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  • January 11, 2017
  • 03:24 AM

"the patient improved significantly when a gluten-free diet was started"

by Paul Whiteley in Questioning Answers

The quote making up the title of this post comes from the case report described by Albino J Oliveira-Maia and colleagues [1] talking yet again about how coeliac disease - the archetypal autoimmune condition where dietary gluten is the baddie - may have effects well beyond just the physical.Describing the experiences of a woman who was admitted to a psychiatry inpatient unit on the basis of "suicidal behaviours" who also "developed an agitated catatonic state", a mix of "antidepressants, anxiolytics, antipsychotics and electroconvulsive therapy" seemingly did very little to her state at/during admission we are told. Further, some diagnostic work-up beyond just her psychiatric features "allowed for the diagnosis of coeliac disease" and instigation of a gluten-free diet - the primary management option for coeliac disease - seemed to have something of a 'significant' effect on her psychiatric well-being as per that opening quote.Am I particularly surprised by all of this? No. Regular readers will know that I've previously talked about gluten and psychiatry quite a few times on this blog (see here and see here for example) and there is other research out there in the peer-reviewed domain pertinent to discussions [2]. Without trying to over-generalise a case report to anything further, there are a number of notable peer-reviewed papers that have suggested that diet can affect psychiatry and this addition merely adds to the haul.If I did perhaps have to go into further detail on how something like suicidal behaviours might link into gluten and coeliac disease (CD) I would perhaps draw your attention to how gluten does seem to be a 'mood affector' when it comes to at least some cases of CD (see here) and the link between something like depression and suicidality. I'm sure however that this is not the final word on any such link and please, don't generalise with any sweeping suggestions about how all depression is somehow caused solely by gluten. Depression is a very complicated entity.More research is of course indicated but I do wonder how many more case reports on previously unidentified coeliac disease (or non-coeliac gluten sensitivity even?) and similar psychiatric symptoms there may be out there? Time for more screening of vulnerable populations perhaps...----------[1] Oliveira-Maia AJ. et al. Case of coeliac disease presenting in the psychiatry ward. BMJ Case Rep. 2016 Dec 21;2016. pii: bcr2016216825.[2] Ludvigsson JF. et al. Increased suicide risk in coeliac disease--a Swedish nationwide cohort study. Dig Liver Dis. 2011 Aug;43(8):616-22.----------Oliveira-Maia AJ, Andrade I, & Barahona-Corrêa JB (2016). Case of coeliac disease presenting in the psychiatry ward. BMJ case reports, 2016 PMID: 28003229... Read more »

Oliveira-Maia AJ, Andrade I, & Barahona-Corrêa JB. (2016) Case of coeliac disease presenting in the psychiatry ward. BMJ case reports. PMID: 28003229  

  • January 10, 2017
  • 09:00 AM

The Rise Of Superbugs: How Bacteria Defeat Antibiotics

by Bill Sullivan in The 'Scope

Mechanisms of antibiotic resistance... Read more »

Blair, J., Webber, M., Baylay, A., Ogbolu, D., & Piddock, L. (2014) Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology, 13(1), 42-51. DOI: 10.1038/nrmicro3380  

  • January 10, 2017
  • 03:19 AM

PACE trial recovery data and chronic fatigue syndrome

by Paul Whiteley in Questioning Answers

PACE mentioned in the title of this post refers to the PACE trial [1] which concluded that: "CBT [cognitive behaviour therapy] and GET [graded exercise therapy] can safely be added to SMC [specialist medical care] to moderately improve outcomes for chronic fatigue syndrome, but APT [adaptive pacing therapy] is not an effective addition."The recent paper by Carolyn Wilshire and colleagues [2] who drew on "relevant normative data and other research" continues a peer-reviewed research theme focused on some of the details included in the original and subsequent PACE trial publications specifically that discussing the topic of recovery [3]. To quote from that 2013 paper [3] on the topic of the PACE trial: "The percentages (number/total) meeting trial criteria for recovery were 22% (32/143) after CBT, 22% (32/143) after GET, 8% (12/149) after APT and 7% (11/150) after SMC."OK, anyone that knows anything about chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) will probably have seen or heard about the debates around the PACE trial; the trial now having it's own -gate suffix (see here). The ups-and-downs, twists-and-turns, surrounding this trial have rumbled on for years now; merging with more general criticism of the biopsychosocial (BPS) model (see here), moving into debates about data-sharing, including Information Commissioner legal stuff and allowing the word 'vexatious' to be banded around quite a few times. The term 'bad science' has also been used on occasion (see here) albeit not necessarily in the peer-reviewed domain context...Quite a few of the authors on the Wilshire paper have been central to many of the discussions around the PACE trial, also including the respondent who is credited with getting the raw trial data released alongside the UK Information Commissioner. They set out to examine the recovery definition used in that 2013 PACE trial add-on paper and "whether these recovery claims are justified by the evidence". Their answer: "None of the changes made to PACE recovery criteria were adequately justified. Further, the final definition was so lax that on some criteria, it was possible to score below the level required for trial entry, yet still be counted as ‘recovered’." The sorts of recovery figures they arrived at were "only single-digit rates of “recovery” for all four groups in the study" according to another write-up of the study in comparisons to the 22% offered in the 2013 paper. Whilst this is important research, this is not the first time that the recovery criteria included in the PACE trial has been discussed. Indeed, this latest publication really just gets the whole thing into the peer-reviewed domain."The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments." Strong words indeed from the authors and I expect there will eventually be a reply from the original PACE authors on this matter too. PACE-gate is set to rumble on into 2017...----------[1] White PD. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36.[2] Wilshire C. et al. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior. 2016. Dec 14.[3] White PD. et al. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med. 2013 Oct;43(10):2227-35.---------- Wilshire, C., Kindlon, T., Matthees, A., & McGrath, S. (2016). Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial Fatigue: Biomedicine, Health & Behavior, 1-14 DOI: 10.1080/21641846.2017.1259724... Read more »

