Wednesday 30 September 2015

Regular exercise and motor skills training for autism?

I approach the study results presented by Serge Brand and colleagues [1] (open-access available here) with some caution given the preliminary nature of the findings suggesting that: "regular AET [aerobic exercise training] and MST [motor skill training] impact positively on sleep, MSs, and mood among children with ASD [autism spectrum disorder]." The caution is due to the fact that the Brand results report on an uncontrolled pilot study (we've all done them) and included only 10 children diagnosed with an autism spectrum disorder (ASD).

Researchers report how "an individual training plan was created" for each participant, consisting of three sessions weekly including "a 30-minute bicycle workout (AET) followed by 30 minutes of training in coordination and especially in balance (MST)." Cycle training was chosen because it: "is easily adapted to individual motor abilities and allows specific progressive steps" and "allows training in the endurance zone." Further: "The intervention was executed in a highly structured manner and was based on the “Applied Behavioral Analysis” (ABA) method."

Whilst the intervention was running, various measures were employed to primarily look at aspects of sleep. This included sleep EEGs and sleep polygraphs. More subjective data were also obtained from sleep schedules and "the Insomnia Severity Index (ISI), a screening tool for insomnia."

Results: perhaps unsurprisingly, some aspects of sleep were 'unusual' for quite a few of the small participant group. So: "Mild-to-moderate insomnia was reported in 70% of children." Further: "a 3-week intervention involving AET and MST improved specific MSs and led to improved objectively assessed sleep on nights following PA as compared to nights not preceded by PA. Mood also improved over time." I might reiterate that this was an uncontrolled pilot study and, as the authors suggest: "future studies might also add control groups such as children with ASD on a waiting list and healthy controls."

This is not the first time that physical activity and sleep patterns in relation to autism have been looked at in the peer-reviewed literature (see here). As per the results from Wachob & Lorenzi [2] using a similarly 'preliminary' study design, there may be quite a bit more to see in this area subject to more robust research strategies. As to how far this will go, well others have their own views on this [3]. That physical fitness might not necessarily be the deciding factor here (see here) but rather the level of physical activity is something else to consider in this area.

One final note that I might make in this whole area of physical activity with autism in mind, is the idea that there may be more than one way to get kids/adults up and active. Martial arts is something that I'm particularly keen on seeing more research done on in light of some initial research in this area with autism in mind (see here) and other potentially 'over-represented' comorbidity such as attention-deficit hyperactivity disorder (ADHD) (see here). I know it's probably not going to be suitable for everyone (avoiding sweeping generalisations!) but given the emphasis on motor skills and aerobic exercise that disciplines such as karate offers, it could be one option to consider...

To close, Alan Whicker on karate - "so deadly that most of the Japanese are frightened of it" (apparently).


[1] Brand S. et al. Impact of aerobic exercise on sleep and motor skills in children with autism spectrum disorders - a pilot study. Neuropsychiatr Dis Treat. 2015 Aug 5;11:1911-20.

[2] Wachob D. & Lorenzi DG. Brief Report: Influence of Physical Activity on Sleep Quality in Children with Autism. J Autism Dev Disord. 2015; 45: 2641-2646.

[3] Archer T. Exercise Alleviates Autism Spectrum Disorder Deficits. Autism Open Access 2015; 5:146.

---------- Brand S, Jossen S, Holsboer-Trachsler E, Pühse U, & Gerber M (2015). Impact of aerobic exercise on sleep and motor skills in children with autism spectrum disorders - a pilot study. Neuropsychiatric disease and treatment, 11, 1911-20 PMID: 26346856

Tuesday 29 September 2015

Herpes simplex virus (HSV) infection and cognitive ability

So: "our findings indicate that infection with HSV-1 [Herpes simplex virus] is associated with reduced cognitive functioning in healthy individuals."

That was the conclusion reached in the study by Eyal Fruchter and colleagues [1] who based on a "representative, random sample of 612 soldiers before active duty in the Israeli military (Israeli defense force — IDF)" looked at cognitive functioning and language abilities as a function of HSV status ("62.2% HSV positive (n = 381) and 38.8% HSV negative (n = 231)").

They observed some key differences between the HSV positive and negative groups whereby IQ scores were on average lower for the seropositive group compared with the seronegative group. This difference also stretched to language scores too and stayed pertinent as and when various psychopathology (anxiety, depression) were controlled for. The authors plant their findings within the context of schizophrenia and that their results indicate "that many research findings seemingly characteristic of schizophrenia are related to the association between HSV exposure and cognitive functioning in general, and are not illness specific."

This is an interesting branch of research. I was unaware that HSV-1 seropositivity was potentially correlated to cognitive functions but a quick trawl through some of the other literature in this area does indeed reveal that this is not the first time that such an association has been made [2] (with appropriate caveats). Even some big names in schizophrenia research (Faith Dickerson & Robert Yolken) have discussed HSV-1 and cognitive functions, within the context of schizophrenia [3].

There are some potentially pretty stark implications from such findings. That there may be a 'link' between cognitive and intellectual functions and infectious agents is a primary one (see here). That processes such as inflammation (and immune functions) might also play a role is another (see here). Whilst further research is required to put some scientific flesh on the bones of the potential biological / genetic processes involved in such a relationship, the tantalising question is whether 'treating' such viral infections (if treatment is available) might have a knock-on effect for intellectual functions?

Music: Mumford & Sons - Ditmas.


[1] Fruchter E. et al. The impact of Herpes simplex virus type 1 on cognitive impairments in young, healthy individuals — A historical prospective study. Schizophrenia Research. 2015. Sept 8.

[2] Tarter KD. et al. Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey. J Infect Dis. 2014 Mar;209(6):837-44.

