Saturday, 6 February 2016

Sleep as a target of antibiotic use in chronic fatigue syndrome?

"The primary finding from the study was evidence of an improvement in several objective sleep parameters in participants in whom the increased colonization of lactic acid producing organisms was resolved after antibiotic treatment."

Those were the words written by Melinda Jackson and colleagues [1] (open-access) who, during an open-label trial, looked at whether administration of an antibiotic (erythromycin 400 mg) over the course of 6 days might have some important effects on elements of sleep in a patient group diagnosed with chronic fatigue syndrome (CFS). Yes, sleep did seem to be [positively] affected was the finding. The suggested mode of action of antibiotic administration was linked to colonisation "with gram-positive faecal Streptococcus (determined by stool analysis and suggestive of abnormal gut functioning)" onwards to the idea that the those trillions of wee beasties that inhabit us all might show some specific connection to elements in cases of CFS.

From an initial study population of 70 recruited for study, data for 22 participants (who completed the trial and met study inclusion criteria) were reported on. Those 22 all had "increased colonization of Streptococcus sp. (defined as >3×105 cfu/g of faecal sample)" as a pre-requisite to taking part in the trial based on the results of a "faecal microbiota analysis (FMA)." Actigraphy and sleep diaries were kept for a week before antibiotic use, during use and for 8 days after. Various facets of CFS symptoms were also examined during points of the study.

Bearing in mind some 'malfunctions' affecting actigraphy results, the authors describe some interesting findings. First and foremost, is the idea that not everyone who took erythromycin showed the same profile (behavioural or biochemical). The authors talk about "responders" to the intervention (music to my ears) on the basis that: "Thirteen of the patients showed a reduction in Streptococcus counts after treatment, whereas four patients showed an increase level of Streptococcus and four patients had no change at the end of the trial." Outside of the idea that there may be some significant individual variation in the effects of antibiotics on gut flora (remembering the idea of 'swallowing a grenade'), questions abound as to why some people did not seem to be so affected by this strain of antibiotics whilst others did. Further: "While 13 participants showed a reduction in Streptococcus only 7 of these had a significant change as defined by a percentage distribution post-therapy of less than 6% of Streptococcus after antibiotic treatment." Mmm, indeed.

Second, and linked back to the idea of 'responders' and 'non-responders' on the basis of microbiological results are the findings that there were: "more improvement in actigraphic sleep with treatment in responders compared to non-responders from baseline to post-treatment 2." Indeed, we are told that responders tended to increase their total sleep time by about 40 minutes between baseline and end of study, whereas: "non-responders slept an average of 15 min less from baseline to post-treatment 2."

Finally, and quite importantly: "No significant change in any of the subjective measures was observed between baseline and the two follow-up points for responders versus non-responders." The subjective measures in question were linked to things like self-reported fatigue, mood and the such like. The authors have suggested that there may be some 'correlation' between a subscale on 'vigour' and "Streptococcus viable count" but when you're talking about 7 participants as your responder group, one has to be mighty careful of making too many sweeping generalisations.

Although this is a preliminary study, I'd like to think that the Jackson findings might eventually be worked up into a larger, more methodologically sound research agenda encompassing a placebo arm and the like. We know for example, that sleep patterns can be affected by CFS and that at least subjective measures of sleep may affect the presentation of elements of CFS [2]. That children and adolescents with CFS may be particularly vulnerable to sleep disturbances [3] is an area in specific need of further investigation. Moves therefore to improve sleep measures in CFS are perhaps to be welcomed mindful of the idea that persistent use of antibiotics is not exactly a great long-term strategy particularly in these days of growing antibiotic resistance. I could offer a possible alternative to antibiotic use that has been initially tried with CFS in mind (see here) but again, more research is indicated first and perhaps also some PR! Still, the focus on the gut microbiota and CFS/ME continues at a pace (er, maybe a should rephrase that) and with the promise of much, much more to come.

I'll also be talking about the paper by Collin and colleagues in the not-too-distant future so watch this space...


[1] Jackson ML. et al. Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study. Sleep Sci. 2015 Nov;8(3):124-33.

[2] Russell C. et al. Subjective But Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study. Sleep. 2015 Dec 22. pii: sp-00453-15.

[3] Snodgrass K. et al. Sleep Disturbances in Pediatric Chronic Fatigue Syndrome: A Review of Current Research. J Clin Sleep Med. 2015 Jul 15;11(7):757-64.

