Saturday, 22 November 2014

Children as research participants: assessing competence

I was brought to writing about this topic after reading an interesting post by Virginia Hughes titled: Personhood Week: Do Kids Count? Among the various points raised in that article was some discussion about minors having medical autonomy and how this might impinge on areas outside of just medical decision-making. It also reminded me about something which was raised on more than one occasion when I undertook a stint on a University Ethics committee...

Most people involved in the medical or social care of children in the UK will probably have heard about Gillick competence or the Fraser guidelines. Coupled together under the heading of assessing competency to consent to treatment, these guidance derived from judgements in law offer details on how and when a child under the age of 16 years old is able to consent to his or her own medical treatment without parental input and/or knowledge. Contraception was the test case upon which such guidance was first introduced, but the guidance has subsequently been more widely applied to cover many areas of childhood competence in medicine.
You wouldn't eat your spinach

Gillick competence has also drifted into the arena of research (as members of any University ethics committee might know), alongside questions about whether child participation in research should be similarly governed by such guidance [1].

The recent paper by Irma Hein and colleagues [2] adds to the discussion in this area, specifically with their analysis of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the question of when competency to participate in research studies might actually come about in the paediatric population. I will also direct you to some of the preamble about their study by the same authorship group [3] (open-access).

Hein et al based on data derived from some 160 children aged between 6-18 years of age, concluded that the MacCAT-CR is a pretty good instrument when it comes to its use as a tool for assessing children's competence to consent to clinical research involvement. Perhaps more importantly however based on their results: "[in] children younger than 9.6 years, competence was unlikely (sensitivity, 90%); in those older than 11.2 years, competence was probable (specificity, 90%)". Further that: "The optimal cutoff age was 10.4 years (sensitivity, 81%; specificity, 84%)".

Acknowledging that there is quite a bit more to do in this area, including whether there may geographic variations in the age cut-off described (this was a study conducted in The Netherlands), I found these results to be potentially very important. Not only because "consent may be justified when competence can be demonstrated in individual cases by the MacCAT-CR" suggestive that the MacCAT-CR can be administered to paediatric populations, but also because of the implications for whole disciplines involving children under the age of 16 as research participants.

And on the basis of this being a blog about autism research, the question is: what influence the Hein findings might have on top of previous other ethical issues [4]?

Music to close. Mr Pharmacist by The Fall.


[1] Hunter D. & Pierscionek BK. Children, Gillick competency and consent for involvement in research. J Med Ethics. Nov 2007; 33(11): 659–662.

[2] Hein I. et al. Accuracy of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) for Measuring Children’s Competence to Consent to Clinical Research. JAMA Pediatrics. 2014. October 13.

[3] Hein IM. et al. Assessing children's competence to consent in research by a standardized tool: a validity study. BMC Pediatr. 2012 Sep 25;12:156.

[4] Hoop JG. et al. Ethical issues in psychiatric research on children and adolescents. Child Adolesc Psychiatr Clin N Am. 2008 Jan;17(1):127-48, x.

---------- Hein IM, Troost PW, Lindeboom R, Benninga MA, Zwaan CM, van Goudoever JB, & Lindauer RJ (2014). Accuracy of the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) for Measuring Children's Competence to Consent to Clinical Research. JAMA pediatrics PMID: 25317644

Friday, 21 November 2014

Genomic instability not linked to autism?

An eyebrow was raised upon reading the findings reported by Penelope Main and colleagues [1] concluding that: "it appears unlikely that genomic instability is a feature of the aetiology of autism." Based on results derived in part from "the cytokinesis-block micronucleus cytome (CBMN-cyt) assay" [2] looking at markers of DNA damage, authors reported very little to see in their small cohort of children with autism (n=35) compared with siblings (n=27) and asymptomatic controls (n=25) although with the requirement for: "replication using a larger cohort".
"Nah. I don't need one. I got a Donk".

Of equal interest to this blog was the discovery that there was no significant difference in B vitamins - outside of vitamin B2 - nor homocysteine (the 'big H') levels across the study groups. As regular readers might already know, I've covered homocysteine a few times on this blog with autism in mind (see here for example). Indeed, this authorship group have talked around this topic previously (see here).