[3] Thomas P. et al. Exposure to herpes simplex virus, type 1 and reduced cognitive function. J Psychiatr Res. 2013 Nov;47(11):1680-5.

---------- Fruchter, E., Goldberg, S., Fenchel, D., Grotto, I., Ginat, K., & Weiser, M. (2015). The impact of Herpes simplex virus type 1 on cognitive impairments in young, healthy individuals — A historical prospective study Schizophrenia Research DOI: 10.1016/j.schres.2015.08.036

Monday 28 September 2015

Autism traits in older adults with depressive disorders

"ASD [autism spectrum disorder] might be overlooked in older adults and especially within geriatric psychiatry when diagnosing and treating depression and anxiety in older patients one should be attentive to ASD."

So concluded Hilde Geurts and colleagues [1] as a function of their results looking for the presence of autistic traits in older adults with and without depressive disorders participating in the Netherlands study of depression in older persons (NESDO) initiative. Based on the analysis of some 250 older adults (aged between 60-90 years) fulfilling DSM-IV depressive disorder criteria compared against 114 non-depressed older adults, researchers noted quite a few more autistic traits in the depressed older adults based on the use of the "abbreviated Autism Spectrum Quotient [AQ]." In more detail: "Of the older adults with a depressive disorder 31% showed elevated ASD characteristics, which is much higher than the observed 6% in the comparison group."

I don't want to dwell too long on these results but there are some potentially important things to say about them. First is the emphasis on autistic traits over and above a diagnosis of autism. There is a difference; as I've discussed in other recent work (see here). Second is the authors' use of the AQ and how one has to be a little careful about what the AQ is actually measuring (see here). Third is the importance of the related finding reported by Geurts et al on how: "High ASD characteristics were associated with elevated depression and anxiety symptoms, and more comorbid anxiety disorders." As I've mentioned before on this blog, depression and anxiety can represent significant 'loading' when autism is diagnosed (see here and see here). These latest findings potentially further strengthen the links. Finally, is the intriguing prospect that autism screening in older adults might contribute to all those debates about the prevalence of autism and specifically adult autism (see here).

No music to close today, just some rather peculiar news about the end of the world (again).


[1] Geurts HM. et al. Autism characteristics in older adults with depressive disorders. The American Journal of Geriatric Psychiatry. 2015. Sept 3.

---------- Geurts, H., Stek, M., & Comijs, H. (2015). Autism characteristics in older adults with depressive disorders The American Journal of Geriatric Psychiatry DOI: 10.1016/j.jagp.2015.08.003

Saturday 26 September 2015

T. gondii infection and autism?

I was interested to read the paper by Joseph Prandota and colleagues [1] who observed that: "latent chronic T. gondii [Toxoplasma gondii] infection have an important impact on triggering and development of ASD [autism spectrum disorders], at least in a subset of autistic children, and this requires some modification(s) of its diagnostic procedures and treatment regimens." Big words, I'm sure you'll agree.

From the start I'll indicate that I'm interested in T. gondii on this blog. This parasitic protozoan is one of nature's survivors (and thrivers) with effects that may go far beyond your ordinary parasite. Aside from potentially making rats attracted to cats (or cat urine), I've been particularly interested in the collected research looking at a possible association between T. gondii and the presentation of schizophrenia (see here for example). The idea that infection with T. gondii under the right circumstances may be associated with a condition as complicated as schizophrenia is not without its critics, but in a world of increasing pluralisation of such labels (see here) I'd be minded to keep T. gondii on the research agenda (see here) for now.

The Prandota findings, based on a small-ish group of children diagnosed with ASD living in Egypt, take things one step further when it comes to T. gondii and it's potentially wide-ranging effects. Working with the aim to "estimate the seroprevalence of chronic toxoplasmosis among autistic children" researchers set about assaying for "anti-T. gondii IgG antibody seroposivity" alongside a couple of other parameters including "serum levels of IFN-g and nitric oxide (NO) in T. gondii-positive and T. gondii-free patients." I might add that a positive anti-T. gondii IgG result indicates previous exposure to T. gondii. It does not necessarily mean current or on-going infection which can only be reliably ascertained via other tests (see here).

Results: "11 (29.3%) out of the 46 autistic children... were positive for serum anti-T. gondii IgG antibodies as compared with 2 patients (4%) with toxoplasmosis found among 50 control children." Age was one of the parameters that seemed to play a role in infection history which kinda stands to reason (the older you are, the more likely that you have an exposure). Further: "Autistic children with toxoplasmosis had markedly increased both serum IFN-g and NO concentrations... as compared with the values obtained in patients without toxoplasmosis."

I don't want to over-analyse the Prandota results at this stage in terms of what elevations of IFN-γ and NO might mean to T. gondii infection in autism, so I won't. The authors go into some detail about immune function, tryptophan metabolism and even glutathione gets a mention in relation to these issues, but I'd prefer to stick to the T. gondii estimates for now.

As far as I can see, this is one of the first times that T. gondii infection has been discussed with autism in mind. That over a quarter of cases in the Prandota sample were found to have been in immunological contact with the protozoan is interesting and suggests that further independent investigations should be initiated in this area. I would, for example, be interested to know whether such findings are transferable to other geographical sites? Does cat ownership show any link to findings as per some discussions in schizophrenia (see here)? Are there any links with other 'autism-related' issues as suggested by Abdoli & Dalimi [2]? And, with some of my own research interests in mind (see here) could such findings further extend the observations of Emily Severance and colleagues [3] talking about T. gondii infection and "sensitivity to gluten" beyond schizophrenia (see here)? Well, it's not as if anti-gliadin antibodies (IgG) are strangers to [some] autism (see here).

As for treating any on-going toxoplasmosis, well in the US at least, this might just have got a little bit more expensive...

Questions (and answers) remain.

