Thursday, 18 September 2014

Anxiety and sensory over-responsivity linked to gut issues in autism

"The name's Lonnegan! Doyle Lonnegan!"
Consider this micropost an extension of some previous discussions on this blog about how gastrointestinal (GI) issues present in cases of autism might show some connection to the presence of anxiety and sensory issues (see here). Today I'm discussing further research by Micah Mazurek and colleagues [1] which follows a previous publication by this author [2] on this topic.

In the latest paper, Dr Mazurek and colleagues describe the course of abdominal pain in 225 children diagnosed with an autism spectrum disorder (ASD). Of the quarter of participants who presented with "chronic abdominal pain at baseline", the majority (over 80%) still had the same GI issue at 1-year follow-up. Indeed, a further 25% of those who did not present with abdominal pain at the start of the study finished the study with such an issue. The authors conclude: "Abdominal pain appears to be common and persistent among children with ASD". Further, anxiety and sensory over-responsivity also seemed to correlate with bowel features which is probably not unexpected.

Yes, you might indeed say that this study was based on "the parent-reported GI Symptom Inventory Questionnaire" among other things and so one has to be slightly cautious about inferring states. But as I've mentioned before on this blog, parents/primary caregivers tend to be pretty good at picking up when such issues are present in their children (see here) if not precise to all the technical details [3].

Perhaps the most important detail about the Mazurek study is their mention of the word 'pain' and how so many of their cohort seemed to be enduring quite a bit of it for such a long period of time. You wouldn't think that there was guidance on identifying and managing these issues [4] would you? And whilst we are on the topic of GI issues and autism, I might as well bring your attention to the potentially important question asked by Heitzer and colleagues [5]: Should clinical trial research of psychotropic medication in autism control for gastrointestinal symptoms? Answers on a postcard please (although I will blogging about this paper in times to come).

So then, how about William Shatner singing Pulp to close. Replacing a Sheffield accent with a Montreal one... mmm, maybe he needs a little Henderson's Relish with that cheese?

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[1] Mazurek MO. et al. One-year course and predictors of abdominal pain in children with autism spectrum disorders: The role of anxiety and sensory over-responsivity. Research in Autism Spectrum Disorders. 2014; 8: 1508-1515.

[2] Mazurek MO. et al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol. 2013 Jan;41(1):165-76.

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

[4] Buie T. et al. Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report. Pediatrics. 2010; 125: S1-S18.

[5] Heitzer AM. et al. Should clinical trial research of psychotropic medication in autism control for gastrointestinal symptoms? J Clinical Pharmacology. 2014. 6 May.

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ResearchBlogging.org Mazurek, M., Keefer, A., Shui, A., & Vasa, R. (2014). One-year course and predictors of abdominal pain in children with autism spectrum disorders: The role of anxiety and sensory over-responsivity Research in Autism Spectrum Disorders, 8 (11), 1508-1515 DOI: 10.1016/j.rasd.2014.07.018

Wednesday, 17 September 2014

Autoimmune disease risk and eating disorders

"We were set up. The cops were waiting for us."
"We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders".

So said the paper by Anu Raevuori and colleagues [1] (open-access) based on an analysis of over 2300 people "treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010" compared with nearly 10,000 control participants (so yes, this was quite a well-powered study).

The Raevuori paper is open-access but if you want a few choice details, here goes...

  • Based on a body of research literature looking at a possible association between eating disorders and autoimmune conditions like type 1 diabetes [2], authors set about testing the hypothesis on a large scale on whether "the risk of autoimmune diseases would be increased in individuals with eating disorders both prior and after the onset of the treatment for an eating disorder".
  • Having already mentioned how large a scale the authors' participants groups were, various eating disorder diagnoses were confirmed based on ICD-10 criteria [3] and both research and control populations were assessed for some 30 autoimmune conditions based on existing hospital discharge registry. "Period and lifetime prevalences" were calculated from the data. 
  • Results: "Participants with BN [bulimia nervosamade up the largest patient group (54.0%), followed by those with AN [anorexia nervosa] (38.8%), and those with BED [binge eating disorder] (7.3%)". Over 5% of those diagnosed with an eating disorder had been diagnosed with one or more autoimmune conditions compared with just under 3% of controls when it came to looking at period prevalence (at the onset of treatment). Long quote coming up... "The risk of prior diagnosis of endocrinological autoimmune diseases (OR 3.3, 95% CI 2.4–4.6, P<0.001), of gastroenterological immune-mediated diseases (OR 2.0, 95% CI 1.3–3.1, P = 0.002), and of autoimmune diseases combined (OR 2.1 95% CI 1.7–2.7, P<0.001) was significantly higher among patients than among matched controls".
  • With regards to lifetime prevalence (over the whole study period) "8.9% (N = 209) of patients and 5.4% of control individuals (N = 509) had ever been diagnosed with one or more autoimmune disease". 