---------- Jackson ML, Butt H, Ball M, Lewis DP, & Bruck D (2015). Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study. Sleep Science (Sao Paulo, Brazil), 8 (3), 124-33 PMID: 26779319

Friday, 5 February 2016

Vitamin D supplementation and 'clinical improvement' in autism?

"Vitamin D deficiency might contribute to the aetiology of ASD [autism spectrum disorder]. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children."

More big words have appeared from a research group who seem to be particularly interested in how vitamin D (the sunshine vitamin/hormone) might have some important links to at least some cases of autism. The findings this time around come in the form of the paper by Feng and colleagues [1] who following on from their case-report [2] on what happened when a 2 (nearly 3) year old boy diagnosed with an ASD was given a supplement to correct an underlying vitamin D deficiency, now report on a larger participant cohort.

In line with their clinical trial registration (see here) "last refreshed on 2015-05-02" a selection of 37 children from a bank of 215 diagnosed with an ASD "received vitamin D3 treatment" for 3 months alongside various measures of autistic behaviours (CARS and ABC) being delivered. Compared with a control group of 285 'do-not-have-autism' children, serum levels of 25(OH) vitamin D were lower in the children with autism as a group (n=215). Given what has been discussed before in the peer-reviewed literature, and from more than one independent source, these findings are not a great surprise. Further, we are told that: "After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD."

Whilst potentially important findings, I do think we have to be slightly careful before singing the [universal] praises of what vitamin D might do for all autism at the current time. As far as I can make out, this was not a clinical trial insofar as pitting vitamin D supplementation against a placebo, nor was it the case that comparisons on behavioural or biological measures were made between supplementing children with autism and supplementing controls. This was, in effect, a study of 37 autistic children receiving a vitamin D supplement and the reporting on scores 'of autism' before and after such supplementation, all the while knowing that children were taking a vitamin D supplement.

That's not however to say that my cautious view on this might not change in future as more controlled research is on-going in this area (see here and see here) and indeed, even talking about the possibility that vitamin D might affect the recurrence of autism in families where a child has already been diagnosed with autism (see here). We await the results of these various investigations in the peer-reviewed journal press to further inform clinical practice and perhaps also determine who might be the 'best' and non-responders to such intervention.

The final question concerns what the possible mechanism(s) could be such that vitamin D supplementation, more traditionally indicated to treat skeletal issues, could potentially impact on the presentation of behaviours pertinent to autism. I don't have any substantial ideas about possible ways of working at the present time, outside of highlighting the various extra-skeletal effects that have been talked about outside of the primary autism research literature (see here and see here). I just might be tempted to suggest that any biological effect is likely to be complicated and not necessarily just related to how much vitamin D a person gets or doesn't (see here and see here). I'm also minded to bring in the idea that vitamin D might show some 'connection' to autoimmune diseases (see here) and where that could potential lead with at least some autism in mind (see here and see here). And then there is the possibility that supplementing with vitamin D might not be the only option to be explored [3] potentially also tied to other autism findings (see here).

Speculation abounds and science has a lot more to do to catch up.

Music: The Carpenters - Top Of The World.


[1] Feng J. et al. Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutr Neurosci. 2016 Jan 18.

[2] Jia F. et al. Core symptoms of autism improved after vitamin D supplementation. Pediatrics. 2015 Jan;135(1):e196-8.

[3] Jain SK. et al. L-cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25-hydroxy-vitamin D in Zucker diabetic fatty rats. Mol Nutr Food Res. 2016 Jan 17.

---------- Feng J, Shan L, Du L, Wang B, Li H, Wang W, Wang T, Dong H, Yue X, Xu Z, Staal WG, & Jia F (2016). Clinical improvement following vitamin D3 supplementation in Autism Spectrum Disorder. Nutritional neuroscience PMID: 26783092

Thursday, 4 February 2016

Establishing environmental exposures as risk factors for bipolar disorder: Difficult.

The findings reported by Ciro Marangoni and colleagues [1] made for some interesting reading recently and their systematic review of longitudinal studies looking at the various environmental exposures put forward as possible risk factors pertinent to the development of bipolar disorder (BD).

Trawling through the peer-reviewed material on this topic, the authors were able to 'clump' the various proposed risk factors into one of three categories: "neurodevelopment (maternal influenza during pregnancy; indicators of fetal development), substances (cannabis, cocaine, other drugs - opioids, tranquilizers, stimulants, sedatives), physical/psychological stress (parental loss, adversities, abuses, brain injury)."

