Subthreshold autism signs in childhood OCD

OCD in the title of this post, refers to obsessive compulsive disorder and the intriguing observation put forward by Arildskov and colleagues [1] suggesting that: "Pediatric OCD patients were found to exhibit elevated rates of ASD [autism spectrum disorder] symptoms compared to a norm group of school-age children."

Taking advantage of data collected as part of the Nordic Long-term OCD Treatment Study and specifically where "parents of 257 children and adolescents with OCD aged 7-17 completed the Autism Spectrum Screening Questionnaire", researchers looked at the possible manifestations of autism traits in their participant group. As per the opening paragraph, there was potentially more to see in this area. The authors added: "ASD symptoms were concentrated in a subgroup with a prevalence of 10-17 %" and further: "This subgroup was characterized by a male preponderance."

Bearing in mind the authors' use of the term 'subclinical' when it came to the description of autism traits in their OCD group, this is interesting research. Quite a few moons ago I took to writing about OCD and autism on this blog (see here) and the question of whether overlap between OCD and autism is just that or rather the two labels should be seen as more discrete conditions. I don't think I actually arrived at a specific answer in that previous post; just that papers such as the one from Francisca van Steensel and colleagues [2] reporting that ~17% of their cohort with autism met criteria for OCD mean that clinicians should be aware of the possibility of a connection.

Alongside other research suggesting that autistic traits are probably over-represented in quite a few clinical labels (see here for example) there are some important lessons that can be perhaps learned from such work. Invoking the paradigm of ESSENCE (see here) and specifically that the signs and symptoms of autism rarely appear in some sort of diagnostic vacuum (even clusters) I'd be minded to suggest that when it comes to assessments for autism for example, inclusion of various other screening instruments pertinent to other diagnoses might be something to consider...

Music: Gomez - 78 Stone Wobble.

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[1] Arildskov TW. et al. Subclinical autism spectrum symptoms in pediatric obsessive-compulsive disorder. Eur Child Adolesc Psychiatry. 2015 Oct 30.

[2] Van Steensel FJA. et al. Anxiety Disorders in Children and Adolescents with Autistic Spectrum Disorders: A Meta-Analysis. Clinical Child and Family Psychology Review. 2011;14(3):302-317.

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Arildskov, T., Højgaard, D., Skarphedinsson, G., Thomsen, P., Ivarsson, T., Weidle, B., Melin, K., & Hybel, K. (2015). Subclinical autism spectrum symptoms in pediatric obsessive–compulsive disorder European Child & Adolescent Psychiatry DOI: 10.1007/s00787-015-0782-5

Vitamin D levels and autism meta-analysed

A quote to begin: "Levels of serum 25(OH) D in participants with ASD [autism spectrum disorder] were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD."

That was the bottom line finding reported by Tiantian Wang and colleagues [1] following their systematic review and meta-analysis of the existing peer-reviewed science literature looking at whether serum concentrations of 25-hydroxy vitamin D - the typically measured compound reflective of vitamin D status - might be something to look at when it comes to autism.

Of course these results are nothing new to this blog and the various occasions that I've covered research suggesting that lower vitamin D levels may be 'associated' with autism (see here and see here for example). That body of work also includes the idea that some of the genetics of the vitamin D receptor might also be implicated in some autism (see here).

There is still quite a bit more to do in this area notwithstanding the idea that screening for vitamin D issues in cases of autism should be rather more prevalent than it already is. The use of vitamin D supplements in cases of insufficiency / deficiency with autism is mind is a bit of a growth area as per other research from the Wang research group (see here). The idea that vitamin D issues in autism might also overlap with various other data from other conditions / labels is also of interest (see here) given that quite a few of those labels seem to be over-represented when it comes to a diagnosis of autism or ASD (see here and see here for example). With such multiple associations in mind, one wonders whether quite a bit more 'integrated' research taking a wider view of autism and labels such as depression might be in order...

Music: The Chemical Brothers - Block Rockin' Beats.

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[1] Wang T. et al. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2015 Oct 29.

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Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, & Jia F (2015). Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. European child & adolescent psychiatry PMID: 26514973

Heavy metals, heavy conflicts and autism?