Music: Artful Dodger - Movin' Too Fast.


[1] Prandota J. et al. Increased Seroprevalence of Chronic Toxoplasmosis in Autistic Children: Special Reference to the Pathophysiology of IFN-γ and NO Overproduction. International Journal of Neurology Research. 2015; 3: 102-122.

[2] Abdoli A. & Dalimi A. Are There any Relationships between Latent Toxoplasma gondii Infection, Testosterone Elevation, and Risk of Autism Spectrum Disorder? Front Behav Neurosci. 2014 Sep 24;8:339.

[3] Severance EG. et al. Anti-gluten immune response following Toxoplasma gondii infection in mice. PLoS One. 2012;7(11):e50991.

---------- Joseph Prandota, Noha Abdel Fattah Elleboudy, Khadiga Ahmed Ismail, Osama Kamal Zaki, & Hanan Hussein Shehata (2015). Increased Seroprevalence of Chronic Toxoplasmosis in Autistic Children: Special Reference to the Pathophysiology of IFN-γ and NO Overproduction International Journal of Neurology Research, 1 (3), 102-122 : 10.17554/j.issn.2313-5611.2015.01.30

Friday 25 September 2015

Baby teeth and autism research

"This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism."

That was one of the conclusions reached in the paper by Raymond Palmer and colleagues [1] (open-access available here) who played science tooth fairy with 71 deciduous teeth (baby teeth) provided by children with autism from a "tooth repository consisting of 928 children’s deciduous teeth." As per other reports with autism in mind using these potentially important biological samples [2], there is quite a lot of information potentially available from baby teeth assuming one knows how to handle such samples.

For Palmer et al the analytical methods of choice were "liquid chromatography tandem mass spectrometry and gas chromatography" echoing other autism biomarker research discussed on this blog (see here) and fairly commonly appearing in the peer-reviewed literature [3]. Levels of various compounds were assessed in the pulverised baby teeth samples including "acetaminophen [paracetamol], ARA [arachidonic acid], DEET [diethyl-m-toluamide], TCPy [3,5,6-trichloro-2-pyridinol], IMPy [2-isopropyl-6-methyl-4-pyrimidinol], and MEHP [mono-2-ethylhexyl phthalate]." Just in case you aren't an organic chemist, many of those compounds are metabolites of "pesticides, plastics, or medications" and were studied in light of previous work from this authorship group [4] and the suggestion that some of them might be relevant to autism risk and/or onset (see here for example) or at least serving up an interesting correlation.

Consistent with that previous report, Palmer and colleagues "demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth." Drawing on information from both US children with autism (a "collection of deciduous teeth through collaborative efforts with the Interactive Autism Network (IAN)") and Mexican children with autism, various results are presented. "Despite demographic differences in the two samples, there were similar rates of detection for all chemicals" was one of the primary findings. So, round about 40% of samples from both geographic groups were detected to have traces of acetaminophen (paracetamol) in them for example. This finding tallied to some degree with parent report about paracetamol use during pregnancy and infancy. Other results can be seen in some of the accompanying tables (see here for example).

Importantly, Palmer and colleagues discuss what their findings do and do not mean. "While we have demonstrated that chemicals relevant to ASD [autism spectrum disorders] can be detected in deciduous teeth and are associated with mothers’ self-reported exposures, our results are limited in generalizability—largely due to the sample consisting entirely of children with ASD." In other words, the sole focus on baby teeth from children with autism does not necessarily mean that any compounds detected 'cause' autism given the snapshot view of their study and the lack of appropriate asymptomatic control samples analysed. Further work is indicated in this area to "include more diverse participants and neurotypical children as controls will allow case/control comparisons."

The use of baby teeth represents an interesting addition to tissue analysis when it comes to autism. Given the availability of such teeth, the timing of their availability and the relatively non-invasive way that such samples can be collected, there are quite a few positives to the use of such as resource in autism research. Combined with other fairly non-invasively collected samples such as urine (see here), saliva samples (see here) and potentially even things like nail clippings [5], there is quite a bit of information potentially available for autism research. That being said, the word 'biomarker' with autism in mind, needs to be rather carefully used in light of things like plurality...

Music: Maroon 5 - Sugar.


[1] Palmer RF. et al. Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples. J Environ Public Health. 2015;2015:862414.

[2] Adams JB. et al. Mercury, lead, and zinc in baby teeth of children with autism versus controls. J Toxicol Environ Health A. 2007 Jun;70(12):1046-51.

[3] Wang H. et al. Potential serum biomarkers from a metabolomics study of autism. J Psychiatry Neurosci. 2015 Sep 22;40(5):140009.

[4] Camann DE. et al. Acetaminophen, pesticide, and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure. Journal of Exposure Science and Environmental Epidemiology. 2013; 23: 190–196.

[5] Shu I. et al. Detection of Drugs in Nails: Three Year Experience. J Anal Toxicol. 2015 Oct;39(8):624-8.

---------- Palmer, R., Heilbrun, L., Camann, D., Yau, A., Schultz, S., Elisco, V., Tapia, B., Garza, N., & Miller, C. (2015). Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples Journal of Environmental and Public Health, 2015, 1-9 DOI: 10.1155/2015/862414

Thursday 24 September 2015

HERVs as a mechanism of genetic deletion formation: relevance to some autism?

My stark lack of knowledge in the area of genetics and specifically that linked to the human endogenous retroviruses (HERVs) that litter the genome is likely to shine through in this post so be ready with that pinch of salt.

The starting point for today's post is the paper by Ines Quintela and colleagues [1] detailing a case report of "a 9-year-old female patient with autistic disorder, total absence of language, intellectual disability, anxiety disorder and disruptive, and compulsive eating behaviors." Following some genetic analysis of this young girl researchers reported on "the identification of a de novo recurrent 3q13.2-q13.31 deletion encompassing 25 genes." This in itself is interesting and adds to a growing tide of research suggesting that there may be lots of different genetic influences acting in different cases of autism; all pertinent to a more plural view of the label: the autisms.

