Monday, 2 March 2015

Systemic low grade inflammation and bowel issues in autism?

The paper from Katarina Babinská and colleagues [1] (open-access here) presents an interesting, if preliminary take on two potentially important issues linked to at least some cases of autism: gastrointestinal (GI) issues and inflammation (see here and see here respectively).

Detailing the examination of plasma levels of a compound called high mobility group box 1 protein (HMGB1), a protein which has the apparent ability to 'bend DNA' and has some pretty potent immune effects [2] (one paper talked about HMGB1 as being a 'nuclear weapon in the immune arsenal'), authors reported results based on the examination of 31 people on the autism spectrum compared with 16 asymptomatic controls. As well as finding as a group, that those with autism presented with significantly higher levels of plasma HMGB1, they also reported that those with some of the highest levels of HMGB1 were more likely to present with GI issues. Ergo: "Results of the study support the involvement of the systemic low-grade inflammation in the pathomechanisms of autism and its possible association with GI symptoms."

Reiterating that this was a small study in terms of participant groups and that among control group participants were "10 siblings of the individuals with autism", these are interesting results. Whilst I might disagree with some of the terminology used by the authors in their paper such as the concept of 'low-functioning autism' and the term 'mental retardation' as a descriptor of the cognitive status of their participants with autism, I believe that there may be quite a bit more to do in this research area.

A quick trawl through some of the other literature where autism and HMGB1 are mentioned reveals that this is not the first time that elevations in HMGB1 have been reported. The paper from Emanuele and colleagues [3] for example, looking at a similarly small number of participants reported that: "HMGB1 levels may be affected in autistic disorder". Further: "Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder." I'm not overly sure that based on data from 22 adults with autism one can make such statements about a single biological parameter being linked to one of the core traits that makes up a diagnosis of autism, but certainly this paper adds to the Babinská data. The paper from Russo [4] on epidermal growth factor (EGF) and HMGB1 with autism in mind has been previously discussed on this blog (see here). In that entry, I also linked to a piece of research correlating HMGB1 to up-regulation of something like MMP-9 (which again has been discussed here before). Follow-up work from this author [5] has also been published.

What's more to say about HMBG1 and autism? Well, one might entertain the idea of adding HMBG1 to further research on markers of immune function in autism (see here) not forgetting the adhesion molecules too (see here). In light of the idea that there may be a link between the genetics of immune function and [some] autism (see here) one might also look at the gene producing HMBG1 and perhaps some of the other genetic/biological drivers controlling or moderating HMBG1 production.

Assuming that some people on the autism spectrum are in a state of "systemic low-grade inflammation" (accepting that this description probably covers most people with and without a diagnosis at some point in their lives) and that initial correlation noted with GI issues, one might also entertain the idea of looking at what happens to HMGB1 levels as and when bowel issues are 'treated'. I say this acknowledging that bowel issues and autism can mean quite a few things (see here and see here) and that science is not quite there yet in understanding how such bowel issues come about and what one might be able to do about them. Aside that is, from the Buie papers back in 2010 (see here and see here)...

Music: Dreaming of You by The Coral. You may not know their name, but you'll probably have heard the song before...

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[1] Babinská K. et al. Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiol Res. 2015 Feb 10;63 Suppl 4:S613-8.

[2] Bianchi ME. & Manfredi AA. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev. 2007 Dec;220:35-46.

[3] Emanuele E. et al. Increased serum levels of high mobility group box 1 protein in patients with autistic disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):681-3.

[4] Russo AJ. Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism. Biomark Insights. 2013 Apr 4;8:35-41.

[5] Russo AJ. Increased Epidermal Growth Factor Receptor (EGFR) Associated with Hepatocyte Growth Factor (HGF) and Symptom Severity in Children with Autism Spectrum Disorders (ASDs). J Cent Nerv Syst Dis. 2014 Sep 9;6:79-83.

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ResearchBlogging.org Babinská K, Bucová M, Ďurmanová V, Lakatošová S, Jánošíková D, Bakoš J, Hlavatá A, & Ostatníková D (2015). Increased plasma levels of the high mobility group box 1 protein (HMGB1) are associated with a higher score of gastrointestinal dysfunction in individuals with autism. Physiological research / Academia Scientiarum Bohemoslovaca, 63 Suppl 4 PMID: 25669692

Sunday, 1 March 2015

Vitamin D status affecting autoimmune disease risk?