Two papers are presented for your reading delight today, both based on the often contentious issue of heavy metals and autism.

The first paper is from Farida El Baz Mohamed and colleagues [1] (open-access available here) and further substantiates the claim that for whatever reason(s) the levels of various heavy metals seem to be increased or raised in some children diagnosed with an autism spectrum disorder (ASD). The second paper by Janet Kern and colleagues [2] (open-access available here) provides results based on a systematic review of the literature on one specific heavy metal, mercury (Hg), with autism in mind and concludes that: "of the studies with public health and/or industry affiliation, 86 % reported no relationship between Hg and ASD" whilst "among studies without public health and/or industry affiliation, only 19 % find no relationship between Hg and ASD."

The Mohamed paper continues a theme that for some on the autism spectrum (remember: the autisms) there may be quite a bit more to see when it comes to the burden of heavy metals (see here). Based on hair analysis for various heavy metals - "mercury, lead, and aluminum" - researchers looked at samples from 100 children diagnosed with ASD compared with 100 age- and gender-matched controls. "Comparison between cases and controls as regards heavy metal levels shows that the mean levels of the three toxic heavy metals in hair were significantly higher among the studied ASD cases than the controls" was the primary finding. The authors further report that said heavy metal findings correlated with "maternal fish consumptions, living nearby gasoline stations, and the usage of aluminum pans" and that: "Environmental exposure to these toxic heavy metals, at key times in development, may play a causal role in autism."

I know that to talk about issues with mercury for example, can be a contentious topic with autism in mind but as uncomfortable as it might be to accept, there is some evidence of a 'connection' between elevated levels of the stuff and at least some autism (see here). The link is not, I might add, seemingly generalisable to all autism (see here) but for those children/adults presenting with elevated levels of this heavy metal, further inspection is warranted save any further health inequalities appearing when the label of autism is discussed. As to the suggestion of a connection between some autism and lead (Pb) exposure, well, again this is not the first time that this has been mentioned in the peer-reviewed literature following a more general assertion that there is nothing very good to come from when lead and children in particular meet (see here).

The paper by Kern and colleagues pours further fuel on to something of an on-going debate in some autism circles about how much factors such as conflicts of interest and research transparency may impact on autism research. Focused specifically on the issue of mercury and autism (again), the authors argue that public health or pharmaceutical industry affiliation seems to show something of a potential relationship with study outcomes when it comes to mercury and autism research. So: "over 80 % of the studies without public health or industry affiliation found evidence a relationship between Hg exposure and ASD." This contrasted with something quite a bit less when it came to studies with a public health or industry affiliation slant. Further: "The dramatic discrepancy in these results... provides evidence of biased outcomes, indicative of a conflict of interest."

The authorship group involved in the Kern paper have something of a peer-reviewed research history when it comes to this topic [3] including independent findings that hair levels of mercury might show an association with autism [4]. Their mention of mercury related compounds found in certain vaccines [5] as potentially showing a correlation with risk of autism makes for controversy in some quarters in view of the 'hot potato' that such as association has become down the years.

Appreciating that whilst the Kern findings report something of a connection between affiliations and research outcomes, I'm hard-pressed to suggest that this is hard evidence of some sort of deliberate scheme to exonerate mercury of any potential role in the very wide autism spectrum. Taking for example one paper that is cited in the Kern analysis - the paper by Barry Wright and colleagues [6] - which I've discussed before on this blog (see here) who found no overall connection between urinary mercury levels and autism, they did also call for further research in this area in light of 'outliers' being reported in their autism and their learning disability group. To quote: "further research is warranted to better understand whether a subgroup with autism or learning disabilities have mercury poisoning or excretion difficulties." In these days of plural autism (see here) one can see the logic in such a suggestion.

Music: Radiohead - Lucky.

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[1] Mohamed Fel B. et al. Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism. Behav Neurol. 2015;2015:545674.

[2] Kern JK. et al. Systematic Assessment of Research on Autism Spectrum Disorder and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research. Sci Eng Ethics. 2015 Oct 27.

[3] Geier DA. et al. Thimerosal: Clinical, epidemiologic and biochemical studies. Clinica Chimica Acta. 2015; 444: 212-220.

