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  • September 15, 2016
  • 04:25 AM
  • 300 views

Eicosapentaenoic acid (EPA)-predominant fatty acid supplements and the treatment of depression

by Paul Whiteley in Questioning Answers

"Further RCTs [randomised-controlled trials] should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA [eicosapentaenoic acid] -predominant omega-3 HUFA [highly unsaturated fatty acids] formulations."So went the conclusions of the review article published by Brian Hallahan and colleagues [1] who searched the peer-reviewed science literature for clinical trials "evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder." They found over 30 trials of omega-3 supplementation vs. placebo published between 1980 and 2014 that together included participant numbers in the thousands.They reported that among those diagnosed with depression, the type of fatty acid supplement used might matter: "eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo." When it came to that other commonly discussed omega-3 fatty acid - docosahexaenoic acid (DHA) - the results were not so great for those diagnosed with depression in terms of changes to symptom presentation(s). Importantly too, the authors noted that: "EPA failed to prevent depressive symptoms among populations not diagnosed for depression."Interesting. More so when read alongside another recent review paper by Husted & Bouzinova [2] who similarly suggest that more targeted research is needed to "clarify an optimal dosage of EPA and DHA in [the] prevention of depression." They also described the idea that various processes particularly pertinent to the concept of inflammation (yes, depression and inflammation do seem to have some commonalities) might be a target for certain omega-3 fatty acids and onwards the presentation of depression. There may even be 'critical windows' where such supplementation might be more useful (see here) than others.What's the critical difference between EPA and DHA that could account for the Hallahan findings? Well, there are a few good articles on how not all omega-3 fatty acids are the same, but I found one that is pretty informative (see here). Chemically-speaking, there are differences in structure which might account for where and when these compounds might fit when it comes to various chemical reactions in the body. Going back to the whole inflammation thing, I understand that EPA might also have some important effects on an enzyme called delta-5-desaturase (D5D) but I'd guess this is not the only difference that might be important.I'll be keeping a watch out for developments in this area of study but for now, yet more evidence that food and nutrition might have some important influences on behaviour and psychiatry. Nutritional psychiatry is starting to come out from the clinical shadows perhaps...Music: The Fall and Eat Y'Self Fitter ('Up the stairs mister').----------[1] Hallahan B. et al. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British Journal of Psychiatry. 2016; 209: 192-201.[2] Husted KS. & Bouzinova EV. The importance of n-6/n-3 fatty acids ratio in the major depressive disorder. Medicina (Kaunas). 2016;52(3):139-47.----------Hallahan B, Ryan T, Hibbeln JR, Murray IT, Glynn S, Ramsden CE, SanGiovanni JP, & Davis JM (2016). Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British journal of psychiatry : the journal of mental science PMID: 27103682... Read more »

Hallahan B, Ryan T, Hibbeln JR, Murray IT, Glynn S, Ramsden CE, SanGiovanni JP, & Davis JM. (2016) Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. The British journal of psychiatry : the journal of mental science. PMID: 27103682  

  • September 14, 2016
  • 04:26 AM
  • 281 views

Unexpected improvement in core autism symptoms following a probiotic?

by Paul Whiteley in Questioning Answers

The paper by Enzo Grossi and colleagues [1] (open-access) is definitely worthy of a post today and the suggestion that the "appropriate use of probiotics" might be something to consider for at least some diagnosed as being on the autism spectrum.Accepting that I'm slightly curious as to what would be considered 'inappropriate use of probiotics', the Grossi paper describes the clinical journey of a boy aged 12 diagnosed with an autism spectrum disorder (ASD) accompanied by learning (intellectual) disability who was concurrently diagnosed with coeliac disease (CD). The CD diagnosis was a slightly complicated affair given that whilst he presented with the relevant 'genetics' of CD (HLA genotypes) and "a slight elevation of transglutaminase antibodies" a gluten-free diet seemingly did very little in terms of clinical benefits and when it came to the "blood-specific tests for celiac disease" they were always negative. I'll come back to some of these points shortly but his chronic gastrointestinal (GI) symptoms that were first thought to be CD related were subsequently put down to irritable bowel syndrome (IBS).In light of the IBS diagnosis and given some pretty important research suggesting that specific probiotic formulations might have treatment-potential for some IBS (see here), a probiotic intervention was prescribed: VSL#3. What happened next is intriguing...After a few weeks of probiotic treatment, some 'apparent improvements' were noted in the boy's behavioural presentation. This led the authors to start looking more systematically at whether said improvements could be charted and possibly tied into his probiotic use. We are told that the various components of his behavioural plan that had been in place for some 6 years were continued without "any particular change." Use of the gold-standard assessment tool that is the ADOS - Autism Diagnostic Observation Schedule - was employed over a period of about a year-and-a-half to covering the period of probiotic use. Data for two ADOS assessments were available before the probiotic was installed and four assessments were carried out during and post-intervention. The results suggested that scores relevant to social affect (the DSM-5 term describing issues with social and communicative domains) changed over the intervention period in line with some of the observations made of this boy. Further: "This change was surprising since in our assessment records over several years, the patient status had remained steadily unchanged." It should also be noted that the GI symptoms, the initial target of probiotic use, also reduced "as expected."Yes, I know that this is a case report (and N=1) and given what we (think we) know about autism, such results can by no means be generalised to all autism. There could also be a million and one other variables potentially accounting for the results including something called puberty potentially playing a role (see here) given the age of the boy. One needs to be cautious.But... these are still potentially important results for quite a few different reasons. Going back to the description of CD being diagnosed and then un-diagnosed, regular readers might know about my interest in something called non-coeliac gluten sensitivity (NCGS) when it comes to something like autism (see here). The suggestion being that although a diagnosis of autism is not protective against a diagnosis of CD, the still emerging peer-reviewed data seems to suggest something slightly more gluten-fuzzy when it comes to at least some autism. That elevated levels of tissue transglutaminase are also not an uncommon finding in relation to [some] autism (see here) adds to the curiosity in this area.Bowel or GI issues occurring alongside autism? Well, I've said it before and I'll say it again: GI issues (both functional and pathological) are over-represented when  it comes to autism (see here). You can call it IBS or similar other bowel related label but the fact of the matter is that such issues are not uncommon and lots more resources need to be poured into looking at and importantly, treating such issues save any further health inequalities appearing alongside the label of autism. It makes good sense that if something like IBS is diagnosed, and the various meta-analyses suggest that probiotics might be one part of an intervention strategy for IBS, their use where IBS clusters with autism should be the same as when autism is not part of the equation. Simple as.The Grossi case report also highlights how gut and brain, with a healthy portion of gut microbiome, might show some important links for some on the autism spectrum [2]. This is by no means 'a new thing' (see here) and to some extent, justifies the various studies where gut bacteria for example, have been looked at in the context of autism (see here for example). That such a connection might also include issues with gut permeability (see here) is another important detail and is evidenced by the possibility that probiotics may also work on the gut membrane [3] as well as those trillions of wee beasties that call us home.In short, more research on the use of probiotics with autism is very much implied (and indeed is already in progress). Watch this space.To close, first we had Mr Pharmacist from The Fall. Now we have Oxymoronic from NOFX. Spot the difference...----------[1] Grossi E. et al. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Medical Case Reports. 2016; 4: 2050313X16666231.[2] Inoue R. et al. A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism spectrum disorders. Biosci Biotechnol Biochem. 2016 Sep 1:1-9.[3] Mennigen R. et al. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1140-9.----------... Read more »

