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  • March 28, 2017
  • 04:48 PM

Bottlenose Dolphins: The Ultimate Sea Bully? (A Guest Post)

by Miss Behavior in The Scorpion and the Frog

By Kayla FullerImagine this situation: you’ve brought your favorite lunch to work. Everyone is jealous of your food, continuously eyeing it up. A few coworkers, who have brought in disappointing lunches in comparison, approach and demand that you hand it over. After you refuse, they beat you until your body lies lifeless and they take your lunch anyway. Woah, woah, woah… that took a dramatic turn! Photo of a harbour porpoise, taken by AVampireTear (Wikimedia Commons)But for harbour porpoises in the northeastern Atlantic, this fight for food has become a reality, and bottlenose dolphins are the suspected culprit. In 1996, Harry M. Ross (SAC Veterinary Services, U.K.) and Ben Wilson (University of Aberdeen, U.K.) documented fractured rib cages, damaged internal organs and joint dislocations of deceased harbour porpoises in the northeastern Atlantic. Why would bottlenose dolphins be causing such damage? Who could ever associate such a cute and cuddly creature with a horrific crime like this? Photo of a bottlenose dolphin, taken by NASA (Wikimedia Commons)Researchers Jérôme Spitz, Yann Rousseau, and Vincent Ridoux with the Center for Research on Marine Mammals: Institute for Coastal and Environmental Research at the University of La Rochelle in France become the judge and jury in this trial. Jérôme, Yann, and Vincent obtained 29 harbour porpoises and 25 bottlenose dolphins that had been beached and died in the Bay of Biscay (between Spain, France, and England). At the time of the study, more harbour porpoises were being found dead in the bay than in previous years. They hypothesized that bottlenose dolphins and harbour porpoises may have had similar enough diets to cause competition and violence between the two species. Photo of a harbour porpoise that received injuries thought to be from abottlenose dolphin before death (circled), from Ross and Wilson (1996)The researchers’ goal was to analyze stomach contents to directly see what each mammal was eating at the time of their death. To do this, Jérôme, Yann, and Vincent removed the stomachs from the harbour porpoise bodies and weighed them with all contents included. After weighing stomach casings separately, they calculated total weight inside of the animals’ stomachs. Then, they washed stomach contents through a filter to separate out larger matter. Now, if you have a weak stomach, this probably wouldn’t be the job for you. Jérôme, Yann, and Vincent separated food items within the stomachs into identifiable categories. It could sometimes be difficult to recognize whole animals in a stomach due to breakdown, so methods like pairing dismantled eyes or counting fish bones was necessary to identify them! This same process was repeated for bottlenose dolphin carcasses. From there, the scientists compared specimens for prey presence, abundance, mass, and size to see if there was overlap between diets of the harbour porpoises and bottlenose dolphins.So what did they find? More food mass, a greater number of species, and a more diverse size range of prey was found in the stomachs of bottlenose dolphins in comparison to harbour porpoises. Although bottlenose dolphins have a habitat that includes more deep-ocean areas while harbor porpoises inhabit coastal surroundings, certain prey species were eaten by both. Since bottlenose dolphins are bigger and hunt in larger groups, they would logically be more dominant in a face-off over a common prey item. Why are they fighting more over the same foods? This shift could be a result of humans harvesting species from the ocean that are diet items for bottlenose dolphins. It could also be a result of warming ocean temperatures that could be changing the dwelling places of available food for bottlenose dolphins. This would explain why more habour porpoises are being attacked by these marine tyrants moving into shallower waters. Poor porpoises, all they want to do is eat their lunch in peace. Who knows, maybe in the next few million years, we’ll see highly evolved harbour porpoises covered in spikes to ward off the dolphins. That’ll teach those bullies! References:Ross, H., & Wilson, B. (1996). Violent Interactions between Bottlenose Dolphins and Harbour Porpoises Proceedings of the Royal Society B: Biological Sciences, 263 (1368), 283-286 DOI: 10.1098/rspb.1996.0043 Spitz, J., Rousseau, Y., & Ridoux, V. (2006). Diet overlap between harbour porpoise and bottlenose dolphin: An argument in favour of interference competition for food? Estuarine, Coastal and Shelf Science, 70 (1-2), 259-270 DOI: 10.1016/j.ecss.2006.04.020 ... Read more »

  • March 28, 2017
  • 04:34 AM

Presenting with the symptoms of autism and then diagnosed with phenylketonuria (PKU)

by Paul Whiteley in Questioning Answers

The case report from Betül Mazlum and colleagues [1] (open-access available here) illustrates once again that (a) the plural 'autisms' exist (see here) and (b) screening for inborn errors of metabolism (IEM) should be an important part of any autism assessment (see here). Indeed, screening for IEM should really be part of assessments for many different labels...Detailing a case report wherein a 3-year old child came to clinical attention for "speech delay and social problems", the authors describe how following a diagnosis of "autism according to DSM-IV criteria" further investigations were undertaken. Said investigations included analysis of blood and urine amino acid levels and, voilà, high levels of phenylalanine were detected and a diagnosis of phenylketonuria (PKU) made. Initiation of a low phenylalanine diet (the treatment of choice for PKU) followed and was accompanied by some important [positive] changes to behaviour and cognition. Of particular note to the presentation of autism we are told that: "At 4 months follow-up improvement was noticed in his eye contact, joined attention and speech."The authors further note: "This case was not at particular risk for PKU at first thought, being born to non-consanguineous parents and during a period when newborn screening with Guthrie test was widely applied in Turkey. Although the child had a heel prick in the hospital where he was delivered, the results are unavailable and therefore whether his sample was analyzed is questionable."OK, this was a case report and whilst an important 'N=1' is not necessarily generalisable to all autism (or rather all autisms). Insofar as the methods talked about for establishing raised phenylalanine - "Blood and urine amino acid chromatography" - I would have liked to have seen a little more detail in relation to the specific 'chromatography' methods used and any results related to another aromatic amino acid (tyrosine). We don't also have any data on follow-up either (repeat biological testing)...PKU is an important but quite rare IEM. This is not however the first time that PKU has been linked to autism or the presentation of autistic traits (see here) particularly in cases of 'untreated' PKU. Aside from PKU providing quite a good template for how diet - certain aspects of diet - can affect behaviour and mental state for some (see here) there are other potential implications and 'correlations' on the back of this work. Not least is the intersection between another intervention measure potentially indicated for PKU - tetrahydrobiopterin (sapropterin or BH4) - and research suggesting that the 'mopping up phenylalanine' properties of this compound might be potentially effective for some cases and facets of autism too (see here) based on double-blind, placebo-controlled trial results [2]."The possibility of a metabolic disorder including PKU should be considered in any child presenting with symptoms of autism, learning or speech problems and PKU should be tested unless the newborn screening results are available." I wouldn't argue with those sentiments [3], allowing for the fact that other correlates should also be considered (see here for example) particularly it seems, when autism appears alongside something like intellectual (learning) disability. The question of whether the quite restrictive low phenylalanine diet typically indicated for PKU might also impact autistic signs and symptoms is something that science still perhaps needs to look into...Music to close, and how about something lively from The King?----------[1] Mazlum B. et al. A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood. Turk J Pediatr. 2016;58(3):318-322.[2] Klaiman C. et al. Tetrahydrobiopterin as a treatment for autism spectrum disorders: a double-blind, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2013 Jun;23(5):320-8.[3] Bilder DA. et al. Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study. Mol Genet Metab. 2017 Mar 6. pii: S1096-7192(17)30052-5.----------Mazlum B, Anlar B, Kalkanoğlu-Sivri HS, Karlı-Oğuz K, Özusta Ş, & Ünal F (2016). A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood. The Turkish journal of pediatrics, 58 (3), 318-322 PMID: 28266201... Read more »

Mazlum B, Anlar B, Kalkanoğlu-Sivri HS, Karlı-Oğuz K, Özusta Ş, & Ünal F. (2016) A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood. The Turkish journal of pediatrics, 58(3), 318-322. PMID: 28266201  