I want to bring the paper from Tea Skaaby and colleagues [1] to your attention for today's brief blog post and their observation that there may be: "a possible protective role of a higher vitamin D status on autoimmune disease". Autoimmune disease by the way, reflects a breakdown in communication and tolerance of 'self' whereby the body attacks healthy tissue.

Their findings, based on an analysis of "a total of 12,555 individuals from three population-based studies with measurements of vitamin D status (25-hydroxy vitamin D)" hinted that "for a 10 nmol/l higher vitamin D" the hazard ratios for quite a few autoimmune conditions seemed to be reduced albeit with some quite wide confidence intervals (CIs). Overall however, the authors found a reduced HR "for any autoimmune disease (HR = 0.94 % CI 0.90, 0.98)" with that increasing levels of vitamin D.

It's not necessarily new news that vitamin D seems to have some important biological effects when it comes to immune function [2] outside of the more classical physiological connections made to the stuff. Indeed, the paper by Tamblyn and colleagues [3] talking about an immunological role for vitamin D at the 'maternal-fetal interface' (where immune tolerance is required to "prevent fetal rejection") represents an area requiring far greater inspection particularly in light of guidance recommending vitamin D supplementation to pregnant women among other groups (see here).

Without hopefully cherry-picking from the growing research literature looking at vitamin D and autoimmunity, I would also like to bring in the paper by Dong Yeob Shin and colleagues [4] (open-access) and the suggestion that low vitamin D status might be "associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis." Anti-thyroid peroxidase antibody (TPOAb) and autoimmune thyroiditis have been of particular interest to this blog in light of some initial data suggesting a connection with certain cases of depression (see here). That also depression has been looked at through the vitamin D lens specifically from the deficiency point of view is an interesting correlation (see here) perhaps connecting psychiatry, autoimmunity and vitamin D. I say all this acknowledging that correlation is not the same as causation and that not everyone with depression will present with autoimmune thyroiditis or other autoimmune conditions.

Certainly however, I'd wager that there is perhaps more to see when it comes to how the sunshine vitamin/hormone might link up with immune function (and dysfunction) and perhaps beyond taking into account some interesting work with autism in mind too. I'd be minded to also bring in the idea that permeability of a particular membrane might also be a spot requiring a little more study in light of other research suggestions [5] and some preliminary tie up with vitamin D (see here) combined with more recent data [6]. Just sayin'.

Bloodbuzz Ohio by The National to close, and what a baritone...

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[1] Skaaby T. et al. Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 2015 Feb 11.

[2] Antico A. et al. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012 Dec;12(2):127-36.

[3] Tamblyn JA. et al. Immunological role of vitamin D at the maternal-fetal interface. J Endocrinol. 2015 Mar;224(3):R107-R121.

[4] Shin DY. et al. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J. 2014 Mar;55(2):476-81.

[5] Fasano A. et al. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-100.

[6] Assa A. et al. Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation. J Infect Dis. 2014 Oct 15;210(8):1296-305.

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ResearchBlogging.org Skaaby T, Husemoen LL, Thuesen BH, & Linneberg A (2015). Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine PMID: 25666936

Saturday, 28 February 2015

ME/CFS is real: confirmation if it is needed...

"Scientists discover robust evidence that chronic fatigue syndrome is a biological illness" went the title of the press release for the study by Mady Hornig and colleagues [1] (open-access) detailing an immune 'signature' and also possible staging of the illness.

I couldn't help but wince at some of the media headlines reporting on this study as 'proof' that chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) is a real illness. As I've indicated before on this blog (see here) anyone who has trawled through the collected peer-reviewed research in this area would be hard pressed to arrive at any other conclusion than that CFS/ME is very real and severely impacts on a person's quality of life. I say that accepting that the various definitions and descriptions of the conditions (note the plural) have not always been kind to CFS/ME research and to a large extent, perhaps held back science from making the breakthroughs we've potentially seen with the Hornig results. Hopefully SEID [systemic exertion intolerance disease] might help this process along a little...