  • January 9, 2017
  • 04:26 AM

T. gondii and OCD?

by Paul Whiteley in Questioning Answers

It's been a while since I've talked about Toxoplasma gondii on this blog; the parasite that more than most, has been linked with all-manner of different psychiatric labels (see here for example). Although still the topic of some discussion, I'm swayed towards the possibility that there may be some important *associations* to be seen when it comes to this survivor and human behaviour(s) outside of just making rats attracted to cat urine (see here) to improve reproduction chances.Indeed, in that context I offer up the findings reported by Flegr & Horáček [1] who presented results pertinent to "earlier reports of the association between toxoplasmosis and OCD [obsessive compulsive disorder]." OK, the first thing to note about this study is that: "Examined subjects provided the information about their toxoplasmosis and OCD statuses themselves, which could result in underrating the strength of observed associations." Most people probably wouldn't falsely admit to being toxoplasmosis positive but I can imagine that a few people might not want to share such sensitive information for various reasons.Researchers examined data from over 7400 volunteers (participants), asking about their toxoplasmosis status and also whether they had been diagnosed with OCD, a condition characterised by obsessive thoughts and compulsive behaviours, or one or more of a variety of other neuropsychiatric labels. The symptoms of OCD were also characterised on the basis of the use of the Obsessive-Compulsive Inventory-Revised (OCI-R) (self-completed).They observed the incidence of OCD to be present in approximately 2% of their cohort. They also observed that where toxoplasmosis was reported, these participants were quite a bit more likely to also report being diagnosed with OCD. A similar relationship also held when it came to the presence of a learning (intellectual) disability too. When researchers also took into account those self-report scores on the OCI-R, they noted that in those with toxoplasmosis "even the OCD-free subjects, scored higher on the OCI-R." Ergo, something of a relationship between T. gondii and OCD (diagnosed or symptoms) may exist.Accepting the methodological failings of the Flegr / Horáček study, their data do indeed seem to tally with other independent study [2] in this area, albeit still quite limited in quality and amount. Such research also potentially ties into other investigations on other behavioural/psychiatric labels where the gondii has been implicated (see here for example) that might overlap with cases of OCD. There are however still questions to answer, not least which came first, psychiatric presentation or infection with the gondii? Could a behavioural or psychiatric diagnosis increase the risk that someone is more likely to become infected by the gondii? I suppose given what OCD encompasses - "fear of contamination by disease, infection or an unpleasant substance" - one could argue that OCD is not exactly a great template for coming into contact with T. gondii and becoming infected. But before I, or anyone else, jumps to conclusions, more investigation(s) are implied on the nature of the relationship and onward any pertinent biological mechanisms...----------[1] Flegr J. & Horáček J. Toxoplasma-infected subjects report an Obsessive-Compulsive Disorder diagnosis more often and score higher in Obsessive-Compulsive Inventory. Eur Psychiatry. 2016 Dec 16;40:82-87.[2] Miman O. et al. Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder? Psychiatry Res. 2010 May 15;177(1-2):263-5----------Flegr J, & Horáček J (2016). Toxoplasma-infected subjects report an Obsessive-Compulsive Disorder diagnosis more often and score higher in Obsessive-Compulsive Inventory. European psychiatry : the journal of the Association of European Psychiatrists, 40, 82-87 PMID: 27992837... Read more »

  • January 7, 2017
  • 04:15 AM

ADHD and vitamin levels

by Paul Whiteley in Questioning Answers

"ADHD [attention-deficit hyperactivity disorder] patients were overrepresented in the group with low levels of some vitamins, possibly indicative of inadequate dietary intake of these micronutrients in a subgroup of patients. It is important to identify these patients in dietary intervention trials of ADHD."So said the study findings reported by Elisabeth Toverud Landaas and colleagues [1] (open-access) providing some potentially important data on how nutritional factors might intersect with the diagnosis of ADHD. So: "Owing to the important and neurologically relevant functions of vitamins and the lack of studies exploring this topic in ADHD, we measured serum levels of the major vitamin classes in a sample of adult ADHD patients and controls to determine whether vitamin levels are associated with ADHD diagnosis and psychiatric symptoms." Said participants (n=133) were young adults and most were listed as having ADHD according to a "Norwegian national registry of adult ADHD patients." Vitamin levels were assessed from blood samples and compared with results for 131 control participants as per other studies on this cohort from this authorship group [2]. It's worth pointing out that samples were in deep freeze storage for between 2-9 years between collection and thawing for analysis.Various vitamins were measured in those samples (vitamins A, B6, , B9, B12 and D to name a few) alongside levels of cotinine "to assess [tobacco] smoking status." The analytical assay(s) of choice was, in the most part, a familiar one to this blog: liquid- or gas chromatography-tandem mass spectrometry.Results: "The concentrations of vitamins B2, B6 and B9 were all significantly lower in the ADHD group." When results were analysed according to percentiles based on blood levels of the various vitamins results similarly showed that those with ADHD were 'over-represented' in the lower levels bandings of those previously described vitamins. Smokers, as defined by a "widely used cut-off of 80 nmol/L" of blood cotinine, were also over-represented in the ADHD group (66%) compared with control participants' samples (12%). The authors reported that: "vitamin B6 and B9 levels were significantly higher in non-smoking ADHD patients compared with smokers" suggesting that lifestyle choices may play a role in some of the results obtained. Finally, when it came to looking at any possible association(s) between measured vitamin levels and behaviours pertinent to ADHD (derived from responses to the Adult ADHD Self-report Scale (ASRS), the authors report some preliminary observations but I'd like to see a little more data before anything further is made of this.These are interesting results (aren't they always!). I note that the authors make reference to the findings reported by Julia Rucklidge and colleagues on a vitamin-mineral mix for ADHD (see here) and the idea that correcting vitamin deficiencies might have effects beyond just the somatic. There are however caveats to the latest results: "The reason why we observed association between lower levels of some vitamins and ADHD is uncertain and probably multifactorial. Regrettably, we do not have information on lifestyle and nutrient intake from the participants to help in the interpretation of our observations. It is reasonable to think that differences in dietary factors may partly be responsible for the differences." Indeed.There is also one final observation to touch upon in the Landaas results concerning the vitamin/hormone of the hour: vitamin D. Although there was no overall difference in vitamin D concentrations in the ADHD and not-ADHD group samples, the authors did observe that: "for vitamin D, ADHD patients were significantly overrepresented both in the lowest and highest 10th percentile groups." Bearing in mind past research has suggested that ADHD might be yet another diagnosis/label where vitamin D deficiency might be a feature (see here) it is pertinent that the authors suggest: "One reason for the overabundance of ADHD patients in the highest 10th percentiles of vitamin D may thus be that relatively more ADHD patients take vitamin D supplements, either as part of an experimental treatment of symptoms or as a consequence of a diagnosed vitamin D deficiency."Finally: "It is possible that low levels of certain vitamins may contribute to ADHD symptoms. Dietary intervention trials have shown promising effects in ADHD. Thus, identification and correction of low vitamin levels could be beneficial in treatment of ADHD. Further studies are warranted for replication and for examination of the underlying mechanisms."----------[1] Landaas ET. et al. Vitamin levels in adults with ADHD. BJPsych Open. 2016 Dec 13;2(6):377-384.[2] Aarsland TI. et al. Serum concentrations of kynurenines in adult patients with attention-deficit hyperactivity disorder (ADHD): a case-control study. Behav Brain Funct. 2015 Nov 5;11(1):36.----------Landaas ET, Aarsland TI, Ulvik A, Halmøy A, Ueland PM, & Haavik J (2016). Vitamin levels in adults with ADHD. BJPsych open, 2 (6), 377-384 PMID: 27990293... Read more »

Landaas ET, Aarsland TI, Ulvik A, Halmøy A, Ueland PM, & Haavik J. (2016) Vitamin levels in adults with ADHD. BJPsych open, 2(6), 377-384. PMID: 27990293  

  • January 6, 2017
  • 06:09 AM

Particulate matter exposure and autism risk systematically reviewed?