They did not however, report the presence of any specific 'smoking gun' on the basis of their investigations, concluding that: "Only preliminary evidence exists that exposure to viral infection, substances or trauma increase the likelihood of BD." That also the various risk categories seemed to be 'correlated' with various other psychiatric and/or behavioural labels is also an important point to make in these days of overlap and RDoC.

I personally am not surprised by these results. Appreciating that diagnostic labels do not equal homogeneous groups, and that just as when defining the genetics of something like BD, so defining the non-genetic correlates is an equally difficult task, studies of this type remind us just how complicated and individual the paths are bringing someone to such a clinically-relevant label. I say this with the understanding that just because an specific environmental (or non-environmental) risk factor might not be generalisable to all BD does not mean it can't exert a more pronounced effect in smaller groups or individuals. Lessons from other labels teach us this (see here).

Whilst important to understand whether there may be specific environmental exposures that might be more generally linked to an enhanced risk of developing BD, I do believe that the [research] future lies in a couple of other areas looking at: (a) how many different types of BD are there and what are the 'other' conditions/labels potentially related? (b) what does the biology of BD look like and does it include some common targets with other labels? and (c) outside of the array of interventions put forward for managing symptoms (see here), are there other intervention strategies that might fit with the findings of (a) and (b)?

To close, LEGO do it best...


[1] Marangoni C. et al. The role of environmental exposures as risk factors for bipolar disorder: A systematic review of longitudinal studies. J Affect Disord. 2016 Jan 1;193:165-174.

---------- Marangoni C, Hernandez M, & Faedda GL (2016). The role of environmental exposures as risk factors for bipolar disorder: A systematic review of longitudinal studies. Journal of affective disorders, 193, 165-174 PMID: 26773919

Wednesday, 3 February 2016

Estimated autism rate in 2 regions of Poland

"The average prevalence of ASD [autism spectrum disorder] was 35/10 000 children and was about 4-fold higher in males."

I don't have too much to add to the findings reported by Karolina Skonieczna-Żydecka and colleagues [1] who estimated the prevalence of ASD in two regions of Poland: "West Pomeranian and Pomeranian regions." Based on the analysis of data from "Provincial Disability Services Commissions", researchers concluded that approximately 3 children in 1000 in those regions have a diagnosis on the autism spectrum. As always: "More studies are necessary."

Accepting that there may true geographical variations in the rate of autism around the globe [2] (including effects potentially related to factors such as migration for example), these figures are surprisingly conservative compared with what has been mentioned in other parts of the world in recent times (see here). Yes, one could eventually look at issues around the identification and diagnosis of autism (including translation of the appropriate screening and assessment instruments), what criteria you use to define autism, the potential effect(s) of service availability and delivery following a diagnosis and specific cultural factors to account for the low estimates, but at the moment we can only go with the data that is available. Indeed, this is not the first time that I've talked about other geographic areas also reporting a low prevalence of autism and the possible factors around that example (see here).

I do expect to see the autism prevalence estimates increase in Poland as more detailed study is done such as that actually going looking for those who possibly fall on the autism spectrum (see here) rather than relying on more passive methods of reporting. As per previous peer-reviewed research coming out of Poland [3], fulfilling the criteria for autism and actually receiving a diagnosis are not necessarily one and the same for whatever reason(s).

But again, we can only go with the available data...

Music: Frank Sinatra - Come Fly With Me.


[1] Skonieczna-Żydecka K. et al. The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland. J Appl Res Intellect Disabil. 2016 Jan 14.

[2] Fombonne E. et al. Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey. J Autism Dev Disord. 2016 Jan 21.

[3] Wolańczyk T. et al. Features of autism, autistic traits, autism: retrospective analysis of clinical symptoms in children treated in the Pediatric Psychiatric Clinic. Psychiatr Pol. 2001 Jan-Feb;35(1):59-69.

---------- Skonieczna-Żydecka K, Gorzkowska I, Pierzak-Sominka J, & Adler G (2016). The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland. Journal of applied research in intellectual disabilities : JARID PMID: 26771078

Tuesday, 2 February 2016

Risk of cancer in autism: probably not excessive as more data emerge

A quote to begin: "Taken together, there are no published evidence to suggest that there is a high overall concordance between ASD [autism spectrum disorders] and cancer or between ASD and specific cancers."

Those words reported by Svend Erik Mouridsen and colleagues [1] (who knows a thing or two about autism research) should offer some relief to both people on the autism spectrum and their loved ones.