  • March 27, 2017
  • 12:07 PM

Theory of Mind in Brain Development

by William Yates, M.D. in Brain Posts

Theory of Mind (ToM) is a concept describing the ability to understand what another person is thinking or feeling.Today in my neuroscience medicine news review I ran across a novel, interesting and important research study targeting brain development in ToM.Normally developing children develop ToM around 4 years of age. In the study published in Nature Communications, a research team at the Max Planck Institute in Germany studied white matter development in 3 to 4 year old children.Using a series of neuropsychological tasks, they studied white matter development using diffusion tensor brain imaging as it related to ToM skill.The research team was able to identify the following brain development features in ToM:White matter changes in the temperoparietal regions, the precuneus and the medial prefrontal cortexIncreased white matter connectivity between temperoparietal and inferior frontal brain regionsThese changes were independent of development of non-ToM cognitive abilityThe authors note in the discussion section that non-human primates fail to develop explicit ToM cognitive ability. Non-human primate brain show poor arcuate fascicle connectivity. They note that arcuate fascicle white matter connectivity appears to be key for ToM cognitive skills.This manuscript is available in free full-text format and readers with more interest in this study can access the manuscript by clicking on the citation link below.Follow me on Twitter @WRY999Image of white matter tract in human brain is from the iPad app Brain Tutor.Grosse Wiesmann C, Schreiber J, Singer T, Steinbeis N, & Friederici AD (2017). White matter maturation is associated with the emergence of Theory of Mind in early childhood. Nature communications, 8 PMID: 28322222... Read more »

  • March 27, 2017
  • 04:38 AM

Detecting stereotypic behaviours through technology

by Paul Whiteley in Questioning Answers

"We have designed an Internet-of-Things (IoT) framework named WearSense that leverages the sensing capabilities of modern smartwatches to detect stereotypic behaviors in children with autism."So said the paper by Amir Mohammad Amiri and colleagues [1] (open-access available here) and, I have to say, something that really piqued my [research] attention. Describing how authors managed to design and construct a smartwatch with the ability to "detect three behaviors, including hand flapping, painting, and sibbing [hitting themselves on the top of their head] that are commonly observed in children with autism" they report some preliminary findings.When I say these are preliminary findings, I do indeed mean preliminary, as a two-phase preliminary trial included data from "12 healthy subjects aged between 23–33" and "two subjects (ages 15 and 16) diagnosed with autism." Aside from the implication that young adults with autism are somehow 'not healthy' (I think the correct terminology should be 'not diagnosed with autism/autism spectrum disorder'), you can perhaps see that much of the data for this study came from artificial, induced behaviours not necessarily produced by those on the spectrum - "The tasks that the subjects were invited to do included three different types for 20 s." I do have some other quibbles about the write-up of this study as per very generalised sentences like: "These stereotypic behaviors happen when a child is trying to regulate the sensory input from their surrounding environment."But I don't want to take anything away from the potential of this kind of research and where, with a bit more study and refinement, it could take many areas of autism research and practice. Accepting the argument that stereotypic behaviours that can accompany autism are not always something that needs to be tinkered with, I can perhaps see a use for this technology when it comes to screening and assessment. If for example, this kind of technology could be applied to something like an ADOS assessment, you could perhaps see how there may be additional information to be garnered (and indeed, built up coincidental to the 'objectivity' linked to such an exam). Coupled with other technology in relation to things like gaze monitoring for example, the potential gets even more exciting. And then also are the potentials of this kind of tracking software in relation to monitoring physical activity and autism (see here for example) or even in the context of epilepsy occurring alongside autism (see here for another WearSense use). There may be lots more to see when it comes to such technology and autism...----------[1] Amiri AM. et al. WearSense: Detecting Autism Stereotypic Behaviors through Smartwatches. Healthcare (Basel). 2017 Feb 28;5(1).----------Amiri AM, Peltier N, Goldberg C, Sun Y, Nathan A, Hiremath SV, & Mankodiya K (2017). WearSense: Detecting Autism Stereotypic Behaviors through Smartwatches. Healthcare (Basel, Switzerland), 5 (1) PMID: 28264474... Read more »

Amiri AM, Peltier N, Goldberg C, Sun Y, Nathan A, Hiremath SV, & Mankodiya K. (2017) WearSense: Detecting Autism Stereotypic Behaviors through Smartwatches. Healthcare (Basel, Switzerland), 5(1). PMID: 28264474  

  • March 25, 2017
  • 05:37 AM

Including the "full intellectual range" in autism vision research

by Paul Whiteley in Questioning Answers

The paper by Alyse Brown and colleagues [1] (open-access available here) is probably not going to gain any significant media headlines (unlike other recent studies - see here and see here) but does cover a rather important question regarding the autism research landscape: how representative is autism research?Specifically looking at the collected research on visual processing (distinct from physical issues with the eyes that still require greater awareness) with autism in mind, the authors surveyed the research literature to determine "what extent the ASD with-ID [intellectual disability] population has been excluded from visual research." Intellectual or learning disability is one of the more frequently over-represented comorbidities that can accompany a diagnosis of autism or autism spectrum disorder (ASD). Their answer: "our searches indicate that 80% of the vision research associated with ASD is representative of less than 60% of the appropriate population, i.e., those with ASD without ID while the ASD with ID group who we argue currently represent 42% of the ASD population, have not been adequately considered."You may well quibble with the "recalculation of ASD prevalence figures, using the criteria of DSM-5" as a means of calculating that '~40% of those with autism have ID too' figure. For me however, the message is quite stark: autism research - specifically related to visual processing issues - is not yet representative of  'all autism'."Reluctance to test individuals who are below 80 in IQ is presumably a practical stance as the data collected from these individuals are often hard to obtain, and often close to floor level performance." The authors note however that the presence of ID alongside autism in the area of visual processing is not something that cannot be 'overcome' by researchers with some creative thinking and a few modification(s) to their experimental designs. Indeed, visual processing research lends itself well to quite a few alterations to methods [2]...How applicable might these results be to other areas of autism research? Well, we just don't know. I daresay that quite a lot of the 'psychology' based autism research in particular might show a bias towards autism without intellectual disability for just those reasons listed above. The problem then of grand, over-arching generalisations to 'all autism' on the basis of results from the more 'cognitively-able' becomes apparent. Of course, in these days of the plural 'autisms' (see here) and the realisation that 'heterogeneity means heterogeneity' when it comes to autism (see here) one could argue that even characterisations based on the presence of ID or not when it comes to autism are equally 'simplistic' and equally 'useless'. How many autisms might well have an ID element to them? Is ID a comorbidity or something rather more central to some of the autisms? These questions and related others are ones that autism research as a whole will eventually have to start looking at and taking into account.And going back to the issue of eye disorders being potentially over-represented and under-diagnosed in relation to autism, the paper by Mouridsen and colleagues [3] reiterates that intellectual ability when accompanying autism needs more health equality: "The rate of eye disorder was particularly high (24.5%) in those with a co-occurring profound or severe learning disability (IQ < 50)."----------[1] Brown AC. et al. Vision Research Literature May Not Represent the Full Intellectual Range of Autism Spectrum Disorder. Front Hum Neurosci. 2017 Feb 14;11:57.[2] Boot FH. et al. Delayed visual orienting responses in children with developmental and/or intellectual disabilities. J Intellect Disabil Res. 2013 Dec;57(12):1093-103.[3] Mouridsen SE. et al. Eye Disorders among Adult People Diagnosed with Infantile Autism in Childhood: A Longitudinal Case Control Study. Ophthalmic Epidemiol. 2017 Mar 15:1-4.----------Brown AC, Chouinard PA, & Crewther SG (2017). Vision Research Literature May Not Represent the Full Intellectual Range of Autism Spectrum Disorder. Frontiers in human neuroscience, 11 PMID: 28261072... Read more »