Although no expert on the whys and wherefores of the CBMN-cyt assay outside of reading through the Fenech paper [2] and other material around the subject, I gather that this is quite a widely used method for measuring DNA damage covering: "(a) micronuclei (MNi), a biomarker of chromosome breakage and/or whole chromosome loss, (b) nucleoplasmic bridges (NPBs), a biomarker of DNA misrepair and/or telomere end-fusions, and (c) nuclear buds (NBUDs), a biomarker of elimination of amplified DNA and/or DNA repair complexes".

A quick trawl of the other research literature in this area reveals that this is not the first time that members of this group have looked at DNA damage with autism in mind as per another paper by Main and colleagues [3] (including Michael Fenech on the authorship list). On that occasion, lymphoblastoid cell lines (LCLs) from an even smaller group of children with autism and their asymptomatic siblings (N=6 pairs) were analysed for the possible presence of "increased DNA damage events" following artificial challenge to an oxidative stressor (hydrogen peroxide) among other things. They concluded: "(i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally susceptible to DNA damage." The issue of oxidative stress and autism has been discussed quite a bit in the research literature (see here).

I would tend to agree that this is still an area of autism research deserving of further investigations on the basis of that proposed oxidative stress link. I might be further showing my incompetence in this area of endeavour by also referring you back to the paper by Shuvarikov and colleagues [4] and their suggestion that HERV (human endogenous retrovirus) elements may: "mediate other recurrent deletion and duplication events on a genome-wide scale" on the basis of their findings in relation to particular types of de novo deletions including autism as part of the clinical presentation. HERVs are something I've been quite interested in for some time now, with autism (see here), attention-deficit hyperactivity disorder (ADHD) (see here) and myalgic encephalomyelitis (ME) (see here) in mind. Other retrotransposons have also cropped up in more recent times too (see here). The relationship with DNA methylation taps into the rising star discipline that is epigenetics (see here) and potentially back to the reason why homocysteine was included in the most recent Main paper (see here for my lovely hand-drawn picture of the methylation cycle). Certainly with all the recent continued interest in de novo mutations potentially linked to autism [5] it strikes me that further scrutiny of this area is perhaps warranted.

Music then... Emeli Sandé - Next To Me.


[1] Main PA. et al. Lack of Evidence for Genomic Instability in Autistic Children as Measured by the Cytokinesis-Block Micronucleus Cytome Assay. Autism Res. 2014 Nov 4. doi: 10.1002/aur.1428.

[2] Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc. 2007;2(5):1084-104.

[3] Main PA. et al. Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress. Mutagenesis. 2013 Jul;28(4):475-84.

[4] Shuvarikov A. et al. Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays. Hum Mutat. 2013 Oct;34(10):1415-23.

[5] Iossifov I. et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature. 2014 Oct 29. doi: 10.1038/nature13908.

---------- Main PA, Thomas P, Angley MT, Young R, Esterman A, King CE, & Fenech MF (2014). Lack of Evidence for Genomic Instability in Autistic Children as Measured by the Cytokinesis-Block Micronucleus Cytome Assay. Autism research : official journal of the International Society for Autism Research PMID: 25371234

Thursday, 20 November 2014

Intestinal permeability: an emerging scientific area (also with autism in mind)

What is the intestinal barrier? What is intestinal permeability? What factors affect the permeability of the intestinal barrier? How do you measure intestinal permeability? How might [altered] intestinal permeability link to health, well-being and various clinical diagnoses?
The new triad @ Bischoff SC et al. 2014

These are some of the questions tackled by the excellent open-access review by Stephan Bischoff and colleagues [1] which I would like to draw your attention to in today's ramblings.

Regular readers of this blog might already know about my borderline obsession with the inner workings of the barrier that separates the contents of our deepest, darkest recesses from the rest of the body. That and the potentially very important triad that is: gut barrier, gut bacteria and gut immune function.

I know the words 'leaky gut' still send shivers down the spines of quite a few people, particularly when mentioned in the context of autism or rather some of 'the autisms'. The NHS Choices website provides a very handy section called: "Why we should be sceptical about 'leaky gut syndrome'" further illustrating the contempt held against this area of science. But peer-reviewed science is peer-reviewed science and leaky gut is beginning to take a foothold in at least some autism research. Indeed, these past few weeks I've also seen quite a lot more positive discussion on the need for more research in this area with autism in mind (see here and see here and see here); real gut-brain science you might say.

