a person drinks some water with any tablets that need to be taken. You may again think this is a rather obvious thing to say but sadly, there have been occasions when choking on food [3] has led to rather extreme consequences in the context of the autism spectrum.In short, death by injury in relation to autism is not something that should ever be accepted. Yes, injury and accidents happen, but that's not to say nothing that can be done to prevent some/many of them...----------[1] Guan J. & Li G. Injury Mortality in Individuals With Autism. American Journal of Public Health. 2017. Mar 21.[2] Pan CY. Effects of water exercise swimming program on aquatic skills and social behaviors in children with autism spectrum disorders. Autism. 2010 Jan;14(1):9-28.[3] Hudson A. et al. Packing and Problematic Feeding Behaviors in CHARGE Syndrome: A Qualitative Analysis. Int J Pediatr Otorhinolaryngol. 2016 Mar;82:107-15.----------Guan, J., & Li, G. (2017). Injury Mortality in Individuals With Autism American Journal of Public Health DOI: 10.2105/AJPH.2017.303696... Read more »

Guan, J., & Li, G. (2017) Injury Mortality in Individuals With Autism. American Journal of Public Health. DOI: 10.2105/AJPH.2017.303696  

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