  • March 24, 2017
  • 03:46 AM

Autism and anxiety disorder: zooming in on the details

by Paul Whiteley in Questioning Answers

Although it is not necessarily new news that (a) autism rarely exists in some sort of diagnostic vacuum, and (b) that some of the comorbidity 'over-represented' when it comes to autism can actually be more disabling than autism itself, there are still more investigations to be done.The paper by Vicki Bitsika & Christopher Sharpley [1] represents an example of how autism science is starting to go past the whole 'is there a connection between...' bit when it comes to autism and various comorbidity, specifically focused on the issue of anxiety. Looking at parental responses on "the Social Responsiveness Scale (SRS) and the GAD subscale of the Child and Adolescent Symptom Inventory (CASI-4 GAD) about their sons" researchers reported some rather interesting trends when it came to the two based on a cohort of young males diagnosed with autism. The authors used the term 'high-functioning' to describe the particular 'type' of autism being looked at in their study but I'm rather less sure this is an appropriate description ('high- and low-functioning' tend to be very generalised terms).I should back-track slightly and point out that the reasoning behind this research was to "assist in treatment or avoidance of GAD [generalised anxiety disorder] by identifying ASD [autism spectrum disorder]-related behaviours as 'targets' for intervention with anxious children as well as for preventative treatments that could be implemented into daily routines before children become anxious." Of all the debates past and present in relation to autism, specifically on the topic of 'treatment' (or even 'cure'), I don't think anyone would be opposed to the idea that anxiety (whether symptoms or disorder) should be treated and potentially 'cured' in this context. Anxiety can be absolutely disabling including when tied into autism.Results: bearing in mind their focus on only two parameters (SRS scores and GAD scores) in this study, there are some interesting trends in need of further investigation. So: "For pre-adolescents, high levels of tension in social situations were associated with 3.5-times greater likelihood of having GAD; for adolescents, experiencing difficulty in changes in routine was associated with a 10-fold increase in risk of GAD." The pre-adolescents and adolescents bit in that sentence was due to the division of their cohort on the basis of age. The results suggest therefore that anxiety (or at least GAD) might express itself for various different reasons potentially linked to the age/maturity of the person.I know some people might be shrugging their shoulders at such a finding and saying 'we already knew that'. Well, I'm not one of them. Take for example the 'change in routines' as being a possible factor in the expression of GAD in adolescents. The recent work by Joyce and colleagues [2] looking at another important term relevant to this issue - intolerance of uncertainty - adds an additional layer to the Bitsika/Sharpley findings as per their conclusion that: "replicated previous findings based on parent report showing a significant positive relationship between RRB [restricted and repetitive behaviours] and anxiety." RRBs can, amongst other things, include responses to routine (and changes to said routines).As to the question of what such findings might mean in the context of intervention, the authors talk about how intervening in the symptoms of GAD (a kind of reactionary approach) might also benefit from also trying to focus intervention on certain autistic symptoms too. Outside of the [careful] use of some of the talking/behavioural therapies and perhaps the whiff of some effect from certain pharmacological interventions when it comes to RRBs and autism, there isn't a great deal on offer at the moment in autism science and practice in this area. Indeed, if the relationship between RRBs and anxiety is further confirmed (and I mean confirmed [3]), I'd perhaps suggest that moves to target RRBs in the context of autism could/should be a research priority if only to potentially reduce the effects of anxiety.And the inquiry continues [4]...----------[1] 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.[2] Joyce C. et al. Anxiety, Intolerance of Uncertainty and Restricted and Repetitive Behaviour: Insights Directly from Young People with ASD. J Autism Dev Disord. 2017 Feb 25.[3] Wang S. et al. Sex Differences in Diagnosis and Clinical Phenotypes of Chinese Children with Autism Spectrum Disorder. Neurosci Bull. 2017 Feb 25.[4] South M. et al. Symptom overlap on the srs-2 adult self-report between adults with asd and adults with high anxiety. Autism Res. 2017. March 7.----------Bitsika, V., & Sharpley, C. (2017). The association between parents’ ratings of ASD symptoms and anxiety in a sample of high-functioning boys and adolescents with Autism Spectrum Disorder Research in Developmental Disabilities, 63, 38-45 DOI: 10.1016/j.ridd.2017.02.010... Read more »

  • March 23, 2017
  • 04:02 AM

Congenital cytomegalovirus (CMV) infection and autism continued

by Paul Whiteley in Questioning Answers

I wanted to briefly talk about the paper by Francesca Garofoli and colleagues [1] on congenital cytomegalovirus (CMV) infection and autism not because it contains any novel data (see here), but because it reminds us that the potential 'pathways' to a diagnosis of autism are multiple and not necessarily 'pre-programmed' as per the 'it's all genetic' arguments that frequently figure in various domains.Congenital CMV infection refers to the transmission of CMV - "a common virus that belongs to the herpes family of viruses" - from mother to foetus during pregnancy. The details are still under investigation as to how and why CMV affects a foetus (bearing in mind this is quite a common virus) but autism as a consequence of [some] congenital CMV infection has growing evidence-based support [2].Garofoli et al included 70 'proven' cases of CMV "congenitally-infected infants" in their study; specifically looking "to correlate congenital cytomegalovirus (CMV) infection with autism spectrum disorder (ASD) and to define its prevalence." They determined that 2 of their 70 strong cohort met criteria for an ASD at the age of 3 years. Two of 70 translated as 2.8% of their cohort and contrasts with [estimated] autism prevalence "in general Italian population (0.66-1.36%)." The figure of 2.8% is also not a million miles away from other estimates of autism suggested via congenital CMV infection [3].Although 2.8% of the cohort (2/70) might not sound like a lot I'm inclined to suggest that it does prompt quite a lot more additional investigation. Not least is the question: 'why was autism/ASD not diagnosed in the other 68 children?' and onward whether other factors (genetics(!), biology, infection timing, immunologic response, etc) might come into play [4] in relation to the congenital CMV infection - autism association? Taking also into account the estimated prevalence of ASD in Italy, these figures (estimates) do seem to be a little lower than that described in other geographical locations (see here and see here for examples). Indeed, bearing in mind the research evidence already looking at estimated ASD prevalence in Italy [5] it's not unfair to say that 'under-estimation' might be a familiar theme...----------[1] Garofoli F. et al. An Italian Prospective Experience on the Association Between Congenital Cytomegalovirus Infection and Autistic Spectrum Disorder. J Autism Dev Disord. 2017 Mar 3.[2] Ornoy A. et al. Prenatal factors associated with autism spectrum disorder (ASD). Reprod Toxicol. 2015 Aug 15;56:155-69.[3] Engman ML. et al. Prenatal acquired cytomegalovirus infection should be considered in children with autism. Acta Paediatr. 2015 Aug;104(8):792-5.[4] 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. March 21.[5] Ferrante M. et al. Prevalence and age at diagnosis of Autism Spectrum Disorder in south Italy, 2004–2014. Eur J Public Health. 2015; 25 (suppl_3).----------Garofoli F, Lombardi G, Orcesi S, Pisoni C, Mazzucchelli I, Angelini M, Balottin U, & Stronati M (2017). An Italian Prospective Experience on the Association Between Congenital Cytomegalovirus Infection and Autistic Spectrum Disorder. Journal of autism and developmental disorders PMID: 28258350... Read more »