Back to the paper:

  • The authorship of the latest research paper includes the great and the good of CFS/ME (and autism) research. Mady Hornig and Ian 'virus hunter' Lipkin have talked quite a bit in recent times about their research commitment to CFS/ME following the whole XMRV de-discovery issue a few years back (see here). José Montoya has similarly impressed with the idea that certain anti-virals *might* be indicated for some cases of CFS/ME (see here).
  • Cytokines - those chemical messengers of the immune system - were the target molecules predominating in the Hornig paper taking into account "diagnosis and other clinical variables". Said immune molecules (over 50 of them) were analysed in nearly 300 participants diagnosed with CFS/ME compared against nearly 350 asymptomatic controls. Authors drew on participants derived from two large US studies of CFS/ME, and those all-important case definitions relied on meeting either or both of the "1994 CDC Fukuda criteria... and the 2003 Canadian consensus criteria for ME/CFS." Participants were also categorised according to how long they had reported experiencing symptoms.
  • Results: "No substantive differences were found between cases and controls when short- and long-duration cases were combined and compared with healthy control subjects." You could see how that sentence could be taken by certain people/groups. But... "Analyses that considered duration of illness revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as a dissociation of characteristic intercytokine regulatory networks." Those describing a shorter duration of illness, as a group, presented with elevated levels of several proinflammatory cytokines than controls or longer illness duration participants. As per the press release: "The association was unusually strong with a cytokine called interferon gamma that has been linked to the fatigue that follows many viral infections, including Epstein-Barr virus (the cause of infectious mononucleosis)." When they say 'unusually strong association', they talk about an odds ratio (OR) of 104.77 (95% CI, 6.975 to 1574.021; P = 0.001) (noting the very wide confidence intervals too).
  • Various other analyses were also applied to the data. "The CART (Classification and Regression Tree) decision tree machine learning method was applied to plasma cytokine and clinical covariate data to find predictors that distinguished ME/CFS cases of short illness duration (≤3 years) from those with a long illness duration (>3 years)." In that respect, the age of participants seemed to play something of a role in the results obtained. But, the authors also acknowledge that this data was "not then validated on an independent test set."
  • Discussions surround the possible reasons for the results obtained, particularly how symptom duration seemed to play an important role in the authors' findings. I do like the idea that "an “exhaustion” of the cytokine-producing cells" might account for why there seems to be a 'burst' of immune system involvement in the early stages of the disease followed by a kind of cytokine burn-out. "The study supports the idea that ME/CFS may reflect an infectious "hit-and-run" event" is one way of looking at it.

What's more to say about this work? Well, we might be seeing 'immune markers' mentioned a little more in CFS/ME research circles in the near future on top of what has been previously reported (see here). Whether specific cytokine profiles might be considered 'diagnostic' for CFS/ME needs quite a bit more replication before anyone gets too ahead of themselves. That being said, as and when such a profile is detected, one might reasonably assume that there could be ways and means to intervene. Another quote: "There are already human monoclonal antibodies on the market that can dampen levels of a cytokine called interleukin-17A that is among those the study shows were elevated in early-stage patients." I say this without making any judgement calls nor providing anything that looks, sounds or smells like clinical/medical advice. I might also advance the idea that other factors might also link into something like IL-17A (see here).

I'm also minded to say that the excitement over immune issues being associated with CFS/ME shouldn't also push other areas back into the shadows as per the very interesting findings being reported on things like mitochondrial function (see here), the gut microbiota (see here) and potential intervention options (see here) to name but a few.

Still, only a few months into 2015 and CFS/ME (or SEID if you wish) is really making some research headlines...

[Update: 2 March 2015: The full IoM report is available here].

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[1] Hornig M. et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Science Advances. 2015; 1: 1: e1400121.