Whilst only looking like a relatively small percentage difference in the rates of autoimmune conditions between the groups, it is the scale of the Raevuori study in terms of participant numbers which gives the data some 'edge'. As the authors also note, their use of the category BED - binge eating disorder - is also another plus to their study given it's recent inclusion into DSM-5 (see here).

As I always seem to be about papers mentioned on this blog, I was really quite interested in the results presented by Raevuori et al and their potential implications for how we describe eating disorders and the potential mechanisms involved in onset. Research into autoimmune conditions has recently been producing some rather important associations as per my covering of things like a [possible] link between autoimmune disorders following trauma and PTSD (see here) and even a suggested connection with some epilepsy (see here).


Raevuori and colleagues discuss several pertinent mechanisms potentially linking their findings including the ever-present issue of inflammation and: "Pro-inflammatory cytokines and antibodies/autoantibodies against neuronal antigens". They also mention some possible role for "intestinal microflora contributing to the development of cross-reactive neuronal autoantibodies [providing] a link between gut and brain" and the growing fascination with all-things gut microbiome. Their finding of a greater frequency of the inflammatory bowel disease (IBD), Crohn's disease in their eating disorder cohort offers some evidence for this assertion as a function of the growing interest in gut bacteria and IBDs [4].

Without hopefully going too far off tangent from the Raevuori paper, I started to think about how these results might also fit in with some of the research done on autism and whether there may be a bigger picture here. Eating disorders have been mentioned alongside the label autism quite a few times in the research literature [5]. My previous discussions on signs of autism in cases of eating disorders (see here) is one example. Likewise, autoimmune conditions and autism also seem to have something of a connection (see here) alongside presented data on markers of autoimmunity in cases of autism (see here and see here). One can perhaps see how the various elements - immune function, inflammation, gut bacteria, gut permeability? - might be intertwined, albeit in a rather complex fashion...?

Music then, and Naive by The Kooks.

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[1] Raevuori A. et al. The increased risk for autoimmune diseases in patients with eating disorders. PLoS One. 2014 Aug 22;9(8):e104845.

[2] Young V. et al. Eating problems in adolescents with Type 1 diabetes: a systematic review with meta-analysis. Diabet Med. 2013 Feb;30(2):189-98.

[3] Herpetz S. et al. The Diagnosis and Treatment of Eating Disorders. Dtsch Arztebl Int. Oct 2011; 108(40): 678–685.

[4] Manichanh C. et al. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):599-608.

[5] Huke V. et al. Autism spectrum disorders in eating disorder populations: a systematic review. Eur Eat Disord Rev. 2013 Sep;21(5):345-51.

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ResearchBlogging.org Raevuori A, Haukka J, Vaarala O, Suvisaari JM, Gissler M, Grainger M, Linna MS, & Suokas JT (2014). The increased risk for autoimmune diseases in patients with eating disorders. PloS one, 9 (8) PMID: 25147950

Tuesday, 16 September 2014

The schizophrenias (plural)

A micropost if you will, to draw your attention to the paper by Javier Arnedo and colleagues [1] mentioning the concept of 'the schizophrenias' (plural). Some media coverage of this paper can be found here and here. The crux of the paper is that although currently unified by a diagnostic label, schizophrenia seems to be comprised of various conditions: "caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes".
"... dogs and cats living together... mass hysteria!"

I'm going to say little else about this findings aside from stressing how (a) this re-conceptualisation of schizophrenia into a more plural condition is not a million miles away from moves in other areas of psychiatry (see here) and (b) the reliance on genetic mutation (SNPs) in the paper whilst interesting, perhaps overlooks other non-structural genomic factors potentially implicated in cases of the schizophrenias (see here). That also there may be some 'common ground' between the schizophrenias and other conditions (see here) might also be important for this growing tide of psychiatric plurality.

Music to close. Mr Blue Sky (live).

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[1] Arnedo J. et al. Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies. Am J Psychiatry. 2014. September 15.