There's little more for more to say on this issue outside of perhaps providing you with a few additional selected links to where gut permeability has been discussed on this blog, and perhaps a few areas where quite a bit more autism-related research might be indicated...

Oh, and if you want my peer-reviewed views on this whole gut permeability and autism matter with another, often contentious topic in mind, look no further [2]...

That'll do pig, that'll do. Aside that is, from another barrier [3] which might also require some further investigation with autism in mind...


[1] Bischoff SC. et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterology 2014, 14:189

[2] Whiteley P. et al. Gluten- and casein-free dietary intervention for autism spectrum conditions. Front Hum Neurosci. 2013 Jan 4;6:344.

[3] Braniste V. et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014; 6: 263ra158

---------- Bischoff, S., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J., Serino, M., Tilg, H., Watson, A., & Wells, J. (2014). Intestinal permeability - a new target for disease prevention and therapy BMC Gastroenterology, 14 (1) DOI: 10.1186/s12876-014-0189-7

Wednesday, 19 November 2014

Down Syndrome Disintegrative Disorder

"Down syndrome disintegrative disorder seems an appropriate name for this newly recognized clinical association, which may be due to autoimmunity."
"Hi, everyone. I'm Olaf and I like warm hugs!"

That was the bottom line of the study published by Gordon Worley and colleagues [1] reviewing a small number of cases (N=11) of children diagnosed with Down's syndrome presenting at clinic "with a history of new-onset... or worsening... autistic characteristics" among other things. Based on some potentially important hunches (see here for a summary of the grant proposal for the project), researchers at Duke University and the Duke Down Syndrome Comprehensive Clinic reported results based on various behavioural and biochemical findings including that: "Ten of 11 cases (91%) had elevated ("positive") thyroperoxidase antibody titers compared to only 5 of 21 (23%) age-matched control subjects with Down syndrome".

As preliminary as these findings were, I was really rather interested to read about this study. Not only because of the link established between Down's syndrome (DS) and the presentation of autistic features harking back to some other important work (see here), but also the idea that autoimmunity might potentially be a driving force to such regressive features. Of course we already have something of a template for such a 'disintegrative disorder' in the description of Heller's syndrome, also known as childhood disintegrative disorder (CDD) (see here for some background). Until recently, CDD was included under the category 'Pervasive Developmental Disorder' roughly translating as part of the autism spectrum; although in the DSM update (DSM-5), the diagnosis no longer appears as such (see here). CDD and autism have a somewhat convoluted history intersecting with one and another during various research times and under different circumstances (see here).

Insofar as those anti-thyroid peroxidase (anti-TPO) antibodies being [positively] reported in quite a few cases of Down syndrome disintegrative disorder (DSDD), my interest is maintained. Issues potentially affecting thyroid function in relation to DS are not uncommonly reported in the research literature [2] and so one might not necessarily be surprised to hear that the presence of anti-TPO antibodies have been recorded previously [3]. Whether this finding overlaps with the Worley results in terms of early evidence for DSDD is a question we can't answer at the moment.

Indeed, autoimmunity in general, has something of a relationship with DS as per reviews such as the one by Chistiakov [4] (open-access). The fact that mention is made of coeliac disease (CD) as part of that autoimmune burden is something of particular interest to me; as the paper by Mårild and colleagues [5] noted: "a sixfold increased risk of CD in individuals with DS". These findings are all the more pertinent given that they also include one Jonas Ludvigsson on the authorship list, he of 'gluten issues not quite coeliac disease linked to some autism' (see here).

Going back specifically to the anti-TPO antibodies, I note that with the 'autistic characteristics' in mind, very little peer-reviewed research has been published in this area. It could be that anti-TPO antibodies are not something commonly seen in relation to autism or perhaps because very few people have actually looked at this issue. I will draw your attention to some of the work by Gustavo Román and colleagues [6] (see this post) which reported: "No [autism] risk was found for children of TPO-antibody–positive mothers".