by Paul Whiteley in Questioning Answers

"To conclude, the evidence from the studies allows us to conclude that there is an association between PM [particulate matter] exposure and ASD [autism spectrum disorder] whose strength varies according to the particle size studied with the association with PM2.5 and diesel PM being stronger."Although probably not great sentence structure to begin a post with a conclusion, the 'bottom line' reported by María Morales-Suárez-Varela and colleagues [1] summarises the current research looking at particulate matter (a.k.a pollution) and risk of autism. Surveying the current research literature - well, a window "from November 2015 up to January 2016" - authors reported finding a majority of studies showing "positive associations restricted to specific exposure windows which however do not reach statistical significance at times." This adds to other reviews of the research in this area [2].I don't want to dwell too much on this paper and topic because it's something that has already received quite a bit of attention on this blog (see here and see here for examples). As with most research areas focused on autism, there is evidence for and evidence against any association/correlation between air pollution exposure and risk of autism. Given the various factors included under the heading of pollution (type, particle size, how exposure is measured) it's perhaps not surprising that there is not yet any 'smoking gun' (pardon the pun) when it comes to any possible association.I however, am taken by the ideas that (a) genes probably play a hand in translating air pollution exposure to a heightened risk of [offspring] autism and (b) other conditions linked to air pollution such as asthma might also feature in any connection (see here for example). Indeed, in these times of seemingly ever-increasing air pollution (see here) and lots of possible connections, further investigations are very much indicated.----------[1] Morales-Suárez-Varela M. et al. Systematic review of the association between particulate matter exposure and autism spectrum disorders. Environ Res. 2016 Dec 13;153:150-160.[2] Lam J. et al. A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder. PLoS One. 2016 Sep 21;11(9):e0161851.----------Morales-Suárez-Varela M, Peraita-Costa I, & Llopis-González A (2016). Systematic review of the association between particulate matter exposure and autism spectrum disorders. Environmental research, 153, 150-160 PMID: 27984759... Read more »

  • January 5, 2017
  • 06:07 AM

A subtype of autism linked to psychosis?

by Paul Whiteley in Questioning Answers

"Our data show there may be a specific subtype of ASD [autism spectrum disorder] linked to comorbid psychosis. The results support findings that psychosis in people with ASD is often atypical, particularly regarding affective disturbance."So said the findings reported by Felicity Larson and colleagues [1] (open-access available here) who bring an important topic into view that has recently been raised in the media too (see here). I appreciate that to talk about yet more comorbidity potentially following an autism diagnosis is not exactly great news. If however, one accepts that various comorbid conditions can actually be pretty disabling for many on the autism spectrum, identifying, screening and managing/treating said comorbidity then actually becomes pretty important.Researchers set about looking to "describe autistic and psychotic phenomenology in a group of individuals with comorbid ASD and psychosis (ASD–P) and compare this group with populations affected by either, alone." Their group comprised of adults aged 16 and over diagnosed with an ASD and comorbid psychosis (N=116). This was an opportunistic cohort insofar as being recruited between January 2010 and June 2013. Eligibility was determined by a formal diagnosis of autism at referral and meeting "criteria on the Autism Diagnostic Observation Schedule (ADOS)... at the time of involvement in the study, or... meet criteria on the Autism Diagnostic Interview-Revised (ADI-R)... for a lifetime diagnosis." Psychotic illness determination was a 2-stage affair. First, inclusion was based on "a prior clinical diagnosis of psychotic illness or gave an account of an episode that was clearly psychotic" followed by evidence of psychotic symptoms being elicited using one or more questionnaires onward to the presentation of 'research-significant psychosis'.Results: "What is clear from this research is that individuals who experience concurrent ASD and psychotic illness exist and are treated in mental health services." I don't think there is anything too earth-shattering about that statement but it does need to be said in the context of the label of autism rarely/not existing in some sort of diagnostic vacuum (see here). Next: "Mental health services in the UK are yet to be fully equipped to support people with both psychotic illness and ASD." Again, nothing new; following a trend of resources not being available or 'ready' to accommodate people on the autism spectrum and the health inequalities that inevitably follow. Insofar as the idea that psychosis presentation may at times be 'atypical' when it comes to autism, this also follows an important trend noted in other comorbidity research (e.g. when it comes to bipolar disorder for example).The other data presented by Larson and colleagues on the profile of autistic symptoms potentially being slightly different when compared to a 'control group' of those diagnosed with autism but without evidence of psychosis - "the ASD–no psychosis (ASD–NP) group" (n=69) - is interesting but requires quite a bit more follow-up work. I might at this point drop in the paper by the wonderfully named Robustelli and colleagues [2] talking about how "youth at high-risk of developing psychosis have fewer and poorer quality social relationships" as being potentially relevant and indeed, how social functioning can be affected long-term when it comes to psychosis. Further investigation is also required around the observation that: "Individuals with ASD–P had lower rates of schizophrenia and higher rates of psychosis-NOS" in light of other work talking about spectrums (autism and schizophrenia) colliding (see here). Although not part of this study, the name of one co-author on this paper being linked to the Autism-Spectrum Quotient (AQ) is also potentially relevant, given other work asking whether the AQ might actually be picking up signs and symptoms of something like schizophrenia too (see here).There is also the question of possible overlapping mechanisms potentially at work when it comes to autism and psychosis. In light of recent chatter about an immune system 'feature' to some psychosis (see here) and the myriad of immune related findings linked to autism, I'd suggest that this could be one area for further research inspection. The idea also that vitamin D for example, shows some relationship to some autism (see here for example) is another area for joint investigation given some chatter about levels of the sunshine vitamin/hormone and cases of psychosis [3]. There will no doubt, be other areas of overlap potentially pertinent too...There is quite a bit more to do in this increasingly important area of research.----------[1] Larson FV. et al. Psychosis in autism: comparison of the features of both conditions in a dually affected cohort. Br J Psychiatry. 2016 Dec 15. pii: bjp.bp.116.187682.[2] Robustelli BL. et al. Social relationships in young adults at ultra high risk for psychosis. Psychiatry Res. 2016 Dec 7;247:345-351.[3] Suetani S. et al. Prevalence and correlates of suboptimal vitamin D status in people living with psychotic disorders: Data from the Australian Survey of High Impact Psychosis. Australian & New Zealand Journal of Psychiatry. 2016. Dec 21.----------Larson, F., Wagner, A., Jones, P., Tantam, D., Lai, M., Baron-Cohen, S., & Holland, A. (2016). Psychosis in autism: comparison of the features of both conditions in a dually affected cohort The British Journal of Psychiatry DOI: 10.1192/bjp.bp.116.187682... Read more »

Larson, F., Wagner, A., Jones, P., Tantam, D., Lai, M., Baron-Cohen, S., & Holland, A. (2016) Psychosis in autism: comparison of the features of both conditions in a dually affected cohort. The British Journal of Psychiatry. DOI: 10.1192/bjp.bp.116.187682  

  • January 4, 2017
  • 05:43 AM

A distinctive microbial signature in kids with autism and GI issues?