[4] Geier DA. et al. Hair toxic metal concentrations and autism spectrum disorder severity in young children. Int J Environ Res Public Health. 2012 Dec 6;9(12):4486-97.

[5] Geier DA. et al. A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States. Translational Neurodegeneration. 2013;2:25.

[6] Wright B. et al. A Comparison of Urinary Mercury between Children with Autism Spectrum Disorders and Control Children. PLoS ONE. 2012;7(2):e29547.

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Mohamed, F., Zaky, E., El-Sayed, A., Elhossieny, R., Zahra, S., Salah Eldin, W., Youssef, W., Khaled, R., & Youssef, A. (2015). Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism Behavioural Neurology, 2015, 1-9 DOI: 10.1155/2015/545674




Kern JK, Geier DA, Deth RC, Sykes LK, Hooker BS, Love JM, Bjørklund G, Chaigneau CG, Haley BE, & Geier MR (2015). Systematic Assessment of Research on Autism Spectrum Disorder and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research. Science and engineering ethics PMID: 26507205

The kynurenine pathway and some autism

"Our data indicated that there were alterations to the KP [kynurenine pathway] in ASD [autism spectrum disorder]. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted."

Those were some of the rather interesting results reported by Chai Lim and colleagues [1] suggesting that when it comes to tryptophan metabolism in relation to autism, the continued sole focus on serotonin and melatonin (see here) might not be the best overall research strategy.

Detailing results based on the examination of an: "Immunological profile and the KP metabolic signature" for a small group of Omani children diagnosed with autism (n=15) and their "age-matched healthy siblings" (n=12), researchers reported their findings. That specific detail about "increased production of the downstream metabolite, quinolinic acid" may indeed be an important one given connections with things like activated microglia for example [2] and the rise and rise of the 'constant gardener' with autism in mind (see here).

Obviously further studies are required to confirm the Lim findings in light of converse findings [3] (albeit reported in cerebrospinal fluid). Mention that their results might "help rationalize the efficacy of sulforaphane treatment in ASD" (yes, broccoli sprouts and autism) is another aspect in need of further investigation in these days of plural autisms (see here) and a focus on 'best' and 'non' responders to the various intervention strategies put forward with autism in mind (see here). One might also need to further expand the links between autism and schizophrenia on the basis of any kynurenine-glutamatergic link (see here).

I might finally add that as quite a fan of the need for more research into the aromatic amino acids (tryptophan, tyrosine and phenylalanine) when it comes to a label like autism (see here), I'm also of the opinion that what goes on in our deepest, darkest recesses might also be a place to look when it comes to this research. Those trillions of wee beasties that call our gut home - the gut microbiota - may seemingly have quite an effect on some of the processes involved in something like tryptophan metabolism (see here) an onwards the (bio)chemistry of how the kynurenine pathway might tie into at least some autism. Investigation of the mechanism pertinent to such processes and whether 'changing' the gut microbiota environment might impact on them, seem to be important areas of further work. Oh and speaking of tryptophan metabolites, I'll be coming to the findings reported by Dieme and colleagues [4] quite soon...

Music: Oliver Cheatham - Get Down Saturday Night (although I was slightly underwhelmed by the film Ex Machina).

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[1] Lim CK. et al. Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity. Autism Res. 2015 Oct 24.

[2] Heyes MP. et al. Human microglia convert l-tryptophan into the neurotoxin quinolinic acid. Biochemical Journal. 1996;320(Pt 2):595-597.

[3] Zimmerman AW. et al. Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol. 2005 Sep;33(3):195-201.

[4] Dieme B. et al. Metabolomics study of urine in autism spectrum disorders using a multiplatform analytical methodology. J Proteome Res. 2015 Nov 5.

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Lim CK, Essa MM, de Paula Martins R, Lovejoy DB, Bilgin AA, Waly MI, Al-Farsi YM, Al-Sharbati M, Al-Shaffae MA, & Guillemin GJ (2015). Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity. Autism research : official journal of the International Society for Autism Research PMID: 26497015

Sex, STEM careers and the 'big data' of the Autism-Spectrum Quotient (AQ)

I'm a fan of 'big data' on this blog (see here) and the particular idea that large participant numbers can offer up some really important results or patterns of results relevant to our knowledge of labels like autism.  I do also believe there is a balance to be struck between big data and somewhat smaller data - specifically the value of the N=1 when it comes to a heterogeneous condition like autism - but big data is a nice way of introducing or confirming more general trends and/or correlations.