  • September 13, 2016
  • 04:27 AM
  • 287 views

A 'characteristic chemical signature' to chronic fatigue syndrome?

by Paul Whiteley in Questioning Answers

Today I'm (belatedly) talking about the paper by Robert Naviaux and colleagues [1] (open-access) and some further peer-reviewed discussion concerning the metabolomics of chronic fatigue syndrome (CFS). Suggesting that "targeted, broad-spectrum metabolomics of plasma not only revealed a characteristic chemical signature but also revealed an unexpected underlying biology" when it comes to CFS, it is not surprising that this work has attracted some media interest (indeed, quite a lot of media interest).I don't want to regurgitate all the findings given that (a) they are numerous, and (b) the paper is open-access, but there are a few details worth noting.So:Some readers might recognise the names Robert and Jane Naviaux listed as authors on this current paper as one and the same team involved in all that suramin for [mouse] autism work (see here). Their previous focus on the application of metabolomics (specifically the use of mass spectrometry) following the use of suramin hints at the skills and expertise this group have in that field.Their research attention was turned to CFS with the aim to put further flesh on the idea that there may be some important biochemistry happening in cases of the condition.Eighty-four adults were included for study; 45 diagnosed with CFS by various criteria (yes, there are quite a few of them). They provided blood samples that were subject to analysis: "Targeted, broad-spectrum, chemometric analysis of 612 metabolites from 63 biochemical pathways was performed."Results: well, first various 'trigger' factors were linked to onset of CFS participants' symptoms. Biological triggers - "viral, bacterial, fungal/mold, and parasitic infections" - were most common but "no single infectious agent or other stressor was statistically more prevalent." There appear to be many [organic] roads to the development of CFS.'A characteristic chemical signature' is something that many media outlets have jumped on to based on these results. Indeed, with some very pretty Venn diagrams included, there did appear to be some chemical 'signatures' that defined CFS vs. not-CFS.  The sorts of compounds seemingly involved related to the: "Sphingolipids, glycosphingolipids, phospholipids, purines, microbiome aromatic amino acid and branch chain amino acid metabolites." I'm particularly interested in the amino acid chemistry detected and how it may overlap with other findings [2].The relevance of those chemical signatures in terms of biological processes were quite diverse but led authors to conclude that "the metabolic features of CFS are consistent with a hypometabolic state." Some media outlets have referred to this as a 'semi-hibernation like state' where metabolism is somehow slowed down. I'm not so sure this is the most accurate definition given that hibernation normally implies a time-limit to such a state. Unfortunately, for many, CFS does not magically stop come the biological Spring. There is also mention of how the findings might relate to other research in CFS including a role for mitochondrial function (see here) and NAD (see here).With some cautions attached to this line of work (see here), not least the quite small participant groups included for study and, I believe, the use of a single blood sample at one specific time point, this is interesting work. Added to a growing tide of research suggesting that if one looks, one might indeed find some biological issues associated with a diagnosis of CFS (see here for example), this is yet another stop in the journey towards understanding CFS is terms of biology not psychology. The next stop is of course independent replication."The study of larger cohorts from diverse geographical areas, and comparison with related medical disorders like depression and posttraumatic stress disorder, will be needed to validate the universality and specificity of these findings. The finding of an objective chemical signature in CFS helps to remove diagnostic uncertainty, will help clinicians monitor individualized responses to treatment, and will facilitate multicenter clinical trials." Big words that indeed require that independent replication, but the research future for CFS is already looking a little brighter as a result of the Naviaux findings.----------[1] Naviaux RK. et al. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016 Aug 29. pii: 201607571.[2] Georgiades E. et al. Chronic fatigue syndrome: new evidence for a central fatigue disorder. Clin Sci (Lond). 2003 Aug;105(2):213-8.----------Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N, Anderson W, & Gordon E (2016). Metabolic features of chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America PMID: 27573827... Read more »

Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N, Anderson W, & Gordon E. (2016) Metabolic features of chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America. PMID: 27573827  

  • September 12, 2016
  • 12:36 PM
  • 294 views

Opioid Abuse: Treatment Guidelines

by William Yates, M.D. in Brain Posts

Molecular model of the drug buprenorphineThe U.S. Surgeon General recently sent a letter to all physicians about the danger of prescription opioids, particularly when used in combination with benzodiazepines (i.e. Valium, Xanax).  This combination greatly increases the risk of overdose death.Clinicians can successfully assist those with opioid use disorders. Marc Schuckit, M.D. recently published a nice summary review of entitled "Treatment of Opioid-Use Disorder" in the New England Journal of Medicine (see citation below).The review contains some nice tables including tables related to:Diagnostic criteria of opioid use disorderAn opiate withdrawal rating scaleOpioid free treatment aids in management of opioid withdrawalOpioid agonist aids in management of opioid withdrawalOpioid agonist use in long-term maintenanceOpioid withdrawal is generally non-life threatening, but extremely uncomfortable and a strong motivator for return to opioid use.Use of opioid agonists such as buprenorphine (pictured in molecular model above) is the best tolerated and least uncomfortable pathway to treatment of opioid withdrawal. However, it is restricted to prescription by a small group of physicians who have completed a special training program.This means many opioid users end up with less tolerated and more uncomfortable withdrawal episodes treated with drugs such as clonidine, diazepam or even over-the-counter drugs such as Imodium.The review notes that with high relapse rates, supervised opioid maintenance with prescribed opioids such as methadone or buprenorphine often are required for long-term abstinence. One barrier to using these types of interventions is availability and cost. Buprenorphine can be expensive and requires regular monitoring in a physicians office.With high costs and lack of access to supervised opioid management, opioid users commonly return to street heroin or prescription opioid pills (licit or illicit). Readers with more interest in this topic can access the free full-text manuscript by clicking on the DOI link in the citation below.Follow me on Twitter @WRY999Model of buprenorphine is from a Wikipedia Creative Commons File attributed to:Crystallographic data from J. Mazurek, M. Hoffmann, A. Fernandez Casares, P. D. Cox and M. D. Minardi (June 2014). "Buprenorphine". Acta Cryst. E70, o635. DOI:10.1107/S1600536814009672Schuckit, M. (2016). Treatment of Opioid-Use Disorders New England Journal of Medicine, 375 (4), 357-368 DOI: 10.1056/NEJMra1604339... Read more »

Schuckit, M. (2016) Treatment of Opioid-Use Disorders. New England Journal of Medicine, 375(4), 357-368. DOI: 10.1056/NEJMra1604339  

  • September 12, 2016
  • 04:31 AM
  • 265 views

The force is strong with autism?

by Paul Whiteley in Questioning Answers

"Tablet and phone games could help diagnose autism, study suggests" went the BBC headline covering the paper by Anna Anzulewicz and colleagues [1] (open-access). The idea being that the way that touch screens are used on tablet and smart phones could potentially 'separate out' those with autism from those with not-autism.Based on a small participant number of "37 children 3–6 years old with autism and 45 age- and gender-matched children developing typically" researchers set about examining "autism-specific motor patterns in the gameplay of children as they engaged with a smart tablet computer (iPad mini) under natural conditions and with minimal instructions." Motor issues accompanying autism are something gaining some renewed (and welcomed) research attention in recent times (see here). Specifically, researchers were utilising the astounding technology that goes into all those swipes and taps that we're also used to these days, and whether under 'serious' game conditions, aspects like force impact and gesture pressure could differentiate the two groups.As per the headline and the rather cheesy title to this post, there were some differences picked up between the autism and control groups based on touch and swiping responses being put through their machine-learning paces (something else that has a growing following in autism research circles). So: "The inertial data indicate children with autism engaged in gameplay with greater force of impact than those developing typically." This and other potential differences led researchers to conclude that: "children with autism applied a significantly different distribution of forces into the device during gameplay than the typically developing children did."Whilst interesting research there is quite a bit more to do before anyone starts using taps and swipes as a means to diagnose autism (or anything else). I don't really need to say that this was a study including a relatively small participant group nor that whilst "All participants had normal or corrected-to-normal vision and no other sensory or motor deficits" this does not preclude the possibility that subtle issues might also be at work (see here). That also recent discussions have suggested moving away from the singular diagnosis of autism as a research starting point is also worth reiterating (see here).Still, I can see some opportunities arising from this area of research and how perhaps combined with other innovative areas of screening and diagnosis there may be much more to see including how subtle differences in movement might also influence variables such as interaction [2]. Yes indeed, "smart tablet technology offers an attractive, new paradigm for clinical autism assessment and bio-behavioural research of pre-school children, enabling engaging, ecological testing of children’s motor behaviour in a fun, accessible format fit for precise computational analysis of neuropsychological function."To close: Danny Boy (from the Proms 2013 although this years version was pretty good too).----------[1] Anzulewicz A. et al. Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism. Scientific Reports. 2016; 6: 31107.[2] Edey R. et al. Interaction Takes Two: Typical Adults Exhibit Mind-Blindness Towards Those With Autism Spectrum Disorder. J Abnorm Psychol. 2016 Sep 1.----------Anzulewicz A, Sobota K, & Delafield-Butt JT (2016). Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism. Scientific reports, 6 PMID: 27553971... Read more »