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ResearchBlogging.org Mady Hornig, José G. Montoya, Nancy G. Klimas, Susan Levine, Donna Felsenstein, Lucinda Bateman, Daniel L. Peterson, C. Gunnar Gottschalk, Andrew F. Schultz, Xiaoyu Che, Meredith L. Eddy, Anthony L. Komaroff, & W. Ian Lipkin (2015). Distinct plasma immune signatures in ME/CFS are present early in the course of illness Science Advances, 1 (1) : http://dx.doi.org/10.1126/sciadv.1400121

Friday, 27 February 2015

Hyperprolactinemia and risperidone use in autism

The findings reported by Yaowaluck Hongkaew and colleagues [1] (open-access) on prolactin levels being "positively and significantly associated with risperidone dose" in cases of children and adolescents diagnosed with an autism spectrum disorder (ASD) is the point of discussion today.

Prolactin by the way, is the hormone most commonly associated with stimulating breast development and milk production in women. To quote from the US National Institute of Health (NIH) entry on prolactin: "There is no known normal function for prolactin in men." Risperidone is a neuroleptic (antipsychotic) which has quite a few clinical indications including for the management of irritability in (some) autism [2]. Indeed, risperidone is one of the few (only?) drugs to be specifically approved for pediatric autism and dealing with irritability.

It's been known for a while that risperidone use is associated with elevations in prolactin levels [3]. More recently, the research base has expanded to suggest that various factors might impact on the elevations in prolactin correlated with risperidone use [4] including "sex, pubertal stage, psychiatric disease, and associated autoimmune disorders."

So, then to the Hongkaew study which is open-access but...

  • Data on 147 children and young adults diagnosed with an autism spectrum disorder (ASD) were included for study. "All participants receiving a risperidone-based regimen for at least 4 weeks were enrolled in this study." Researchers also made sure that (a) medication was taken before the donation of a blood sample, and (b) participants were not taking other medications "that could potentially affect risperidone metabolism and prolactin elevation." This did not however exclude all other medicines.
  • Said blood draws was analysed for serum prolactin concentration using a chemiluminescence immunoassay system.
  • Results: "mean risperidone dose of the subjects was 1 mg/day or 0.03 mg/kg/day" and "mean duration of therapy was 46.06 months". Sixty-six participants (44%) presented with hyperprolactinemia - elevated levels of serum prolactin - most of whom were male. 
  • Dosage of risperidone also seemed to have an effect on prolactin results: "The median prolactin level at the high dose was significantly higher than at the recommended dose and low dose" based on categorisations of dose higher or lower than the FDA recommended amount taking into account body weight.
  • Duration of treatment, age, weight and other variables did not show any statistical correlation with prolactin levels.
  • The authors conclude: "This information will be helpful to clinicians by providing significantly important clinical information to properly inform therapeutic practice and prevent sexual dysfunction consequently in autistic children treated with risperidone."

I don't mean to come down too hard on risperidone with this post but this is not the first time that prolactin levels have been reported as elevated when it comes to autism [5] following the use of this pharmaceutic. Aside from the aesthetic changes potentially associated with higher prolactin levels and in particular, their potential effects on males (the subject of litigation), there is some suggestion in the literature that elevations in prolactin over the longer term might elevate risk of certain other issues [6] albeit correlation not necessarily being the same as causation and reiterating the duration of treatment measured by Hongkaew et al. As an aside, I'm going to be coming to the paper by Stubbs and colleagues [7] in the near future in light of other work on the potential effects of elevated prolactin.

Insofar as the use of risperidone for managing irritability in cases of autism, I've talked before about it's usefulness in this area and how certain adjuvant therapies might also help (see here). Accepting that irritability under the heading of 'challenging behaviours' is a mighty complicated issue (see here) and potentially tied into many different factors, there remains a place for risperidone under certain circumstances (assuming good medicines management accompanies such use). 

Still, the collected literature on prolactin and risperidone use with autism in mind adds a cautionary note to this medicine and other relations allied to other important side-effects such as weight gain. Use and monitor with care is perhaps the important message from the Hongkaew and other data...

Music: the quite controversial Disarm from the Smashing Pumpkins.

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[1] Hongkaew Y. et al. Hyperprolactinemia in Thai children and adolescents with autism spectrum disorder treated with risperidone. Neuropsychiatr Dis Treat. 2015 Jan 22;11:191-6.

