Paul Whiteley

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Autism research, research blogging and health science stuff (picture is accurate)

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  • February 23, 2017
  • 02:59 AM
  • 33 views

"Autoimmune epilepsy is an underrecognized condition..."

by Paul Whiteley in Questioning Answers

"Among adult patients with epilepsy of unknown etiology, a significant minority had detectable serum Abs [autoantibodies] suggesting an autoimmune etiology."So said the findings reported by Divyanshu Dubey and colleagues [1] continuing a research theme previously discussed on this blog (see here) on how epilepsy / seizure-type disorder(s) for some might have more to do with immune function than many people might think.OK, a brief bit of background: epilepsy is a blanket term covering a wide variety of different presentations that affect the brain and specifically, 'the electrics' of the brain. Seizures are the most common symptom. Treatment typically comes in the form of anti-epileptic medicines (although other options are being considered for some). It's been known for a while that outside of the 'brain' focus of epilepsy, other biological systems might also play a role in the development/maintenance of the condition(s); specifically the immune system and quite often in cases where traditional anti-epileptic medicines don't seem to be able to control seizures effectively. The details are still a little sketchy but studies like the one from Dubey et al are trying to put some scientific flesh on to the bones of what facets of the immune system are potentially involved, specifically under 'autoimmune' conditions where the body fails to recognise 'self' as self and mounts an immune response against the body's own tissue(s).Dubey and colleagues looked at a group of participants "presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology" and tested donated serum samples "for Abs reported to be associated with autoimmune epilepsy (NMDAR-Ab, VGKCc-Ab, leucine-rich glioma-inactivated protein 1 [LGI1] Ab, GAD65-Ab, γ-aminobutyric acid type B receptor [GABAB] Ab, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor [AMPAR] Ab, antineuronal nuclear antibody type 1 [ANNA-1 or anti-Hu] Ab, Purkinje cell cytoplasmic antibody type 2 [PCA-2] Ab, amphiphysin Ab, collapsin-response mediator protein 5 [CRMP-5] Ab, and thyroperoxidase [TPO] Ab)." Quite a lot of those autoantibodies probably sound like gibberish to the lay reader but some of them have been discussed in other contexts on this blog (see here and see here for examples).Results: some (15) of the 127 participants initially enrolled in the study were "subsequently excluded after identification of an alternative diagnosis." This in itself is interesting, as diagnoses such as "hypoxic or anoxic injury following cardiac arrest" and "ischemic stroke" are mentioned, illustrating how several different roads can lead to epilepsy and/or the presentation of seizures.Then: "Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases." Over a third of the cohort showed serological evidence of autoantibodies and some presented with more than one type of autoantibody as being present. Breaking down those serologically positive participants, we are told that: "19 patients (48.7%) had new-onset epilepsy and 20 patients (51.3%) had established epilepsy." The authors did also subsequently limit their findings to those cases excluding TPO-Ab and low-titer GAD65-Ab (autoantibodies where a specific role to epilepsy is unclear or not specific) but even then reported that: "23 patients (20.5%) with unexplained epilepsy had positive serologic findings strongly suggestive of an autoimmune cause of epilepsy." There is also a final part to the Dubey paper which also merits mention: "Among the 23 patients who were seropositive, 15 (65.2%) received some sort of immunotherapy. Better seizure outcome was associated with use of immunomodulatory therapy... especially with use of intravenous methylprednisolone... or plasmapheresis."Alongside other (independent) studies in this area, the peer-reviewed evidence does seem to growing to suggest that within the wide (and heterogeneous) 'spectrum' that is epilepsy, at least some of that epilepsy might have an important immune component to it. To quote again from Dubey: "The data presented here suggest that autoimmune encephalitis may explain at least 20% of adult-onset epilepsies of unknown etiology." Aside from the importance of screening for said autoantibodies when certain cases of epilepsy appear at clinic, there are a few other potentially important points that could be raised about such data. Autism is area that I would be interested to see some further investigations carried out on with the Dubey findings in mind. Epilepsy is an important comorbidity 'over-represented' when it comes to autism (see here) and given the suggestions down the years that immune function (specifically autoimmunity) might be a facet of 'some' autism (see here for example) it's not beyond the realms of possibility that comorbid epilepsy might be a further facet of any autoimmune processes. Birds of an autoimmune feather tend to stick together and all that (see here). Add in the findings specifically talking about 'anti-NMDA-receptor encephalitis "mimicking an autistic regression"' (see here) and how methlyprednisolone might not be an uncommon medicine for some types of (autoimmune-related autistic presentation) and the hypotheses to be tested are laid out in front of you. By saying that, I don't want to take anything away from the more typical forms of epilepsy that can present (either alone or alongside autism) but rather point to the expanding knowledge base suggesting that immune functions may extend much further than just protecting the host from infection et al...To close, slightly related to some of the content included in this post, the trailer for the film Brain on Fire (from the book of the same name) is out and looking like required viewing.----------[1] Dubey D. et al. Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology. JAMA Neurol. 2017 Feb 6.----------Dubey D, Alqallaf A, Hays R, Freeman M, Chen K, Ding K, Agostini M, & Vernino S (2017). Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology. JAMA neurology PMID: 28166327... Read more »

Dubey D, Alqallaf A, Hays R, Freeman M, Chen K, Ding K, Agostini M, & Vernino S. (2017) Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology. JAMA neurology. PMID: 28166327  

  • February 22, 2017
  • 04:20 AM
  • 54 views

History of bipolar disorder = elevated risk of dementia: is vitamin D important?

by Paul Whiteley in Questioning Answers

"History of BD [bipolar disorder] is associated with significantly higher risk of dementia in older adults."So said the systematic review and meta-analysis published by Breno Diniz and colleagues [1] taking in the accumulated peer-reviewed literature on this topic. Including data for some 3000 individuals diagnosed with bipolar disorder and nearly 200,000 controls (without bipolar disorder), authors calculated something of a significantly higher risk of dementia in those with a documented history of bipolar disorder. They note that there is more research to do in this area, specifically on mechanisms and "to evaluate interventions that may reduce the risk of dementia in this population."Outside of the literature included in the Diniz study, similar findings have been reported in the science literature. The paper by Almeida and colleagues [2] noted that: "Bipolar disorder in later life is associated with increased risk of dementia" based on their analysis of ~38,000 older men (65-85 years old) and their "13-year risk of dementia." Perhaps more worryingly were their findings that: "Bipolar disorder was also associated with increased mortality" in relation to "death by suicide, accidents, pneumonia or influenza, and diseases of the liver and digestive system." Other data looking more generally at clinical depression paints a similar picture [3] suggesting something of a connection between various types of depression and risk of various types of dementia: "depressive symptomatology is associated with pathological mechanisms associated with neurodegeneration."I've tackled the topic of dementia a couple of times on this blog; most recently in relation to how incidental vitamin D deficiency *could be* something important when it comes to at least some cases of dementia (see here). Minus any sweeping generalisations and accepting that there may be many different roads leading to dementia and/or bipolar disorder, I am intrigued at the possibility that the sunshine vitamin might be something to consider as a 'connector' between elements of the depression and dementia spectrums as per other findings (see here for example). At the very least, it invites lots more targeted investigation, including whether vitamin D might indeed be a nootropic of choice for some (see here)...----------[1] Diniz BS. et al. History of Bipolar Disorder and the Risk of Dementia: A Systematic Review and Meta-Analysis. The American Journal of Geriatric Psychiatry. 2017. Jan 4.[2] Almeida OP. et al. Risk of dementia and death in community-dwelling older men with bipolar disorder. Br J Psychiatry. 2016 Aug;209(2):121-6.[3] Cherbuin N. et al. Dementia risk estimates associated with measures of depression: a systematic review and meta-analysis. BMJ Open. 2015 Dec 21;5(12):e008853.----------Diniz BS, Teixeira AL, Cao F, Gildengers A, Soares JC, Butters MA, & Reynolds CF 3rd (2017). History of Bipolar Disorder and the Risk of Dementia: A Systematic Review and Meta-Analysis. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry PMID: 28161155... Read more »

Diniz BS, Teixeira AL, Cao F, Gildengers A, Soares JC, Butters MA, & Reynolds CF 3rd. (2017) History of Bipolar Disorder and the Risk of Dementia: A Systematic Review and Meta-Analysis. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. PMID: 28161155  

  • February 21, 2017
  • 03:39 AM
  • 67 views

Neuropsychiatric disorder onset "temporally related to prior vaccinations"?