One sentence however took my specific interest in this paper insofar as: "a 3.4 Mb recurrently altered region at 3q13.2-q13.31 has been recently described and non-allelic homologous recombination (NAHR) mediated by flanking human endogenous retrovirus (HERV-H) elements has been suggested as the mechanism of deletion formation."

As I indicated at the start of this post, the finer details of genetics are not really my forte so be warned. I was however really interested in the suggestion that the process of NAHR - when "highly similar portions of the genome wrongly recombine, deleting and sometimes duplicating a portion of the genome that lies between them" - might be linked to the presence of all/some of those fossil viruses that make us who we are [2].

The long-and-short of it is the idea that some of those little variants that we ALL have in our genome might not be all due to just chance if described as de novo (as in not inherited from mum or dad). Take CNVs (copy number variants), small alterations to the genome characterised by gains and losses in segments of DNA (I think!), as the starting point. The idea is that the location of said CNVs in relation to HERVs and other transposable elements means that there may be some kind of relationship between the two. Preliminary research has suggested that HERVs flanking particular parts of the genome might be involved in the formation of CNVs [3]. Other research has noted this process as potentially being relevant in other case reports [4] similar to that described by Quintela and colleagues where behaviour and autism have been mentioned.

Just to make the whole process even more complicated (and interesting) is the idea that CNVs when talked about with autism in mind might tend to be concentrated in 'hypomethylated' regions of the genome [5]. This brings in the potentially important process of DNA methylation (yes, epigenetics yet again) into proceedings, made further interesting by suggestions that hypomethylation of DNA = more genomic instability [6] and that certain HERVs might also to some degree be 'kept in check' by methylation means [7]. Add in some evidence of methylation issues associated with some autism (see here) and preliminary evidence of certain HERVs expression correlating with autism (see here) and comorbidity (see here), and there is the making of some potentially important hypotheses ripe for further testing.

But please, don't take my word for it.

Music: Purple Rain - Prince.


[1] Quintela I. et al. Female patient with autistic disorder, intellectual disability, and co-morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2-q13.31 microdeletion. Am J Med Genet A. 2015 Aug 29.

[2] Nelson PN. et al. Demystified . . . Human endogenous retroviruses. Molecular Pathology. 2003;56(1):11-18.

[3] Campbell IM. et al. Human endogenous retroviral elements promote genome instability via non-allelic homologous recombination. BMC Biol. 2014 Sep 23;12:74.

[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] Li J. et al. Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome. PLoS Genetics. 2012: 8: e1002692.

[6] Wilson AS. et al. DNA hypomethylation and human diseases. Biochimica et Biophysica Acta. 2007; 1775: 138–162.

[7] Lavie L. et al. CpG Methylation Directly Regulates Transcriptional Activity of the Human Endogenous Retrovirus Family HERV-K(HML-2). J. Virol. 2005; 79: 876-883

---------- Quintela I, Gomez-Guerrero L, Fernandez-Prieto M, Resches M, Barros F, & Carracedo A (2015). Female patient with autistic disorder, intellectual disability, and co-morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2-q13.31 microdeletion. American journal of medical genetics. Part A PMID: 26332054

Wednesday 23 September 2015

Parental autoimmunity and offspring autism risk... yet again

Here we go again.

"A positive association between maternal autoimmune diseases and the risk of ASD [autism spectrum disorder] in offspring was identified assuming a fixed effect model." Further: "Maternal autoimmune disease is likely to be an independent risk factor of ASD in offspring."

Those were the findings and conclusions published by Shao-wei Chen and colleagues [1] as part of their systematic review and meta-analysis of the available peer-reviewed literature looking at how maternal autoimmune disease might influence offspring risk of autism. Researchers specifically observed "statistically significant associations between maternal autoimmune diseases developed during pregnancy or maternal thyroid disease and the risk of ASD in offspring."

This is not new news. Not so long ago I discussed another meta-analysis that concluded that there was an overall increased risk of autism in children with a family history of autoimmune disease (see here) including a focus on specific autoimmune conditions (see here). The idea that thyroid issues might be linked to offspring autism has also been covered on this blog (see here) and not just with core autism as a possible feature (see here). Such a relationship might, I assume, be complicated by issues with iodine availability too (see here).

The implications of the Chen findings? Well, the calls for quite a bit more research on how autoimmune disease might be 'linked' to some autism grow a little louder. The possibility of preferential screening of offspring where certain autoimmune diseases might be a feature in mums and/or dads also garners a little more support.

Music: Foster The People - Pumped up Kicks.


[1] Chen SW. et al. Maternal autoimmune diseases and the risk of autism spectrum disorders in offspring: a systematic review and meta-analysis. Behav Brain Res. 2015 Aug 29. pii: S0166-4328(15)30170-4.

---------- Chen SW, Zhong XS, Jiang LN, Zheng XY, Xiong YQ, Ma SJ, Qiu M, Huo ST, Ge J, & Chen Q (2015). Maternal autoimmune diseases and the risk of autism spectrum disorders in offspring: a systematic review and meta-analysis. Behavioural brain research PMID: 26327239

Tuesday 22 September 2015

The ketogenic diet and autism: where are we up to?

Today I'm bringing the paper by Kamila Castro and colleagues [1] to the blogging table and their systematic review of the available peer-reviewed literature on the use of a ketogenic diet (KD) when it comes to real life autism and various mouse models trying to map the label.