Based on the analysis of over 100 adults "diagnosed with infantile autism (IA) in childhood" compared with over 330 asymptomatic (not-autism) controls in Denmark, researchers found that 8 adults (6.8%) with autism has registered at least one cancer diagnosis and 17 people (5.1%) of the comparison group the same over a 30+ year period. The authors suggest that although there was no statistically significant increased risk in their cohort of people with autism "it is important to recognize that adults with IA [infantile autism] are at similar risk for these diseases." Once again, a diagnosis of autism is seemingly protective against nothing when it comes to other diseases/conditions/labels appearing.

Although to some degree reassuring about the excess risk of cancer in cases of autism, I am minded to bring in a previous post I wrote on this topic (see here) based on some important work coming out of the research powerhouse that is Taiwan [2]. Based on a considerably larger participant sample (~8400 people diagnosed with autism), the numbers of those with autism developing cancer were equally small to that of Mouridsen but greater than generally expected. The excess cancer risk on that occasion seemed to be specifically linked to being male and also covered a younger age group. I say this accepting that cancer risk with autism in mind might not be the same the world over.

The currently available peer-reviewed research literature in this population does not seem to indicate any wildly significantly greater risk of cancer as a function of being diagnosed on the autism spectrum. What it does suggest is that outside of specific overlap between cancer genes and so-called autism genes (see here) is that people with autism need to be screened the same way everyone else is for their risk of cancer save any health inequalities emerging, particularly as the population ages and eyes start to turn towards ageing and autism (see here). I might also add that if there is certain psychiatric comorbidity attached to a diagnosis of autism, one may need to be mindful that this could potentially impact on mortality rates (see here) and therefore adjust care accordingly.


[1] Mouridsen SE. et al. Risk of cancer in adult people diagnosed with infantile autism in childhood: A longitudinal case control study based on hospital discharge diagnoses. Research in Autism Spectrum Disorders. 2016; 23: 203-209.

[2] Chiang H-L. et al. Risk of Cancer in Children, Adolescents, and Young Adults with Autistic Disorder. J Pediatrics. 2014. 18 November.

---------- Mouridsen, S., Rich, B., & Isager, T. (2016). Risk of cancer in adult people diagnosed with infantile autism in childhood: A longitudinal case control study based on hospital discharge diagnoses Research in Autism Spectrum Disorders, 23, 203-209 DOI: 10.1016/j.rasd.2015.12.010

Monday, 1 February 2016

On (pre)pregnancy obesity and inflammation and offspring autism risk

At the time of writing this [long read] post there has been a flurry of autism research articles making news.

The headline: 'Scientists create the first ever autistic monkeys' referring to the work published by Liu and colleagues [1] who reported on "lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene" started the ball rolling. Anyone who knows a little bit about autism will realise that mutations in the MeCP2 gene generally refers to Rett syndrome. Whilst linked to the expression of certain autistic-like behaviours, Rett syndrome is but one part of the very heterogeneous spectrum called autism. I'd also suggest that other primate research had previously 'modelled' autism, or at least, certain facets of autism (see here).

Next up was the headline: 'Autism Diets: Can Nutrition Have An Impact On Autism Risk?' portraying the findings reported by Xie and colleagues [2] (open-access) who talked about inborn errors of carnitine metabolism potentially being linked to some autism. This follows some important research history in this area (see here) specifically linked to a gene called trimethyllysine hydroxylase, epsilon (TMLHE) (see here). Inborn errors of metabolism potentially linked to autism (some autism) is a woefully under-researched and under-screened area (see here).

And then we have two papers that make up the core of today's post. The first by Mengying Li and colleagues [3] continues something of an important theme in autism research circles these days on how mum's weight and risk of diabetes during pregnancy might have a bearing on offspring development [4], and specifically the risk of autism and comorbid learning disability. This time around researchers "examined the independent and combined effects of maternal prepregnancy obesity and maternal diabetes on the risk of autism spectrum disorder (ASD) in parallel with other developmental disorders (DDs)." They did this by analysing data - "a subset of the Boston Birth Cohort who completed at least 1 postnatal study visit at Boston Medical Center between 1998 and 2014" - and comparing rates of autism ("based on physician diagnoses as documented in electronic medical records") and other diagnoses "among 6 groups defined by maternal prepregnancy obesity and diabetes status." They found that yes, those mums who were obese and presented with pregestational diabetes (PGDM) had a [significantly] increased risk of offspring autism as were those with both obesity and gestational diabetes. Interestingly: "This pattern of risk was mostly accounted for by cases with co-occurring ASD and ID."