by Paul Whiteley in Questioning Answers

"Given the modest magnitude of these findings in contrast to the clear public health benefits of the timely administration of vaccines in preventing mortality and morbidity in childhood infectious diseases, we encourage families to maintain vaccination schedules according to CDC guidelines."The quote opening this post comes from the paper published by Douglas Leslie and colleagues [1] (open-access) and offers not a conclusion from their study looking at the possibility that "the onset of some neuropsychiatric disorders may be temporally related to prior vaccinations in a subset of individuals" but a caution that cause-and-effect were not 'proven' in their study. Anyone with any knowledge about previous occasions where administration of vaccines have been correlated with specific psychiatric or behavioural outcomes (see here and see here for examples) will recognise how important such a caution is, bearing in mind that vaccines are medicines (albeit preventative) and are subject to similar monitoring for safety and the small possibility of adverse effects as other medicines.Based on the examination of "the MarketScan® Commercial Claims and Encounters database", a US drug and medical insurance claims database, researchers looked at various diagnoses of interest including OCD (obsessive compulsive disorder), AN (anorexia nervosa), anxiety disorder, tic disorder, major depression, bipolar disorder and ADHD (attention-deficit hyperactivity disorder) in children/young adults aged 6-15 years old. This alongside several other classes of diagnosis including broken bones and 'open wounds'. Participants were matched one-to-one with controls without said neuropsychiatric diagnoses and exposure(s) to various vaccinations - "influenza, tetanus and diphtheria (TD), hepatitis A, hepatitis B, meningitis, and varicella" - were 'tracked'. Interestingly, this is not the lead authors' first foray into using the MarketScan database [2], where autism was the previous topic of analysis (specifically healthcare service use and costs).Results: bearing in mind that samples sizes varied according to those diagnoses under investigation, the authors report: "Receipt of any vaccine in the previous 6 months was highest for children with AN (21.4%), followed by OCD (15.9%) and tic disorder (15.8%), and was lowest for children with open wounds (10.3%)." This information needs to be treated carefully because - again - it tells us nothing about any cause-and-effect relationship, just correlation and trend; trends that could be there for all-manner of different reasons outside of the variables looked at. Further: "HRs [hazard ratio] associated with receipt of any vaccine were highest for children with AN... followed by OCD."The authors also looked at specific vaccinations in relation to those neuropsychiatric disorders included in their study. They report: "Influenza vaccinations during the prior 3, 6, and 12 months were... associated with incident diagnoses of AN, OCD, and an anxiety disorder." Conversely: "children with major depression were less likely to have received the influenza vaccine in the previous 3 months" and "children with bipolar disorder were also less likely to have received the influenza vaccine in the previous 3 or 6 months."OK, it is worth reiterating - yet again - that this was a study looking at possible associations and not necessarily cause-and-effect. Indeed, judging by that last paragraph and the table of HRs produced by the authors (see here) one might easily claim that flu vaccination might potentially shield someone from developing major depression as much as 'cause' AN, OCD and/or anxiety disorder. Such is the nature of such studies and the findings being reported. And indeed someone has actually looked at depressive symptoms (symptoms that is, not depression as a clinical diagnosis) before and after an influenza vaccination and found very little...I note that with specific regard to the influenza vaccine and the findings that "children with AN, OCD, or a tic disorder were more likely to have received the influenza vaccine in the preceding periods" the authors head into the research talking about narcolepsy and the "AS03-adjuvanted H1N1 vaccine" as a possible template for their findings. This despite not covering the diagnosis of narcolepsy in their study (they could have). I've touched upon this area of research before on this blog (see here) (something that continues to appear in media discussions) and whilst not disputing the findings, do for example, wonder why in the work of Szakács and colleagues [3] ADHD was picked up as a comorbidity present in their "post-H1N1 vaccination (PHV) narcolepsy group" but in the Leslie data the HRs showed little evidence of any relationship. Yes, H1N1 vaccination is not necessarily the same as influenza vaccination reported in the Leslie data (we don't actually know what specific influenza vaccines were administered), but surely if discussions turn to an 'autoimmune' element as a possible mechanistic feature potentially linking vaccination and [some] neuropsychiatric disorder(s), one would expect to see the same/similar pattern of conditions being represented and reported? For balance, I should also point out that other independent study has talked about eating disorders potentially having "immune-mediated mechanisms" connected, particularly those associated with autoimmunity [4] although I don't doubt such a connection is likely complicated and probably not universally applicable.It's not difficult to find issues with the Leslie paper and no doubt these will be emphasised in any further discussions about the data reported even when the authors stress throughout that "findings do not demonstrate a causal role of vaccination in the pathoetiology of any of these conditions." The strengths of the data - e.g. the use of that administrative database for confirming diagnoses and vaccine exposure - are worth mentioning again in light of other debates on data sources from other 'disappearing' manuscripts in this area. I might also add that by focusing in on various diagnoses but not autism (which again, they could have done) and not a certain vaccine, the authors seem well aware of the history in this area - "the association of the measles, mumps, and rubella vaccine with autism spectrum disorder has been convincingly disproven" - and probably either thought nothing more of it or chose to steer well clear of it (or perhaps a combination of both).Is there a 'where next' when it comes to the Leslie data? To quote again from the paper: "findings require replication in a larger population-based sample, possibly including assessments of various potentially important host factors, e.g., the individual’s ... Read more »

  • February 20, 2017
  • 04:33 AM
  • 79 views

Catatonic symptoms and autism

by Paul Whiteley in Questioning Answers

"Catatonic symptoms are more prevalent in young people with autism than previously thought" said the article recently published by Breen and Hare [1]. Continuing a research theme of at least one of the authors [2], the idea that catatonic symptoms - primarily manifesting as stupor, unresponsiveness to light, noise or touch, mutism, etc - might be over-represented when it comes to autism is not a new one by any means.Breen & Hare set about looking for "the presence and nature of such attenuated behaviours in children and adolescents with autism" based on something called the Attenuated Behaviour Questionnaire. This was delivered to parents/caregivers online alongside looking at information from other measures based on the presence of repetitive behaviour and depression."Attenuated behaviour indicative of catatonia was relatively common in young people with autism with up to 20.2% having an existing diagnosis of catatonia and evidence of a relationship between attenuated behaviours and measures of depression and repetitive and restricted behaviours." Such findings as I said, are by no means novel but once again highlight how a diagnosis of autism or autism spectrum disorder (ASD) is seemingly protective of nothing when it comes to comorbidity. To quote another author on this topic: "an unabashed drumroll for increased recognition and treatment of catatonia in autism spectrum disorders (ASD)" [3] is needed.Catatonia appearing alongside [some] autism leads into a number of areas in relation to the 'closeness' of any relationship (some people have talked about 'autistic catatonia') and the management strategies that may be subsequently indicated. On the issue of management, guidance is available [4] albeit including a strategy - electroconvulsive therapy (ECT) - that is probably not going to win any awards in terms of popularity given its historical basis. Accepting that still today ECT as an 'intervention' option when it comes to autism still courts heated discussion (see here), there is the requirement for much greater study of catatonic symptoms in relation to autism and whether there may be several presentations ripe for more novel intervention [5] (in light of a growing area of research interest). Said intervention might also take into account the plurality of autism too (see here)...To close, yet another song for my brood and a very proud father who saw some real talent in the karate competition yesterday (those first place trophies are proof that team kata and team kumite are definitely the way forward)...----------[1] Breen J. & Hare DJ. The nature and prevalence of catatonic symptoms in young people with autism. J Intellect Disabil Res. 2017 Feb 1.[2] Hare DJ. & Malone C. Catatonia and Autistic Spectrum Disorders. Autism. 2004; 8: 183-195.[3] Dhossche DM. Decalogue of Catatonia in Autism Spectrum Disorders. Frontiers in Psychiatry. 2014;5:157.[4] Mazzone L. et al. Catatonia in patients with autism: prevalence and management. CNS Drugs. 2014 Mar;28(3):205-15.[5] Kiani R. et al. Anti-NMDA-receptor encephalitis presenting with catatonia and neuroleptic malignant syndrome in patients with intellectual disability and autism. BJPsych Bull. 2015 Feb;39(1):32-5.----------Breen J, & Hare DJ (2017). The nature and prevalence of catatonic symptoms in young people with autism. Journal of intellectual disability research : JIDR PMID: 28150394... Read more »