  • March 22, 2017
  • 04:08 AM

On genotype and environmental exposure patterns

by Paul Whiteley in Questioning Answers

I was rather interested to read the paper by Michela Traglia and colleagues [1] (open-access available here) concluding that: "maternal and fetal genetic make-up are important determinants of mid-gestational maternal circulating levels of some environmental organohalogens." Interested because, in these days of gene-environment interactions being applied to just about everything, the detail that is missing - which genes might potentially be linked to which environmental factors - has not yet been suitably addressed in the peer-reviewed science literature.So, based on data - "serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children" - derived from participants included in the Early Markers for Autism (EMA) Project, researchers set about assessing how genetics might impact on environmental pollutant exposure profiles. Maternal blood samples were collected at around 15-20 weeks pregnancy. Children provided blood samples via the fabulous resource that is the newborn screening program, where: "Newborn blood spots were collected on filter paper 1-2 days after birth." Maternal samples were analysed for various environmental pollutants and both sets of samples were analysed for the genetic material they contained pertinent to whether "circulating mid-gestational levels of organohalogens would be driven by common maternal genetic determinants, and that these results could shed light on the observed associations between the organohalogens and ASD [autism spectrum disorder]."Results: yes, the authors "found evidence that a large proportion of maternal circulating levels of BB-153, BDE-47, -100, -153 [polybrominated congeners] and their sum was significantly controlled by common genetic factors." Those 'common genetic factors' typically referred to the presence of point mutations (SNPs) that litter everyone's genome and on occasion, can affect the function/production of specific biological processes. So: "Genome-wide association analyses identified significant maternal loci for p,p'-DDE... in the CYP2B6 gene and for BDE-28... near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism." In other words, although the environmental pollutants measured are not great products in the first place (in terms of safety), a person's genetic make-up can influence how such products are eventually dealt with by the body and potentially onwards, what subsequent effects they might have.Additionally: "results suggest that the maternal circulating levels of some compounds were more highly influenced by fetal genetic factors than maternal genetics." This leads into another aspect of the current study whereby foetal genetic factors might also play a part in "controlling the toxicant disposition between mother and fetus." Specifically, authors noted that aspects of the individual genetics of a foetus (distinct from its mother) "contributed to the levels of BDE-100... and PCB187... near the potential metabolic genes LOXHD1 and PTPRD, previously implicated in neurodevelopment."And finally: "We confirmed that the serum levels of BDE-100, -153 and the total sum of PBDEs were significantly lower in mothers of ASD-affected children compared to mothers of control children." This is interesting in light of other discussions about PBDEs and autism in particular (see here). The authors do discuss various scenarios to account for their results not least that "transplacental transfer of organohalogens during pregnancy may be driven by the fetal genome expressed in placenta." Further analyses of the 'placentome' might therefore be indicated.To reiterate, this is interesting research. It tells us that many [adverse] environmental exposures, whilst typically to be avoided, don't act on the body in a uniform way as a function of differing genomes and differences in the ways that the body 'handles' such exposures. With autism in mind, this is not necessarily new news (remember paraoxonase gene variants and organophosphate metabolism [2] and air pollution and offspring autism?) but is a useful reminder. Such work also provides a template for looking at the myriad of other environmental factors put forward to influence autism risk and whether individual product safety is necessarily the only or most important factor when it comes to assessing relative risk profiles.I might finally also draw your attention to a recent interesting meta-analysis of the various environmental risk factors potentially linked to autism [3] (open-access) and another article talking about similar things [4] (open-access) (thanks Annabelle). Genes and environment, genes and environment...Music: Petula Clark sings the Beatles? Personally, I think it's better than the original...----------[1] Traglia M. et al. Independent Maternal and Fetal Genetic Effects on Mid-gestational Circulating Levels of Environmental Pollutants. G3 (Bethesda). 2017 Feb 24. pii: g3.117.039784.[2] D'Amelio M. et al. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions. Mol Psychiatry. 2005 Nov;10(11):1006-16.[3] Modabbernia A. et al. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Molecular Autism. 2017; 8: 13.[4] Parker W. et al. The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism. Journal of International Medical Research. 2017. Jan 20.----------Traglia M, Croen LA, Lyall K, Windham GC, Kharrazi M, DeLorenze GN, Torres AR, & Weiss LA (2017). Independent Maternal and Fetal Genetic Effects on Mid-gestational Circulating Levels of Environmental Pollutants. G3 (Bethesda, Md.) PMID: 28235828... Read more »

  • March 21, 2017
  • 10:04 AM

The Weirdest Animals on Earth: 12 Amazing Facts About Platypuses

by Miss Behavior in The Scorpion and the Frog

What IS that? A photo by Stefan Kraft at Wikimedia Commons.1. Platypuses are so strange, that when British scientists first encountered one, they thought it was a joke: A Governor of New South Wales, Australia, sent a platypus pelt and sketch to British scientists in 1798. Even in their first published scientific description of the species, biologists thought that this duck-beaked, beaver-bodied, web-footed specimen may be some Frankenstein-like creation stitched together as a hoax. But this is only the beginning of their oddities…2. Platypuses are egg-laying mammals. Mammals are animals that have a backbone, are warm-blooded, and females produce milk for their young. Most females that nurse their young also carry their developing babies in their bodies and give birth to live young… But platypuses don’t play by those rules. Platypuses are monotremes, egg-laying mammals that include the platypus and four species of echidna. Most female mammals have two functional ovaries, but female platypuses, like most female birds, only have a functional left ovary. Once a year, a female platypus may produce a clutch of two or three small, leathery eggs (similar to reptile eggs), that develop in her uterus for 28 days. Because female platypuses don’t even have a vagina, when the eggs are ready, she lays them through her cloaca, an opening that serves for reproduction, peeing and pooping. (In fact, monotreme comes from the Greek for “one hole”). She then curls around them and incubates them for another 10 days until they hatch. 3. Platypuses sweat milk! Not only do female platypuses not have vaginas, they don’t have nipples either! Instead, lactating mothers ooze milk from pores in their skin, which pools in grooves on their bellies so the babies can lap it up. …And they’re not even embarrassed about it! 4. Adult platypuses are toothless. Baby platypuses (that is the actual technical term for them, by the way… not “puggles”, which would be way more fun) are born with teeth but they lose them around the time that they leave the breeding burrow. In their place are rigid-edged keratinized pads that they use as grinding plates. When they catch their prey (worms, bugs, shrimp, and even crayfish), they store it in their cheek pouches and carry it to the surface, where they use gravel to crush it in their toothless maw.5. The platypus “duck bill” is a sensory organ used to detect electric fields. Muscles and neurons use electrical impulses to function, and these impulses can be detected by electroreceptors. Although common in shark and ray species, electroreception is rare in mammals, only having been discovered in monotremes and the Guiana dolphin. Platypuses have rows of around 40,000 electroreceptors on their highly sensitive bill, which they wave back and forth in the water, much like a hammerhead shark, to determine the location of their prey. It’s a good thing this sense is so sensitive, since they close their eyes, nose and ears every time they dive. 6. Platypuses don’t use their tails like beavers do. Whereas beavers use their large, flat, leathery tails for swimming and slapping the water to send signals, platypuses don’t use their tails for any of that. Platypuses have large, flat tails for storing fat in case of a food shortage. Unlike beaver tails, platypus tails are covered in fur, which the mothers use to snuggle with their incubating eggs.A platypus ankle spur. Photo by E.Lonnon at Wikimedia Commons.7. Male platypuses have venomous ankle spurs. Their venom is strong enough to kill small animals and to create excruciating pain in humans. Since only males have it and they produce more venom during the breeding season, we think its main function may be to compete for mates and breeding territories.8. Platypuses are knuckle-walkers with a reptilian gait. Although they are well-built for swimming with their webbed feet and legs on the sides of their bodies, these traits make it quite awkward to get around on dry land. To walk, they pull in their webbing and walk on their knuckles, exposing their claws. Like reptiles and salamanders, platypuses flex their spines from side-to-side, supported by their sprawling legs. 9. Platypuses have unusually low body temperatures. As unusual as they are, platypuses are still mammals, which are defined, in part, by their ability to generate most of their own body heat with their metabolism. Platypuses do this as well, but whereas most mammals maintain body temperatures between 37-40 degrees C (99-104 degrees F), platypuses are happy with a body temperature of 32 degrees C (90 degrees F). This lower metabolism reduces the amount of calories they need to eat.10. They have no stomach. Stomachs are specialized protein-digesting chambers of digestive tracts that contain protein-digesting enzymes and acids to activate them. Not all animals have them, but most carnivores do. The most common exceptions to this rule are fish… and platypuses. Why? We don’t know for sure, but many of these animals consume diets high in calcium carbonate, which is a natural antacid. If their own diet would constantly neutralize their stomach acid, then the stomach really isn’t going to do them any good anyway.11. They have 10 sex chromosomes! Most mammals have two sex chromosomes, one from each parent. An individual that has two X chromosomes is usually female and an individual that has one X and one Y chromosome is usually male. Thus, female mammals pass along an X chromosome to each offspring and males can pass along an X or a Y. But platypuses are not content to be normal in any way…They have 10 sex chromosomes: 5 from mom and 5 from dad. All 5 chromosomes from mom are Xs, whereas a male sperm either contains 5 Xs or 5 Ys. Birds also have two sex chromosomes, but in birds, individuals with two of the same type are usually male and individuals with different chromosomes are usually female. Their system is called ZW, where the mammalian system is XY. The platypus X chromosome is more similar than the X chromosome of other mammals to the bird Z chromosome.12. The platypus genome is as much of a hodgepodge as its body. Only 80% of the platypus’ genes are like other mammals. Some of their genes have only previously been found in birds, reptiles, fish, or amphibians.To learn about more weird animals, go here.References: ... Read more »