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ResearchBlogging.org Javier Arnedo, Dragan M. Svrakic, Coral del Val, Rocío Romero-Zaliz, Helena Hernández-Cuervo, Molecular Genetics of Schizophrenia Consortium, Ayman H. Fanous, Michele T. Pato, Carlos N. Pato, Gabriel A. de Erausquin, C. Robert Cloninger, & Igor Zwir (2014). Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies The American Journal of Psychiatry : doi:10.1176/appi.ajp.2014.14040435

Monday, 15 September 2014

Zinc and copper and autism

The paper by Li and colleagues [1] looking at serum copper (Cu) and zinc (Zn) levels in a group of participants diagnosed with an autism spectrum disorder (ASD) is the source material for today's post. Highlighting how "mean serum Zn levels and Zn/Cu ratio were significantly lower in children with ASD compared with normal cases... whereas serum Cu levels were significantly higher" the continued focus on the metallome in autism carries on at a pace. I should at this point out that I'm not in favour of the use of the word 'normal' in this or any context (anyone who feels that they are normal, please make themselves known to the population at large).

"Bring me... the bore worms!"
Anyhow... I've talked zinc and autism / other conditions on this blog quite a few times (see here and see here). Alongside other more recent data [2] there is a growing realisation that zinc deficiency present in at least some diagnosed on the autism spectrum might have quite a few implications. With this thought in mind, I might also draw your attention to the recent paper by Chaves-Kirsten and colleagues [3] talking about how zinc might also show some connection to the protein kinase of the hour, mTOR (see here) and in particular reducing mTOR levels in a rodent model of autism. This follows other work in this area [4].

The Li paper alongside looking at individual levels of zinc and copper and how they seemed to correlate with presented symptoms according to the Childhood Autism Rating Scale (CARS) also talks about the zinc/copper ratio which is something that has been previously discussed in the peer-reviewed literature with reference to autism and various other conditions as per the excellent review by Osredkar & Sustar [5] (open-access). The paper by Faber and colleagues [6] for example, indicated that a low Zn/Cu ratio may "indicate decrement in metallothionein system functioning". They also talked about how issues with this ratio "may be a biomarker of heavy metal, particularly mercury, toxicity in children with ASDs" as per the various biological uses of metallothionein [7]. I know this moves discussions into some quite uncomfortable realms but science is science (see here) and one should not be afraid to have scientific discourse on any topic. Importantly too, the Faber results also seemed to show more than a passing similarity to those presented by Li et al. Same goes for the paper by Russo and colleagues [8].

The other interesting point recorded by Li and colleagues was their use of the good 'ole ROC curve as a means to indicate an "auxiliary diagnosis of autism". More frequently linked to a certain Egyptian-Saudi autism research group (see here), ROC curves - "a fundamental tool for diagnostic test evaluation" - basically plots the true positive rate against the false positive rate for a test. Li et al projected the cut-off value for the Zn/Cu ratio to be 0.665 for a diagnosis, with "a sensitivity of 90.0% and a specificity of 91.7%". Bearing in mind the relatively small participants included for analysis (n=60), those aren't bad figures for sensitivity and specificity remembering my recent discussions on the observation-based classifier (OBC) from Wall and colleagues [9] (see here) and what they got.

There's little more for me to say about the Li data that I haven't already said here and in other posts on this topic. If you want to read a little more about the possible role of zinc and copper in cases of autism, the report by Bjorklund [10] covers quite a bit of the literature on possible links. The next question is what might we be able to do about any issues in this area? [11]

So then, The Last of the Famous International Playboys? (not me of course..)

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[1] Li SO. et al. Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport. 2014 Aug 26.

[2] Grabrucker S. et al. Zinc deficiency dysregulates the synaptic ProSAP/Shank scaffold and might contribute to autism spectrum disorders. Brain. 2014 Jan;137(Pt 1):137-52.

[3] Chaves-Kirsten GP. et al. Prenatal zinc prevents mTOR disturbance in a rat model of autism induced by prenatal lipopolysaccharide. Brain, Behavior & Immunity. 2014; 40: e11-e12.

[4] McClung JP. et al. Effect of supplemental dietary zinc on the mTOR signaling pathway in skeletal muscle from post-absorptive mice. FASEB J. 2006; 20 (Meeting Abstract Supplement) A627.