  • February 18, 2017
  • 04:30 AM
  • 135 views

Social interaction and autism: it takes two to tango

by Paul Whiteley in Questioning Answers

Psychology experiments are not generally fodder for this blog when it comes to autism. The main reason being that quite a few appearing in the peer-reviewed literature tend to look at quite abstract features perhaps somewhat removed from the daily lives of autistic people and their significant others. A few also seem to struggle with the idea that grand over-arching psychological theories (that seem to inevitably follow psychological findings in particular) are not required when it comes to autism in these days of heterogeneity and plurality.I am making an exception today however with the paper by Noah Sasson and colleagues [1] (open-access) and their findings suggesting advocating "for a broader perspective of social difficulties in ASD [autism spectrum disorder] that considers both the individual’s impairments and the biases of potential social partners." In other words, it takes two to [socially, interactively] tango. I might add that a doctoral thesis by one of the co-authors on the Sasson paper (Daniel Faso) is also available for further inspection too (see here).Based on the idea that issues with social interaction "quantity and quality" might not be something exclusively under the control of those diagnosed with autism, Sasson et al devised a series of experiments to test their hypothesis: "three studies conceived and conducted independently by three research groups assessing observers’ first impressions of—and intentions to socially engage with— children and adults with ASD based upon “thin slices” of their real-world social behavior." I'm not going to go into too much detail about the experiments because the paper is open-access and you can read about them for yourselves. 'Thin slices' in the context of the experiments carried out referred to media that were rated pertinent to "observers’ first impressions of individuals with ASD engaging in real-world social behavior."The results make for some important reading as across the different experiments undertaken the key messages were that: "first impressions of individuals with ASD are significantly less favorable than those of matched TD [typically developing] controls, and are associated with greater reluctance on the part of observers to pursue social engagement." Further: "social interaction difficulties in ASD are not solely an individual impairment but also a relational one, and consideration of both of these factors is necessary for a full understanding of social impairment in ASD." I relay all of that bearing in mind that these were experiments carried out under controlled conditions (I don't know about you, but I don't generally rate people at first contact using a "0-3" Likert scale or a "non-graduated slider" on 'how approachable' they were or the likelihood of a friendship developing).Although important, I don't think anyone should be too surprised by the results reported in the context of how first impressions count and how people are generally quick to judge from "personality and character traits" whether social engagement with a person or group of people is going to be a short or longer-term thing. I say this also bearing in mind that minus any psychobabble, people generally take into account things like context, familiarity and similarity when it comes to their social interaction decisions too [if for example, you happen to be a fan of Star Wars or a Shotokan karateka, I might be more inclined to chat with you than say if you talked about the goings-on on various reality TV shows]. Indeed, the authors note: "these studies present only group-wise comparisons and do not address individual differences among those with ASD, nor whether individual characteristics of the raters (e.g., gender, personality, etc.) affect the results reported here." I'd also forward the idea that they might also include important concepts such as self-monitoring for example when it comes to future studies in this area. Similarly, it would also be handy to see if 'comorbidity counts' when it comes to further investigations on this topic in light of expanding links between different labels and traits (see here).The question of what to do about the Sasson findings similarly provide some food for thought. The authors suggest that: "intervention and education approaches that target both those with ASD as well as their TD [typically developing] peers may offer a more comprehensive approach for improving social and functional outcomes in autism." In the context of other studies looking at social interaction and autism particularly in the school setting (see here) I can see how this might work in terms of raising awareness of how people are not always the same when it comes to the presentation of their social persona. Intervening with a wider group (i.e. peers) and taking the onus off 'just the person with autism' is a win-win situation and will no doubt have other positive knock-on effects in terms of self-esteem and helping to remove barriers around the 'disability' framing of autism. I might add that in these days of the potential virality of personality traits, it makes sense to include everyone.In a wider context - outside of school - and in the big, wide [adult] world however, I'm slightly less sure of how such intervention is going to be achieved. Yes, we would all love people to be more understanding and less 'judgemental' in their first (and subsequent) impressions, but when it comes to influencing aspects such as views on "awkwardness, attractiveness, [and] likability" I'm not so sure that this can be universally achieved. Indeed, facets such as attractiveness and likability are probably going to be influenced by lots of variables outside of those just linked to an autism diagnosis and its presentation (frank or not). By saying all that, I'm not suggesting that we shouldn't try to educate and perhaps even move people away from the whole 'first impressions last' [2] thing, but rather am looking at the realistic prospect of achieving such a societal goal, mindful that it takes two to tango...And on the topic of first impressions, at least get the handshake right (i.e. let go)...----------[1] Sasson NJ. et al. Neurotypical Peers are Less Willing to Interact with Those with Autism based on Thin Slice Judgments. Sci Rep. 2017 Feb 1;7:40700.[2] Gunaydin G. et al. Impressions Based on a Portrait Predict, 1-Month Later, Impressions Following a Live Interaction. Social Psychological and Personality Science. 2017. 8: 36-44.----------Sasson NJ, Faso DJ, Nugent J, Lovell S, Kennedy DP, & Grossman RB (2017). Neurotypical Peers are Less Willing to Interact with Those with Autism based on Thin Slice Judgments. Scientific reports, 7 PMID: 28145411... Read more »

  • February 17, 2017
  • 03:16 AM
  • 143 views

Vitamin D halting colds and flu?

by Paul Whiteley in Questioning Answers

"Overall, the study said one person would be spared infection for every 33 taking vitamin D supplements. That is more effective than flu vaccination, which needs to treat 40 to prevent one case, although flu is far more serious than the common cold."That was some of the media interpretation of the paper - "systematic review and meta-analysis of individual participant data" - published by Adrian Martineau and colleagues [1] looking at the collected data on vitamin D supplementation "on risk of acute respiratory tract infection." Including data on approximately 11,000 'randomised' participants reported in 25 studies, authors assessed whether the quite messy data on vitamin d supplementation potentially decreasing the risk of acute respiratory tract infection showed any semi-definitive trends.Results: "Vitamin D supplementation resulted in a statistically significant reduction in the proportion of participants experiencing at least one acute respiratory tract infection." Further: "Use of vitamin D did not influence risk of serious adverse events of any cause... or death due to any cause. Instances of potential adverse reactions to vitamin D were rare." And finally: "Subgroup analysis revealed that daily or weekly vitamin D supplementation without additional bolus doses protected against acute respiratory tract infection, whereas regimens containing large bolus doses did not."I note that in the BBC news report on the Martineau paper we are told: "Public Health England (PHE) says the infections data is not conclusive, although it does recommend supplements." This slightly counter-intuitive position follows more general advice from the powers-that-be that perhaps we should all be taking a little more vitamin D (see here) given what is emerging when it comes to the varied functions of the sunshine vitamin/hormone. But bear in mind that supplementation comes with potential risks too (see here) particularly when people forget to treat their vitamins and minerals as what they are: biologically active pharmaceutics. Neither is everyone completely sold on the idea that vitamin D 'could stop colds or flu' as an accompanying editorial to the Martineau paper makes clear [2]: "The results are heterogeneous and not sufficiently applicable to the general population."What such research does advance however, is that vitamin D is a potentially important nutrient (more so for some groups) and one that we should be [cautiously] dedicating a lot more investigation to for all-manner of possible reasons (see here and see here) outside of just bone health and the English disease. And within that scheme of research, don't forget a few things: (a) there's more to vitamin D metabolism than just 'getting enough' and (b) even today, science is still finding out new things about the chemistry of vitamin D [3]. In short, the scheme of science around vitamin D needs to be broad...----------[1] Martineau AR. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583.[2] Bolland MJ. & Avenell A. Do vitamin D supplements help prevent respiratory tract infections? BMJ 2017; 356: j456.[3] Pauwels S. et al. 1β,25-Dihydroxyvitamin D3: A new vitamin D metabolite in human serum. J Steroid Biochem Mol Biol. 2017 Feb 10. pii: S0960-0760(17)30040-7.----------Adrian R Martineau, David A Jolliffe, Richard L Hooper, Lauren Greenberg, John F Aloia, Peter Bergman, Gal Dubnov-Raz, Susanna Esposito, & et al (2017). Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ : 10.1136/bmj.i6583... Read more »

Adrian R Martineau, David A Jolliffe, Richard L Hooper, Lauren Greenberg, John F Aloia, Peter Bergman, Gal Dubnov-Raz, Susanna Esposito, & et al. (2017) Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. info:/10.1136/bmj.i6583