That would have been all I would have said on the matter had the paper from Alan Brown and colleagues [7] not recently emerged indicating that within their cohort: "The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab + [positive for anti-TPO antibodies] during pregnancy (OR = 1.78, 95% CI = 1.16–2.75, p = 0.009), compared to mothers negative for this autoantibody". As interesting as this finding is, it still tells us very little about anti-TPO antibody status for those diagnosed with autism or an autism spectrum disorder (ASD) and how this might overlay with the DSDD description. I might also add that I have talked previously about research suggesting that such autoantibodies might have some link to certain kinds of depression (see here) which also draw in the possibility of comorbidity playing some role [8].

The Worley results, as preliminary as they are, are certainly worthy of further research consideration. It is a revelation to me even having an extended family member with DS, that beyond the classical presentation, there may be quite a bit more medical comorbidity which may require clinical attention. If Worley et al are indeed correct that for those with DSDD autoimmunity plays such an important role, it strikes me that directing efforts to tackle specific symptoms [9] or even autoimmune processes (as per other autoimmune conditions) might yield quite a few benefits for at least some.

Music: The Clash - Rock the Casbah.


[1] Worley G. et al. Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. J Child Neurol. 2014 Nov 3. pii: 0883073814554654.

[2] Prasher VP. Down syndrome and thyroid disorders: a review. Downs Syndr Res Pract. 1999 Aug;6(1):25-42.

[3] Chen MH. et al. Thyroid dysfunction in patients with Down syndrome. Acta Paediatr Taiwan. 2007 Jul-Aug;48(4):191-5.

[4] Chistiakov D. Down syndrome and coexistent autoimmune diseases. J Applied Biomed. 2007; 5: 71-76.

[5] Mårild K. et al. Down syndrome is associated with elevated risk of celiac disease: a nationwide case-control study. J Pediatr. 2013 Jul;163(1):237-42.

[6] Román GC. et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Aug 13. doi: 10.1002/ana.23976.

[7] Brown AS. et al. Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2014. 29 October.

[8] Walker JC. et al. Depression in Down syndrome: a review of the literature. Res Dev Disabil. 2011 Sep-Oct;32(5):1432-40.

[9] Hegedüs L. et al. Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto's thyroiditis. Clin Endocrinol (Oxf). 1991 Sep;35(3):235-8.

---------- Worley G, Crissman BG, Cadogan E, Milleson C, Adkins DW, & Kishnani PS (2014). Down Syndrome Disintegrative Disorder: New-Onset Autistic Regression, Dementia, and Insomnia in Older Children and Adolescents With Down Syndrome. Journal of child neurology PMID: 25367918

Tuesday, 18 November 2014

Paediatric congenital heart disease and autism risk?

"Children aged 2-17 with CHD [congenital heart disease] were more likely than those without CHD to have had a diagnosis of autism spectrum disorder (crude OR, 4.6; 95% CI, 1.9-11.0) or intellectual disability (Crude OR, 9.1; 95% CI, 5.4-15.4)".
The traveller @ Wikipedia 

That was a key conclusion reported in the study by Hilda Razzaghi and colleagues [1] based on their analysis of data from "the 1997-2011 National Health Interview Survey", a US initiative which aims to provide "information on the health of the U.S. civilian noninstitutionalized population through confidential interviews conducted in households" (see here).

I have to say that I was pretty interested in these findings (even though this is not the first time that neurodevelopmental outcomes have been tied to CHD); a view it seems, that was shared by the authors of the paper, bearing in mind the very wide confidence intervals (CIs) detailed for both conditions and the reliance on second-hand reporting over actual independent screening results. I can't readily offer any one 'smoking gun' explanation for the findings specifically in relation to the autism spectrum but will draw your attention to some discussion about the potential causes of congenital heart disease provided by the NHS Choices websites and how they might tie in.

So: various genetic conditions including Down's syndrome are linked to CHD [2] and the net seems to be closing in on some of the underlying genetics around the association [3]. Although still in need of quite a bit more study, there is a growing appreciation that a diagnosis of autism / autistic traits can coexist alongside a diagnosis of Down's syndrome (see here). As per a recent conversation (thanks Marilyn), one also wonders how this autism - Down's syndrome link might also play out with regards to other areas of the autism research landscape such as dietary effects for example...

Next up is maternal diabetes. As per the NHS Choices entry: "It is estimated that 3 to 6% of women with diabetes who become pregnant will give birth to a baby with a heart defect". Autism and maternal diabetes is an interesting topic which has again cropped up in the autism research literature [4]. If you want my take on the Xu meta-analysis paper and related literature, look no further...