  • September 11, 2016
  • 03:12 PM
  • 310 views

A microRNA plays role in major depression

by Dr. Jekyll in Lunatic Laboratories

A tiny RNA appears to play a role in producing major depression, the mental disorder that affects as many as 250 million people a year worldwide. Major depression, formally known as major depressive disorder, or MDD, brings increased risk of suicide and is reported to cause the second-most years of disability after low-back pain.

... Read more »

  • September 10, 2016
  • 03:09 PM
  • 352 views

Social connectedness can increase suicide risk

by Dr. Jekyll in Lunatic Laboratories

Community characteristics play an important role in perpetuating teen suicide clusters and thwarting prevention efforts, according to a new study by sociologists who examined clusters in a single town. The study illustrates how the homogeneous culture and high degree of social connectedness of a community can increase suicide risk, particularly among teenagers.

... Read more »

  • September 10, 2016
  • 04:27 AM
  • 299 views

Prevalence of self-injurious behaviors among children with autism

by Paul Whiteley in Questioning Answers

Just over a quarter of children diagnosed with an autism spectrum disorder (ASD) present with self-injurious behaviour (SIB).That was the headline finding reported by Gnakub Soke and colleagues [1] who surveyed the 8000+ children "in the Autism and Developmental Disabilities Monitoring (ADDM) Network during the 2000, 2006, and 2008 surveillance years." THE ADDM network, as some people might know, is one and the same network that comes up with the [estimated] prevalence of autism in the United States (see here) and so carries quite a lot of statistical and clinical clout when it comes to data production. The actual figure for SIB was 27% when taking all the various ADDM sites into consideration but, much like the estimated prevalence stats, "with some variation between sites."SIB is a topic that has been discussed on this blog a few times before (see here and see here for example). It's not something that generally makes for polite dinner table conversation and not something that many people would say makes for 'good PR' when it comes to the public perception of autism. Nevertheless, these and other estimates of SIB in autism (including its persistence) are one of the more pressing issues for those that present with such behaviours given not only the damage and distress that SIB can do to a person but also the effect(s) on family and loved ones too."Clinicians should inquire about SIB during assessments of children with ASD." I think that sentence is taken as read in light of the coincidence of autism and SIB. More than that however I think many people would like to see a lot more research into the potential hows and whys of SIB [2] and what can be done to minimise such 'challenging behaviour'. Yes, such acts may in some way be communicative for some people on the autism spectrum (i.e. pain, discomfort, etc), and if so, the use of a 'chemical cosh' is likely to have repercussions for such possible communication attempts. But where such SIB acts place someone at risk of permanent physical injury and/or increase the likelihood of extremes such as the need for corrective surgery, I don't think many people would hold back with the idea of appropriate management for such extreme behaviours.----------[1] Soke GN. et al. Brief Report: Prevalence of Self-injurious Behaviors among Children with Autism Spectrum Disorder-A Population-Based Study. J Autism Dev Disord. 2016 Aug 26.[2] Yuan X. & Devine DP. The role of anxiety in vulnerability for self-injurious behaviour: studies in a rodent model. Behavioural Brain Research. 2016; 311: 201-209.----------Soke GN, Rosenberg SA, Hamman RF, Fingerlin T, Robinson C, Carpenter L, Giarelli E, Lee LC, Wiggins LD, Durkin MS, & DiGuiseppi C (2016). Brief Report: Prevalence of Self-injurious Behaviors among Children with Autism Spectrum Disorder-A Population-Based Study. Journal of autism and developmental disorders PMID: 27565654... Read more »

Soke GN, Rosenberg SA, Hamman RF, Fingerlin T, Robinson C, Carpenter L, Giarelli E, Lee LC, Wiggins LD, Durkin MS.... (2016) Brief Report: Prevalence of Self-injurious Behaviors among Children with Autism Spectrum Disorder-A Population-Based Study. Journal of autism and developmental disorders. PMID: 27565654  

  • September 9, 2016
  • 02:16 PM
  • 303 views

Study could herald new treatment for muscular dystrophy

by Dr. Jekyll in Lunatic Laboratories

New research has shown that the corticosteroid deflazacort is a safe and effective treatment for Duchenne muscular dystrophy. The findings could pave the way for first U.S.-approved treatment for the disease.