by Paul Whiteley in Questioning Answers

"Our findings identify distinctive mucosal microbial signatures in ASD [autism spectrum disorder] children with FGID [functional gastrointestinal disorders] that correlate with cytokine and tryptophan homeostasis."So said the study results published by Ruth Ann Luna and colleagues [1] who "compared mucosa-associated microbial communities in children with ASD to previous reports characterizing stool in this population" among other things. If you are eating breakfast/lunch/dinner at the time of reading this post, maybe give it a few minutes before reading on...So rectal biopsies and blood specimens were the samples under investigation and the focus was very much on those children on and off the autism spectrum who also presented with various functional bowel issues. Just before anyone starts to question the ethics of taking biopsies and the like, the authors expand by reporting that participants were "undergoing a lower endoscopy for one of the following symptoms: abdominal pain, altered stool patterns, or painless bright red blood per rectum." In these days of health inequality attached to the label of autism (see here for an example), these were children who were being investigated for their bowel issues and not being unnecessarily subjected to such invasive techniques just for the sake of science.The various analyses undertaken on those blood and biopsy samples were pretty wide-ranging. Bacterial species present in mucosal samples and their supernatants were included but so researchers also looked at cytokines (various chemical markers linked to immune function among other things) in blood samples and supernatants and levels of "serotonergic metabolites" (chemicals related to the aromatic amino acid tryptophan) pertinent to their "microbiome-neuroimmune signatures" hypothesis testing. Bear in mind that when it comes to the neurotransmitter called serotonin (5-HT), the gut truly is the second brain.Results: taking into account the relatively small participant numbers included for study - "ASD children with functional GI disorders (ASD-FGID, n=14), as compared to neurotypical (NT) children with (NT-FGID, n=15) and without abdominal pain (NT, n=6)" - there were some interesting, if not unexpected, results to be seen. "Principal component analysis showed clear separation between the ASD-FGID group and the NT-FGID and NT groups" on the basis of the bacterial communities present in those mucosal samples. In the autism group, several mucosa-associated Clostridiales species were predominant as per that noted in other independent findings (see here). Interestingly authors also observed "marked decreases in Dorea and Blautia, as well as Sutterella" species perhaps contrasting with other research in this area (see here). I'll let readers trawl through the other bacterial families talked about in the paper including those potentially linked to the presence of specific functional bowel states derived from questionnaire data from participants.Looking at any potential associations between mucosal bacterial communities, cytokines and those tryptophan metabolites, researchers also reported some important, if preliminary, observations. So: "Group comparisons revealed that IL-6 [interleukin 6] and tryptophan release by mucosal biopsies was highest in ASD children with abdominal pain, whereas serotonergic metabolites were generally elevated in children with FGIDs." I'd like to see these findings replicated in larger groups before I make anymore of what their potential significance could be but it is intriguing that pain might play some hand in immune signalling and the production of amino acid metabolites. More so when one considers other related research [2].On the back of a recent post talking about blood-based 'biomarkers' pertinent to more pathological bowel states occurring alongside cases of autism (see here) it is good to see that autism + GI issues is starting to receive a little more scientific attention. It shows that science has moved on from the question 'are bowel symptoms over-represented when it comes to autism?' (answer: yes) and actually started to look at the questions of 'why? and 'how?' The focus on gut bacteria is a worthy cause (see here) and if replicated and found to be important, opens up various intervention options derived from work in other areas of medicine (see here). Indeed, there is a 'watch this space' call for investigations looking at probiotics and autism for example (see here) with the promise of more to come [3]. Oh, and don't forget the good old 'gut-brain axis' when it comes to a possible tie-up between bowel and brain with at least some autism in mind.But for now, autism, gut disorder, gut bacterial composition, mucosal immune function and little old tryptophan and its metabolites get some well deserved combined research attention...----------[1] Luna RA. et al. Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. CMGH Cellular and Molecular Gastroenterology and Hepatology. 2016. Dec 11.[2] Ahmad SF. et al. Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children. Mol Immunol. 2016 Dec 24;82:57-65.[3] Navarro F. et al. Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol. 2016 Dec 14;22(46):10093-10102.----------Luna, R., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G., Savidge, T., & Williams, K. (2016). Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder CMGH Cellular and Molecular Gastroenterology and Hepatology DOI: 10.1016/j.jcmgh.2016.11.008... Read more »

Luna, R., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G., Savidge, T., & Williams, K. (2016) Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. CMGH Cellular and Molecular Gastroenterology and Hepatology. DOI: 10.1016/j.jcmgh.2016.11.008  

  • January 3, 2017
  • 06:28 AM

Suicidality in children and young adults with 'high-functioning' autism

by Paul Whiteley in Questioning Answers

"Consistent with the previous findings, [the] rate of suicidality is higher in individuals with ASD [autism spectrum disorder]."That was one of the conclusions reported in the paper by Sevcan Karakoç Demirkaya and colleagues [1] (open-access) yet again touching on a most important topic when it comes to autism, particularly the part of the autism spectrum labelled as 'high-functioning'. Personally, I'm not a great fan of the 'functioning' description typically added to autism to somehow denote can from can't do. As science is starting to realise, high-functioning does not automatically imply 'can function' across the board just as the even worse description 'low-functioning' does not necessarily generalise to mean 'can't function'. I know it's the best we have at the moment but...Anyhow, Karakoç Demirkaya et al report results following a review of medical charts for some 55 adolescents (mostly boys) aged between 7 and 20 years of age. All were diagnosed with an ASD and all had "capability of reading, writing and speaking" and were deemed to have cognitive abilities in the typical range (i.e. no learning disability). Included in the data examined were responses to the Eskin’s Suicide Screening Questionnaire; specifically answers to 5 questions on thoughts of (suicidality) and actual attempts at suicide.Results: "Suicidality was observed in 16 individuals in our group which accounts for a rate of suicide of 29%. Among the suicidal ones, seven individuals had the diagnosis of AD [autistic disorder], eight had AS [Asperger syndrome], and an individual had PDD-NOS [pervasive developmental disorders - not otherwise specified]." Because no 'not autism' control group was included in this specific study, authors draw attention to how their figure compared with "the result of previous studies implemented on a typically developing adolescent population in our country" (Turkey) and suggest that their figure was slightly higher (29% vs 25%). I have to say that I'm pretty shocked by the suicidality figures reported in both the autism and not-autism groups.On the issue of actual suicide attempts, Karakoç Demirkaya and colleagues report that about 12% of their small-ish cohort had some history of this type of behaviour. Again, this contrasted with data from other independent studies where around 4-5% of adolescents were reporting such a history. Worrying figures again.Further: "Rates of comorbid psychiatric disorders such as mood disorders, anxiety disorders and disruptive behaviors were 23.6%, 43.6% and 65.4% respectively. Groups with the psychotic features, positive family history for suicidal behaviors and completed suicide showed more suicidality than the non-suicidal group." This is an important part of the results obtained. It implies that when we say suicidality (thoughts and/or behaviours) is 'elevated' when it comes to the autism spectrum, we can't at the present time, tease autism apart from other comorbidities that may also have an important bearing on this type of behaviour. It's a point that has been raised in relation to suicidality accompanying other labels too (see here).I'm gonna leave it at that with the Karakoç Demirkaya findings save any charges of 'going beyond the data'. As I seem to do quite a lot these days, the primary message is that screening - preferential screening - should be an important part of the continued 'management' of autism (see here). Alongside other media headlines illustrating how for example, psychosis can be (a) present and (b) can sometimes exert a powerful effect on some people on the autism spectrum, further investigation(s) on the role of such issues (minus any stigma) in relation to suicidality and autism is also indicated.----------[1] Karakoç Demirkaya S. et al. Assessment of suicidality in children and adolescents with diagnosis of high functioning autism spectrum disorder in a Turkish clinical sample. Neuropsychiatr Dis Treat. 2016 Nov 11;12:2921-2926.----------Karakoç Demirkaya, S., Tutkunkardaş, M., & Mukaddes, N. (2016). Assessment of suicidality in children and adolescents with diagnosis of high functioning autism spectrum disorder in a Turkish clinical sample Neuropsychiatric Disease and Treatment, Volume 12, 2921-2926 DOI: 10.2147/NDT.S118304... Read more »

  • January 2, 2017
  • 04:06 AM

This Month in Blastocystis Research (DEC 2016)

by Christen Rune Stensvold in Blastocystis Parasite Blog

2016 is coming to an end, and in the last post of the year, I highlight three of the most important articles on Blastocystis published in 2016.... Read more »

Scanlan PD, Knight R, Song SJ, Ackermann G, & Cotter PD. (2016) Prevalence and genetic diversity of Blastocystis in family units living in the United States. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 95-97. PMID: 27545648  