After that is a role for alcohol consumption during pregnancy and mention of the condition called foetal alcohol syndrome (FAS). I have talked about FAS and foetal alcohol spectrum disorder (FASD) before on this blog in the context of autism (see here) but can't readily conclude that the links are overly strong between FAS/FASD and autism presentation.

"A rubella infection can cause multiple birth defects, including congenital heart disease". An interesting association given the history of rubella and autism based to quite a large extent on the work from Stella Chess [5]. I don't know enough about the rate of rubella infection in pregnant women to make any informed statement about how this risk factor might tie into both CHD and autism but the numbers of non-immune women do seem to be quite alarming here in the UK [6].

Influenza during pregnancy? "Women who get flu during the first trimester (three months) of pregnancy are twice as likely to give birth to a baby with congenital heart disease than the general population" according to the NHS Choices website. Regular readers of this blog might already know that I tend to talk quite a bit about how infection - immune system response to infection - during pregnancy seems to have some link to subsequent offspring psychology and development (see here). The link is not altogether straight forward with autism in mind and potentially better related to concepts like fever or fever control [7] but still, there might be more to do here.

The final links - certain medications taken during pregnancy, phenylketonuria (PKU) and exposure to organic solvents during pregnancy - have also, to various extents, been linked to autism (see here and see here for example).

I may very well just be plucking at straws trying to link the causes of CHD with some of the suspected 'causes' of autism (some autism at least) but it strikes me that if one was to further pursue the findings reported by Razzaghi et al those would be the places to start (assuming some shared effect). As per the reports of other physiological findings potentially manifesting alongside a diagnosis of autism (see here), some additional screening of children on the autism spectrum where one or more of the correlates of CHD are suspected might be indicated.

Peter Gabriel and Kate Bush with a beautiful song to close: Don't Give Up.


[1] Razzaghi H. et al. Long Term Outcomes in Children with Congenital Heart Disease: National Health Interview Survey. J Pediatr. 2014 Oct 8. pii: S0022-3476(14)00820-8.

[2] Laursen HB. Congenital heart disease in Down's syndrome. Br Heart J. Jan 1976; 38(1): 32–38.

[3] Ramachandran D. et al. Contribution of copy-number variation to Down syndrome-associated atrioventricular septal defects. Genet Med. 2014 Oct 23. doi: 10.1038/gim.2014.144.

[4] Xu G. et al. Maternal diabetes and the risk of autism spectrum disorders in the offspring: a systematic review and meta-analysis. J Autism Dev Disord. 2014 Apr;44(4):766-75.

[5] Chess S. Follow-up report on autism in congenital rubella. J Autism Child Schizophr. 1977 Mar;7(1):69-81.

[6] Skidmore S. et al. Is the MMR vaccination programme failing to protect women against rubella infection? Epidemiol Infect. 2014 May;142(5):1114-7.

[7] Zerbo O. et al. Is maternal influenza or fever during pregnancy associated with autism or developmental delays? Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) study. J Autism Dev Disord. 2013 Jan;43(1):25-33.

---------- Razzaghi H, Oster M, & Reefhuis J (2014). Long Term Outcomes in Children with Congenital Heart Disease: National Health Interview Survey. The Journal of pediatrics PMID: 25304924

Monday, 17 November 2014

Social anxiety in one in four adults with autism

"Twenty-eight percent (14 of 50) of individuals with ASD [autism spectrum disorder] fulfilled the diagnostic criteria for SAD [social anxiety disorder]".
"I am Vulcan, sir. We embrace technicality."

So said the findings reported by Susanne Bejerot and colleagues [1] (open-access) as part of their investigations looking at SAD occurrence among adults diagnosed with ASD. Once again the sometimes very disabling issue of anxiety resurfaces with autism in mind. Before going on, I'm minded to reiterate that SAD in the context of this research/post means social anxiety disorder and not seasonal affective disorder (which also uses the same acronym).