[5] Osredkar J. & Sustar N. Copper and Zinc, Biological Role and Significance of Copper/Zinc
Imbalance. Journal of Clinical Toxicology. 2011; S3.

[6] Faber S. et al. The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Biomarkers. 2009 May;14(3):171-80.

[7] Coyle P. et al. Metallothionein: the multipurpose protein. Cell Mol Life Sci. 2002 Apr;59(4):627-47.

[8] Russo AJ. et al. Plasma copper and zinc concentration in individuals with autism correlate with selected symptom severity. Nutr Metab Insights. 2012 Feb 28;5:41-7.

[9] Duda M. et al. Testing the accuracy of an observation-based classifier for rapid detection of autism risk. Transl Psychiatry. 2014 Aug 12;4:e424.

[10] Bjorklund G. The role of zinc and copper in autism spectrum disorders. Acta Neurobiol Exp (Wars). 2013;73(2):225-36.

[11] Russo AJ. & Devito R. Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger's Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism. Biomark Insights. 2011;6:127-33.

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ResearchBlogging.org Li SO, Wang JL, Bjørklund G, Zhao WN, & Yin CH (2014). Serum copper and zinc levels in individuals with autism spectrum disorders. Neuroreport PMID: 25162784

Friday, 12 September 2014

Insulin, growth hormone and risk of schizophrenia?

"Overall, the present findings suggest that metabolic and hormonal disturbances such as effects on insulin and growth hormone may represent a vulnerability factor to develop mental disorders". That was the conclusion reported by van Beveren and colleagues [1] (open-access) looking at "disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia".
"Years ago you served my father in the Clone Wars"

Drawing on data derived from participants taking part in the Genetic Risk and Outcome of Psychoses (GROUP) study [2] researchers looked at blood serum samples "to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls". Multiplex immunoassay was the analytical weapon of choice.

The results indicated that "10 proteins were present at significantly different levels between schizophrenia patients and controls" which can be seen here. The insulin synthesis pathway showed more than a passing connection to group differences as per the appearance of insulin and precursor molecules such as proinsulin and C-peptide (connecting peptide). Some of these pathway molecules were also reported to be altered in the sibling group(s) too. Growth hormone also featured as a potentially distinguishing marker, as did adiponectin among others.

The authors conclude (again) their findings for "the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia". Perhaps even more interesting is their view of the body of work [3] suggesting that "antipsychotic drugs are known to increase peripheral glucose levels" and how, in light of their findings, "these effects may be intrinsically related to the therapeutic mechanism of action by increasing the peripheral blood glucose levels and thereby increasing glucose availability in the brain".

As the authors point out, there is still quite a bit more to do in this area including examining larger samples sizes and importantly, looking at blood glucose levels as a measure of insulin resistance to further complement their findings. I note however that issues with insulin function being potentially related to mood and other psychiatric conditions are nothing new as per the various literature in this area. Anderson and colleagues [4] for example, talked about a diagnosis of diabetes doubling the odds of comorbid depression. Bearing in mind, the possible interfering effect of medication, Verma and colleagues [5] found that in drug-naive (unmedicated) patients with first-episode psychosis there was a significantly increased likelihood of diabetes to be present compared with age and sex-matched asymptomatic control participants. I don't doubt however, that any relationship is going to be complicated.

Finally, and bearing in mind the prime directive of this blog (no medical or clinical advice given or intended), there is the question of how this research might translate into therapeutic intervention. A final quote from the authors on this and the possibility of: "novel disease prevention approaches, which could involve nutrition modification, stress reduction and pharmaco-therapeutic interventions, including the application of well-tolerated drugs that combat insulin resistance". Alongside the dietary aspect (which is something very favourable to this blog for lots of reasons), I am wondering whether we could also learn something from times gone by [6]? Perhaps even the appliance of prophylactic psychiatry [7]?

Music to close and Andrea Bocelli sings Funiculì, Funiculà...

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[1] van Beveren NJM. et al. Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia. Translational Psychiatry. 2014; 4: e430.

[2] Korver N. et al. Genetic Risk and Outcome of Psychosis (GROUP), a multi-site longitudinal cohort study focused on gene-environment interaction: objectives, sample characteristics, recruitment and assessment methods. Int J Methods Psychiatr Res. 2012 Sep;21(3):205-21.

[3] Wirshing DA. et al. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002 Oct;63(10):856-65.

[4] Anderson RJ. et al. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001 Jun;24(6):1069-78.