[2] Dinnissen M. et al. Clinical and pharmacokinetic evaluation of risperidone for the management of autism spectrum disorder. Expert Opin Drug Metab Toxicol. 2015 Jan;11(1):111-24.

[3] Aboraya A. et al. Hyperprolactinemia associated with risperidone: a case report and review of literature. Psychiatry (Edgmont). 2004 Nov;1(3):29-31.

[4] Margari L. et al. Prolactin variations during risperidone therapy in a sample of drug-naive children and adolescents. Int Clin Psychopharmacol. 2015 Mar;30(2):103-8.

[5] Anderson GM. et al. Effects of short- and long-term risperidone treatment on prolactin levels in children with autism. Biol Psychiatry. 2007 Feb 15;61(4):545-50.

[6] Tworoger SS. et al. A 20-year prospective study of plasma prolactin as a risk marker of breast cancer development. Cancer Res. 2013 Aug 1;73(15):4810-9.

[7] Stubbs B. et al. Schizophrenia and the risk of fractures: a systematic review and comparative meta-analysis. Gen Hosp Psychiatry. 2015 Jan 15. pii: S0163-8343(15)00005-5.

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ResearchBlogging.org Hongkaew Y, Ngamsamut N, Puangpetch A, Vanwong N, Srisawasdi P, Chamnanphon M, Chamkrachchangpada B, Tan-Kam T, Limsila P, & Sukasem C (2015). Hyperprolactinemia in Thai children and adolescents with autism spectrum disorder treated with risperidone. Neuropsychiatric disease and treatment, 11, 191-6 PMID: 25653528

Thursday, 26 February 2015

Carnitine and autism continued

The paper from everyone's favourite Saudi - Egyptian autism research tag-team that is Gehan Mostafa and Laila AL-Ayadhi [1] (open-access) on plasma polyunsaturated fatty acids and serum carnitine levels in a cohort of children diagnosed with autism / autism spectrum disorder (ASD) is served up for your reading delight today.

Regular readers of this blog might have heard me talk before about the pretty interesting research findings to come from this research partnership (see here and see here for example) covering all-manner of different sectors of the autism research environment.

This times around the name of the game was: "to investigate plasma levels of PUFAs [polyunsaturated fatty acids] and serum carnitine in relation to GI [gastrointestinal] manifestations in autistic children." The idea being that: "Carnitine and PUFAs are antiinflammatory molecules and their deficiency may result in GI inflammation and gut injury" following other work with autism in mind (see here).

A few pointers about the study might be in order:

  • "This cross-sectional study was conducted on 100 children with autism." Participants ranged in age between 3-10 years and importantly were not taking additional fatty acids or anticonvulsants. A control group of 100 age- and sex-matched children asymptomatic for autism were also studied: "not related to the children with autism, and demonstrated no clinical findings suggestive of immunological, GI or neuropsychiatric disorders."
  • Autism severity was assessed using the CARS and GI issues were examined "by an experienced pediatric gastroenterologist according to the Questionnaire on Pediatric Gastrointestinal Symptoms - Rome III Version used by previous studies that assessed gastrointestinal dysfunction in autism." Fasting blood samples were also provided and serum carnitine and plasma PUFAs examined.
  • Results: both biological measures were lower as a group for the children with autism compared to controls. Indeed: "Low serum carnitine and plasma DHA [Docosahexaenoic acid], AA [Arachidonic acid], linolenic and linoleic acids, below the 5th percentile of the control values, were found in 66%, 62%, 60%, 43% and 38%, respectively of autistic children."
  • Bearing in mind that PUFAs can exist in more than one form as per the old omega-3 / omega-6 issue (see here), authors also reported a group difference in the ratio of ω6/ω3 PUFAs: "ω6/w3 ratio (AA/DHA) was significantly higher in autistic patients" compared with controls. This is something also reported by the authors in other publications [2].
  • GI symptoms were reported to be present in about half of the autism group. An important sentence is included about GI issues: "They were recurrent, severe and the patients were attending the clinic because of these agonizing symptoms." Further: "Autistic patients with GI manifestations had significantly lower serum carnitine and plasma DHA than patients without such manifestations."