Scheich, H., Langner, G., Tidemann, C., Coles, R., & Guppy, A. (1986) Electroreception and electrolocation in platypus. Nature, 319(6052), 401-402. DOI: 10.1038/319401a0  

Warren, W., Hillier, L., Marshall Graves, J., Birney, E., Ponting, C., Grützner, F., Belov, K., Miller, W., Clarke, L., Chinwalla, A.... (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature, 453(7192), 175-183. DOI: 10.1038/nature06936  

  • March 21, 2017
  • 03:57 AM

PACE trial recovery data and chronic fatigue syndrome - a reply

by Paul Whiteley in Questioning Answers

I'd encourage readers interested in the background to the response paper by Michael Sharpe and colleagues [1] to have a look at a previous blogging occasion when the topic of the PACE trial, chronic fatigue syndrome (CFS) and 'recovery' were discussed (see here).Suffice to say that this latest paper is a reply to one published by Carolyn Wilshire and colleagues [2] who concluded that: "The claim that patients [with CFS] can recover as a result of CBT [cognitive behaviour therapy] and GET [graded exercise therapy] is not justified by the data, and is highly misleading to clinicians and patients considering these treatments." Said discussions linking back to some quite extensive debates on how one should (and shouldn't) treat/manage conditions like CFS (see here).I wanted to highlight the latest Sharpe paper because (a) I anticipated a reply from these authors following the Wilshire paper criticism of their recovery paper [3], and (b) although the debates in this area have been quite extensive already, the use of the scientific peer-reviewed medium to discuss and even argue is an important avenue. The authors have a right to scientific reply.So how did Sharpe et al respond? Well the words 'recovery', 'threshold' and ''no generally agreed measure of recovery" when it comes to CFS form the crux of the response to the Wilshire paper. They address the issue of recovery thresholds that have been a real source of discussion in relation to the PACE trial secondary analysis concluding that: "No participant met our full criteria for recovery at baseline." They point out that whilst "13% of participants met the recovery criterion of being within the normal range... for physical functioning when entering the trial" physical functioning was but one measure they used to determine recovery.They also approach the topic of 'changing thresholds' when it came to the definition of recovery in the PACE trial. To quote: "We changed these thresholds for our detailed analysis plan because after careful consideration and consultation, we concluded that they were simply too stringent to capture clinically meaningful recovery." They also report that elements of their assessment - the PACE walking test - are "not comparable with data collected in other studies" as a function of their reliance on personal motivation/ability over and above the use of encouragement as in other studies.Finally, authors also talk about 'what other studies have found regarding recovery' when it comes to CFS. They note that their findings in relation to the use of standard medical care (SMC) for CFS in the PACE trial were similar to other reports [4]. They also point to research suggesting that the use of CBT in independent study for CFS show similar rates of recovery [5] to theirs originally reported. In other words, they make a case for their findings fitting in with some of the other literature on this topic.A quick trawl of PubMed with the terms 'chronic fatigue syndrome' and 'recovery' reveals that there is indeed quite a bit more to do in this area of science. To quote from one paper (a critical review) [4]: "Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies." What this tells us is that (a) how recovery is reported in relation to CFS is still in need of some clarification [6] and perhaps more importantly, agreed uniformity is still required in its assessment; (b) some of the measures used to form judgements of recovery when it comes to CFS are not necessarily fit for purpose [7] (bearing in mind not everyone agrees with this); and (c) further efforts need to go into looking at many more aspects of CFS recovery outside of just a reliance on the fatigue parameter (see here and see here for examples). In short, science does not really know what recovery looks like in relation to CFS [8] despite it seemingly happening for all manner of reasons...Where do we go from here? This is a difficult question to answer. It is doubtful that the response from Sharpe and colleagues is going to change too many opinions about PACE given the strength of feeling on the topic and the various goings-on that have occurred around debate in this area (see here). Still today, other comments on the PACE trial continue to emerge in the peer-reviewed domain [9] from notable CFS researchers and there are even calls to retract the original recovery paper (see here). Yes, there are lessons to be learned from the PACE trial (e.g. stick to your "original protocol thresholds", make your data 'open-access' and think about how to do this in the planning/recruitment stages of your trial, be mindful that short-term gains don't necessarily translate into long-term ones, work with the ME/CFS community (rather than labelling elements of them 'vexatious' or worse when they ask questions or request data) but I can't see how these factors will immediately and positively affect the lives of people living with CFS/ME here and now. That recommendations on the use of CBT for CFS have already altered in some parts of the world (see here) - "The strength of evidence on global improvement is downgraded from moderate to low when considering CBT separately from other counseling and behavioral interventions" - and are potentially likely to change here in Blighty perhaps signifies that science and medicine is moving on when it comes to this topic. Science should be doubling its efforts to expand its research boundaries when it comes to managing CFS outside of just a reliance on the [outdated?] psychosomatic model and indeed, it is...And on the topic of other CFS research avenues, I've already talked about a few interesting avenues on this blog (see here and see here and see here) mindful that when we talk about CFS/ME, we're probably not talking about just one entity (see here). Also alongside, that there seems to be an awful lot of 'over-represented' comorbidity accompanying quite a lot of CFS/ME (see here for example) to also contend with...Music: Lush Life (even if you don't know the song title, you might rec... Read more »

M Sharpe, T Chalder, AL Johnson, KA Goldsmith, & PD White. (2017) Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments?. Fatigue: Biomedicine, Health , 1-5. info:/10.1080/21641846.2017.1288629

  • March 20, 2017
  • 04:31 PM

Why ear plugs are great for clubbing and concerts

by Richard Kunert in Brain's Idea

I enjoy clubbing and pop/rock concerts exclusively with my ear plugs in. Does that mean I miss out? No, I enjoy the music exactly as it is meant to be. Picture by Melianis at fi.wikipedia (CC BY 2.5) Since 2004 the urban dictionary includes the term ‘deaf rave’ to describe a ‘rave, or party, organised […]... Read more »

Huang J, Gamble D, Sarnlertsophon K, Wang X, & Hsiao S. (2013) Integration of auditory and tactile inputs in musical meter perception. Advances in experimental medicine and biology, 453-61. PMID: 23716252  

Russo FA, Ammirante P, & Fels DI. (2012) Vibrotactile discrimination of musical timbre. Journal of experimental psychology. Human perception and performance, 38(4), 822-6. PMID: 22708743  

Zhao F, Manchaiah VK, French D, & Price SM. (2010) Music exposure and hearing disorders: an overview. International journal of audiology, 49(1), 54-64. PMID: 20001447  

  • March 20, 2017
  • 11:25 AM

Opioids, Benzos and Risk for Overdose

by William Yates, M.D. in Brain Posts

The evolving epidemic of opioid overdose and overdose deaths is receiving increased public and research attention.Opioids overdoses and overdose deaths are often unintentional or accidental. It has been known that concurrent use of opioids with alcohol or benzodiazepines (i.e. Valium or Xanax) increases risk for overdose toxicity.A recent study published in the British Medical Journal confirmed the association of concurrent benzodiazepine prescription with opioid overdose.This research team examined confidential medical database records from over 500,000 patients in the U.S.Those that were enrolled in a medical plan including pharmaceutical benefits between 2001 and 2013 were included in the analysis.The key findings from the study included the following:The percentage of opioid users concurrently using a benzodiazepine rose from 9% of opioid users in 2001 to 17% of opioid users in 2013Chronic users of opioids nearly doubled their risk of opioid overdose if they took a concurrent benzodiazepine medication (4/100 persons/year to 7-8/100 person years)If the association is causal, the authors estimate emergency room visits and inpatient admissions could be reduced by 15% by stopping concurrent prescriptionsThis association of risk seems reasonable given the toxicities of opioids and benzodiazepines. Both at higher doses decrease respiratory drive potentially contributing to hypoxia and death.The authors note several take home messages for clinicians. Chronic users of benzodiazepines should be prescribed opioids cautiously if at all. Opioid prescriptions should be for short periods of time and low doses for chronic benzodiazepine patients.Likewise, if chronic opioids are necessary they should rarely be combined with intermittent or long-term benzodiazepine prescriptions.Readers with more interest in this topic can access the free full-text manuscript by clicking on the PMID link in the citation below.Photo of NCAA men's basketball tournament in Tulsa, OK is from my files.Follow me on Twitter WRY999Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, & Mackey S (2017). Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ (Clinical research ed.), 356 PMID: 28292769... Read more »