[5] Verma SK. et al. Metabolic risk factors in drug-naive patients with first-episode psychosis. J Clin Psychiatry. 2009 Jul;70(7):997-1000.

[6] Anderson K. et al. Salsalate, an old, inexpensive drug with potential new indications: a review of the evidence from 3 recent studies. Am Health Drug Benefits. 2014 Jun;7(4):231-5.

[7] Sawa A. & Seidman LJ. Is Prophylactic Psychiatry around the Corner? Combating Adolescent Oxidative Stress for Adult Psychosis and Schizophrenia. Neuron. 2014; 83: 991-993.

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ResearchBlogging.org van Beveren NJ, Schwarz E, Noll R, Guest PC, Meijer C, de Haan L, & Bahn S (2014). Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia. Translational psychiatry, 4 PMID: 25158005

Thursday, 11 September 2014

Treating autism in the first year of life

I had been waiting y'know. Waiting a while for the paper by Sally Rogers and colleagues [1] to finally appear quite a few days after the media headlines about 'reducing', 'reversing' and even 'eliminating' the signs and symptoms of autism in early infancy had appeared. Personally, I prefer the New Scientist headline: 'Early autism intervention speeds infant developmentgiven the text of the paper. I should perhaps also add the words 'for some' to that sentence as you will hopefully see...

I'm sure most people have already read about the study ins and outs: take an intervention called 'Infant Start' (IS), a relation of the Early Start Denver Model (ESDM), and apply it with a small (very small) group of "symptomatic" young infants (n=7, aged between 6-15 months old) showing signs and symptoms of autism. Plot baseline measures and progress of those children under IS using various psychometric tools including something like the Autism Observation Scale for Infants (AOSI) and old reliable: the ADOS (the Autism Diagnostic Observation Schedule) compared against four comparison groups. One of those control groups included those with similar early autism symptoms as judged by "elevated AOSI scores and clinician concerns" but who did not receive IS; a so-called "declined referral (DR) group" (n=4). Record results and report outcome based on said 12-week program and added extra sessions a few months down the line.

The headline conclusion: "At 36 months, the treated group had much lower rates of both ASD [autism spectrum disorder] and DQs [developmental quotients] under 70 than a similarly symptomatic group who did not enroll in the treatment study". Further: "the pilot study outcomes are promising". I should add that when it came to the "final visit" and "based on standardized assessments and clinical judgement" 2 of the 7 children in the IS group did eventually receive a diagnosis of ASD/PDD-NOS (pervasive developmental disorder not otherwise specified). This compared with 3 of the 4 children in the DR group who met criteria for ASD/PDD-NOS (the other child "presented with intellectual disability"). Insofar as DQ - specifically "overall DQ at or below 70 at 36 months" - well, one child in the IS group fell into this category compared with 3 children in the DR group (note to authors, you've called this the 'DE' group... sorry to be pedantic). You can um-and-ah about the links between ASD and PDD-NOS for example, but suffice to say that any effect from IS was not universal across all participants included in the trial. If you'd like a few more details about the trial and results, I'll refer you to the press release from UC Davis (see here).

Of course this is not the first time that this type of very early intervention has been discussed in the peer-reviewed domain. Take for example another paper by Rogers and colleagues [2] (open-access) talking about the use of ESDM with a cohort of 14-24 month old toddlers "at risk for autism spectrum disorders". The results on that occasions were slightly less dramatic than the more recent ones with the caveat that "both younger child age at the start of intervention and a greater number of intervention hours were positively related to the degree of improvement in children's behavior for most variables". I talked about this in a previous post (see here). Indeed it appears that age at start of intervention might be an important variable after all.

So, where next with this research? Well, aside from some discussions reiterating how useful it would be to have something to aid early diagnosis (see here) bearing in mind that it has not been conclusively proven that all autism is present from birth (see here), discussions have turned to why such early intervention might have had the effect that it had. Brain plasticity has been mentioned, and how critical periods in early development might be particularly amenable to such intensive intervention. Of course, without the all-important "testing the treatment’s efficacy" under more controlled conditions and with larger groups, one cannot discount some role for chance in the recent findings. Not buying that as an answer? How about differing developmental trajectories then?

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[1] Rogers SJ. et al. Autism Treatment in the First Year of Life: A Pilot Study of Infant Start, a Parent-Implemented Intervention for Symptomatic Infants. Journal of Autism and Developmental Disorders. 2014. 12 September.