Drawing on data derived from 8 studies - "three studies with animals and five studies with humans" - that met the relevant inclusion criteria for study, authors concluded that although the evidence looks promising for the ketogenic diet (high fat, low carbohydrate intake) with autism in mind, there is insufficient evidence "to attest to the practicability of the KD as a treatment for ASD [autism spectrum disorder]."

I've been following the research on the ketogenic diet and autism for some time now (see here). The paper from Evangeliou and colleagues [2] providing preliminary data on what promise a KD might hold for 'some' autism really got the research ball rolling. Subsequent studies and cases reports (some of which have been covered on this blog, see here and see here) have generally been favourable about the possibilities of the KD in a real-world setting. Other animal model based research has similarly demonstrated "attenuation of some autistic-like features" following the use of the KD specifically with the dangermouse that is the BTBR mouse (see here) and the valproic acid mouse model (see here). And yes, I know that mice are not people.

I do think the time is right for more scientifically controlled trials of the KD with autism (some autism) in mind as per suggestions for various other labels too [3]. I know for some people this will be met with a rolling of the eyes and look of disdain in light of other dietary interventions put forward with autism in mind (see here) and where that has led down the years. But, and it is perhaps an important point, the utility of a KD in [some] cases of refractory epilepsy [4] perhaps give the KD something of a grounding when it comes to the presentation of some autism on top of continuing interest in nutritional medicine in modern day psychiatry (see here). Given for example, the quite noticeable connection between autism and epilepsy (see here) perhaps even more complicated than anyone had recognised (see here), one might entertain the notion that some cases of autism(s) overlapping with epilepsy might be a good starting point for further investigations?

Music: Of Monsters And Men - Dirty Paws (a band who make some of the best music videos around these days).


[1] Castro K. et al. Effect of a ketogenic diet on autism spectrum disorder: A systematic review. Research in Autism Spectrum Disorders. 2015; 20: 31-38.

[2] Evangeliou A. et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003 Feb;18(2):113-8.

[3] Paoli A. et al. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. European Journal of Clinical Nutrition. 2013; 67: 789–796.

[4] Lefevre F. & Aronson N. Ketogenic diet for the treatment of refractory epilepsy in children: A systematic review of efficacy. Pediatrics. 2000 Apr;105(4):E46.

---------- Kamila Castro, Larissa Slongo Faccioli, Diego Baronio, Carmem Gottfried, Ingrid Schweigert Perry, & Rudimar dos Santos Riesgo (2015). Effect of a ketogenic diet on autism spectrum disorder: A systematic review Research in Autism Spectrum Disorders, 20, 31-38 : 10.1016/j.rasd.2015.08.005

Monday 21 September 2015

Autism manifests across a range of genetic and metabolic syndromes

"Autism spectrum disorder (ASD) phenomenology is reported to be more common in individuals with some genetic syndromes than in the general population."

That was the starting point for the systematic review and meta-analysis published by Caroline Richards and colleagues [1] who set about 'synthesising' the various peer-reviewed data "to provide accurate estimates about ASD phenomenology in genetic and metabolic syndromes." A scan of the cumulative literature in this area ("168 papers reporting the prevalence of ASD phenomenology") revealed that autism presentation is indeed a feature of quite a few conditions compared with "the general population taking the current estimate of one in 68 people."

To those with an eye on the autism research scene the list of conditions where autism manifests is not likely to be a surprise. Rett syndrome represented one of the conditions where relative risk and odds ratio "compared to the general population" was highest. Tuberous sclerosis (TS) is also mentioned as is neurofibromatosis type 1 (NF1). I was however a little surprised that Fragile X syndrome was a little further down the frequency line than it was - "male individuals only 30%; mixed sex 22%" - given the quite classical association that I remember being discussed with autism. Down syndrome is also mentioned and perhaps reflects an increasing interest in autism being comorbid that has graced this blog previously (see here) as has the growing connection with Del22 (see here).

The authors conclude by calling for more research "including how ASD in genetic and metabolic syndromes differs from idiopathic autism [autism spontaneously arising with unknown aetiology] and what that can tell us about the mechanisms underlying ASD." This is a discussion also included in a recent paper by Sacrey and colleagues [2]. I would agree with those sentiments within the context of the Richards paper providing more evidence for the plurality of autism - the autisms (see here). I might add that if one extends the findings to autism comorbid to metabolic disorders (as in conditions such as the various inborn errors of metabolism) (see here), further details may indeed be revealing about just how many types of autism there may be, and where desired, what intervention options may present (see here).

Music: The Lumineers - Ho Hey.


[1] Richards C. et al. Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2015. Sept 1.

[2] Sacrey LR. et al. Early Infant Development and Intervention for Autism Spectrum Disorder. J Child Neurol. 2015 Aug 31. pii: 0883073815601500.

---------- Caroline Richards, Christopher Jones, Laura Groves, Jo Moss, & Chris Oliver (2015). Prevalence of autism spectrum disorder phenomenology in genetic disorders: a systematic review and meta-analysis The Lancet Psychiatry

Saturday 19 September 2015

Gluten free diet adherence reduces depression in coeliac disease

I was really quite interested in the paper by Seref Simsek and colleagues [1] looking at how adherence to a gluten-free diet (GFD) in cases of paediatric coeliac disease might also confer psychological benefits too. To quote: "[a] Significant decrease was observed in the depression scores... of celiac patients who were able to actually adhere to the GFD compared with nonadherent patients."

So: "The aim of this study was to investigate the level of depression and quality of life in children with celiac disease (CD). In addition, it aimed to examine the relations of depression level and life quality with adherence to a gluten-free diet (GFD)." Coeliac disease by the way, is the archetypal 'gluten can affect health' condition. It's been known for a while that outside of the intestinal manifestations of the diagnosis, there may also be other effects including those potential influencing psychology and behaviour too [2].