  • March 20, 2017
  • 04:13 AM

ALSPAC says no to cat ownership - psychosis risk hypothesis but...

by Paul Whiteley in Questioning Answers

"While pregnant women should continue to avoid handling soiled cat litter, given possible T. gondii exposure, our study strongly indicates that cat ownership in pregnancy or early childhood does not confer an increased risk of later adolescent PEs [psychotic experiences]."So said the findings reported by Francesca Solmi and colleagues [1] (open-access) who brought a smile to any reader of the title of their paper: "Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population cohort." For those who might not be aware of the hypothesis, cat ownership has been previously linked to 'adverse' psychological outcomes (see here) tied into some peer-reviewed evidence on one possible environmental factor linked to psychosis and conditions manifesting psychosis: Toxoplasma gondii.ALSPAC - Avon Longitudinal Study of Parents and Children - brought it's quite significant scientific prowess to bear on the question of whether "cat ownership in pregnancy and childhood (ages 4 and 10 years) was associated with psychotic experiences (PEs) in early (age 13, N = 6705) and late (age 18, N = 4676) adolescence, rated from semi-structured interviews." Having a cat in the house was not the only question asked by Solmi et al as the presence of other pets were also investigated: "dogs, rabbits, rodents, birds (all waves), and tortoises and fish (from 21 months)." PEs were assessed at approximate ages of 13 and 18 years old via responses to the "psychotic-like symptoms interview (PLIKSi), a semi-structured interviewer-rated screening assessment for PEs." Various other variables were also factored into the examination of any effect or not.Results: well, as per the opening sentence to this post, cat ownership did not seem to be related to later PEs. The potential caveat being that in some of their analyses there did seem to be a possible association - "Owning a cat at age 4 years was associated with higher odds of having PEs at age 13 years in univariable models" - but the significance of this association disappeared when adjustments for other potentially confounding variables were made. Obviously this kind of study can't control for every single potentially confounding variable but they did at least try.Why the disparity between these results and the previous ones suggestive of a possible connection between childhood cat ownership and later adverse psychological health? Well, an important point is made by Solmi and colleagues: "Our study was based on PEs in early and late adolescence, unlike other studies which were based on a clinical diagnosis of schizophrenia." In other words. psychotic experiences might be part and parcel of schizophrenia but not necessarily all that schizophrenia encompasses and not necessarily just enough to merit a diagnosis of schizophrenia. They do also go on to highlight how the previous report on the association may also not have included the range of potentially confounding variables that were included and controlled for in the current study as another possibility for the differences reported. Having said that [2]...Does the T. gondii - schizophrenia hypothesis fall as a result of the Solmi results? Probably not. Solmi et al hint that even though cat ownership probably isn't related to PEs, they do not totally debunk the idea that there may be a connection. They did not for example, look for the presence of contact with T. gondii in this particular study (others have) as per serological examination of participants. I say this bearing in mind that not every moggy is necessarily infected with T. gondii or anything else. Sweeping generalisations on all cats are not required.Music to close, and containing the lyric 'Caringosity killed the Kerouac cat', a chirpy little number from a band with quite a contentious name...----------[1] Solmi F. et al. Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population cohort. Psychol Med. 2017 Feb 22:1-9.[2] Fuller Torrey E. et al. The antecedents of psychoses: a case-control study of selected risk factors. Schizophr Res. 2000 Nov 30;46(1):17-23.----------Solmi F, Hayes JF, Lewis G, & Kirkbride JB (2017). Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population cohort. Psychological medicine, 1-9 PMID: 28222824... Read more »

  • March 18, 2017
  • 04:58 AM

HSV-2 gestational infection and offspring autism risk

by Paul Whiteley in Questioning Answers

"In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may contribute to the pathogenesis of autism spectrum disorder and have the potential to drive new efforts to monitor women more closely for cryptic gestational infection and to implement suppressive therapy during pregnancy."That was the conclusion reached in the paper published by Milada Mahic and colleagues [1] including the research tag-team that is Mady Hornig and Ian 'virus hunter' Lipkin in the list of contributing authors. Having already received some media attention (see here), it doesn't need much more from me but I do want to include a few details and relevant points in this blog entry.So, the Autism Birth Cohort was the starting point, and "442 mothers of children with ASD... and 464 frequency-matched controls" who all provided plasma samples "(903 samples acquired at midpregnancy and 878 acquired after delivery)." Said samples were analysed for IgG antibodies to ToRCH agents: "Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), and herpes simplex viruses 1 (HSV-1) and 2 (HSV-2)." Some of those viruses and parasites have previously been mentioned with [some] autism in mind (see here and see here and see here).Results: well, an important detail first: "Because rubella vaccination is part of the routine child vaccination schedule in Norway, almost all individuals had IgG antibodies to rubella virus." Indeed, other authors have speculated that rubella vaccination has actually "prevented substantial numbers" of autism as a knock-on effect of reducing the numbers of cases of congenital rubella syndrome [2]. Vaccination doing more than just saving lives eh?Next: "Our data suggest that the presence of high levels of anti-HSV-2 antibodies at midpregnancy increases the risk of ASD [autism spectrum disorder] in boys." The authors complemented this finding by some rather neat statistical wizardry whereby odds ratios were calculated based on "four different anti-HSV-2 reference levels (60, 120, 180, and 240 arbitrary units [AU]/ml)." Having said that: "High levels of antibodies, which are typically indicative of recent infection, were found in only a small number of subjects." They also reported "no statistically significant association with risk was found with high levels of HSV-2 antibodies at delivery" and saw nothing significant when it came to the other infections examined. These important points have been picked up in the NHS Choices entry on this study (see here).These are interesting findings and, as far as I can see, represent something quite novel to the quite vast autism research landscape (assuming you count maternal HSV-2 levels and not antibody levels in actual people diagnosed with autism). The reliance on data from an initiative like the Autism Birth Cohort ensured some rigour in terms of the diagnosis of autism [3] and with the reputations following Drs Hornig and Lipkin, one would have to be pretty brave to question their virus-hunting credentials also with autism in mind [4].Then to the million-dollar question: how might elevated HSV-2 antibodies during pregnancy affect offspring risk of autism? There is a familiar theme offered by the authors to this question as per statements like: "ASD risk associated with high levels of antibodies to HSV-2 is not specific to HSV-2 but instead reflects the impact of immune activation and inflammation on a vulnerable developing nervous system." I know some people still have a bit of a problem with the idea that something like maternal immune activation (MIA) might up the risk for various offspring outcomes [hint: if an article contains the word 'truth' in the title, step away] but please, stop with the 'it can never happen' generalisations and instead look to the existing peer-reviewed evidence on the topic [5]. Yes, science needs to do more on the topic of MIA and autism but clues are emerging all the time...Oh, and I'll be coming to research talking about another member of the herpesviruses in relation to autism quite soon on this blog.To close, operation hardtack and other videos (best viewed in full-screen mode).----------[1] Mahic M. et al. Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring. mSphere. 2017. Feb 22.[2] Berger BE. et al. Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination - United States, 2001-2010. BMC Public Health. 2011; 11: 340.[3] Stoltenberg C. et al. The Autism Birth Cohort (ABC): A Paradigm For Gene-Environment-Timing Research. Molecular Psychiatry. 2010;15(7):676-680.[4] Hornig M. et al. Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLoS One. 2008 Sep 4;3(9):e3140.[5] Careaga M. et al.  Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry. 2017 Mar 1;81(5):391-401.----------Milada Mahic, Siri Mjaaland, Hege Marie Bøvelstad, Nina Gunnes, Ezra Susser, Michaeline Bresnahan, Anne-Siri Øyen, Bruce Levin, Xiaoyu Che, Deborah Hirtz, Ted Reichborn-Kjennerud, Synnve Schjølberg, Christine Roth, Per Magnus, Camilla Stoltenberg, Pål Surén, Mady Hornig, & W. Ian Lipkin (2017). Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring. mSphere : ... Read more »