I know I tend to say this about nearly every study I blog about but this is interesting work. Carnitine and autism is an area which I've got quite a bit of time for on this blog and the growing consistency in results suggesting lower levels of this stuff in quite a few cases of autism (see here). Some of the genetics of carnitine metabolism might also be 'linked' to at least some autism too (see here) with a particular focus on the idea of inborn errors of metabolism. Certainly, autism research should know a thing or two about them (see here).

The relationship between fatty acids and autism reflects a slightly less clear picture in terms of results. In a post going back to 2011, I talked about some of the peer-reviewed research on the use of supplementary fatty acids for autism (see here) and how certain comorbidity present in quite a bit of autism (see here) might be the bigger target. More recent research has kinda corroborated that idea (see here).

"How GI factors are related to autism is not yet clear" is another important quote from the authors. Yes, we are now in an era where there is general acceptance that certain functional GI issues are over-represented among those with autism (see here) but the hows and whys are still the source of significant speculation. I'd be minded to suggest that it's likely to be complicated and probably without a universal factor for everyone with autism and GI issues. There are some areas emerging that may yield further information such as examination (not hype) of those trillions of wee beasties which call our gut home (see here) and a 'possible' relationship with more pathological bowel states (see here). The Mostafa/AL-Ayadhi findings suggest another possible correlate.

I leave you with a quote from the authors: "these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the occurrence of GI manifestations is a mere association or a consequence to reduced plasma PUFAs and serum carnitine levels in autistic patients." I couldn't agree more.

Music then. The Strokes with New York City Cops.

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[1] Mostafa GA. & AL-Ayadhi LY. Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations. Behavioral and Brain Functions 2015, 11:4.

[2] Mostafa GA. et al. A possible association between elevated serum levels of brain-specific auto-antibodies and reduced plasma levels of docosahexaenoic acid in autistic children. J Neuroimmunology. 2015. Jan 27.

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ResearchBlogging.org Mostafa, G., & AL-Ayadhi, L. (2015). Reduced levels of plasma polyunsaturated fatty acids and serum carnitine in autistic children: relation to gastrointestinal manifestations Behavioral and Brain Functions, 11 (1) DOI: 10.1186/s12993-014-0048-2

Wednesday, 25 February 2015

Analysing the salivary proteome in autism

The paper from Armand Ngounou Wetie and colleagues [1] (open-access here) reporting pilot results from a mass spectrometry based proteomic analysis of saliva in cases of autism or autism spectrum disorder (ASD) compared with asymptomatic controls is served up for your reading delight today. There has already been some media attention about this paper (see here).

It's an interesting paper for quite a few reasons; not least the continuing voyage of the analytical technique known as mass spectrometry into autism research (see here) and further beyond [2]. Mass spec by the way, represents a rather advanced way of looking at biological samples for potential biomarkers or compounds of interest to specific states or conditions (among other things). Ngounou Weite et al have some research form in this area as per a previous paper titled: 'Mass spectrometry as a tool for studying autism spectrum disorder' [3] which I would encourage you to peruse for some background reading.

Their latest study delves into an interesting analytical medium, saliva, something we all generally have and importantly, something pretty non-invasive when it comes to collecting a sample [4]. "Using nano liquid chromatography-tandem mass spectrometry, we found statistically significant differences in several salivary proteins" the authors report, comparing saliva samples from those with autism vs. asymptomatic controls. The sorts of differences detected between the groups - quite small groups (N=6 per) - tended to fall into the domain of 'immune function' as per issues with neutrophil elastase and various antigen binding sites of immunoglobulin. Indeed, the authors conclude: "Our results indicate that this is an effective method for identification of salivary protein biomarkers, support the concept that immune system and gastrointestinal disturbances may be present in individuals with ASDs." I would agree with those sentiments.

Aside from the small participant groups and the fact that all participants were male and many carried some comorbidity (ADHD, epilepsy) alongside their autism label, 4 of the participants with autism were taking some kind of pharmaceutic/nutraceutical compared with none of the controls. As per other biomarker studies of autism, one always needs to be a little mindful of any effects from these factors particularly when looking at functional biofluids. In terms of the mass spec method, it all looks pretty comprehensive including the use of Q-ToF as the detector of choice and pooled group samples run in triplicate to ensure some kind of reproducibility in results. The authors did subject saliva samples to some preparation before analysis as per their focus on peptide content and a "full MS scan [that] covered the m/z range from 400 to 1,350". What this might mean is that some very low molecular weight compounds and indeed, potentially important larger compounds might have escaped their attention. But certainly I'm not going to quibble about this for now.