Before heading further into the potential whys and wherefores to account for the Li results, I want to bring in another paper making news. Gloria Choi and colleagues [5] report results that have created headlines such as: 'Autism caused by immune response to viral infection during pregnancy?' Accepting that again, the use of the singular term 'autism' in that media piece does little to accentuate the degree of diversity that the label includes and the various 'routes' that might bring someone to a diagnosis (see here for example), I found this to be an interesting paper.

Building on the idea that viral infection during pregnancy might be able to affect offspring risk of autism or other behavioural outcomes (see here), researchers set about looking at some of the possible mechanisms involved in this process. The work of the late Paul Patterson (see here) gets a mention in the Choi study write-up and the concept of maternal immune activation (MIA). Pregnant mice were initially artificially 'immune stimulated' and offspring were found to display the sorts of behaviours that had previously been mentioned in the science literature in this area. Researchers then took out some key elements of the cells involved in the inflammatory response to immune activation - specifically Th17 cells - and repeated the artificial immune activation procedure. Offspring mice did not appear to show the same behavioural issues as those whose mother mice possessed their Th17 cells intact. Further, when pregnant mother mice were given an antibody that blocks interleukin-17 (IL-17) (produced by Th17 cells), offspring mice also showed behavioural differences compared with those offspring whose mother mice received immune stimulation but nothing else. Ergo, the suggestion that: "therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes." The idea of an 'inflammation-induced autism phenotype' by the way is not a new one (see here).

Whilst remembering that mice are mice (and monkeys are monkeys) and so not necessarily able to model all of the complexity of human autism (and its important comorbidities), these are potentially important findings. I've covered the idea that immune function and inflammatory processes might be part and parcel of some autism previously on this blog (see here for example) as part of a larger shift in psychiatry circles (see here). Indeed, some of that research has specifically talked about IL-17 and at least some autism (see here for example) and the idea that levels might be increased compared to other groups. Insofar as the notion of blocking the effects of IL-17 (or Th17), I'm minded to suggest that we need a lot more data first before specific interventions are discussed or attempted including looking at compounds linked to the maturation of Th17 cells [6] as possible targets.

What the Li and Choi papers share in common are several variables. First is the idea that 'the nine months that made us' might indeed be an important time insofar as future behavioural outcome. Indeed the Li results also suggest that what happens prepregnancy might also exert a significant effect. Second is the notion that inflammation (or response to inflammation) in-utero might be an important concept for at least some 'types' of autism and indeed other future diagnoses (see here). If you're wondering what obesity might have to do with inflammation, well, let's just say that quite a few researchers/research groups believe there is an important link [7] and certainly some write-up on the Li paper makes that point. I say this acknowledging that Li and colleagues also noted the children with autism in their cohort were also more likely to be born preterm and with a low birth weight. Finally, is the question of whether disrupting inflammatory processes or responses particularly during critical times of prepregnancy and/or pregnancy might be something to look at with a view to altering any 'programmed' offspring autism or other risk. Appreciating that not everyone might receive this question the same way, I do think we need to have some frank discussions about this option. That Li and colleagues reported on prepregnancy obesity/diabetes as being particularly associated with autism and learning (intellectual) disability perhaps provides an important detail pertinent to the idea of improving child outcomes and quality of life (particularly if pregnancy inflammation translates into offspring inflammation and where that could lead).

Some important future research directions are indicated.

Music, and what else but Terry Wogan and The Floral Dance. Rest in peace Sir Terry and not forgetting your best quotes...


[1] Liu Z. et al. Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2. Nature. 2016 Jan 25.

[2] Xie Z. et al. Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism. Cell Reports. 2016. Jan 28.

[3] Li M. et al.  The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics. 2016. Jan 29.

[4] Connolly N. et al. Maternal metabolic risk factors for autism spectrum disorder-An analysis of electronic medical records and linked birth data. Autism Res. 2016 Jan 29.

[5] Choi GB. et al. The maternal interleukin-17a pathway in mice promotes autism like phenotypes in offspring. Science. 2016. 28 Jan.

[6] Huang W. et al. DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature. 2015 Dec 24;528(7583):517-22.

[7] Lumeng CN. & Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011 Jun;121(6):2111-7.