Kurt Ö, Doğruman Al F, & Tanyüksel M. (2016) Eradication of Blastocystis in humans: Really necessary for all?. Parasitology international, 65(6 Pt B), 797-801. PMID: 26780545  

  • December 30, 2016
  • 06:30 PM

This Month in Blastocystis Research (DEC 2016)

by Christen Rune Stensvold in Blastocystis Parasite Blog

2016 is coming to an end, and in the last post of the year, I highlight three of the most important articles on Blastocystis published in 2016.... Read more »

Scanlan PD, Knight R, Song SJ, Ackermann G, & Cotter PD. (2016) Prevalence and genetic diversity of Blastocystis in family units living in the United States. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 95-97. PMID: 27545648  

Kurt Ö, Doğruman Al F, & Tanyüksel M. (2016) Eradication of Blastocystis in humans: Really necessary for all?. Parasitology international, 65(6 Pt B), 797-801. PMID: 26780545  

  • December 30, 2016
  • 02:51 PM

What is Turmeric and How to Use it to Prevent of Heart Diseases

by Maggie Martin in United Academics

If you are thinking of using turmeric for heart disease, first understand how it works and then know how it is supposed to be consumed. Turmeric works in numerous ways to boost heart health. It is considered a powerful antioxidant with an active ingredient known as curcumin, responsible for the antioxidant, anti-inflammatory and antiseptic properties of turmeric.... Read more »

Govindarajan, V., & Stahl, W. (2009) Turmeric — chemistry, technology, and quality. C R C Critical Reviews in Food Science and Nutrition, 12(3), 199-301. DOI: 10.1080/10408398009527278  

  • December 29, 2016
  • 08:20 PM

Believe in miracles... and yourself

by Aurametrix team in Aurametrix Blog

End of the year is a very special time as Holiday lights melt away our inner Grinch and we start to believe in miracles and new beginnings. ​Belief is not a religious phenomenon. It is our way of coping with the future and finding existential meaning. Scientific studies show that belief in miracles contributes to greater life satisfaction. Belief in science and technological progress can make people satisfied with their lives even more. The stronger the sense of personal control, the higher satisfaction with life. [...] ... Read more »

  • December 27, 2016
  • 06:10 AM

2016 autism research review on Questioning Answers

by Paul Whiteley in Questioning Answers

Time flies! Once again, I'm posting my annual 'state of the science' autism research review, this time covering the particularly unusual year of 2016.With around 300 blog entries to choose from, I'm changing the format this year to list a 'top 5' of areas where I think some scientific progress has been made. The caveat as ever being that there are still mountains to climb in terms of delineating aetiology, nature and importantly, how one can actually improve quality of life for those on the spectrum. At the foot of this post I've also detailed a few 'areas to watch' in the coming months/years too.So, in no particular order, here goes:1. Vitamin D and autism. As per my 'one to watch' prediction from the 2015 end-of-year review, there has been a veritable science feast focused on the sunshine vitamin/hormone in connection to autism (see here). The research discussions in 2016 started with some initial talk about 'clinical improvements' following supplementation with vitamin D (see here). This was accompanied by chatter about the possible use of pregnancy vitamin D affecting risk of offspring autism (see here and see here). Screening for vitamin D levels as and when a diagnosis of autism is received was also discussed (see here). Then, towards the end of the year, things got really interesting as one of the first controlled trials of vitamin D supplementation in autism was published (see here) with the promise of more to come (see here). The findings (double-blind, placebo-controlled) suggested that for some at least, vitamin D over placebo might have the ability to affect the presentation of some aspects of autism. The caveats? Well, larger controlled trials are required and one has to be careful about doses of vitamin D in light of some cautionary tales (see here). What else needs to be done on the topic of vitamin D and autism? Given the number of conditions the sunshine vitamin has been linked to - some labels potentially crossing over with autism - a wider view of any 'effects' outside of those just on core autism symptoms might be useful. This will probably also provide some more potentially information about the possible hows-and-whys of vitamin D action.2. Autism as a plural condition. 'The autisms' is a phrase not unfamiliar to this blog (see here) but this year, a couple of papers really started putting some scientific flesh on to the bones of the argument for why we need to rethink autism. Discussions on the paper by Lynn Waterhouse and colleagues [1] (see here) set the tone for such a debate and how the label of autism serves a purpose in defining / describing symptoms but seemingly does little else when it comes to a research perspective looking at the hows-and-whys of autism. That autism seemingly appears alongside a long list of other conditions including quite a few of the various inborn errors of metabolism (see here and see here) substantiates the idea that a singular labels says very little about the 'essence' of autism. And speaking of ESSENCE (see here), there was yet more on this important topic. Another part of this 'pluralisation' debate is the fact that the 'autism is a lifelong condition' mantra rolled out again and again and again might not necessarily ring true for everyone who was once diagnosed on the autism spectrum (see here and see here). And to say that these children/adults were 'never autistic in the first place' does a real disservice to them, their parents and loved ones and the professionals who diagnosed them...3. Meta-analysing autism. Mirroring what seems to be apparent in the research literature in general, a whole slew of meta-analyses and systematic reviews on the topic of autism emerged this year. We had reviews on long-term outcome and quality of life (see here), behavioural outcomes following exercise (see here), medication (see here and see here), joint intervention strategies (see here), pregnancy infection and offspring autism risk (see here) and allergic asthma and autism (see here) to name but a few. One of the particularly notable reviews of the collected data was that by Nevill and colleagues [2] on the topic of parent-mediated interventions for young children with autism. Covering a topic with more than a pinch of media hype this year (see here), the science behind the hype in this area actually turns out to be not that strong at the moment...4. Real-world autism. Although I'm partial to reading quite a bit on the science about autism, one thing I hope I never forget is how that science translates into 'action' when it comes to autism, either in terms of 'hows-and-whys' or impacting on the day-to-day positives and negatives of living with the label. This year I've talked about more research on the topic of 'real world autism' covering various angles including: wandering and autism (see here), parents lived experience of offspring autism diagnosis and beyond (see here and see here), early mortality and autism (... Read more »

Waterhouse, L., London, E., & Gillberg, C. (2016) ASD Validity. Review Journal of Autism and Developmental Disorders, 3(4), 302-329. DOI: 10.1007/s40489-016-0085-x  

  • December 23, 2016
  • 05:03 AM

ADHD symptoms and chronic fatigue syndrome?