When I therefore came across the paper by Emily Ruzich and colleagues [1] (open-access available here) talking about "Autism-Spectrum Quotient (AQ) scores in a 'big data' sample" it was music to my ears. Describing how researchers tapped into data connected to a medical TV show - "Embarrassing Bodies: Live from the Clinic" - specifically AQ scores and other data for over 450,000 people living in the UK, results are presented on the value of the AQ with autistic traits in mind and the idea that sex and occupation type might influence such self-reported characteristics.

I've been particularly interested in the AQ on this blog and its various research uses down the years. Ranging from autistic traits in those adults diagnosed with epilepsy (see here) through to autistic traits in older adults diagnosed with depressive disorders (see here), this simple to use self-report instrument is proving to be a research choice for many. I still have some reservations about the instrument; specifically, it's discriminating power when it comes to autism and schizophrenia (see here) for example, but as a rough-and-ready 'screening' instrument we have little else currently on offer and importantly, the instrument is open-access to all.

Ruzich et al reported results examining "correlations between the AQ and age, sex, occupation, and UK geographic region" as a function of the airing of a particular episode of the Embarrassing Bodies program "that included a brief TV segment following an individual with Asperger Syndrome." I hasten to add that the program title in no way describes Asperger syndrome or any other part of the autism spectrum as being 'embarrassing', merely reflecting the program content that at other times can be rather 'personal' in nature. Researchers reported that whilst age and geographic area of AQ completers did not seem to correlate with total AQ scores, there was something statistically to see when it came to scores across the sexes/genders and when taking into account the career option selected by participants. So: "[A] Career in a STEM [science, technology, engineering, and mathematics] area of work is associated in an increase in AQ scores in both genders" and "on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52)."

The authors interpret this data as further evidence "that traits commonly associated with autism are strongly linked to traits associated with being male and with STEM occupations, regardless of other factors." Those with some appreciation of the research literature in this area might know about the discussions on how parental career choice might tie into offspring outcomes specifically with autism in mind [2]. Indeed, how concepts such as 'hyper-systemising' [3] have been suggested to represent a core cognitive style in relation to autism.

These are interesting data allowing for the fact that various caveats are included in the Ruzich paper when it comes to the data collected and the participant group included. Investigations remain about how such results might generalise to the autism spectrum in terms of career paths (see here) and performance data (see here) and indeed, whether one might consider the wider schizophrenia spectrum as potentially being relevant also to the current results (see here) as part of any comorbidity.

I do think we also need to exercise a little caution in how the results are presented; the generalised idea for example, that 'extreme maleness' might be somehow connected to a career in STEM and what that might mean for the issue of women in science and specifically recruiting more women into such career paths needs to be handled with due care and respect. I'd also suggest that media headlines like: 'Are you on the autistic spectrum? Take the test' related to the Ruzich results need to be taken with a pinch of salt in light of the difference between a self-report screening instrument and a detailed assessment for autism (I'll be posting about this soon enough...)

Music: Portishead - Wandering Star.

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[1] Ruzich E. et al. Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PLoS One. 2015 Oct 21;10(10):e0141229.

[2] Wheelwright S. & Baron-Cohen S. The link between autism and skills such as engineering, maths, physics and computing: a reply to Jarrold and Routh. Autism. 2001 Jun;5(2):223-7.

[3] Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002 Jun 1;6(6):248-254.

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Ruzich E, Allison C, Chakrabarti B, Smith P, Musto H, Ring H, & Baron-Cohen S (2015). Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PloS one, 10 (10) PMID: 26488477

Symptom profiles of chronic fatigue syndrome across borders

To quote from the paper by Maria Zdunek and colleagues [1] (open-access available here): "These findings suggest that there may be important differences in illness characteristics across individuals with CFS [chronic fatigue syndrome] in the US [United States] and the UK [United Kingdom], and this has implications for the comparability of research findings across these two countries."