Milada Mahic, Siri Mjaaland, Hege Marie Bøvelstad, Nina Gunnes, Ezra Susser, Michaeline Bresnahan, Anne-Siri Øyen, Bruce Levin, Xiaoyu Che, Deborah Hirtz.... (2017) Maternal Immunoreactivity to Herpes Simplex Virus 2 and Risk of Autism Spectrum Disorder in Male Offspring. mSphere. info:/10.1128/mSphere.00016-17

  • March 17, 2017
  • 03:39 AM

Fatty acids and autism meta-analysed yet again (with a different result?)

by Paul Whiteley in Questioning Answers

OK I'm a little confused right now.Not so long ago I talked about the paper from Horvath and colleagues [1] (see here) concluding that "the limited data currently available suggest that ω-3 FA [omega-3 fatty acid] supplementation does not enhance the performance of children with ASD [autism spectrum disorder]." Such a conclusion was based on the application of a systematic review and meta-analysis of the available peer-reviewed literature up to August 2016.Now however, another systematic review and meta-analysis on the topic has emerged from Mazahery and colleagues [2] and reported something a little bit different: "Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms." Don't you just love science!OK, so what could be the reason(s) for the differing conclusions reached by the reviews on this topic? Well, Mazahery and colleagues (the most recent review) actually conducted two meta-analyses: "meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD." Horvath et al only conducted one meta-analysis in their study roughly equivalent to meta-analysis 2 presented by Mazahery looking at the effects of fatty acid supplementation on the presentation of autism. Mazahery and colleagues also surveyed the literature up to May 2016 and found four randomised-controlled trials (RCTs) (N=107) whereas Horvath et al (who published earlier!) surveyed the literature up to August 2016 and found five RCTs (N=183). Indeed, it appears that based on that last 'difference' one might see how the grand 'top of the scientific hierarchy' meta-analysis is yet again, only as good as the data it contains. And a certain celebrity in science circles seems to agree...Where next I hear you ask? Well, I'd be tempted to follow the recommendations of Mazahery and colleagues when they suggest that: "Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA." Indeed, there are already studies to watch in this area. That and recognising that within the vast plurality that is the autisms it is not totally outside the realms of possibility that specific parts of the autism spectrum might be more vulnerable to fatty acid issues than others. Oh, and don't forget that outside of impacting autistic 'performance' (or not), fatty acid supplementation does seem to have other health-related properties too...----------[1] Horvath A. et al. ω-3 Fatty Acid Supplementation Does Not Affect Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis. J Nutr. 2017 Jan 11. pii: jn242354.[2] Mazahery H. et al. Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials. Nutrients. 2017 Feb 19;9(2). pii: E155.----------Mazahery H, Stonehouse W, Delshad M, Kruger MC, Conlon CA, Beck KL, & von Hurst PR (2017). Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials. Nutrients, 9 (2) PMID: 28218722... Read more »

  • March 16, 2017
  • 03:44 AM

Autoimmune disease(s) and ADHD: birds of a feather?

by Paul Whiteley in Questioning Answers

"A personal history and a maternal history of autoimmune disease were associated with an increased risk of ADHD [attention-deficit hyperactivity disorder]. The previously reported association between type 1 diabetes and ADHD was confirmed. In addition, specific parental autoimmune diseases were associated with ADHD in offspring."So said the study results published by Nielsen and colleagues [1] including "a study population of 983,680 individuals followed from 1995 to 2012." Reliant once again on one/some of those marvellous Scandinavian population registries (every country should have them), researchers "investigated the association between a personal history and a family history of autoimmune disease and the risk of developing attention-deficit/hyperactivity disorder (ADHD)." Autoimmune disease refers to the development of symptoms when the body's own immune system fails to recognise 'self' as 'self' and starts attacking its own tissue(s). I might add that the authors on the Neilsen paper have some research history when it comes to the behavioural correlates of autoimmune disease (see here).Drawing on data for around 23,000 children diagnosed with ADHD, researchers reported a modest but significant 'risk' of ADHD being diagnosed where an autoimmune condition was reported. The presence of an autoimmune condition being diagnosed in mums also elevated the risk of offspring being diagnosed with ADHD (again modestly but significantly). Further: "a paternal history of autoimmune diseases was not significantly associated with ADHD in the offspring." Various types of autoimmune disease in the immediate family were potentially associated with offspring ADHD diagnosis: "a family history of thyrotoxicosis, type 1 diabetes, autoimmune hepatitis, psoriasis, and ankylosing spondylitis." This follows other population registry studies in this area [2].Based on the Nielsen and other data, I don't yet think we're in the realm of calling something as diverse as ADHD an autoimmune condition on the basis that autoimmune conditions tend to 'flock together' [3]. But I do think this adds to a growing body of literature talking about immune function and ADHD (see here for example) and some quite 'strong' data (see here). Hopefully without being too speculative, I'd also draw your attention to some interesting work talking about some possible reasons why autoimmunity might be over-represented when it comes to [some] ADHD on the basis of the expression of those fossil viruses that we all have and their 'super-antigen' and 'molecular mimicry' properties. Just one possibility among many...Music: Nana Mouskouri sings Hey Jude...----------[1] Nielsen PR. et al. Associations Between Autoimmune Diseases and Attention-Deficit/Hyperactivity Disorder: A Nationwide Study. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):234-240.e1.[2] Instanes JT. et al. Attention-Deficit/Hyperactivity Disorder in Offspring of Mothers With Inflammatory and Immune System Diseases. Biol Psychiatry. 2017 Mar 1;81(5):452-459.[3] Assa A. et al. Large population study shows that adolescents with celiac disease have an increased risk of multiple autoimmune and non-autoimmune comorbidities. Acta Paediatr. 2017 Mar 1.----------Nielsen PR, Benros ME, & Dalsgaard S (2017). Associations Between Autoimmune Diseases and Attention-Deficit/Hyperactivity Disorder: A Nationwide Study. Journal of the American Academy of Child and Adolescent Psychiatry, 56 (3), 234-2400 PMID: 28219489... Read more »

  • March 15, 2017
  • 12:57 PM

Emotional Intelligence and the Physician

by William Yates, M.D. in Brain Posts

Emotional intelligence (EI) is characterized by the ability to recognize emotional states in self and in others.This emotional recognition may be helpful in guiding behavior and in improving interpersonal relationships.It seems logical on a face validity level to assume that higher levels of EI would be good in the selection of students for medical school.However, there are few studies assessing EI in physicians. There are fewer studies that examine whether EI influences physician behavior, patient satisfaction and ultimately patient outcomes.Rhamzan Shahid and colleagues at the Stritch School of Medicine at Loyola University Medical examined levels of EI in a group of resident physicians in training in the specialties of pediatrics and combined internal medicine-pediatrics.This was a cross-sectional study design that included comparison of residents in the first two years of training versus those in years 3 and 4. The main findings included the following:Residents tended to score high on EI overall with the highest scores on impulse control and the interpersonal composite subscaleResidents scored relatively lower on assertiveness and independence subscalesAssertiveness subscale scores were higher in the more senior residentsEmpathy scores were lower in the the more senior residentsIncreased assertiveness sub-scale scores in more senior residents might be a good thing, possibly indicating a growth in confidence and skill level. This cannot be stated definitely as this study was not longitudinally designed.The lower empathy sub-scale scores in senior residents is an interesting finding. Some might argue it is a negative consequence of training and reflects an increasing disenchantment with being a physician. The authors of the study encourage interventions to "ensure they (resident physicians) do not lose empathy".However, it may be that in a group selected for high empathy, a reduction may also represent a normal maturational process. Maybe high empathy contributes to higher physician distress in the clinical setting and potentially more burnout and depression. Maybe empathy levels that are too high produce emotional states that actually impair physician behavior and reduce effectiveness of clinical decision making.These possibilities should prompt studies correlating EI with patient satisfaction, patient outcome, physician satisfaction with medicine and their specialty and risk for physician burnout.The manuscript reviewed and commented on today is available in free full-text format by clicking on the link in the citation below.Follow me on Twitter @WRY999Photo of the lesser scaup duck is from my personal photography files.Shahid, R., Stirling, J., & Adams, W. (2016). Assessment of Emotional Intelligence in Pediatric and Med-Peds Residents Journal of Contemporary Medical Education, 4 (4) DOI: 10.5455/jcme.20170116015415... Read more »