by Paul Whiteley in Questioning Answers

With the pinnacle of the season of 'jolly' almost upon us, I'd like to make some brief discussion on the findings reported by Denise Rogers and colleagues [1] and specifically the observation that: "ADHD [attention-deficit hyperactivity disorder] symptoms were significantly greater in the CFS [chronic fatigue syndrome] group than in HC [healthy controls]."With the aim of examining both the prevalence of fatigue in cases of ADHD and the prevalence of ADHD symptoms in adults with CFS (a term 'linked to' the condition called myalgic encephalomyelitis), researchers set about investigating several measures including self-reported (that's 'self-reported') fatigue "across groups of adults with ADHD (N = 243), CFS (N = 86), and healthy controls (HC) (N = 211)." The results were interesting insofar as that previous sentence on ADHD symptoms perhaps not being uncommon in cases of CFS vs. asymptomatic controls but also that: "Fatigue is a common clinical feature of attention deficit hyperactivity disorder (ADHD) in adulthood."Accepting that there may be important implications from the notion that fatigue may be part and parcel of at least some ADHD (see here for example), the idea that ADHD signs and symptoms might be over-represented in cases of CFS is interesting, if not necessarily novel [2]. Minus any sweeping generalisations or psychobabble explanations of hows-and-whys (we've had quite enough of those in relation to CFS), I'd like to think that such an association could shed some light on the possible shared genetics, epigenetics and biochemistry of both conditions. Given also some initial data emerging on the potential usefulness of something like methylphenidate (indicated for cases of ADHD) for cases of CFS (see here) there are also avenues to explore in relation to shared drug targets across both conditions (see here for some discussion on oxidative stress for example). I'd like to see more study on this topic, bearing in mind how broad labels like CFS and ADHD can be. I'm also wondering whether researchers might also one day replace examination of ADHD traits with autistic traits so as to perhaps provide data on whether there may be other important associations to be had...And with that I wish you all a very Merry Christmas and a happy and healthy New Year. I'm not done just yet with this years blogging adventures as my annual 'what was hot in autism research in 2016' post is scheduled sometime next week (if you're interested/bored of turkey/bored of watching Christmas films - delete as appropriate).Music to close and as always at this time of year, it wouldn't be the same without Kirsty and Shane. And please, do try to stay out of the drunk tank this Christmas...----------[1] Rogers DC. et al. Fatigue in an adult attention deficit hyperactivity disorder population: A trans-diagnostic approach. Br J Clin Psychol. 2016 Dec 5.[2] Sáez-Francàs N. et al. Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients. Psychiatry Res. 2012 Dec 30;200(2-3):748-53.----------Rogers, D., Dittner, A., Rimes, K., & Chalder, T. (2016). Fatigue in an adult attention deficit hyperactivity disorder population: A trans-diagnostic approach British Journal of Clinical Psychology DOI: 10.1111/bjc.12119... Read more »

  • December 22, 2016
  • 03:31 AM

Psychosis (sometimes) as an immune disorder?

by Paul Whiteley in Questioning Answers

"Some psychosis cases an 'immune disorder'" went the BBC headline with reference to the paper by Belinda Lennox and colleagues [1] talking about the detection of antibodies against the N-methyl-D-aspartate receptor (NMDAR) in cases of first-episode psychosis (FEP).Although by no means a universal phenomenon, researchers reported that 3% of their 228 participants diagnosed with FEP who provided a blood sample showed the presence of NMDAR antibodies compared with none of the healthy controls (n=105) included for study. As part of the condition known as anti-NMDAR encephalitis, the presence of NMDAR antibodies can indeed include/induce psychotic features [2].This is interesting work. For anyone that has come across the book 'Brain on Fire' by Susannah Cahalan, there is a growing interest in how the presentation of psychiatric features can, on occasion, include a significant role for the immune system and particularly, the concept of autoimmunity (where the body's own immune system fails to differentiate between 'self' and 'other'). Some of the authors included on the Lennox paper have previously summarised and discussed the idea that NMDAR antibodies might show a connection to some cases of psychosis and conditions manifesting psychosis such as schizophrenia [3]. The current data tally with their previous conclusion that: "A minority of patients with psychosis are anti-NMDA receptor antibody positive" and onwards the idea that there may be many different 'roads' to psychosis in these days of plural conditions (see here).Where next for this research area I hear you ask? Well, set against the idea that various autoimmune diseases might be over-represented alongside a diagnosis like schizophrenia (see here), one needs to tease out some of the hows-and-whys details. Does, for example, a history of autoimmune disease 'set someone up' for psychosis and/or schizophrenia? Or is the autoimmune element of it something that follows a diagnosis of psychosis and/or schizophrenia? I have some opinions on this based on other findings on how autoimmunity may come about for some (see here for some discussion on HERVs) taking into account other peer-reviewed ideas and data [4]. I don't profess to be right or offer any universal answer but it is interesting that endogenous virus expression does seem to be heightened in a condition like schizophrenia and said elements might be considered important in processes such as molecular mimicry as one mechanism of autoimmunity [5]. There is a research plan to carry out and specifically on the topic of how NMDAR antibodies come about.The other important 'where next' for this area of investigation is the tantalising prospect that 'treating' said autoimmune reaction might have some important effects on the presentation of something like FEP. There are hints out there in the peer-reviewed literature of possible treatment options being available. I might for example, draw your attention to some overlapping work looking at anti-NMDAR encephalitis ('encephalitis' that is) and cases of autism (see here and see here) where intervention options are discussed. With no medical advice given or intended, methylprednisolone seems to have found therapeutic favour for some. Other, more aggressive treatment options have also been reported but further investigations are required.I note the words 'immuno-psychiatry' are mentioned in the media reporting of the Lennox findings and I'm happy to see the profile of this area of research being elevated through such work. The idea that immune function(s) might be doing so much more than just identifying and eradicating foreign bodies to maintain our physical health continues to gather pace...----------[1] Lennox BR. et al. Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study. Lancet Psychiatry. 2016. Dec 7.[2] Dalmau J. et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurology. 2011;10(1):63-74.[3] Pollak TA. et al. Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med. 2014 Sep;44(12):2475-87.[4] Slokar G. & Hasler G. Human Endogenous Retroviruses as Pathogenic Factors in the Development of Schizophrenia. Frontiers in Psychiatry. 2015;6:183.[5] Trela M. et al. The role of molecular mimicry and other factors in the association of Human Endogenous Retroviruses and autoimmunity. APMIS. 2016 Jan-Feb;124(1-2):88-104.----------Lennox, B., Palmer-Cooper, E., Pollak, T., Hainsworth, J., Marks, J., Jacobson, L., Lang, B., Fox, H., Ferry, B., Scoriels, L., Crowley, H., Jones, P., Harrison, P., & Vincent, A. (2016). Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study The Lancet Psychiatry DOI: 10.1016/S2215-0366(16)30375-3... Read more »

  • December 21, 2016
  • 06:02 AM

"New form of autism found"

by Paul Whiteley in Questioning Answers

"New form of autism found" went one of the headlines reporting on the paper by Dora C. Tărlungeanu and colleagues [1] and findings that "elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA [branched-chain amino acids] in human brain function." This work continues a rather important research story talking about how one 'type' of autism might have some important roots in relation to the branched-chain amino acids and their metabolism (see here and see here for more information).So, mice were the focus on the paper by Tărlungeanu et al (including one Gaia Novarino on the authorship list) and an extension of the idea that the BCAAs may play an important role in some autism in these days of the plural 'autisms' (see here). SLC7A5 represents a gene that codes for a protein involved in the transport of BCAAs into the brain among other things. Researchers studied mice who were genetically 'edited' to present with a "deletion of Slc7a5 from the endothelial cells of the BBB [blood-brain barrier]." In effect, the area of the body where SLC7A5 serves those important transport duties, a hold-my-hand partner was missing resulting in lower brain levels of the BCAAS. Researchers noted a few important things in those SLC7A5-missing mice; not least in relation to their mouse behaviour(s) and how bearing in mind mice are mice not people, they seemed to present with behavioural issues not a million miles away from that noted in relation to autism. 'Social interaction' was as I understand it, something potentially affected in those SLC7A5-missing mice. Further: "we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene" suggesting that their results might stretch to people too.And then something else that might eventually be important: "we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice." Intracerebroventricular administration basically means an injection straight into the brain. After a few weeks of such injections, researchers noted that mouse behaviours began to change coincidental to the direct administration of those BCAAs.This is interesting research. I know that not everyone on the autism spectrum presents with issues with the BCAAs (as far as we know). But in these days of increasing plurality when it comes to autism coupled to the rise and rise of study on the various inborn errors of metabolism in relation to autism (see here), this could be pertinent to at least one type of autism. I also appreciate that 'brain injections' of something like BCAAs are not exactly a desirable option for anyone so there is still some work to do in terms of how to correct any central BCAA deficiency if and when identified. Talk about a possible relationship between the BBB and autism in the Tărlungeanu paper also continues a theme (see here) where this important barrier separating the brain from the other contents of the body (and indeed, the outside world) might represent something potentially quite important to autism (see here) and indeed, with 'transporters' also in mind (see here).Much more research is implied.----------[1] Tărlungeanu DC. et al. Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell. 2016. Dec 1.----------Tărlungeanu, D., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., Galluccio, M., Tesulov, M., Morelli, E., Sonmez, F., Bilguvar, K., Ohgaki, R., Kanai, Y., Johansen, A., Esharif, S., Ben-Omran, T., Topcu, M., Schlessinger, A., Indiveri, C., Duncan, K., Caglayan, A., Gunel, M., Gleeson, J., & Novarino, G. (2016). Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder Cell, 167 (6), 1481-2147483647 DOI: 10.1016/j.cell.2016.11.013... Read more »