Of course this is not the first time that saliva has been used as an analytical medium in autism research (see here) outside of just looking at parameters such as cortisol (see here). And I assume it won't be the last either...

Music to close: Jane's Addiction and Stop.

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[1] Ngounou Wetie AG. et al. A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder. Autism Res. 2015 Jan 27. doi: 10.1002/aur.1450.

[2] Dumas M-E. & Davidovic L. Metabolic Profiling and Phenotyping of Central Nervous System Diseases: Metabolites Bring Insights into Brain Dysfunctions. Journal of Neuroimmune Pharmacology. 2015. Jan 24.

[3] Wood AG. et al. Mass spectrometry as a tool for studying autism spectrum disorder. Journal of Molecular Psychiatry 2013; 1: 6.

[4] Wormwood KL. et al. Salivary proteomics and biomarkers in neurology and psychiatry. Proteomics Clin Appl. 2015 Jan 29.

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ResearchBlogging.org Ngounou Wetie AG, Wormwood KL, Russell S, Ryan JP, Darie CC, & Woods AG (2015). A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder. Autism research : official journal of the International Society for Autism Research PMID: 25626423

Tuesday, 24 February 2015

Maternal recall vs. medical records: implications for autism research

I don't want to dwell too much on the findings reported by Paula Krakowiak and colleagues [1] talking about the accuracy of "maternally-reported diabetes and hypertensive disorders, and reliability of BMI [body mass index] measurements during periconception and pregnancy compared with medical records when mothers are interviewed 2-5 years after delivery" but they are potentially important.

With authors such as Krakowiak and Irva Hertz-Picciotto on the paper in question, those who follow the autism research scene might have already made the connection back to the CHARGE (CHildhood Autism Risks from Genetics and the Environment) study (beincharge!) as the source of the current data. Indeed from CHARGE, findings such as a link between maternal obesity and offspring autism risk (see here) and maternal diabetes and autism (see here) have been previously discussed on this blog. For the most part, examination of such factors linked to subsequent offspring autism diagnosis has been through self-report and post-event questioning which potentially opens up such studies to various forms of bias.

The results from Krakowiak et al seemed to suggest when questioned about such issues: "self-reported diabetes and hypertensive disorders during periconception and pregnancy show high validity among mothers." Further: "Recall of pre-pregnancy BMI is reliable compared with self-reported values in medical records." In other words, still with some caution, families involved in initiatives such as CHARGE can and do quite accurately communicate their medical history. Of course this is not the first time that science has shown parentally-derived medical information to be pretty accurate when it comes to autism as per the Gorrindo findings [2]: "sensitive to the existence, although not necessarily the nature of" gastrointestinal issues related to autism (see here). That being said, developmental history recall is still subject to some forms of bias (see here).

There's little more for me to say about this topic aside from highlighting how: "Multiparity was associated with higher discrepancies in BMI and misreporting of hypertensive disorders" suggestive that 'the state of having borne a number of children' might interfere with recall in these areas. Still, when it comes to asking parents about their health and wellbeing before, during and after the birth of their children with autism research in mind and without over-generalising, one might be a little less critical of the value of the information received.

Music to close: The Flaming Lips and Race For The Prize. Scientists... don't race for the prize!

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[1] Krakowiak P. et al. Maternal Recall Versus Medical Records of Metabolic Conditions from the Prenatal Period: A Validation Study. Matern Child Health J. 2015 Feb 6.

[2] Gorrindo P. et al. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012 Apr;5(2):101-8.

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ResearchBlogging.org Krakowiak P, Walker CK, Tancredi DJ, & Hertz-Picciotto I (2015). Maternal Recall Versus Medical Records of Metabolic Conditions from the Prenatal Period: A Validation Study. Maternal and child health journal PMID: 25656730