The Bejerot paper is open-access but a few factoids from the study might be in order:

  • Drawing on participant data derived from another study by the authors [2] talking about [some] autism as potentially being representative of a "gender defiant disorder", 50 adults diagnosed with autism were compared with 53 asymptomatic controls and 100 participants diagnosed with SAD.
  • Various measures were used to ascertain things like autistic traits and the presence of any other psychiatric issues including the Mini International Neuropsychiatric Interview (M.I.N.I.) and the Autism Spectrum Quotient (AQ). When it came to looking at social anxiety and social avoidance, the Liebowitz Social Anxiety Scale Self-Report (LSAS-SR) was used and "SAD diagnosis was established by diagnostic interview using the Structure Clinical Interview for DSM-IV (SCID)".
  • Results: those diagnosed with SAD (not comorbid to autism) showed the highest (mean) scores when it came to social anxiety and avoidance based on the LSAS-SR measure. This is probably not an unexpected finding given that they were already diagnosed with SAD. But... the ASD group were not that far behind based on their scores on these parameters and ahead of the asymptomatic controls: "[significantly] higher scores of anxiety and avoidance in ASD relative to subjects in the non-ASD comparison group".
  • Then the headline result suggesting that over a quarter of those with autism also fulfilled diagnostic criteria for SAD (based on their M.I.N.I results) and further that: "the 14 individuals that fulfilled the criteria for social anxiety had a higher AQ score... than the rest of the group". This last point potentially ties the two diagnoses (autism and SAD) together as per some recent chatter about intolerance of uncertainty and autism (see here) and with social communication issues specifically in mind, the findings reported by Georgia Halls and colleagues [3] (open-access).

There are some potentially very important points to take from the Bejerot findings specifically in relation to the requirement for further screening as and when a diagnosis of ASD is received. It's an all too common theme these days, that the label 'autism' rarely exists in a diagnostic vacuum both during childhood (see here) and into adulthood (see here for example). Although not exactly making great reading, some of that comorbidity (if that is what it actually is) can for some people on the autism spectrum, lead down some very dark roads indeed (see here). The first step it seems, is screening for said comorbidity in order to start thinking about how such issues can be mitigated and quality of life improved (as and when required).

Just before I leave you to further mull over the Bejerot findings, I'll also draw your attention to a few other details discussed by the authors. They talk about possible "differences in the quality of social anxiety in ASD and SAD" as a function of some of the unique issues which follow a diagnosis of autism. So, social awkwardness is discussed, and the quite sweeping statement that "the ASD group is socially awkward" as being a possible differentiator from the SAD group who: "sense that they are socially incompetent" despite possessing the appropriate skills to socialise. I assume this idea stems from the developmental aspect of autism?

Interestingly too, the authors also suggest that issues with the concept of insight might be something which may help protect some on the autism spectrum from developing social anxiety. The idea being that the realisation of said social awkwardness might promote social anxiety and conversely "individuals with ASD and poor insight may be protected from developing social anxiety". As difficult an issue this might be to think about, the authors draw on other data which proposed that: "either unawareness of, or perhaps being unconcerned with how people perceive them, could be protective factors for social anxiety [in cases of autism]". Certainly there seems to be quite a bit more to do in this area outside of other potentially important work [4]. I wonder also for example, whether the concept of self-monitoring might come into play here too?

Music to close and having seen Bryan Adams last evening, I have something of a new found admiration for some of his music, so here is a classic: Summer of '69.


[1] Bejerot S. et al. Social anxiety in adult autism spectrum disorder. Psychiatry Research. 2014; 220: 705-707.

[2] Bejerot S. et al. The extreme male brain revisited: gender coherence in adults with autism spectrum disorder. Br J Psychiatr. 2012; 201: 116-23.

[3] Halls G. et al. Social communication deficits: Specific associations with Social Anxiety Disorder. Journal of Affective Disorders. 2015; 172: 38–42.

[4] White SW. et al. Social-cognitive, physiological, and neural mechanisms underlying emotion regulation impairments: understanding anxiety in autism spectrum disorder. Int J Dev Neurosci. 2014 Dec;39:22-36.

---------- Bejerot S, Eriksson JM, & Mörtberg E (2014). Social anxiety in adult autism spectrum disorder. Psychiatry research PMID: 25200187

Saturday, 15 November 2014

Milk has gotta lotta bottle?