  • February 16, 2017
  • 03:14 AM
  • 157 views

"early medical events are associated with clinical ASD phenotypes"

by Paul Whiteley in Questioning Answers

The paper by Charlotte Willfors and colleagues [1] (open-access) provides some food for thought today and the observation that various individual and cumulative medical events - "early medical events likely to be caused by environmental factors" - may be important to at least some autism.Researchers "scrutinized the early medical histories of a rare and informative sample of 13 MZ [monozygotic] twin pairs discordant for clinical ASD [autism spectrum disorder]" also including "13 MZ typically developing (TD) control pairs (n=52) matched for sex" as an 'exploratory step. Discordant for autism means that one twin had autism and the other did not.This research first step looked at medical events (likely to be caused by environmental factors!) included things like delivery and neonatal variables (e.g. foetal distress, hypoxia), minor and frequent infections (e.g. ear infections), allergy and epilepsy to name a few. Data was acquired from a few sources including medical records and medical history "assessed from a parent reported questionnaire." They examined exposure to the medical events "in relation to either quantitative or qualitative discordance for ASD." Qualitative discordance referred to when "only one twin within a pair meeting the diagnostic criteria of ASD." A 'confirmatory' study was also carried out whereby a larger, independent cohort of 100 twin pairs "quantitatively discordant for autistic traits" were also quizzed and findings cross-validated.Results: a few non-shared environmental (NSE) events seemed to be important based on their analysis. So: "Single early medical factors, likely to be caused by NSE, that discriminated between twins in qualitative ASD discordant pairs were dysregulation during the first year of life (comprising feeding and sleeping problems, excessive crying and worrying) and birth weight." Authors also reported that cumulatively, the appearance of early medical events were significantly different in MZ twins with autism compared with their non-ASD co-twin. It's worth mentioning that some of those 'dysregulation' events have been talked about in the earliest descriptions of autism (see here). Birth weight too has something of a long-standing connection to [some] autism (see here). When it came to analysis based on autistic traits (the confirmatory study) it seemed that "early dysregulation and the cumulative load of a variety of early adverse medical events" continued to be important variables (although birth weight linked to ASD traits lost its significance).These are important findings. The focus on MZ twins (who share a common structural genetic blueprint) means that the genetics side of things is to a large extent 'controlled for' and the results are more likely to reflect some environmental or, more accurately, non-genetic influence. There is a caveat to this though, as per the authors recognition: "with the exception of putative post-twinning de novo mutations." I might also add that MZ twins are also not necessarily epigenetically the same too so gene expression can (and does) differ. What causes these epigenetic differences is still the source of some debate but I might chime in with one idea (see here) out of many possibilities."Our data indicate that taking into account the cumulative load of early medical factors might strengthen or discourage a suspicion of ASD, at least in a minority of cases." This is an interesting thought provided by the authors based on their findings. It ties in well with the idea that although behavioural presentation is core to autism presentation and diagnosis, behaviour might not be the only important feature present in relation to autism. I do have to express a degree of caution however with such an approach based on the idea that various types of regression have been noted in the peer-reviewed literature to accompany some autism (see here) and with it, the concept of 'acquired autism' should really be properly recognised (see here for example) in these days of the plural 'autisms'. Indeed, there's a research study idea for anyone out there: looking at MZ twins discordant for autism with onset of said autism tied into a regression of skills?Scientific replication is the name of the [future] game in this area of study, drawing on larger cohorts and perhaps based in other geographical areas outside of Sweden. We also need to find out what mechanisms might be potentially associating something like 'early dysregulation' with the onset of autism, taking into account how factors such as early feeding practices/issues for example, might provide at least one avenue for future study (see here).To close, in light of some recent media headlines about the 'myth' that autism rates are on the up (and quite significantly so over past two decades), I offer some past posts suggesting that the word 'myth' should be reserved for other [non-peer-reviewed] matters (see here and see here and see here) and not this particular branch of epidemiological science. As to what may be 'causing' the upswing in numbers of diagnosed cases, well, it's likely to be very, very, very complicated (and without any need for sweeping generalisations please)...----------[1] Willfors C. et al. Medical history of discordant twins and environmental etiologies of autism. Transl Psychiatry. 2017 Jan 31;7(1):e1014.----------Willfors C, Carlsson T, Anderlid BM, Nordgren A, Kostrzewa E, Berggren S, Ronald A, Kuja-Halkola R, Tammimies K, & Bölte S (2017). Medical history of discordant twins and environmental etiologies of autism. Translational psychiatry, 7 (1) PMID: 28140403... Read more »

Willfors C, Carlsson T, Anderlid BM, Nordgren A, Kostrzewa E, Berggren S, Ronald A, Kuja-Halkola R, Tammimies K, & Bölte S. (2017) Medical history of discordant twins and environmental etiologies of autism. Translational psychiatry, 7(1). PMID: 28140403  

  • February 15, 2017
  • 04:30 AM
  • 142 views

"Androgens were not associated with autistic traits at 12 months of age"

by Paul Whiteley in Questioning Answers

EARLI - the Early Autism Risk Longitudinal Investigation study - has been mentioned on this blog before (see here) with the aim of the initiative to "examine possible environmental risk factors for autism and study whether there is any interplay between environmental factors and genetic susceptibility."In this post I'm bringing the paper by Bo Park and colleagues [1] (open-access) to your attention and the observation(s) that umbilical cord blood levels of testosterone and other related androgens were seemingly not associated with autistic traits at 12 and 36 months of age in their cohort. Such findings represent yet another biological research blow (see here) to facets of the Extreme Male Brain (EMB) theory of autism and the suggestion that "ASD [autism spectrum disorder] is an extreme presentation of a typical male cognitive profile where the drive to “systemize” is stronger than the drive to empathize."So, looking at cord blood samples from 137 children recruited on to EARLI - "a high autism-risk cohort following pregnant mothers with an older child diagnosed with an ASD (autistic disorder, Asperger syndrome, or pervasive developmental disorder not otherwise specified)" - researchers looked at whether measures of various androgens might correlate with scores on the Autism Observation Scales for Infants (AOSI) and Social Responsiveness Scale (SRS). Said schedules were administered at 12 months and 36 months respectively and various potentially confounding variables were taken into account when it came to looking at any associations. It's also worth pointing out that the technology of choice when it came to those measures of cord blood levels of androgens was an old favourite of this blog: liquid chromatography-tandem mass spectrometry (LC-MS/MS).Results: well as per the title of this post, and after adjustment for potentially confounding variables - "maternal age, gestational age, and cesarean delivery" - there wasn't a great deal to see in terms of levels of androgens and the presence of autistic traits. Indeed, the title of this post only tells half the story as testosterone was also found not to be associated with the SRS scores at 36 months too. The authors do note that: "Male infants (n=75) showed significantly higher umbilical cord testosterone levels and greater social deficits at 36 months of age" than females, but after adjustment for confounders this observation was left wanting. They also talk about some interesting observations about when a child had an older female sibling diagnosed with autism - "androgen levels and autistic traits may depend on sex of the older affected sibling" - but I'm not so sure about the strength of such findings and whether other mechanisms might also be at work. I might reiterate that autistic traits were the name of the research game in this study not a diagnosis of autism.As mentioned, the Park findings represent another setback for the generalisability of the role of androgens (prenatal and beyond) in relation to autism and/or autistic traits. I guess that in these days of the plural 'autisms' (see here) it's perhaps not entirely unexpected that grand theories of autism seem doomed to fail when put up to scientific scrutiny. Indeed someone recently has talked about this [2]. I still however remain interested in the discussions around the EMB theory of autism, and although this and other research has not been entirely kind to the hypothesis, it is still perhaps deserving of further study in order to see who it may be most relevant to in these days of plural autisms and subgroupings...To close, isn't this why Twitter was invented?----------[1] Park BY. et al. Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study. Molecular Autism. 2017; 8: 3.[2] Müller R-A. & Amaral DG. Editorial: Time to give up on Autism Spectrum Disorder? Autism Res. 2017. Jan 27.----------Park, B., Lee, B., Burstyn, I., Tabb, L., Keelan, J., Whitehouse, A., Croen, L., Fallin, M., Hertz-Picciotto, I., Montgomery, O., & Newschaffer, C. (2017). Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Molecular Autism, 8 (1) DOI: 10.1186/s13229-017-0118-z... Read more »

Park, B., Lee, B., Burstyn, I., Tabb, L., Keelan, J., Whitehouse, A., Croen, L., Fallin, M., Hertz-Picciotto, I., Montgomery, O.... (2017) Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study. Molecular Autism, 8(1). DOI: 10.1186/s13229-017-0118-z  