Looking at responses from 25 children diagnosed with CD and 25 asymptomatic controls, researchers reported finding no significant differences "in the depression scores between the patients and the control subjects." Said depression scores were based on the use of the Depression Scale for Children.

But... "total scores and scores of the emotional well-being subscale of the measure of Quality of Life Scale for Children were significantly lower in patients with CD compared with the control group." This is perhaps not new news. Further: "Adherence to GFD was associated with reduction in depression symptoms."

Although there are a few ways that one can interpret the Simsek findings, I'm gonna set them within the context of some of that other research talking about psychological outcomes associated with CD and it's management via a GFD including that related to psychopathology. On the periphery of CD is the suggestion of a spectrum of gluten-related 'issues' many of which have gathered under the label of non-coeliac gluten sensitivity (NCGS). There is still some debate about NCGS and whether it is real or not (see here) but for the purposes of this post I'm gonna err on the side of saying yes, for some people it might be a real issue [3]. With that in mind, other research has similarly suggested that gluten exposure might, under certain circumstances, have an effect on 'emotional disposition' (see here). The paper discussed in that previous post was a gold-standard randomised, double-blind trial by Simone Peters and colleagues [4] who concluded that current feelings of depression may indeed be linked to gluten consumption albeit with more research to do.

Obviously this research area is crying out for a lot more investigations. I draw back from saying that the very wide spectrum of depression is merely a 'gluten thing' because the evidence does not corroborate such an assertion. Depression is multi-faceted and probably has lots of aetiological factors associated with the various presentations of it (see here and see here). If however, there may be certain types of depression or depressive symptoms that overlap with real medical conditions such as CD, the onus should be on determining whether a gluten-free diet might be doing so much more than managing the physical presentation of the condition. Y'know, the gut-brain axis thing...

Music: Birdhouse In Your Soul - They Might Be Giants.


[1] Simsek S. et al. Effects of Gluten-Free Diet on Quality of Life and Depression in Children With Celiac Disease. J Pediatr Gastroenterol Nutr. 2015 Sep;61(3):303-306.

[2] Häuser W. et al. Anxiety and depression in adult patients with celiac disease on a gluten-free diet. World Journal of Gastroenterology : WJG. 2010;16(22):2780-2787.

[3] Zanini B. et al. Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity. Aliment Pharmacol Ther. 2015 Aug 27.

[4] Peters SL. et al. Randomised clinical trial: gluten may cause depression in subjects with non-coeliac gluten sensitivity - an exploratory clinical study. Aliment Pharmacol Ther. 2014 May;39(10):1104-12.

---------- Simsek S, Baysoy G, Gencoglan S, & Uluca U (2015). Effects of Gluten-Free Diet on Quality of Life and Depression in Children With Celiac Disease. Journal of pediatric gastroenterology and nutrition, 61 (3), 303-306 PMID: 26322559

Friday 18 September 2015

Elevated offspring autism in women with systemic lupus erythematosus (SLE)

"Compared to children from the general population, children born to women with SLE [systemic lupus erythematosus] have an increased risk of ASD [autism spectrum disorder], although in absolute terms it represents a rare outcome."

That was the bottom line reported in the results published by Évelyne Vinet and colleagues [1]. Based on data derived from the "Offspring of SLE mothers Registry (OSLER)", researchers identified children born to mothers with SLE alongside a matched control population and "ascertained ASD." They concluded that: "Children born to women with SLE had more ASD compared to controls [1.4% (95%CI 0.8,2.5) versus 0.6% (95%CI 0.5,0.8)." Further: "These hypothesis-generating data provide direction for additional studies of maternal autoimmunity and ASD risk."

I believe that we had seen mention of these findings in previous publications from this authorship group (see here) with accompanying press release (see here). Indeed, other results from OSLER analyses have yielded similarly interesting findings when it comes to offspring outcome of mums diagnosed with SLE as per findings related to congenital heart defects risk [2]. I'm no expert when it comes to congenital heart defects (CHDs) but did wonder if they were one and the same as congenital heart disease and whether there may be additional 'autism' slant there to any association (see here).

Anyhow... "In primary multivariate analysis, SLE offspring had substantially increased risk of ASD versus controls (OR 2.19, 95%CI 1.09,4.39)." That being said, I would re-iterate the authors' caveat about autism still being a rare outcome when it comes to maternal SLE. I do however find some logic in the idea that maternal autoimmunity is worthy of far greater research inspection when it comes to offspring autism risk. Not so long ago I talked about other data (systematic review and meta-analysis) that confirmed a connection between familial autoimmune disease and offspring autism risk (see here). This adds to other independent research talking about specific autoimmune conditions potentially being linked as for example, with work looking at maternal thyroid antibodies and autism risk (see here). This also brings us back to a concept previously discussed in the autism research literature - maternal autoantibody related (MAR) autism - and potentially a whole new chapter of autism research including further investigation of the antibody manifestation of SLE in offspring themselves (see here).

Music: Whitesnake - Is This Love. Maybe.


[1] Vinet É. et al. Increased Risk of Autism Spectrum Disorders in Children Born to Women with Systemic Lupus Erythematosus: Results from the OSLER Cohort. Arthritis Rheumatol. 2015 Aug 28.

[2] Vinet É. et al. Increased congenital heart defects in children born to women with systemic lupus erythematosus: results from the offspring of Systemic Lupus Erythematosus Mothers Registry Study. Circulation. 2015 Jan 13;131(2):149-56.