... Read more »

Griggs, R., Miller, J., Greenberg, C., Fehlings, D., Pestronk, A., Mendell, J., Moxley, R., King, W., Kissel, J., Cwik, V.... (2016) Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology, 10. DOI: 10.1212/WNL.0000000000003217  

  • September 9, 2016
  • 12:10 PM
  • 393 views

Statin Therapy: Rethinking Benefits and Risks

by William Yates, M.D. in Brain Posts

A recent 30-page manuscript provides an exhaustive review of the evidence for the efficacy and safety of statin therapy.The authors of this excellent review provide some context for the relative value of statins.The note that putting 10000 individuals with a history of a vascular event on a statin drug for 5 years would prevent 1,000 subsequent events. This is an example of secondary prevention--preventing another adverse outcome in those already experiencing an adverse event.But the statin drugs also appear very powerful in primary prevention-preventing a first event in those at high risk for vascular disease. They estimate putting 10,000 individuals at high risk for vascular events on statins would result in prevention of 500 vascular events over five years.This review provides an up-to-date review of the safety of statins and generally supports the therapy as very low risk.One proposed adverse event of statin therapy is concern about memory and cognition. However, the authors note that well-designed studies of statin therapy in older individuals find no evidence of adverse cognitive effects compared to placebo.They argue that:"..given the weight of evidence against adverse effects of statin therapy on memory or other adverse effects of cognition, it would now be appropriate for regulatory authorities to consider removal from the lists of potential adverse effects on the drug labels so that patients are not inappropriately deterred from using statin therapy." (emphasis mine).The authors go on to emphasize the potential adverse public health consequences of misleading claims regarding the safety of the statin drug class.This excellent review is likely to lead to further discussion about extending the indications for statin use in the general population.Readers with more interest in this topic can access the full free-text manuscript by clicking on the link in the citation below.Follow me on Twitter by clicking HERE.Photo of osprey in flight is from my photography files.Collins R, Reith C, Emberson J et al.  (2016). Interpretation of the evidence for the efficacy and safety of statin therapy Lancet : http://dx.doi.org/10.1016/S0140-6736(16)31357-5... Read more »

Collins, Rory, Reith, Christina, & Emberson, Jonathan. (2016) Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. info:/http://dx.doi.org/10.1016/S0140-6736(16)31357-5

  • September 9, 2016
  • 02:40 AM
  • 317 views

Post-exertional malaise (PEM) in CFS might mean more than one thing

by Paul Whiteley in Questioning Answers

"The results suggest that post-exertional malaise [PEM] is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue."So said the findings reported by Stephanie McManimen and colleagues [1] looking at one of the most common and debilitating aspects of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and how rough-and-ready generalised descriptions often do little to reveal the complexities of this particular symptom.The research group at the centre of this new paper based at DePaul University under the stewardship of Leonard Jason have some previous interest in this facet of ME/CFS as per other recent publications [2] talking about the trials and tribulations of defining PEM. Once again, the very multiple and very complicated ways that CFS/ME is currently diagnosed (see here for example) comes into play as the wording used to define PEM seems to count in terms of who is more or less likely to display this symptom. I might also add that even the words 'post-exertional malaise' have been subject to question and redefinition as per the use of the term PENE (Postexertional neuroimmune exhaustion) [3].In their latest paper, McManimen et al set out to "discern whether post-exertional malaise is a unified construct or whether it is composed of two smaller constructs, muscle fatigue and generalized fatigue." As per the opening sentence of this post, researchers came down on the side of PEM meaning more than one thing, and with it the possibility of further revisions being required to the criteria to define this concept. Indeed, going back to yet another paper from this group [4] researchers suggested that several composite items might better define PEM over just one question: "Dead, heavy feeling that occurs quickly after starting to exercise; Next day soreness or fatigue after non-strenuous, everyday activities; Mentally tired after the slightest effort; Physically drained or sick after mild activity; and Minimum exercise makes you physically tired." Words, in a diagnostic sense, need to be used accurately.And finally, whilst on the topic of CFS/ME, there have been some further developments around the science of CBT and graded exercise...----------[1] McManimen SL. et al. Deconstructing post-exertional malaise: An exploratory factor analysis. J Health Psychol. 2016 Aug 24. pii: 1359105316664139.[2] Jason LA.  et al. Problems in Defining Post-Exertional Malaise. Journal of prevention & intervention in the community. 2015;43(1):20-31.[3] Carruthers BM. et al. Myalgic encephalomyelitis: International Consensus Criteria. Journal of Internal Medicine. 2011;270(4):327-338.[4] Jason LA. et al. Fatigue Scales and Chronic Fatigue Syndrome: Issues of Sensitivity and Specificity. Disabil Stud Q. 2011 Winter;31(1). pii: 1375.----------McManimen SL, Sunnquist ML, & Jason LA (2016). Deconstructing post-exertional malaise: An exploratory factor analysis. Journal of health psychology PMID: 27557649... Read more »

  • September 8, 2016
  • 09:16 AM
  • 328 views

CRISPR on my plate, and some GMO’s on the side

by gdw in FictionalFieldwork

A CRISPR recipe Less than a month ago, the world’s first official CRISPR/Cas9 meal was served. CRISPR/Cas9 is a fairly new technology to edit genomes, and cut and paste genes at will. Well, it’s not exactly that new. It’s actually been around for a long time. CRISPR, or *humhum* Clustered regularly interspaced short palindromic repeats […]... Read more »

Snell C, Bernheim A, Bergé JB, Kuntz M, Pascal G, Paris A, & Ricroch AE. (2012) Assessment of the health impact of GM plant diets in long-term and multigenerational animal feeding trials: a literature review. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 50(3-4), 1134-48. PMID: 22155268  