  • February 14, 2017
  • 03:27 AM
  • 142 views

Relative age and ADHD medication

by Paul Whiteley in Questioning Answers

"Youngest children in class 'more likely to be given ADHD drugs'" went the NHS Choices headline that led me to the short report produced by Martin Whitely and colleagues [1] (open-access).ADHD - attention-deficit hyperactivity disorder - is something of interest to this blog; not least the idea that relative age (age relative to peers in the same school year group) might be an important variable when it comes to at least some diagnoses of the condition (see here).The Whitely paper draws on data from a research favourite place - Western Australia (WA) - and focused on "the proportions of WA children born in the early and late months of a recommended school-year intake who received at least one Pharmaceutical Benefits Scheme [PBS] prescription for an ADHD medication in 2013."The results: from a starting population of some 300,000 children, about 6,000 of them (~2%) were in receipt of a state-recognised prescription of an ADHD medication. The article does not actually mention which ADHD medication was given but methylphenidate (a.k.a Ritalin) is listed in the PBS directory and is the typically indicated medication used for ADHD (see here). Boys, we are told, were more likely to be prescribed ADHD medication than girls (2.9% vs. 0.8% respectively).Then to the headline: when splitting the children into two age groups - 6-10 year olds and 11-15 year olds - researchers noted that those born in June (the last birth month influencing year of school intake) were more likely to be prescribed ADHD medication than those born in July. This trend was noted in both age groups. The conclusion being that the youngest children in a year group at school were more likely to be in receipt of prescribed medication for ADHD compared to older children in the year group.Alongside the caveats linked to the Whitely report made by NHS Choices, there is a need for further investigation in this area and in particular, whether the results generalise to places outside of just WA. I've already linked to my previous discussion about relative age and ADHD diagnosis/medication (see here again) and from comparisons with the Taiwanese data [2] on this topic, including the fact that Taiwan have a different cut-off month for school entry (August 31). On that basis, yes the trend appears to generalise across geographies...----------[1] Whitely M. et al. Influence of birth month on the probability of Western Australian children being treated for ADHD. MJA. 2017; 206: Feb 6.[2] Chen MH. et al. Influence of Relative Age on Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder in Taiwanese Children. J Pediatr. 2016 May;172:162-167.e1.----------Martin Whitely, Leanne Lester, John Phillimore, & Suzanne Robinson (2017). Influence of birth month on the probability of Western Australian children being treated for ADHD The Medical Journal of Australia... Read more »

Martin Whitely, Leanne Lester, John Phillimore, & Suzanne Robinson. (2017) Influence of birth month on the probability of Western Australian children being treated for ADHD. The Medical Journal of Australia. info:/

  • February 13, 2017
  • 04:28 AM
  • 153 views

Depression, SMILES and Modified Mediterranean diet (advice)

by Paul Whiteley in Questioning Answers

SMILES in the title of this post refers to the SMILES trial - Supporting the Modification of lifestyle In Lowered Emotional States - and results recently published by Felice Jacka and colleagues [1] (open-access) pertinent to the idea that "dietary improvement" might be something to consider when a diagnosis of major depressive episode (MDE) is received.Having previously published their study protocol [2], researchers set about looking at whether under "single blind, randomised controlled" conditions, the application of advice pertinent to a diet - the 'ModiMedDiet' - focused on increasing diet quality along Mediterranean diet lines, might be useful for those diagnosed with MDE. The results (which had already been revealed before peer-reviewed publication) said 'yes', such an intervention might be something to consider based on scoring of the Montgomery–Åsberg Depression Rating Scale (MADRS) after 3 months of "individual nutritional consulting sessions delivered by a clinical dietician."Looking at two groups, those randomly allocated to dietary advice/intervention (n=31 completing) and those allocated to a control condition (social support) (n=25 completing), researchers noted improvements in the MADRS scores more frequently in the diet intervention group. To quote: "At 12 weeks, 32.3% (n = 10) of the dietary support group and 8.0% (n = 2) of the social support control group achieved remission criteria of a score less than 10 on the MADRS." Similar differences were also noted on other study schedules: the Hospital Anxiety and Depression Scale (HADS)-depression subscale.Caveats? Well as a seasoned veteran of research looking at how dietary intervention for labels generally thought to be outside of the somatic domain can go, I can testify to the limitations attached to this kind of work associated with a lack of double-blindedness and issues associated with dietary compliance. This was also a study providing dietary support and so was not necessarily making study controlled meals for each participant over the course of the study (lessons from other recent research show that advice and prompts can only go so far in dietary studies). The authors also note that they "recruited participants on the basis of existing ‘poor’ quality diet" and how "this may limit the generalisability of our findings to the wider population of individuals with depression." An important point indeed.But this study represents important work and provides yet more evidence that 'nutritional medicine' should perhaps be part of mainstream psychiatry (see here). You can um-and-ah about whether 'food is medicine' and all that jazz (have you never heard of pharmacognosy?) but I'm firmly with the idea that what we eat might, on occasion and for some people, have some pretty profound implications for things other than our physical health and that includes depression (included in several forms)...To close, a note to any would-be ageing karateka, middle-aged hips tend to take a little more time to get used to perfecting yoko geri kekomi (pass the ibuprofen please). But practice does (eventually) make perfect...----------[1] Jacka F. et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Medicine. 2017; 15: 23.[2] O'Neil A. et al. A randomised, controlled trial of a dietary intervention for adults with major depression (the “SMILES” trial): study protocol. BMC Psychiatry. 2013; 13: 114.----------Jacka, F., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., Castle, D., Dash, S., Mihalopoulos, C., Chatterton, M., Brazionis, L., Dean, O., Hodge, A., & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial) BMC Medicine, 15 (1) DOI: 10.1186/s12916-017-0791-y... Read more »

Jacka, F., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., Castle, D., Dash, S., Mihalopoulos, C., Chatterton, M.... (2017) A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Medicine, 15(1). DOI: 10.1186/s12916-017-0791-y  

  • February 11, 2017
  • 04:43 AM
  • 138 views

Pregnancy exposure to SSRIs and offspring autism risk: debate continues

by Paul Whiteley in Questioning Answers

"It remains unclear whether the association between first trimester SSRI [selective serotonin reuptake inhibitor] exposure and child autism that was present in the case-control studies even after adjustment for MMI [maternal mental illness] is a true association or a product of residual confounding."So said the results of the systematic review and meta-analysis undertaken by Hilary Brown and colleagues [1] looking at a potentially important association between pregnancy use of a class of medicines typically used as antidepressants (albeit with some caveats [2]) and risk of offspring autism. This topic has previously received some airtime on this blog (see here and see here) and specifically, how maternal mental health - as per the question 'why were mothers taking SSRIs during pregancy?' - might be a rather large confounding variable affecting any possible correlation.Unfortunately even with the Brown paper, the debates will continue as to whether the SSRI-offspring autism correlation is a 'true' correlation or not. Based on the results of 6 studies - "4 case-control studies and 2 cohort studies" - where MMI was adjusted for/restricted to, authors reported some interesting trends. So in their meta-analysis of the data where results from case-control studies were adjusted for a potential impact from MMI, researchers observed that "first trimester exposure remained statistically significant." In "MMI-restricted analyses" covering the same study type, the collected studies did not show any connection between pregnancy SSRI use and offspring autism during either the first trimester or 'any time during pregnancy'. Similar results were found in the cohort studies included in the Brown paper (although both first trimester and 'any point during pregnancy' SSRI use both showed significant correlations to offspring autism in adjusted studies). I might also add that the Brown meta-analysis on this topic is not the only recent addition to the peer-reviewed literature [3]; indeed, there are several [4] others."Future studies require robust measurement of MMI prior to and during pregnancy" said Brown et al. I would agree with this sentiment added to the caveat that we may never truly know whether there is a definitive connection between pregnancy SSRI use and offspring autism risk on the basis of observational studies alone. Yes, I know it is unethical to withhold treatment such as SSRIs when clinically indicated even during pregnancy and so investigations utilising this kind of 'interventionist' study design are not likely to be undertaken anytime soon. But it does strike me that we could do quite a bit more modelling any potential effects (or not) in animal studies for example, as per some investigations with fish a while back (see here) as a start.And finally, although it is not my place to give clinical or medical advice on this blog, I should point out that much like investigations on another medicine prescribed during pregnancy potentially linked to offspring outcomes (see here), SSRIs are not generally given willy-nilly to pregnant women; there are very valid reasons for managing mum's psychiatric health particularly during pregnancy. If anyone is in doubt, please consult your doctor (and not just Dr Google).To close, before 'fake news' there was The Day Today (and they did it oh so well)...----------[1] Brown HK. et al. The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. J Clin Psychiatry. 2017 Jan;78(1):e48-e58.[2] Jakobsen JC. et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017; 17: 58.[3] Kaplan YC. et al. Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. Reprod Toxicol. 2016 Dec;66:31-43.[4] Kobayashi T. et al. Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reprod Toxicol. 2016 Oct;65:170-178.----------Brown HK, Hussain-Shamsy N, Lunsky Y, Dennis CE, & Vigod SN (2017). The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. The Journal of clinical psychiatry, 78 (1) PMID: 28129495... Read more »