Tărlungeanu, D., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., Galluccio, M., Tesulov, M., Morelli, E., Sonmez, F.... (2016) Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder. Cell, 167(6), 1481-2147483647. DOI: 10.1016/j.cell.2016.11.013  

  • December 20, 2016
  • 04:33 AM

Generation R does gestational vitamin D levels and autistic traits

by Paul Whiteley in Questioning Answers

"Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny."So said the findings reported by Vinkhuyzen and colleagues [1] (open-access) reporting on data derived from "the Generation R Study, a population-based prospective cohort from fetal life onward, based in Rotterdam, The Netherlands." I've talked about this study initiative before on this blog (see here) but this time around its scientific eyes turned towards the possibility that vitamin D - the sunshine vitamin/hormone - might have some important connections to the presentation of some of the facets of autism or at least autistic traits. Yes, yet again, vitamin D and autism comes into view (see here)...The Vinkhuyzen paper is open-access for all to see (and has already received some media exposure) but here are a few choice details:Hypothesis: explore "the association between gestational 25OHD concentrations and a widely used parent-report continuous measure of autism-related traits—the Social Responsive Scale (SRS)." Said levels of 25-hydroxyvitamin D (25OHD) (the functional unit of vitamin D assessment) were obtained from "maternal mid-gestation sera and from neonatal sera (collected from cord blood)." SRS scores relevant to offspring were provided by parents "when the children were ~6 years of age."Results: well, this certainly wasn't an under-powered study as data for "4229 children and their mothers were available with measures of vitamin D concentrations drawn from maternal blood at mid-gestation and/or drawn from cord blood at time of birth as well as data on the SRS, 2489 children and their mothers were available with measures of vitamin D concentrations at both time points." Approximately 16% of mothers were classed as deficient based on that mid-gestation serum sample rising to 36% when looking at cord blood samples. As I've mentioned before, issues with vitamin D generally fall into a few bandings associated with insufficiency and deficiency at the lower end of typical."In all analyses, 25OHD deficiency or lower 25OHD concentrations were associated with higher (more impaired) SRS scores." This was based on the use of an "18-item abridged version of the questionnaire" that specifically looked at "behavioural features related to social cognition, social communication and autistic mannerisms." Remember, this was a study looking at autistic traits not autism diagnoses. Interestingly too, authors were also able to restrict their analysis to "offspring with European ethnicity" and reported similar results associating lower vitamin D levels and higher SRS scores. This subgroup analysis perhaps ties into other research where ethnicity has been suggested to be a factor in relation to vitamin D levels and diagnosed autism (see here).So, there you have it. Yet more evidence linking vitamin D and autism and/or autistic traits; this on the back of my previous entry not-so-long-ago (see here) talking about supplementation as a potential means to affect presentation of at least some autism, with appropriate caveats (see here). It's getting increasingly difficult to say that there is 'no connection' between the two factors.Strengths of the Vinkhuyzen study? Well, as I said, it was big in terms of participant numbers. I note also the authors proudly announce: "We used a gold standard assessment of 25OHD concentrations" in light of the application of "isotope dilution liquid chromatography-tandem mass spectrometry." A gold star for the authors indeed in light of some 'chaos' when it comes to the hows and whys of measuring vitamin D status. Limitations: well, as per every study that looks at the association between a small number of variables, there are potentially a million and one other factors that might also account for the results. Another gold star is due for the authors' mention of the fact that vitamin D seems to be 'associated' with various diagnostic labels outside of rickets these days (see here for example) and hence one cannot rule out that traits or diagnoses not specifically covered by the study could have exerted some effect. More so when one considers how much autistic traits might not be just autism-specific traits (see here). I might also add that subsequent work could/should also be looking at the genetics of vitamin D metabolism not just functional levels of the stuff (see here).A final quote from the authors to close: "Just as prenatal folate supplementation has reduced the incidence of spina bifida, we speculate that prenatal vitamin D supplementation may reduce the incidence of ASD." I know such sentiments might not be welcomed by everyone, and the assumption that autistic traits are 'always a negative thing' needs some continued careful consideration. The ideas however that: (a) nutrition might impact on both psychology and physiology and (b) that where appropriate and/or where wanted, use of vitamin D supplement might impact on risk of autism or the presentation of autism, are ideas that are deserving of a lot more investigation.And again, minus any charges of clinical or medical advice being given on this blog (they're not), here is what the UK Government (or parts of the UK) are currently saying about vitamin D and the population as a whole...----------[1] Vinkhuyzen AA. et al. Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Mol Psychiatry. 2016 Nov 29.----------Vinkhuyzen AA, Eyles DW, Burne TH, Blanken LM, Kruithof CJ, Verhulst F, Jaddoe VW, Tiemeier H, & McGrath JJ (2016). Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Molecular psychiatry PMID: 27895322... Read more »

Vinkhuyzen AA, Eyles DW, Burne TH, Blanken LM, Kruithof CJ, Verhulst F, Jaddoe VW, Tiemeier H, & McGrath JJ. (2016) Gestational vitamin D deficiency and autism-related traits: the Generation R Study. Molecular psychiatry. PMID: 27895322  