---------- Li, M., Fallin, M., Riley, A., Landa, R., Walker, S., Silverstein, M., Caruso, D., Pearson, C., Kiang, S., Dahm, J., Hong, X., Wang, G., Wang, M., Zuckerman, B., & Wang, X. (2016). The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities PEDIATRICS, 137 (2), 1-10 DOI: 10.1542/peds.2015-2206 Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, Hoeffer CA, Littman DR, & Huh JR (2016). The maternal interleukin-17a pathway in mice promotes autismlike phenotypes in offspring. Science (New York, N.Y.) PMID: 26822608

Saturday, 30 January 2016

Autism in phenylketonuria (PKU)

"Autism has been reported in untreated patients with phenylketonuria."

Indeed it has, as the paper by Sameh Khemir and colleagues [1] revisits something of a long known about association whereby the archetypal inborn error of metabolism that is phenylketonuria (PKU) has been linked to the presentation of autism or autistic traits [2].

Looking at 18 participants diagnosed with PKU, Khemir et al "report their clinical, biochemical and molecular peculiarities" (authors words not mine) and how 15 of the 18 presented with autism as per assessment with "The Childhood Autism Rating Scale and the Autism Diagnostic Interview-Revised." Following some molecular biological analysis specifically with the "phenylalanine hydroxylase gene" in mind (a key player in PKU), the authors reported on various potentially important issues but "no correlation between autism and mutations affecting the phenylalanine hydroxylase gene."

I have a lot of time for PKU on this blog. Not only because PKU represents one of the best examples of how certain foods for some can affect development and onwards mental health (see here) but also because some of the other intervention options for PKU (outside of low phenyalanine diet) might hold some promise for some autism too (see here). Indeed, the idea that tetrahydrobiopterin (BH4) - an important cofactor for phenyalanine hydroxylase and related aromatic amino acid hydroxylase enzymes - might be quite good at helping to mop up excess phenylalanine and other compounds continues to find favour in some autism research circles. Dare I also mention the effects of BH4 on tryptophan and 5-HTP as potentially being relevant to some autism too? (see here)

In many parts of the world, the advent of the newborn screening program (built on the genius of people like Robert Guthrie and others) has all but eradicated untreated PKU and perhaps impacted on the number of people presenting with autism too. There remain however, challenges in certain areas of the globe, where people are not so fortunate to have such screening measures in place. Indeed, Khemir and colleagues report their results based in Tunisia and Algeria; other geographically related areas might also benefit from the implementation of such screening practices [3].    

Just before I go, there is one last comment to make on something discussed by Khemir and colleagues: "age of diet onset was the determining factor in autistic symptoms' evolution." Diet, as I've mentioned, refers to the low phenylalanine (low protein) diet commonly used to manage PKU. It appears that there might be more to see in terms of how long PKU goes untreated and the progression of autistic traits similar to other descriptions, particularly the findings reported by Baieli and colleagues [4]: "None out of 62 patients with classic PKU diagnosed early met criteria for autism. In the group of 35 patients diagnosed late, two boys (5.71%) ages 16 and 13 years fulfilled the diagnostic criteria for autism."

Diet potentially affecting the presentation of autism eh? I'll be coming to the paper by Oyarzabal and colleagues [5] soon enough built on some related research...

Music: Led Zeppelin - Rock And Roll.


[1] Khemir S. et al. Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects. J Child Neurol. 2016 Jan 12. pii: 0883073815623636.

[2] Miladi N. et al. Phenylketonuria: an underlying etiology of autistic syndrome. A case report. J Child Neurol. 1992 Jan;7(1):22-3.

[3] Saad K. et al. ADHD, autism and neuroradiological complications among phenylketonuric children in Upper Egypt. Acta Neurol Belg. 2015 Dec;115(4):657-63.

[4] Baieli S. et al. Autism and phenylketonuria. J Autism Dev Disord. 2003 Apr;33(2):201-4.

[5] Oyarzabal A. et al. Mitochondrial response to the BCKDK-deficiency: Some clues to understand the positive dietary response in this form of autism. Biochim Biophys Acta. 2016 Jan 22. pii: S0925-4439(16)30003-5.

---------- Khemir S, Halayem S, Azzouz H, Siala H, Ferchichi M, Guedria A, Bedoui A, Abdelhak S, Messaoud T, Tebib N, Belhaj A, & Kaabachi N (2016). Autism in Phenylketonuria Patients: From Clinical Presentation to Molecular Defects. Journal of child neurology PMID: 26759449