  • September 8, 2016
  • 04:34 AM
  • 300 views

Metformin to tackle medication induced weight gain in autism?

by Paul Whiteley in Questioning Answers

"Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD [autism spectrum disorder]."So said the paper by Evdokia Anagnostou and colleagues [1] (open-access) tackling an increasingly important health issue related to the pharmacological 'management' of some aspects of some autism.Metformin is the treatment of choice when it comes to the management of type 2 diabetes (the one where "the pancreas doesn't produce enough insulin or the body's cells don't react to insulin"). It is thought to work by helping the liver to stop producing new glucose and also helping insulin carry more glucose into muscle cells more effectively. Alongside, an increasing body of research has also suggested that metformin might be a useful intervention measure to offset one of the quite well-known side-effects associated with various antipsychotic agents: weight gain.So Anagnostou et al set about looking to "assess the safety, tolerability, and efficacy of metformin to decrease weight gain associated with the use of atypical antipsychotic medication in children with ASD." They did this using the gold-standard in clinical trial designs: the "double-blind, placebo-controlled, randomized clinical trial" where some 60 children and young adults diagnosed with an ASD and receiving a stable dose of an atypical antipsychotic received either metformin (Riomet) or a placebo over the course of 16 weeks. "The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables." The study protocol was also registered with ClinicalTrials.gov.As per the opening sentence, there were some important differences in body mass index (BMI) z-scores suggestive that compared with a placebo, those prescribed metformin saw decreases in weight gain. The range of decrease in BMI were in some cases between about 8-9% over the course of the 16 week study period (most of the benefits seemed to be apparent after about 8 weeks of metformin use). Insofar as those secondary variables also examined during the course of the study (glucose levels, insulin, triglycerides, etc.) no significant differences were noted across the study. When it came to the important issue of side-effects, the authors noted that gastrointestinal (GI) effects seemed to be more apparent in the group taking metformin during treatment days. Aside from that, short-term side-effects seemed to be few and far between.The authors note that their trial "did not address the question of whether coadministration of metformin at the onset of atypical antipsychotic use prevents initial weight gain" but rather whether metformin use after weight gain associated with antipsychotic use could be effective. In that light, these are important results that very much require further independent investigation.Quite a few times on this blog I've talked about how the physical health of those on the autism spectrum is sometimes neglected as a function on the focus on mental health or behaviour. There is a growing recognition that autism, or at least some of the important comorbidities associated with autism, might somehow predispose to a more sedentary lifestyle and the accompanying health issues that this can bring. Throw into the mix the possibility that some of the pharmacotherapy used in autism might also contribute to something like weight issues [2], and you have a recipe for some pretty severe health issues potentially building up in later life. These latest findings are therefore welcomed as a way to potentially lower the burden of an elevated BMI in cases where such medication is prescribed.I do have questions however about this approach and how one perhaps needs to be slightly cautious about slipping into the old 'medication to tackle medication side-effects' routine with autism in mind (something noted in an accompanying editorial to the Anagnostou study). Metformin, whilst a very useful drug, is not without side-effects as was noted in the Anagnostou study and given the quite high rates of GI issues noted in cases of autism (see here), one really does not want to make this any worse. I would also like to see more data on the use of metformin in antipsychotic-induced weight gain in autism with a focus on other parameters thought to be altered by such antipsychotic use such as the issue of prolactin levels for example (see here). Yes, there is data to suggest that metformin might more generally work on prolactin levels too [3] but does this similarly apply to children on the autism spectrum? And then also there is the issue of sleep [4]...----------[1] Anagnostou E. et al. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder. JAMA Psychiatry. 2016. Aug 24.[2] Shedlock K. et al. Autism Spectrum Disorders and Metabolic Complications of Obesity. Journal of Pediatrics. 2016. Sept 2.[3] Krysiak R. et al. The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia. Eur J Intern Med. 2016 May;30:94-8.[4] Kajbaf F. et al. The relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes referred for potential sleep disorders. Diabet Med. 2014 May;31(5):577-80.----------... Read more »

  • September 7, 2016
  • 02:15 PM
  • 349 views

Antimicrobial chemicals found with antibiotic-resistance genes in indoor dust

by Dr. Jekyll in Lunatic Laboratories

Researchers have found links between the levels of antimicrobial chemicals and antibiotic-resistance genes in the dust of an aging building used for athletics and academics. One of the antimicrobials seen in the study is triclosan, a commonly used antibacterial ingredient in many personal care products.

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Hartmann, E., Hickey, R., Hsu, T., Betancourt Román, C., Chen, J., Schwager, R., Kline, J., Brown, G., Halden, R., Huttenhower, C.... (2016) Antimicrobial Chemicals Are Associated with Elevated Antibiotic Resistance Genes in the Indoor Dust Microbiome. Environmental Science . DOI: 10.1021/acs.est.6b00262  