  • February 10, 2017
  • 03:27 AM
  • 113 views

A few-foods diet for ADHD: a systematic review of meta-analyses of double-blind, placebo-controlled trials

by Paul Whiteley in Questioning Answers

"... the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD [few-foods diet] in subgroups of children with ADHD [attention-deficit hyperactivity disorder], thus offering innovative treatment opportunities for ADHD."So said the "Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials" published by Lidy Pelsser and colleagues [1] (open-access available here) looking at various dietary interventions that have been studied with ADHD in mind. Pelsser, I might add, is a name not completely unfamiliar to this area of investigation as per other research on elimination diets and ADHD (see here).The few-foods diet mentioned in the opening sentence of this post, could include a few things but Pelsser et al make specific reference to it consisting of "lamb, chicken, potatoes, rice, banana, apple and brassica: foods chosen as they were unlikely to produce an adverse response." You'll perhaps note that there are a few food groups missing from that list of foods, not least the grains (including the gluten protein), dairy products (containing the casein protein) and those processed foods that we all like to enjoy.The Pelsser paper is an interesting one insofar as their systematically reviewing meta-analyses that were already conducted on dietary intervention(s) for ADHD. Said meta-analyses included in their paper were only allowed in if they meta-analysed double-blind placebo-controlled trials (the gold-standard of clinical trial design). If one assumes that a meta-analysis - where data from different trials is analysed and condensed into a sort of position statement - sits at the top of the evidence-based science hierarchy, the Pelsser study design perhaps sits on top of the top!Although the FFD receives some welcome scientific backing in the review paper, it was not the only dietary intervention looked at the Pelsser and colleagues. To quote: "six supplement meta-analyses—all investigating the effects of poly-unsaturated fatty acids (PUFA)... —and eight elimination meta-analyses, examining respectively the effects of sugar..., AFC [artificial food colour elimination]..., the Feingold diet..., and the FFD... on ADHD" were reported on. The other interventions did not - for various possible reasons - match up to the research success reported with regards to the current standing of the few-foods diet for ADHD. This included the story on fatty acids for ADHD which has been mentioned previously on this blog (see here for example).I do not make recommendations on this blog when it comes to intervention and the like for anything. I will however, once again quote Pelsser et al based on their very thorough analysis of the peer-reviewed science in the area of dietary intervention for ADHD: "the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD in subgroups of children with ADHD, thus offering innovative treatment opportunities for ADHD". Also: "FFD research should focus on the mechanism of food in children with ADHD." Their words not mine, and based on some rather credible evidence. I might also add that appropriate dietetic input is a must before anyone heads into the FFD willy-nilly and no, this is not about 'clean eating' or any related fad...And just before you go, how about casting your eye over the observations made by Alejandra Ríos-Hernández and colleagues [2] and their raising the question of "whether low adherence to a Mediterranean diet might play a role in ADHD development"? Food for thought in the context of the Pelsser data, although perhaps minus the [pregnancy] licorice?----------[1] Pelsser LM. et al. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS One. 2017 Jan 25;12(1):e0169277.[2] Ríos-Hernández A. et al. The Mediterranean Diet and ADHD in Children and Adolescents. Pediatrics. 2017. Jan 30.----------Pelsser LM, Frankena K, Toorman J, & Rodrigues Pereira R (2017). Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PloS one, 12 (1) PMID: 28121994... Read more »

  • February 9, 2017
  • 03:01 AM
  • 136 views

On dietary and nutritional therapies for ME/CFS

by Paul Whiteley in Questioning Answers

ME/CFS in case you don't already know refers to Myalgic Encephalomyelitis / Chronic Fatigue Syndrome and, according to the findings reported by Nadia Campagnolo and colleagues [1], is in need of quite a bit more scientific investigation when it comes to the application of dietary changes and nutritional supplements to potentially alter the course of the condition(s).Surveying the peer-reviewed literature "from 1994 to May 2016" the authors looked for peer-reviewed studies where "CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing)." They found 17 studies that included 14 different interventions. Unfortunately they concluded that: "Many studies did not show therapeutic benefit on CFS/ME" alongside the observation that the methodological quality of the research in this areas 'could do better'.But it was not all research doom-and-gloom as some approaches seemed to show promise: "Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10." Without wishing to toot my blogging trumpet, some of these approaches have been discussed before on this blog (Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome? and Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome continued) and beyond that, the target organ of something like the use of probiotics for CFS has made an appearance more than once too (see here for example). I might also add that just outside of the search dates used by Campagnolo et al was the suggestion that issues with a staple foodstuff - cows milk - might be over-represented in cases of CFS (see here) and that a milk-free diet could be useful [2] for some at least. By saying all that, I'm not giving any medical or clinical advice...As science starts to move further away from the the biopsychosocial (BPS) model of CFS/ME (see here) and starts looking at genetics, biology and somatic disease processes with regards to the various presentations included under the banner of ME/CFS (see here) I foresee some interesting developments further down the line. Granted, dietary and nutritional approaches to CFS/ME are probably not considered 'mainstream' in terms of management strategies but that does not mean they aren't important or at least important in the context of a diagnosis of ME/CFS seemingly being protective of nothing. Central to any future studies in this or any related area is the idea that there may be lots going on under the 'plural' diagnostic umbrella of ME/CFS (see here). Indeed, something that even the PACE trial is starting to take on board [3].----------[1] Campagnolo N. et al. Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Hum Nutr Diet. 2017 Jan 22.[2] Rowe PC. et al. Cow's milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8.[3] Williams TE. et al. Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial. Psychol Med. 2017 Jan 23:1-12.----------Campagnolo N, Johnston S, Collatz A, Staines D, & Marshall-Gradisnik S (2017). Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association PMID: 28111818... Read more »

Campagnolo N, Johnston S, Collatz A, Staines D, & Marshall-Gradisnik S. (2017) Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. PMID: 28111818  

  • February 8, 2017
  • 04:33 AM
  • 161 views

On atopic disease and ADHD: 'strong evidence' for an association

by Paul Whiteley in Questioning Answers

"This current systematic review provides strong evidence that ADHD [attention-deficit hyperactivity disorder] is associated with atopic diseases and that individuals have a 30% to 50% greater chance of developing ADHD compared to controls."So said the results of the systematic review and meta-analysis published by Jurjen van der Schans and colleagues [1] looking at the collected peer-reviewed science literature on how conditions such as asthma, eczema and rhinitis might increase the risk of a subsequent diagnosis of ADHD.New news? Not to this blog it isn't (see here for example) as the Schans data really just adds the 'cherry on top' to the idea that such somatic conditions might *connect to* behavioural and/or developmental diagnoses. Preferential screening is of course implied but then also comes the million dollar question: what are the biological mechanisms linking atopy to something like ADHD? The answer is likely to be complex - immune system complex for example - but I might suggest that some starting clues may be found in some of the [limited] peer-reviewed literature talking about what happens to ADHD signs and symptoms for some when treatment for atopic disease is initiated (see here).----------[1] van der Schans J. et al. Association of atopic diseases and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses. Neurosci Biobehav Rev. 2017 Jan 19. pii: S0149-7634(16)30359-1.----------Schans JV, Çiçek R, de Vries TW, Hak E, & Hoekstra PJ (2017). Association of atopic diseases and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses. Neuroscience and biobehavioral reviews PMID: 28111269... Read more »