---------- Vinet É, Pineau CA, Clarke AE, Scott S, Fombonne É, Joseph L, Platt RW, & Bernatsky S (2015). Increased Risk of Autism Spectrum Disorders in Children Born to Women with Systemic Lupus Erythematosus: Results from the OSLER Cohort. Arthritis & rheumatology (Hoboken, N.J.) PMID: 26315754

Thursday 17 September 2015

An extremely low prevalence of autism in Quito, Ecuador

The title of this post is taken from the paper by Laura Dekkers and colleagues [1] (open-access) who sought to "get an estimate of ASD [autism spectrum disorder] diagnoses in children and adolescents aged between of five and fifteen at regular schools in Quito."

So, the starting point: "Ecuador has more than 14 million inhabitants... of which over 1.6 million are estimated to live in the capital city of Quito." As part of the "law requiring inclusive education", the authors decided to survey for "cases of ASD in regular schools" in Quito. Said schools were identified via the databanks of the Ministry of Education, of which 161 schools were eventually selected for analysis including just over 51,000 pupils aged 5-15 years. Cases of ASD within that population were "identified by the school administration" and included both autism spectrum diagnoses via DSM-III and DSM-IV criteria.

Results: 33 schools (~20%) reported having at least one pupil officially diagnosed on the autism spectrum. Interestingly the authors report that there was a possible relationship between school reporting one or more pupils on the autism spectrum and the size of the school - "the probability of reporting at least one pupil with an ASD diagnosis decreasing with the size of the school."

"Of the total number of pupils within all schools (N = 51,453) only 57 pupils had an official diagnosis of ASD. This brings the prevalence of ASD in Quito, as reported by schools for regular education, to 11.07 out of 10,000, which is 0.11 %." Most of those diagnosed were so with the label 'PDD-NOS' (Pervasive Developmental Disorder - Not Otherwise Specified). Bearing in mind the small numbers detected, the male: female ratio came in with a familiar statistic - "4.7 times more boys than girls" and mean age at diagnosis was a very poor 7-8 years of age.

Then another statistic: "Out of the 161 schools, 59 schools (36.6 %) mentioned that they thought that at their school there was at least one pupil who did not have an ASD diagnosis, but should have been diagnosed with ASD." In total there were 108 pupils falling into this 'maybe' category. And finally: "Out of all schools (N = 161), 14 schools (8.7 %) reported that they had at least once refused a boy or girl with ASD to their school, because of his or her behavior."

There are a few points to make about the Dekkers findings, some of which the authors already make themselves. First is the quite low prevalence rate estimated from their research. To quote (again): "We propose that the found percentage of 0.11 % reflects the current probability of receiving a diagnosis of ASD in Quito, Ecuador, rather than the proportion of the population that has ASD." Indeed, the authors provide a list of various factors that might have been contributory to the low prevalence rate estimated for autism in Ecuador including issues with accessibility to diagnostic services, the general lack of awareness of autism in the country and the stigma that still surrounds the label ("Autism is often not recognized as such and considered a punishment of God, leaving the family in shame hiding their child with problem behavior"). One might also entertain the notion that autism may not be as prevalent in Ecuador as other countries for genetic / biological or environmental reasons too; perhaps even learning some lessons from other labels (see here).

Second, we can expect more data from this group on this topic. "The ASD prevalence in special education was the second part of phase 1 of the PAE [Prevalence of Autism in Ecuador] project, including 11 special schools and centers, and a total of 1195 pupils; publication of the results is in preparation. We can expect a higher prevalence at these schools, because there is a trend for higher and increasing prevalence of autism in special education in areas with low prevalence of autism." I believe we have a few clues there as to what they found.

Finally, what is missing from the Dekkers data is information about the children themselves outside of just diagnosis and age. Things like whether comorbidity such as ADHD [attention-deficit hyperactivity disorder] is part of the clinical picture in light of what is known about a possible relationship (see here). Indeed, whether part of the low autism prevalence estimate suggested might also part of a wider trend in child psychiatry in Ecuador, and whether we can expect to see increasing rates as per other data from other countries [2]?

Music to close: Sash! - Ecuador.


[1] Dekkers LMS. et al. Prevalence of Autism Spectrum Disorders in Ecuador: A Pilot Study in Quito. Journal of Autism and Developmental Disorders. 2015. Aug 30.

[2] van Bakel MME. et al. Low but Increasing Prevalence of Autism Spectrum Disorders in a French Area from Register-Based Data. JADD. 2015; 45: 3255-3261.

---------- Dekkers, L., Groot, N., Díaz Mosquera, E., Andrade Zúñiga, I., & Delfos, M. (2015). Prevalence of Autism Spectrum Disorders in Ecuador: A Pilot Study in Quito Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2559-6

Wednesday 16 September 2015

Parkinsonism in adults with autism

"We find a high frequency of parkinsonism among ASD [autism spectrum disorder] individuals older than 39 years."

So said the paper by Sergio Starkstein and colleagues [1] (open-access) and Q & A with authors who, during a "a hypothesis-generating, pilot study" with extras looked for parkinsonism motor signs in a small group of adults diagnosed with an autism spectrum disorder.

Parkinsonism is an umbrella term that refers to any condition that leads to a combination of symptoms noted in Parkinson's disease including tremor, slow movement (bradykinesia) speech issues and/or muscle stiffness. Parkinsonism does not necessarily mean just Parkinson's disease (PD) as per the number of conditions that have been mentioned under this umbrella (see here).

Starkstein and colleagues describe their results within the context of a research initiative looking to examine ASD in older individuals. They report: "As the project progressed, we observed what appeared to be high rates of parkinsonian signs in our ASD subjects" (n=19) that was then extended into a more systematic assessment of parkinsonian signs in a different cohort (n=37). In that latter group: "The frequency of occurrence of the cardinal signs for parkinsonism were 46 % (N = 17) with bradykinesia, 19 % (N = 7) with resting tremor, 19 % (N = 7) with rigidity, and 19 % (N = 7) with postural instability." Assessment by the way, was via the Movement Disorders Society-Unified Parkinson’s disease Rating Scale (MDS-UPDRS) with a slight modification whereby "final clinical judgment on the presence of bradykinesia was based on scores rating limb bradykinesia... and/or scores rating global spontaneity of movement."