  • September 7, 2016
  • 12:05 PM
  • 330 views

Nuturing the Gifted: II

by William Yates, M.D. in Brain Posts

Earlier this summer I posted a review and commentary on a Duke University study of the outcome of children identified as gifted.You can access this post by clicking HERE.Today in Nature News, Tom Clynes publishes a nice review of the history of this topic.He notes there have several large scale studies to examine prospectively children with high academic potential. The cohorts include:Study of Mathematically Precocious Youth-SMPY (Johns Hopkins)Duke University Talent Identification ProgramMunich Longitudinal Study of GiftednessThese cohorts typically use outstanding performance on a structured test to identify students at the highest level of performance in a domain. Spatial intelligence, the ability to visualize shapes in various perspectives, has recently received increased attention.This review includes a summary of what is known about nurturing the gifted child. The table recommends aptitude testing to support parents who may feel their child is gifted. Special exposure to accelerated mathematics and other learning domains including AP classes can be helpful. Additionally, several summer camps for gifted are available where students often learn a semester of college level material in just a few weeks.The review notes Facebook's Mark Zuckerberg, Google co-founder Sergey Brin and musician later known as Lady Gaga all were identified by the Hopkins program. They all participated in the Center for Talented Youth at Hopkins.The current talent identification and enrichment programs in the U.S. are valuable and should be continued. More programs need to be developed as many gifted youth still slip through the cracks.Readers with more interest in this topic are directed to the free full-text article that can be accessed by the link in the citation below. This article also includes a nice series of references to primary sources on the topic.Follow me on Twitter WRY999Photo of endangered Florida scrub jay is my pic from my files. Clynes, T. (2016). How to raise a genius: lessons from a 45-year study of super-smart children Nature, 537 (7619), 152-155 DOI: 10.1038/537152a... Read more »

  • September 7, 2016
  • 02:40 AM
  • 288 views

On (banned) organochlorine compounds and autism risk

by Paul Whiteley in Questioning Answers

'Chemicals banned decades ago linked to increased autism risk today' went the press release attached to the findings reported by Kristen Lyall and colleagues [1] (open-access).Observing that "higher levels of some organochlorine compounds during pregnancy are associated with ASD [autism spectrum disorder] and ID [intellectual disability]" the Lyall results once again push environmental factors back into the research spotlight. Indeed, environmental factors that were banned decades ago.Including a cohort of children diagnosed with autism (n=545), those diagnosed with ID (also known at learning disability) (n-=181) and general population (asymptomatic?) controls (n=418) researchers accessed archived biological samples taken from mothers during the second trimester of pregnancy. Using some pretty sophisticated chemical analysis methods - "gas chromatography isotope dilution high resolution mass spectrometry (GCIDHRMS)" - various chemical compounds considered as POPs (persistent organic pollutants) were assayed for. Most if not all of these compounds were banned in the 1970s because of their potential effects on health. Because of their chemical nature however (i.e. enjoying bathing in fats) they can and do still persist in the environment, particularly in the food chain.Results: various PCBs (polychlorinated biphenyl ethers) and "persistent pesticides" were included in the chemical analysis of maternal samples. Some, but not all, were reported in samples across the different groups. After some statistical wizardry in terms of adjusting samples and the results for various factors ("children with ASD were approximately four times as likely to be male than female... have older parents, and mothers with higher education") authors concluded that a few of the metabolites looked at might be linked to autism risk; specifically: "that exposure to PCB congeners in utero may influence risk of ASD in offspring.""Primary analyses highlighted PCB 138/158 and PCB 153 in association with ASD, though other correlated congeners also demonstrated associations above the null." PCB 138/158 also seemed to show some sort of connection to the risk of offspring ID too "suggesting the impact of exposure to this congener on neurodevelopment broadly." Conversely, none of the other organochlorine compounds seemed to show any (significant) connection to autism offspring risk. Something similar has been talked about before with this broad collection of compounds in mind under more direct analysis conditions (see here). The authors conclude that further research is required to both substantiate their findings and also ascertain some of the hows and whys of these compounds in relation to autism and ID. Importantly, they acknowledge that their list of compounds tested may not be the whole story in terms of the 'multiple chemicals' people are exposed to over a lifetime.These are rather interesting results. Not least because the potential legacy of these compounds continues years and years after production of them had all but ceased following health concerns. That researchers also focused on maternal pregnancy blood samples again (see here) puts gestational 'exposure' front and centre when it comes to potential effects and mechanisms too. The idea that immune function could be a target effect of such compounds when it comes to offspring autism risk is also explored by the authors: "effects on the immune system is another particularly likely mechanism." This would also seem to tally with the growing evidence that maternal immune function during the nine months that made us might be an important part of aetiology for at least some autism and/or more general neurodevelopmental issues.The story continues as it might with other compounds too [2] on this 'TENDR' area of research...To close, Worf don't like the lute...----------[1] Lyall K. et al. Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect. 2016. Aug 23.[2] Jeddi MZ. et al. The role of phthalate esters in autism development: A systematic review. Environ Res. 2016 Aug 24;151:493-504.----------Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, & Windham GC (2016). Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environmental health perspectives PMID: 27548254... Read more »