  • February 7, 2017
  • 04:35 AM
  • 188 views

Psychiatric disorders among male juvenile detainees in South Korea

by Paul Whiteley in Questioning Answers

"Juvenile detainees evidence high rates of psychiatric disorders and comorbidities. Assessment of and intervention in psychiatric disorders, especially alcohol use disorder and comorbid alcohol use disorder with disruptive behavior disorders, may help prevent further offenses."So concluded Johanna Inhyang Kim and colleagues [1] (open-access) following their investigation into the prevalence of DSM-IV psychiatric criteria in a sample of 173 male juvenile detainees aged between 15-19 years old held at a "male juvenile detention center in Seoul, South Korea, during the period of December 2015 to January 2016." Most of the detainees were held in relation to crimes against property (49%) but violent crimes (39%), traffic offences (24%) and sexual offences (19%) also featured in offending patterns.The presence of a psychiatric diagnosis was made using the Mini International Neuropsychiatric Interview (MINI) screening for various groups of disorders: disruptive behavioural disorders (DBDs), substance use disorder (SUD) and "any anxiety disorder." Researchers also looked for the presence of psychotic disorder and major depression too, alongside collecting various demographic data and information about recidivism (repeat offending).Results: "In total, 157 (90.8%) participants had at least one psychiatric diagnosis" is the standout figure from the paper compared with other independent data from this part of the world "of 15–38% among the general adolescent population." Alcohol use disorder was the most frequently mentioned label mentioned in the study, but 'comorbidity seems to be the rule' as we are told that: "Alcohol use disorder with DBDs was the most common combination, accounting for 46.2% of the detainees, followed by DBDs with anxiety disorders (22.5%)."When it came to the important issue of repeat offending, researchers also report some interesting patterns. Dropping out of school, present in about a quarter of the total cohort, was reported to be a factor in relation to recidivism (present in about 90% of detainees). The presence of two psychiatric disorders also showed a notable connection to repeat offending particularly where an alcohol use disorder was one of them. The message seems to be that keeping kids/young adults in school and away from alcohol might be an important combination in relation to affecting repeat offending rates.There is quite a lot of other data included in the Kim study and I would encourage interested parties to take a more detailed look. One thing that struck me about the Kim data was the apparent lack of results when it came to attention-deficit hyperactivity disorder (ADHD) in relation to offending and repeat offending outcomes. Minus any sweeping generalisations, I've talked before on this blog about how a diagnosis of ADHD might elevate the risk of contact with law enforcement agencies (see here) for whatever reason(s) and how a combination of ADHD and conduct disorder in particular, might be tied into a range of long-term adverse outcomes including 'risk of criminality' (see here). Kim and colleagues paint a slightly different clinical picture whereby a different combination of psychiatric factors might be specifically related to this group of people in this part of the world.More investigations are implied including reference to what potential nutritional changes might do to [some] behaviour in this population (see here).----------[1] Kim JI. et al. Prevalence of psychiatric disorders, comorbidity patterns, and repeat offending among male juvenile detainees in South Korea: a cross-sectional study. Child Adolesc Psychiatry Ment Health. 2017 Jan 18;11:6.----------Kim JI, Kim B, Kim BN, Hong SB, Lee DW, Chung JY, Choi JY, Choi BS, Oh YR, & Youn M (2017). Prevalence of psychiatric disorders, comorbidity patterns, and repeat offending among male juvenile detainees in South Korea: a cross-sectional study. Child and adolescent psychiatry and mental health, 11 PMID: 28115987... Read more »

  • February 6, 2017
  • 04:41 AM
  • 195 views

Natural course of "chronic disabling fatigue" in adolescents

by Paul Whiteley in Questioning Answers

"We use the term 'chronic disabling fatigue' (CDF) because CFS/ME [chronic fatigue syndrome / myalgic encephalomyelitis] was not verified by clinical diagnosis."That was one of the important details included in the findings reported by Tom Norris and colleagues [1] (open-access) who "aimed to describe the epidemiology and natural course of CFS/ME in adolescents aged 13–18 years." Relying on data derived from The Avon Longitudinal Study of Parents and Children (ALSPAC) (something this research group have previously used in their peer-reviewed research), information on some 6700 adolescents at 13 years old, 5700 at 16 years old and 4200 at 18 years old were available to researchers.At those ages (13, 16 and 18 years old) the estimated prevalence rates of CDF - chronic disabling fatigue - ascertained slightly differently at different ages were: "1.47% (95% CI 1.05% to 1.89%) at age 13, 2.22% (1.67% to 2.78%) at age 16 and 2.99% (2.24% to 3.75%) at age 18." I say that CDF was ascertained slightly differently at each age point because mothers of participants reported on "fatigue lasting >6 months that was associated with absence from full-time school or that had prevented them from taking part in activities ‘quite a lot’ or ‘a great deal’" at aged 13 years which then moved to mothers and participants reporting at aged 16 and finally at aged 17-18 years a computer-based interview being used. The key point of all of this is that CDF is assumed to be a proxy for CFS/ME but is not an actual diagnosis of CFS/ME bearing in mind how complicated that side of things already is (see here for example).Insofar as the 'natural course' of CDF, the authors paint a picture where "the prevalence of CDF increased with advancing age" but also that around 8% of those diagnosed with CDF at aged 13, held on to the 'diagnosis' at 16 and 18 years old. The authors note: "These adolescents may represent a group who were experiencing a more severe form of the disease, characterised by increased persistence or recurrence of the disease." Personally, I would be careful with the word 'disease' in that context because it seems to me that CDF is describing a symptom not necessarily a condition and a symptom that could be present for all manner of different reasons.This is interesting data but I have to say I did feel a little 'misled' by the title of the Norris paper - "Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents" - because of the use of the CDF definition as a proxy for the real thing. I refer you to other instances where ALSPAC has used/formulated measures as a proxy for diagnosis (with autism in mind) but even in that other case, authors used the term 'behavioural traits of autism spectrum disorder' [2] over and above calling it 'autism'. Surely it would have been better for Norris et al to say something like 'a trait of CFS/ME' rather than insinuating that they were examining defined cases of ME/CFS? Peer reviewers, please take note...To close, The Golden Girls and chronic fatigue syndrome. Ground-breaking.----------[1] Norris T. et al. Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents. Arch Dis Child. 2017 Jan 19. pii: archdischild-2016-311198.----------Norris T, Collin SM, Tilling K, Nuevo R, Stansfeld SA, Sterne JA, Heron J, & Crawley E (2017). Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents. Archives of disease in childhood PMID: 28104625... Read more »

Norris T, Collin SM, Tilling K, Nuevo R, Stansfeld SA, Sterne JA, Heron J, & Crawley E. (2017) Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents. Archives of disease in childhood. PMID: 28104625  

  • February 4, 2017
  • 04:27 AM
  • 211 views

ADHD, obesity and bariatric surgery?

by Paul Whiteley in Questioning Answers

"The findings suggest that a considerable number of patients before and after bariatric surgery screened positive for ADHD [attention-deficit hyperactivity disorder]. It can be hypothesized that some core ADHD symptoms improve after surgery."Bariatric surgery, where several surgical options are available to aid weight loss in those who present with 'dangerous' obesity, was the topic of the paper by Nielsen and colleagues [1] (open-access available here) who set out to compare "pre- and post-bariatric surgery patients using the internationally used Conners' Adult ADHD Rating Scale (CAARS™) to screen for ADHD" among other measures. The authors came up with some interesting details. They reported that the rate of 'probably ADHD' (defined using the CAARS and also the Wender Utah Rating Scale Short Version (WURS-k) cut-off scores) were 8.3% in their pre-surgery sample (n=120) and 6.3% in their post-surgery sample (n=128).When looking at the behavioural profiles of those pre- and post-surgery, there were some not entirely unexpected differences when it came to items related to depression and eating-related psychopathology - both scoring lower in the post-surgery participants. But also those post-surgery reported some potentially important information in relation to generally better attention and memory compared to pre-surgery participants. I was intrigued by the authors explanation of this: "The finding of a better attention and memory function in the post-surgery sample is in line with the results of longitudinal studies demonstrating improvements in cognitive functioning following bariatric surgery." Further: "It is reasonable to assume that postoperative cognitive improvement in attention and memory might have impacted the self-report on the respective CAARS subscale." Does this imply that bariatric surgery might act as some kind of nootropic for [some of] those with obesity?In these days of ADHD being 'linked' to obesity (see here), the Nielsen results fit nicely. Alongside the idea that weight loss surgery might link into improved cognitive functioning and onwards, impacting on facets of ADHD I'd have to question what the biological mechanism(s) might be. Does the restriction of food intake as a consequence of surgery indicate a role for food in some cognitive processes? Does such surgery potentially impact on the trillions of wee beasties that populate our gut and then onwards exert an effect of cognitive processes? There are several questions that still need answering...----------[1] Nielsen F. et al. Attention Deficit Hyperactivity Disorder Prevalence and Correlates Pre- and Post-Bariatric Surgery: A Comparative Cross-Sectional Study. Obes Facts. 2017 Jan 20;10(1):1-11.----------Nielsen F, Georgiadou E, Bartsch M, Langenberg S, Müller A, & de Zwaan M (2017). Attention Deficit Hyperactivity Disorder Prevalence and Correlates Pre- and Post-Bariatric Surgery: A Comparative Cross-Sectional Study. Obesity facts, 10 (1), 1-11 PMID: 28103594... Read more »