[2] Rogers SJ. et al. Effects of a brief Early Start Denver model (ESDM)-based parent intervention on toddlers at risk for autism spectrum disorders: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2012 Oct;51(10):1052-65.

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ResearchBlogging.org S. J. Rogers, L. Vismara, A. L. Wagner, C. McCormick, G. Young, & S. Ozonoff (2014). Autism Treatment in the First Year of Life: A Pilot Study of Infant Start, a Parent-Implemented Intervention for Symptomatic Infants Journal of Autism and Developmental Disorders : 10.1007/s10803-014-2202-y

Omega-3 fatty acids rescues Fragile X phenotypes in Fmr1-Ko mice

"These results demonstrate that n-3 PUFAs dietary supplementation, although not a panacea, has a considerable therapeutic value for FXS [Fragile X syndrome] and potentially for ASD [autism spectrum disorder], suggesting a major mediating role of neuroinflammatory mechanisms".

A view @ Wikipedia 
That was the conclusion reached by Susanna Pietropaolo and colleagues [1] who "evaluated the impact of n-3 PUFA dietary supplementation in a mouse model of fragile X syndrome (FXS), i.e., a major developmental disease and the most frequent monogenic cause of ASD". Looking at the Fmr1-KO mouse model of FXS, a mouse specifically bred to mimic the silencing of the FMR1 gene noted in FXS (see here) with onwards adverse effects for the production of FMRP, researchers looked at what happened when diets were "enriched or not with n-3 PUFAs from weaning until adulthood when they were tested for multiple FXS-like behaviors". The results seemed to indicate that "n-3 PUFA supplementation rescued most of the behavioral abnormalities displayed by Fmr1-KO mice, including alterations in emotionality, social interaction and non-spatial memory, although not their deficits in social recognition and spatial memory". Neuroinflammatory imbalances noted in the knock-out mice were also positively affected by omega-3 supplementation.

I don't need to remind you that the Pietropaolo study was a study of mice and one needs to be quite careful about extrapolating animal results when it comes to humans. That being said, given the quite extensive work that has been done on FXS and the detailing of it's molecular background, one might assume that the current results are treated with a little less scepticism than in relation to other more idiopathic 'types' of autism. Still, proper trials with people are indicated as per other research.

Omega-3 fatty acids have been discussed before on this blog with autism in mind (see here). The collected literature on their usefulness as supplements for autism is rather mixed at present [2] despite some emerging evidence on their involvement in various biological processes in cases of autism (see here). That being said, I'm not getting too down on omega-3 fatty acids in light of some associations being made with specific skills over and above any condition-specific relationship and some new light being shed on their use in other conditions [3]. I'm yet to find anything like an experimental trial of fatty acids in real people with FXS but did chance(!) upon the study by Lachance and colleagues [4] (open-access) talking about the use of fenretinide (N-(4-hydroxyphenyl) retinamide (4HPR)) in the test-tube and effects "associated with the normalization of arachidonic acid/docosahexaenoic acid ratio in macrophages". The effect talked about translates as a down-regulation in the "production of arachidonic acid (AA), a pro-inflammatory omega-6 polyunsaturated fatty acid, and to increase levels of omega-3 polyunsaturated docosahexaenoic acid (DHA), which has an anti-inflammatory effect". Mmm... possibly some new targets to replace quite a few disappointments when it comes to FXS therapeutics (see here).

Music to close. Fontella Bass and Rescue Me.

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[1] Pietropaolo S. et al. Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice. Psychoneuroendocrinology. 2014 Jul 9;49C:119-129.

[2] James S. et al. Omega-3 fatty acids supplementation for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2011 Nov 9;(11):CD007992.

[3] Hawkey E. & Nigg JT. Omega-3 fatty acid and ADHD: Blood level analysis and meta-analytic extension of supplementation trials. Clin Psychol Rev. 2014 Jun 2;34(6):496-505.

[4] Lachance C. et al. Fenretinide corrects the imbalance between omega-6 to omega-3 polyunsaturated fatty acids and inhibits macrophage inflammatory mediators via the ERK pathway. PLoS One. 2013 Sep 12;8(9):e74875.

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ResearchBlogging.org Pietropaolo S, Goubran MG, Joffre C, Aubert A, Lemaire-Mayo V, Crusio WE, & Layé S (2014). Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice. Psychoneuroendocrinology, 49C, 119-129 PMID: 25080404