  • December 19, 2016
  • 03:19 AM

Gut barrier integrity meets blood-brain barrier integrity with autism in mind

by Paul Whiteley in Questioning Answers

"In the ASD [autism spectrum disorder] brain, there is an altered expression of genes associated with BBB [blood-brain barrier] integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity."Although pretty enthused to see research linking names like Anna Sapone, Tim Buie and Alessio Fasano in the recent paper published by Maria Fiorentino and colleagues [1] (open-access), I was slightly less impressed with the use of the term 'the ASD brain' in their paper potentially joining two concepts that I've been quite interested in down my research years: gut barrier and blood-brain barrier function in the context of autism. Yes, I accept that those most precious of resources, donated brains from the deceased, represented some of the 'material' under scientific scrutiny, but if science has learned anything about autism down the years, it is that sweeping generalisations such as terms like 'the autism brain' don't reflect what the existing research tells us about the heterogeneity under the label. I might just as well use the term 'blogger brain' to denote some of my activities, but such a label tells you nothing about me aside from my pastime.After that little rant, the paper from Fiorentino is an interesting one in that the goal was to "investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD." To do this, tissue from both brain and gastrointestinal (GI) tract donated by a small number of deceased and non-deceased participants who were diagnosed with autism, schizophrenia or nothing related (not-autism controls) were analysed "for gene and protein expression profiles." This work was undertaken on the basis of "the interconnectivity of the gut–brain axis, [that] suggests that inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of antigens or activated immune complexes through a permissive blood–brain barrier (BBB), can be part of the chain of events leading to neuroinflammation and thereby subsequent disease." I might add that the use of the word 'disease' in that sentence is, I think, aiming to describe the physiological effects of 'leaky barriers' not the diagnosis of autism. It is unfortunate however that 'disease' still continues to be banded around in the context of autism [2].I think it's important to stress that the Fiorentino study was in effect two studies: one that looked at brain samples from one participant group who had died, and one that looked at GI samples from those who were still living (at the time of sample collection) and who presented with "GI symptoms undergoing esophagogastroduodenoscopy (EGD) for clinically indicated reasons." This was not a study where biological samples - brain and gut - came from the same person but rather a mash-up. Keep that in mind for now. The sorts of genes that were focused in on were those "associated with the formation, integrity, and function of the BBB and neuroinflammation" and included the claudins and something called MMP-9 and MMP-2 that have been discussed previously on this blog (see here) with leaky barriers in mind. The key words are 'barrier integrity' when it comes to the list of compounds that were under inspection.Results: well it was good to see the authors list details of each of the participants from which tissue were used in their study. Brain tissue from the deceased with autism for example, is subject to quite a few factors that can influence the outcome of any results obtained; not least whether specific comorbidity accompanied their autism diagnosis and the nature of their death. Indeed, looking through the various case report numbers, I'm struck by how young many participants, particularly those diagnosed with autism, were at the time of their death. This ties into other discussions and debates (see here)."Our molecular analysis of the BBB integrity and function shows an altered BBB in the ASD subjects evaluated." This was evidenced by elevations in the gene expression of MMP-9 and its proposed connection to disturbances of BBB integrity. Further: "Of the four claudins (i.e., CLDN-1, -3, -5 and -12) that to date are thought to be incorporated in the BBB... we found that two were significantly more expressed in the ASD brain as compared in HC [healthy controls]." Once again I might suggest the term 'healthy controls' is not an inappropriate one when it comes to determining not-autism or not-schizophrenia.Then to analysis of those [independent] gut biopsy samples: "results, showing increased expression levels of pore-forming (66% of the ASD samples) and decreased levels of barrier-forming (75% of the ASD samples) TJ [tight junction] components in the duodenal samples, suggest an impaired gut barrier and serve as a proof of concept to support the hypothesis of a gut–brain axis dysfunction in a subgroup of ASD patients." So, those compounds linked to making the gut barrier more 'leaky' were seemingly increased in expression, and those linked to making the gut barrier less 'leaky' were reduced in quite a few of the samples from those diagnosed with autism. Mmm...There is quite a bit more science included in the Fiorentino study but I think I've gone on long enough in this post. Suffice to say that the whole gut-brain axis thing with autism in mind gets a boost but more work is indicated, not least with larger sample groups and perhaps combining tissues from gut and brain from the same person. I would also like to see a little more done on this topic with some 'interventions' in mind, based on the other autism research that potentially links the authors (see here). Drawing for example, on a paper written by Prof Fasano titled: 'Zonulin, regulation of tight junctions, and autoimmune diseases' [3] suggesting that "gliadin, a storage protein present in wheat and that triggers celiac disease in genetically susceptible individuals, also affect the intestinal barrier function by releasing zonulin" one might see how far from being a set-in-stone state of affairs, dietary changes for some on the autism spectrum, might actually set in motion a host of biological changes pertinent to this area of work. And such changes might not be just confined to accepted gluten-related conditions either...----------[1] Fiorentino M. et al. Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular Autism. 2016; 7:49.[2] Simms MD. When Autistic Behavior Suggests a Disease Other than Classic Autism. Pediatr Clin North Am. 2017 Feb;64(1):127-138.[3] Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences. 2012;1258(1):25-33.----------... Read more »

Fiorentino, M., Sapone, A., Senger, S., Camhi, S., Kadzielski, S., Buie, T., Kelly, D., Cascella, N., & Fasano, A. (2016) Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular Autism, 7(1). DOI: 10.1186/s13229-016-0110-z  

  • December 17, 2016
  • 05:51 AM

Pregnancy influenza infection not linked to offspring autism

by Paul Whiteley in Questioning Answers

"There was no association between maternal influenza [flu] infection anytime during pregnancy and increased ASD [autism spectrum disorder] risk."So said the findings reported by Ousseny Zerbo and colleagues [1] continuing a research theme from this author (see here for example) looking at how various infections 'encountered' during critical periods of pregnancy may / may not impact on offspring autism risk. This time around the focus was on viral infections and in particular "maternal influenza infection and vaccination from conception date to delivery date" as derived from either diagnosis using ICD-9 criteria or "a positive laboratory result for influenza based on the Prodesse ProFlu+ Assay (Hologic), a multiplex real-time polymerase chain reaction in vitro diagnostic test." Said participants numbering nearly 200,000 children were all born "at Kaiser Permanente Northern California from January 1, 2000 to December 31, 2010, at a gestational age of at least 24 weeks." The press release accompanying the publication can be seen here."Maternal influenza infection during pregnancy was not associated with increased ASD risk in this study, and the association did not vary by the timing of influenza infection." Importantly, authors also looked at whether maternal influenza vaccination during pregnancy was also related to offspring ASD risk based on the data contained in their patient databases. The results pertinent to pregnancy flu vaccination and offspring risk were not exactly cut-and-dried as "in an initial analysis unadjusted for multiple comparisons" the authors reported seeing a 'slightly increased' risk for offspring autism associated with maternal vaccination during the first few months of pregnancy. This was set against data indicating no significant association between maternal influenza vaccination covering 'anytime' during pregnancy. Indeed, after "adjusting for the multiplicity of hypotheses tested" they concluded that the first trimester vaccination - offspring autism risk was potentially a 'chance finding'. Minus any scaremongering and to be on the safe side the authors suggested that "additional studies are warranted to further evaluate any potential associations between first-trimester maternal influenza vaccination and autism."Aside from a few potential 'weakness' attached to the Zerbo results including the fact that "subclinical infections or illnesses for which women did not seek medical attention" were not counted in the data, these are interesting results. Quite a few times on this blog I've covered the so-called maternal immune activation (MIA) hypothesis - where mum's reprogrammed pregnancy immune system is 'challenged' and potentially has implications for offspring development - and this work kinda falls into that category of autism science. Indeed, I've talked about the possibility quite recently (see here). Drawing also on data looking at season of conception/birth as potentially being important to pregnancy viral/bacterial exposure and onward offspring outcomes (see here) there has been a steady stream of peer-reviewed publications hinting at a potentially important 'association' between infection exposure in-utero and developmental outcomes for the child. The current Zerbo data however put a bit of a research spanner in the works when it comes specifically to any pregnancy flu and offspring autism risk suggestion albeit with the continued requirement for further investigations in this area covering other infections.----------[1] Zerbo O. et al. Association Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum Disorder. JAMA Pediatr. 2016 Nov 28.----------Zerbo O, Qian Y, Yoshida C, Fireman BH, Klein NP, & Croen LA (2016). Association Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum Disorder. JAMA pediatrics PMID: 27893896... Read more »

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