  • February 3, 2017
  • 03:03 AM
  • 209 views

"Schizophrenia confers a high endogenous risk for diabetes"

by Paul Whiteley in Questioning Answers

"Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics."So concluded Anto Rajkumar and colleagues [1] who relied on participant data in the thousands derived from several of those very helpful Scandinavian population registries (this time in Denmark) to add some further science to the idea that psychiatric diagnoses like schizophrenia seem to carry an elevated risk for all-manner of somatic conditions.From a total population of 2.7 millions people born in Denmark between 1977 and 2013, researchers reported that: "14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years)." When looking at the risk of developing diabetes (bearing in mind there is more than one type of diabetes) in those with schizophrenia not following any antipsychotic medication regime, researchers reported that: "The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71–5.41) in antipsychotic-naive schizophrenia compared with the general population." In other words, compared with those without a diagnosis of schizophrenia, there was something of an increased risk of developing diabetes in those diagnosed with schizophrenia.Then to the potential effect of antipsychotic medication, and as the authors note: "The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95–6.82) than the risk in antipsychotic-naive schizophrenia." The use of an adjusted hazard ratio means that researchers took into account potentially confounding variables such as a family history of diabetes known to potentially elevate the risk of the condition. The focus on medication is also perhaps the side of the whole schizophrenia-diabetes story that people might more readily recognise.If all that wasn't enough to convince you that schizophrenia - medicated and unmedicated - might show a rather important relationship with diabetes, perhaps the results reported by Pillinger and colleagues [2] might ease your scepticism and the suggestion (from the authors) that "higher levels of insulin, and increased levels of insulin resistance" are a facet of quite a few cases of schizophrenia alongside demonstrating that "people with schizophrenia had higher levels of glucose in the blood." On the basis of these and various other studies, the onus is on regular screening for diabetes and its symptoms alongside other related measures (see here for example) when it comes to schizophrenia under multiple 'medicated or not' conditions.Music to close, and having bumped into the excellent film 'Stand By Me' again recently, the song of the same name...----------[1] Rajkumar AP. et al. Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study. Am J Psychiatry. 2017 Jan 20:appiajp201616040442.[2] Pillinger T. et al. Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2017 Jan 11.----------Rajkumar AP, Horsdal HT, Wimberley T, Cohen D, Mors O, Børglum AD, & Gasse C (2017). Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study. The American journal of psychiatry PMID: 28103712... Read more »

  • February 2, 2017
  • 03:25 AM
  • 456 views

Hyperuricemia present in both medicated and unmedicated kids with autism

by Paul Whiteley in Questioning Answers

I was intrigued to read the findings reported by Natchaya Vanwong and colleagues [1] talking about the presence of hyperuricemia - an excess of uric acid in the blood - in their cohort of children and young adults diagnosed with an autism spectrum disorder (ASD). Intrigued not only because the authors discuss how the use of the atypical antipsychotic risperidone might *correlate* with elevations of uric acid but also how: "Hyperuricemia was present in 44.70% of risperidone-naïve patients with ASD."Uric acid, more readily associated with the condition gout, has been mentioned before on this blog in the context of autism (see here) and other conditions/states (see here) not totally unfamiliar to autism. It's therefore not necessarily new news that elevations of the stuff might have been found again. The Vanwong study looked at uric acid levels in "127 children and adolescents with ASD treated with risperidone and 76 age-matched risperidone-naïve patients with ASD" alongside a few other biological parameters. They concluded that yes, quite a few participants in their cohort presented with hyperuricemia "defined as the level of uric acid concentration in the blood >5.5 mg/dL" bearing in mind no 'not-autism' control group was included for direct study (including those not diagnosed with autism but in receipt of risperidone).Implications following the Vanwong study? Well, bearing in mind that gout is traditionally seen as a disease of middle-to-older age, the first thing would be to screen for gout in those with high uric acid levels and keep monitoring just in case gout develops. Next up would be to perhaps also look at some of the "rare inherited genetic disorders that cause hyperuricemia" and whether they might 'overlap' with the presentation of autism; y'know in the context that 'autism genes are probably not just genes for autism' and all that. At this point, I'm also minded to remind readers of the important (but often forgotten work) by Mary Coleman and Ted Page [2] on the topic of autism and uric acid, bringing in purine metabolism 'issues' as something potentially important to some autism (uric acid comes about as a consequence of the metabolism of purines). This, in the context of the autisms (plural)...Insofar as the potential correlation posed between uric acid and risperidone usage, a word of caution is perhaps warranted but big words about 'risperidone causing hyperuricemia' are not required at this point in time without further study. Remember: "Hyperuricemia was present in 44.70% of risperidone-naïve patients with ASD and 57.50% of ASD patients treated with risperidone." I say this mindful that there are biological parameters that do need careful inspection when such antipsychotic therapy is put in place (see here) but the data is not yet so convincing when it comes to uric acid elevations and risperidone use.----------[1] Vanwong N. et al. Hyperuricemia in Children and Adolescents with Autism Spectrum Disorder Treated with Risperidone: The Risk Factors for Metabolic Adverse Effects. Front. Pharmacol. 2017. 5 Jan.[2] Page T. & Coleman M. Purine metabolism abnormalities in a hyperuricosuric subclass of autism. Biochim Biophys Acta. 2000 Mar 17;1500(3):291-6.----------Vanwong N, Srisawasdi P, Ngamsamut N, Nuntamool N, Puangpetch A, Chamkrachangpada B, Hongkaew Y, Limsila P, Kittitharaphan W, & Sukasem C (2017). Hyperuricemia in Children and Adolescents with Autism Spectrum Disorder Treated with Risperidone: The Risk Factors for Metabolic Adverse Effects. Frontiers in pharmacology, 7 PMID: 28105014... Read more »

  • February 1, 2017
  • 03:21 AM
  • 450 views

Autism and a 'clear' reduction of behavioural severity in cases diagnosed

by Paul Whiteley in Questioning Answers

"This study provides the first clear evidence of a reduction over time in the behavioral severity of individuals diagnosed with Autistic Disorder during a period of stability in diagnostic criteria."So said the study findings reported by Andrew Whitehouse and colleagues [1] (a man not afraid to make waves when it comes to thinking about autism or about approaches to intervention) looking at "whether there were changes over time in the qualitative and quantitative phenotype of individuals who received the diagnosis of Autistic Disorder."Based on prospective registry data of new autism / autism spectrum disorder (ASD) cases (N=1252) in Western Australia (a research favourite) between 2000 and 2006, researchers reported that the severity of the presentation of autism seemed to 'change' between the years. They concluded: "A shift toward diagnosing individuals with less severe behavioral symptoms may have contributed to the increasing prevalence of Autistic Disorder diagnoses." At least in Australia that is...This is an interesting study. It kinda reiterates that when one talks about the quite phenomenal increase in diagnoses of autism being received, at least one factor contributory to that increase is the inclusion of a wider presentation of the condition. It also feeds into the discussions that have already happened, and will continue to happen, following the introduction of DSM-5 to autism diagnosis and in particular, the future role of the catch-all category that is social (pragmatic) communication disorder (SCD) (see here) when it comes to stiffer ASD diagnostic criteria not being met.But just before anyone breaks out with the sweeping generalisation that the increasing prevalence of autism over the past two decades is somehow all 'manufactured' (exhibit one) according to the diagnostic procedures used, the available data points to something far more multi-faceted and complex (see here for example)...----------[1] Whitehouse AJ. et al. Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses. Autism Res. 2017 Jan 19.----------Whitehouse AJ, Cooper MN, Bebbington K, Alvares G, Lin A, Wray J, & Glasson EJ (2017). Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses. Autism research : official journal of the International Society for Autism Research PMID: 28102641... Read more »

Whitehouse AJ, Cooper MN, Bebbington K, Alvares G, Lin A, Wray J, & Glasson EJ. (2017) Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses. Autism research : official journal of the International Society for Autism Research. PMID: 28102641  

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