  • March 15, 2017
  • 04:08 AM

The extra-intestinal effects of coeliac disease autoimmunity?

by Paul Whiteley in Questioning Answers

"In 3.5-year-old children, CDA [coeliac disease autoimmunity] is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child’s CDA status."So said the findings reported by Laura Smith and colleagues [1] (open-access available here) adding to an emerging body of peer-reviewed research suggesting that the archetypal 'gluten is the baddie' autoimmune condition known as coeliac disease might, when not managed, have effects well beyond the classical somatic presentations. Real gut-brain axis stuff in action, as also agreed in an editorial by the 'godfather' of coeliac disease research Prof. Alessio Fasano [2].Smith et al focused on data derived from the TEDDY study (no, really it was called TEDDY), an initiative "looking for the causes of type 1 diabetes mellitus (T1DM)." T1DM is also categorised as an autoimmune condition, where the body's defences fail to recognise 'self' as 'self' and attack it's own tissues. Researchers were able to access biological samples taken as part of the TEDDY study and screen for something called tissue transglutaminase autoantibodies (tTGA), part and parcel of the typical screening protocol for coeliac disease (CD). Where values were "persistently positive" for tTGA, the authors used the term 'celiac disease autoimmunity (CDA)' to illustrate not necessarily a diagnosis of CD but something potentially very close. The Achenbach Child Behavior Checklist (CBCL) was the questionnaire of choice for assessing child "behavioral and emotional functioning" between 3 and 5 years of age.Results: "At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA." The 'unaware' bit refers to the fact that some participants falling into the CDA grouping "were unaware their child was developing CDA" This number (n=66) was quite a bit smaller than the "already aware their child had CDA" grouping (n=440). For those aware of CDA: "The CBCL responses of mothers in the aware-CDA group were not significantly different from those of mothers in the no-CDA group."The authors also looked at whether instigation of a gluten-free diet (the treatment of choice when it comes to coeliac disease) had any effect on those who were already aware of CDA presence. The answer: "No differences were found in CBCL scores for aware-CDA mothers based on whether the child was on a gluten-free diet."These are important findings. As the authors note: "These results support previous studies documenting depression, anxiety, and sleep problems as possible manifestations of celiac disease." They also try and put their results into some context in terms of how "knowledge of the child’s CDA increases a parent’s sensitivity to physical discomforts of their child while providing an alternative explanation for any psychological symptoms the child exhibits." In other words, maybe there is an unwritten rule that young children with coeliac disease might be more prone to behavioural issues? They even go as far as suggesting that: "pediatricians may want to recommend tTGA testing in children <4 years of age with a family history of celiac disease if parents report child psychological symptoms."  More research is definitely indicated and I'll be coming to related studies soon enough...Music, and a catchy track that always seems to be playing outside my dojo (not great for the concentration I might add)...----------[1] Smith LB. et al. Psychological Manifestations of Celiac Disease Autoimmunity in Young Children. Pediatrics. 2017 Feb 20. pii: e20162848.[2] Fasano A. Celiac Disease, Gut-Brain Axis, and Behavior: Cause, Consequence, or Merely Epiphenomenon? Pediatrics. 2017. Feb 20.[3] Butwicka A. et al. Celiac Disease Is Associated with Childhood Psychiatric Disorders: A Population-Based Study. J Pediatr. 2017 Mar 7. pii: S0022-3476(17)30153-1.----------Smith LB, Lynch KF, Kurppa K, Koletzko S, Krischer J, Liu E, Johnson SB, Agardh D, & TEDDY study group. (2017). Psychological Manifestations of Celiac Disease Autoimmunity in Young Children. Pediatrics PMID: 28219962... Read more »

Smith LB, Lynch KF, Kurppa K, Koletzko S, Krischer J, Liu E, Johnson SB, Agardh D, & TEDDY study group. (2017) Psychological Manifestations of Celiac Disease Autoimmunity in Young Children. Pediatrics. PMID: 28219962  

  • March 14, 2017
  • 03:56 AM

Depression in parents of children with autism

by Paul Whiteley in Questioning Answers

"Mothers (OR 2.95, 95% CI 2.81-3.09) and fathers (OR 2.41, 95% CI 2.25-2.58) of children with ASD [autism spectrum disorder] were more likely to have a diagnosis of depression than parents of children without ASD."The paper by Cohrs and Leslie [1] is probably not going to win any awards for novelty when it comes to their findings that: "Autism Spectrum Disorder (ASD) in children can have secondary effects on the child's parents." It does however represent another important piece of evidence pertinent to the idea that 'caring for the carers' should be a mainstay of the support and services offered when a diagnosis of autism is received in the family.I did say in a post not so long ago that I would talk about the Cohrs/Leslie paper and there, I [briefly] have. Added to the body of literature talking about parental stress (and what we can do about it) in the context of autism, resources aplenty should be poured into this area. That and the fact that we already have some clues as to what areas of child rearing might be primary targets for intervention and support....----------[1] Cohrs AC. & Leslie DL. Depression in Parents of Children Diagnosed with Autism Spectrum Disorder: A Claims-Based Analysis. J Autism Dev Disord. 2017 Feb 18.----------Cohrs AC, & Leslie DL (2017). Depression in Parents of Children Diagnosed with Autism Spectrum Disorder: A Claims-Based Analysis. Journal of autism and developmental disorders PMID: 28214978... Read more »

  • March 13, 2017
  • 11:38 AM

Earliest Brain Changes in Alzheimer's Disease

by William Yates, M.D. in Brain Posts

Amyloid brain plaques are well-known pathological changes associated with Alzheimer's disease. Changes preceding amyloid plaque build up are less well studied and understood. Some of this relates to limitations to current imaging technology.Klementieva and colleagues from Sweden and Spain recently published an important reserach topic in this area.Their studied used a rat model of Alzheimer's disease and imaging techniques that included infrared microspectroscopy and gel electrophoresis.The main findings of their study included the following:Conformation changes of beta amyloid and it's amyloid precursor protein (APP) start before the development of amyloid plaquesThe early changes in beta amyloid localize to the synaptic terminalsThese early changes may provide novel targets for drug developmentThese findings suggest current strategies to alter beta amyloid plaques after development may be too late to alter the course of the disease.Identification and reversal of earlier mechanisms may be a more productive drug development strategy.Readers with more interest in this topic can access the free full-text manuscript by clicking on the citation link below.Follow be on Twitter WRY999Photo of robin in back yard waterer is from my photography files.Klementieva, O., Willén, K., Martinsson, I., Israelsson, B., Engdahl, A., Cladera, J., Uvdal, P., & Gouras, G. (2017). Pre-plaque conformational changes in Alzheimer’s disease-linked Aβ and APP Nature Communications, 8 DOI: 10.1038/ncomms14726... Read more »

Klementieva, O., Willén, K., Martinsson, I., Israelsson, B., Engdahl, A., Cladera, J., Uvdal, P., & Gouras, G. (2017) Pre-plaque conformational changes in Alzheimer’s disease-linked Aβ and APP. Nature Communications, 14726. DOI: 10.1038/ncomms14726  

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