Because medication, particularly certain neuroleptic pharmacotherapy, can impact on parkinsonism, researchers also looked at the 20 participants from both cohorts combined who were not currently on neuroleptics. So: "After excluding subjects currently on neuroleptic medications, the frequency of occurrence of parkinsonism was 20 % in the combined sample and 17 and 25 %, in each sample, respectively." Oh, and 4 participants (7% of the combined sample) were "diagnosed with PD by community neurologists."

"The possibility that individuals with autism are at increased risk for Parkinson’s disease as adults has important implications for detection and assessment, clinical practice, systems of care, training, and public policy." That's an important sentence from the authors about their findings and the implications for screening and care of adults on the autism spectrum. Added to the idea that various other medical comorbidity might be 'over-represented' when it comes to autism (adult autism) (see here and see here and more recently in the paper by Fortuna and colleagues [2]) and how the symptoms of autism can sometimes affect the delivery of appropriate screening and healthcare (see here), and quite a research agenda continues to emerge.

As to the mechanism(s) potentially pertinent to parkinsonism being associated with autism... well, all I can really say is that it is likely to be a complicated relationship insofar as the plurality of autism and all that elevated risk of other comorbidity allied to the label. To single out one area where the possibility of overlap might occur, I'll draw your attention to the findings reported by Cheng and colleagues [3] who, based on that ever-so useful resource called the Taiwan National Health Insurance Research Database (see here), reported that: "Patients with asthma had an elevated risk of developing Parkinson's disease later in life." Given something of an emerging connection between asthma and autism (see here) one might speculate that this could be just one avenue for further investigation.

Music: Florence + The Machine - Rabbit Heart (Raise it Up).


[1] Starkstein S. et al. High rates of parkinsonism in adults with autism. Journal of Neurodevelopmental Disorders 2015, 7:29.

[2] Fortuna RJ. et al. Health Conditions and Functional Status in Adults with Autism: A Cross-Sectional Evaluation. J Gen Intern Med. 2015 Sep 11.

[3] Cheng CM. et al. Risk of developing Parkinson's disease among patients with asthma: a nationwide longitudinal study. Allergy. 2015 Aug 27.

---------- Starkstein, S., Gellar, S., Parlier, M., Payne, L., & Piven, J. (2015). High rates of parkinsonism in adults with autism Journal of Neurodevelopmental Disorders, 7 (1) DOI: 10.1186/s11689-015-9125-6

Tuesday 15 September 2015

ADHD and obesity meta-analysed

I was intrigued by the findings reported by Samuele Cortese and colleagues [1] who, following systematic review and meta-analysis of the current peer-reviewed literature on the topic, found evidence for a "significant association between ADHD [attention-deficit hyperactivity disorder] and obesity/overweight." I believe the protocol for this review and meta-analysis has previously graced the peer-reviewed domain as per a previous paper from Cortese et al [2] (open-access).

Based on data from 42 studies including over 720,000 participants - over 48,000 diagnosed with ADHD - researchers concluded that there was a significant association between obesity and ADHD in both children ("odds ratio=1.20, 95% CI=1.05–1.37") and adults ("odds ratio=1.55, 95% CI=1.32–1.81"). The association remained even when limited to studies "1) reporting odds ratios adjusted for possible confounding factors; 2) diagnosing ADHD by direct interview; and 3) using directly measured height and weight." Being overweight was also associated with ADHD and importantly: "Individuals medicated for ADHD were not at higher risk of obesity."

It may initially seem a little strange that a diagnosis of ADHD might elevate risk for obesity and/or being overweight. ADHD is sometimes referred to as hyperkinetic disorder (kinetic as in movement or motion) and the classical view of the condition is one of excessive activity with terms like restlessness or 'full of energy' heavily used. As with many other labels however, ADHD is not a homogeneous condition in terms of presentation as per the various subtypes covering (i) predominantly hyperactive-impulsive, (ii) predominantly inattentive and (iii) combined hyperactive-impulsive and inattentive.

It's perfectly plausible that where inattention and/or impulsivity predominate this might have implications for eating and lifestyle patterns that may be contributory to weight status. Other research has suggested that there may also be "common underlying neurobiological abnormalities, such as dysfunctions in brain reward pathways" relevant to both ADHD and obesity.

I'd also raise a few other potentially important variables as worthy of further research too. So, sleep problems - known to be associated with cases of ADHD (see here) - might also play a hand given other research suggesting a link between sleeping habits and weight (see here). The rise and rise of gut bacteria in relation to weight status research (see here) might also be an area where any overlap could be explored. Finally, there may be some merit in looking at whether comorbidity accompanying ADHD might play a role in obesity risk. Specifically, the quite remarkable 'over-representation' of ADHD in cases of autism (see here) (and need for further inspection [3]) and the very full peer-reviewed literature on autism and obesity (see here).

Perhaps some food for thought?

Music: R.E.M. - Shiny Happy People.


[1] Cortese S. et al. Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis. American Journal of Psychiatry. 2015. Aug 28.

[2] Cortese S. et al. Prevalence of obesity in attention-deficit/hyperactivity disorder: study protocol for a systematic review and meta-analysis. BMJ Open. 2014 Mar 18;4(3):e004541.

[3] Miodovnik A. et al. Timing of the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. Pediatrics. 2015. 14 Sept.

---------- Cortese, S., Moreira-Maia, C., St. Fleur, D., Morcillo-Peñalver, C., Rohde, L., & Faraone, S. (2015). Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis American Journal of Psychiatry DOI: 10.1176/appi.ajp.2015.15020266