"High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women". Those were some of the conclusions reached in the study by Karl Michaëlsson and colleagues [1] (open-access) looking at milk consumption and "mortality and fractures in women and men". The BBC among other media have covered the study (see here).
Take me out tonight

Based on quite a large participant group (two actually) who completed a food frequency questionnaire among other things, researchers followed over 100,000 people some 10-20 years later to ascertain details on "fracture events" and mortality. For a smaller subgroup, they also reported on: "the urine oxidative stress marker 8-iso-PGF2α, a dominant F2-isoprostane and an ideal standard biomarker of oxidative stress in vivo" on the basis of analysing any connection between: "D-galactose in milk with theoretical influences on processes such as oxidative stress and inflammation". Oh, and a familiar cytokine also gets a mention: interleukin-6.

Authors, with caveats, reported something of a possible connection between milk intake and outcomes: "a dose dependent higher rate of both mortality and fracture in women and a higher rate of mortality in men with milk intake, a pattern not discerned with other dairy products" and "positive associations between milk intake and concentrations of markers for oxidative stress and inflammation". IL-6 levels were also correlated with milk intake (although surprisingly little is made of this association in my opinion bearing in mind some of the other literature in this area [2]). For quite a thorough review of the study and findings, I will refer you to the NHS Choices take on it (see here).

Milk has been something of some interest to this blog down the year based on my preoccupation with diet and [some] autism [3] (see here and see here for examples) and further a possible relationship with other behaviourally-defined conditions (see here). I have tried not to come down too heavy on the white stuff (see here) given that it's not all doom and gloom when it comes to the benefits of milk for quite a few people albeit with the sunshine vitamin/hormone also needing to be considered. As an aside, the recent coverage of the the Caerphilly Cohort Study and their 'roadmap to healthy ageing' (see here) previously also talked about milk products and "a markedly reduced prevalence of the metabolic syndrome" [4], so one has to be slightly cautious about demonising milk generally.

The Michaëlsson results however cannot be readily ignored given the impressive participant size and prospective design of study used. The fact that authors reported findings pertinent to milk consumption but that "intake of fermented milk products such as yogurt and soured milk and cheese were associated with lower rates of fracture and mortality" is also potentially important. I could start going on about how processing might affect lactose / galactose content in some cheeses [5] and yoghurts [6] but this is perhaps fodder for another day. Likewise the findings reported by Ji and colleagues [7] suggesting "people with lactose intolerance, characterised by low consumption of milk and other dairy products, had decreased risks of lung, breast, and ovarian cancers" might also be relevant. I note also that chatter about casein (the protein in milk) content as a function of researchers findings are largely absent from the discussions but are perhaps also potentially relevant in light of the whole A1-A2 milk issue rising in prominence these days (also including mention of oxidative stress too).

Music to close: Lorde - Yellow Flicker Beat.


[1] Michaëlsson K. et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ. 2014; 349.

[2] Labonté MÈ. et al. Dairy Product Consumption Has No Impact on Biomarkers of Inflammation among Men and Women with Low-Grade Systemic Inflammation. J Nutr. 2014 Nov;144(11):1760-7.

[3] Whiteley P. Nutritional management of (some) autism: a case for gluten- and casein-free diets? Proc Nutr Soc. 2014 Oct 14:1-6.

[4] Elwood PC. et al. Milk and dairy consumption, diabetes and the metabolic syndrome: the Caerphilly prospective study. J Epidemiol Community Health. Aug 2007; 61(8): 695–698.

[5] Portnoi PA. & MacDonald A. Determination of the lactose and galactose content of cheese for use in the galactosaemia diet. J Hum Nutr Diet. 2009 Oct;22(5):400-8.

[6] Alm L. Effect of fermentation on lactose, glucose, and galactose content in milk and suitability of fermented milk products for lactose intolerant individuals. J Dairy Sci. 1982 Mar;65(3):346-52.

[7] Ji J. et al. Lactose intolerance and risk of lung, breast and ovarian cancers: aetiological clues from a population-based study in Sweden. Br J Cancer. 2014. October 14.

---------- Michaelsson, K., Wolk, A., Langenskiold, S., Basu, S., Warensjo Lemming, E., Melhus, H., & Byberg, L. (2014). Milk intake and risk of mortality and fractures in women and men: cohort studies BMJ, 349 (oct27 1) DOI: 10.1136/bmj.g6015