Looking at how symptom profiles and the "functional differences experienced by patients with chronic fatigue syndrome (CFS) across cultures" might differ, researchers set about analysing data from two cohorts of participants meeting criteria for CFS as described by the 1994 case definition (see here).

Two cohorts, based in the US (n=154) (termed the DePaul sample as a function of their previous participation in studies at DePaul University) and in the UK (n=73) (clinically referred to the RVI in Newcastle-Upon-Tyne), completed various measures of functioning related specifically to fatigue symptoms and also more general health. Results were then compared across the groups.

Quite a few group differences were noted across the study instruments used. So: "The UK sample was significantly more impaired with regard to role emotional and mental health functioning, multiple symptoms, experienced a more gradual onset of illness, and believed the cause of the illness to be both physical and psychological." In contrast: "The US sample experienced more sudden onset of illness, more frequently believed their illness to be physical, and more often were on disability."

Digging into the data with a little more detail, authors reported that quite a few more people in the DePaul sample were likely to look to the cause of their symptoms as being 'definitely physical' over the UK sample results (78% vs. 57%). Quite a few more participants in the US sample were also more likely to have been diagnosed and/or treated for conditions like fibromyalgia compared to the UK sample. What this could imply outside of more physical factors indeed being linked to symptom onset in the US sample, is something of a greater tendency to medicalise CFS in this group rather than explain it in terms of psychological and physical factors mixed together. I wonder if this might hark back to the unfortunate 'tradition' here in Blighty (UK) of viewing CFS/ME as more of a psychological issue than a physical condition and the various controversy that has surrounded this view in recent times (see here). The authors likewise suggest that: "those who believe their illness is partly psychological may have had previous experience with a psychological illness such as depression, which may influence their perception of the illness." Indeed.

Following on: "These results suggest there may be differences between the UK and US in relation to impairment in functioning, where the UK is more impaired in terms of mental health." The idea that within the constellation of symptoms that surround ME/CFS there may be a mix of physical and psychological aspects is not a new one. As per the previous paragraph, the perception of medical illness may indeed play a role in how one might define the illness. That being said, I'm generally favouring a model whereby the psychological effects noted in CFS are indeed 'effects' that stem from the initial physical/somatic nature of the condition as per other ramblings on this topic (see here). That for example, health-related quality of life is pretty much at the bottom of rankings compared with other conditions (see here) and combined with the impact of various physical ailments not normally noted in the diagnostic criteria as they stand for CFS (see here) and it's little wonder that emotional and mental health also suffer as per other research on psychiatric comorbidity accompanying such somatic complaints (see here). I don't say this to belittle the mental health aspect to CFS but rather to emphasise the continued growth of the view that CFS/ME represent a very real 'medical' condition(s) requiring 'medical' treatment/intervention (see here). Psychological intervention has some way to go in this area [2] despite other results [3] (and their criticism).

The Zdunek study is by no means perfect in terms of applicability to all ME/CFS in either the US or UK so one has to be a little cautious about extrapolating results. That the label itself is undergoing a bit of an overhaul in recent times (see here) is perhaps moving the description of the condition (at least in the US) into a more medical domain matched by the considerable efforts being put into treating it as a physical condition (see here for example). What the Zdunek study does imply, is that alongside such medical research, quite a bit more might need to be done to focus views and opinions on CFS according to geography as a physical condition in both patient and professional circles.

Debates continue in CFS/ME realms and indeed, one of the co-authors on the Zdunek paper is very much part of that debate...

To close, a Dalek relaxation tape anyone?

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[1] Zdunek M. et al. A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. Int J Psychol Behav Sci. 2015;5(2):98-107.

[2] Loades M. et al. he Cognitive Behavioral Treatment of Depression and Low Self-Esteem in the Context of Pediatric Chronic Fatigue Syndrome (CFS/ME): A Case Study. J Child Adolesc Psychiatr Nurs. 2015 Oct 16.

[3] Sharpe M. et al. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry. 2015 Oct 27. pii: S2215-0366(15)00317-X.

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Zdunek M, Jason LA, Evans M, Jantke R, & Newton JL (2015). A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. International journal of psychology and behavioral sciences, 5 (2), 98-107 PMID: 26478826