  • September 6, 2016
  • 11:17 AM
  • 314 views

Keeping the Weight Off

by William Yates, M.D. in Brain Posts

Weight loss and maintenance of weight loss is difficult if not nearly impossible for most people.A registry of individuals who have lost 30 pounds or more and maintained their weight loss over a year exists in the U.S. This research effort is known as the National Weight Control Registry. It currently has over 10,000.I was looking at some of the published research results from this study. A paper published in 2012 used cluster analysis to identify sub-types of individuals with successful long-term weight loss.The study identified four specific sub-types of successful dieters. The varied on a variety of historical, demographic and behavioral variables. However, I was impressed by the amount of exercise the participants documented.Over 90% of the successful dieters burned an average of 2500 calories in a typical week of physical activity. Although calories burned by exercise varies by weight a typical weekly amount of exercise to burn 2500 calories per week would be:Walking 25 miles per week (six plus hours walking per week)Running 18 miles per week (three plus hours running per week)These levels of physical activity are two to three times more than typical recommendations for physical activity in the general population.This study suggests successful weight loss maintenance is hard work. Unless you are committed to and capable of this level of activity it may be nearly impossible to lose weight and keep the weight off.Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.Follow me on Twitter @WRY999Photo of fireworks is a Moto G4 plus smartphone pic from my files.Ogden, L., Stroebele, N., Wyatt, H., Catenacci, V., Peters, J., Stuht, J., Wing, R., & Hill, J. (2012). Cluster Analysis of the National Weight Control Registry to Identify Distinct Subgroups Maintaining Successful Weight Loss Obesity, 20 (10), 2039-2047 DOI: 10.1038/oby.2012.79... Read more »

  • September 6, 2016
  • 08:55 AM
  • 286 views

A Literal "Beer Gut"

by Bill Sullivan in The 'Scope

Free beer, made right inside your stomach! This rare condition converts your gut into a brewery, and it is more of a nightmare than a dream come true.
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  • September 6, 2016
  • 02:51 AM
  • 286 views

"The maternal body as environment in autism science"

by Paul Whiteley in Questioning Answers

Although I'm not really one for deep philosophical discussions or anything related (unless linked to a specific galaxy far, far away...), I was recently interested to read the paper by Martine Lappé [1] talking about how "complex narratives of autism’s causes and social anxieties surrounding child development have helped situate autism risk in women’s bodies before and during pregnancy."I'm as guilty as anyone for discussing the pretty constant stream of peer-reviewed research evidence suggesting that what goes on before and during the nine months that made us might have some important bearing on offspring in terms of behaviour and development. The wide range of potential variables laid at mum's pregnancy doorway with autism risk in mind have grown to overwhelming proportions in recent time, as just about every week some factor or another is said to show involvement.Lappé suggests that such research has turned pregnancy into 'environment' when it comes to discussions about possible autism aetiology and involves "three characteristics: the molecularization of the environment, an individualization of risk, and the internalization of responsibility."  The result being that 'larger questions' have been put to one side, particularly related to the continued medicalisation of the autism label (and various other labels), alongside the idea that within the large heterogeneity of autism, pregnancy factors might not necessarily figure significantly in every single case.I can kinda see where the author is coming from in this article, particularly how suggestions that factor X or Y during pregnancy might increase offspring autism risk does to some extent mirror the darker days of autism research in terms of 'blame'. Where once popular opinion was that autism was due to parenting issues, so now the suggestion that maternal obesity for example, might somehow increase the risk of offspring autism continues the blame-game and indeed, pushes the 'blame window' further back temporally speaking. Yes, parenting style and obesity are not one and the same thing but the common element they possess is the perception that somehow there is a choice being made; a choice to parent one way or another, to become obese or not. That idea of 'choice' moves some people's minds to the concept of blame, and onwards the blame-game once again gathers momentum. The same logic around choice can similarly hold when it comes to whether pharmaceutic A or B taken during pregnancy might elevate offspring autism risk too...There is no easy answer to what to do about turning the maternal [pregnancy] body into 'environment' when it comes to the big question: how does autism come about? Generalising the word 'autism' to denote 'all autism' means that we don't know really know how autism comes about or whether anything can be done more generally to modify a person's risk of autism. Accepting that some people don't even wish to see the words 'modify' and 'risk' in the context of autism, I personally see such philosophical discussions in a more plural context as per all that chatter about 'the autisms' and the label(s) not necessarily existing in some sort of diagnostic vacuum (see here).I for example, look towards the increasingly important idea that for all the different 'types' of autism out there, there may be a similar number of genetic and non-genetic factors playing some role; for some, issues during pregnancy are likely to impact on offspring autism risk more than others. The specific idea that immune function and/or 'inflammation' during critical periods of pregnancy might have offspring outcomes (see here for example) is particularly appealing, given that the whole concept of immune function is moving well outside of the realms of just infection or pathogen identification and control. Accepting also that pregnancy is characterised by a change in maternal immune function (y'know, to accommodate that foreign entity that resides inside mum's body) there is plenty of scope for such tolerance to be affected by one or more agents in quite a few ways.Ultimately, 'the maternal body as environment in autism science' is probably here to stay. The language however of how we chose to represent and transmit information about pregnancy risk factors and autism perhaps requires some further philosophical discussions...And speaking of philosophy, a link to a book that I once enjoyed reading.----------[1] Lappé M. The maternal body as environment in autism science. Social Studies of Science. 2016; Aug 19.----------Lappe, M. (2016). The maternal body as environment in autism science Social Studies of Science DOI: 10.1177/0306312716659372... Read more »

  • September 5, 2016
  • 02:34 PM
  • 346 views

Drugs in the water? Don't blame the students

by Dr. Jekyll in Lunatic Laboratories

With nearly sixty percent of American adults now taking prescription medications--from antidepressants to cholesterol treatments--there is growing concern about how many drugs are flowing through wastewater treatment facilities and into rivers and lakes. Research confirms that pharmaceutical pollution can cause damage to fish and other ecological problems--and may pose risks to human health too.

... Read more »

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