Treating depression: exercise or anti-inflammatory meds?

Reiterating my primary caveat on this blog about not giving anything that looks, sounds or smells like medical and/or clinical advice, I'm bringing three papers to the research blogging table today, all published in the JAMA journal family and all talking about depression / depressive symptoms.

See my hat... @ Wikipedia 

First up is the paper by Ole Köhler and colleagues [1] reviewing "the antidepressant and possible adverse effects of anti-inflammatory interventions". Some media interest in this study can be found here. For those who might not know, there is a growing 'feeling' that the various links being made between inflammation or inflammatory mechanisms and psychiatry (see here) may well also extend into the area of depression or depressive symptoms. Far be it from me to say that inflammation and depression is a 'done deal' in scientific terms, but when reading research papers with titles like: 'So depression is an inflammatory disease, but where does the inflammation come from?' by Michael Berk and colleagues [2] (open-access) one kinda gets the impression that quite a lot of opinion has already come down on the side of a probable link.

The Köhler paper looked at the combined peer-reviewed literature on the use of various anti-inflammatory medication strategies previously trialled "in adults with depressive symptoms, including those who fulfilled the criteria for depression" including the use of "nonsteroidal anti-inflammatory drugs (NSAIDs)" and "cytokine inhibitors". Cytokines, inflammation and psychology is a topic which has graced this blog on previous occasions (see here). The authors concluded that whilst there is quite a bit more to do in this area: "This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted". Touché.

Next up are the papers by Snehal M. Pinto Pereira and colleagues [3] and Umar Toseeb and colleagues [4] both talking about a possible role for physical activity and exercise when it comes to the presentation of depression. The results were a little mixed; Pinto Pereira et al concluding that during adult life "activity may alleviate depressive symptoms in the general population" as a function of "a trend of fewer depressive symptoms with more frequent activity". By contrast, Toseeb et al looking at physical activity (PA) "and depressive symptoms during 3 years of adolescence" noted no "longitudinal association between objectively measured PA and the development of depressive symptoms". Indeed they quite prominently recorded a lack of support for PA being protective against developing depressive-type symptoms in their teenage group.

There are some differences in the way that the Pinto Pereira and Toseeb research groups went about looking at their respective cohorts and the differences in age between their participants is certainly worth noting. Just correlating two variables is also likely to omit other significant factors (such as inflammation!) which might also show some involvement in the onset or continuation of depression/depressive symptoms. That being said I hark back to other reviews on this topic such as the meta-analysis by Mammen & Faulkner [5] as detailing the bigger picture, denoting some "promising evidence that any level of PA, including low levels (e.g., walking <150 minutes/weeks), can prevent future depression".

If we are to assume that anti-inflammatory medication and physical activity (at least for some) can impact on depression or depressive symptoms, the next question really needs to be: what could unite these two findings if anything? Yes, anti-inflammatory meds impact on inflammatory processes, but does this mean that exercise could be doing the same? I found quite a bit of peer-reviewed literature in this area talking about acute and chronic exercise and its short- and long-term effects on inflammation and inflammatory markers (see here for a summary). The long-and-short of it is that nobody really knows at present and, once again, there is quite a lot of merit for the N=1 in this area of study.

I might however also advance a couple of other ideas potentially worth looking into. First is the impact that inflammation / anti-inflammatory techniques and exercise have on an important region: the gut microbiota. Those trillions of wee beasties which reside in our deepest, darkest recesses doing so much more than just helping us digest our food are seemingly cropping up everywhere these days (see here for example). The idea that certain elements of our bacterial passengers might also show involvement with something like depression in a sort of gut-brain axis manner is by no means a new concept as per previous discussions on this blog (see here). Research hinting that exercise may also impact on the gut microbiota [6] particularly when it comes to the diversity of bacteria to be present, offers something a glimpse into how exercise may provide effects. Gut bacteria diversity and depression is however still wanting in research terms...

Second up, and potentially related to the gut microbiota [7] is the introduction of some epigenetic effect from both anti-inflammatory strategies and exercise when it comes to depression. The science of epigenetics has again been something of a talking point on this blog (see here and see here) from quite a few behavioural perspectives down the years. The idea being that above and beyond your structural genome, there is an added layer of chemical complexity pertinent to the switching on or off of genes which might influence risk for all manner of things. Hype aside, there is growing evidence looking at epigenetic mechanisms being potentially pertinent to depression [8] (open-access) although the precise hows and whys remain somewhat elusive. At the same time, the epigenetics of exercise is also an up-coming area [9] albeit with further investigation needed. Marrying the two concepts together - the epigenetics of exercise and depression - might be a good research idea because at present, there is something of a void in this area. That being said, the epigenetics of immune functions is an area of some note (see here).

I really hope that I've not gone beyond my blogging remit with this post in emphasising the potential links between depression, inflammation and physical activity. By no means did I intend to boil something like depression down to just a lack of exercise or inflammation running amok, given the complexity of the condition and the seemingly many ways that one can arrive at the condition. Similar things were noted in a recent post on zinc and depression (see here). At the very least, I'd like to think my musings are nothing like as sweeping as suggesting that major depression is "an infectious disease" [10]. I do however think that the further moves by disciplines like psychiatry to understanding conditions like depression as potential 'whole body' conditions (either in causation or manifestation) brings us closer to understanding how one might further alleviate the often severe symptoms of depression and, to some degree, potentially mitigate signs and symptoms before they ever get the chance to severely impact on a person's life.

Music to close, and what else but Physical by Olivia Newton-John.

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[1] Köhler O. et al. Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects. JAMA Psychiatry. 2014. October 15.

[2] Berk M. et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013; 11: 200.

[3] Pinto Pereira SM. et al. Depressive Symptoms and Physical Activity During 3 Decades in Adult Life. JAMA Psychiatry. 2014. October 15.

[4] Toseeb U. et al. Exercise and Depressive Symptoms in Adolescents. JAMA Pediatrics. 2014. October 13.

[5] Mammen G. & Faulkner G. Physical activity and the prevention of depression: a systematic review of prospective studies. Am J Prev Med. 2013 Nov;45(5):649-57.

[6] Clarke SF. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Jun 9. pii: gutjnl-2013-306541.

[7] Stilling RM. et al. Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis. Genes Brain Behav. 2014 Jan;13(1):69-86.

[8] Vialou V. et al. Epigenetic Mechanisms of Depression and Antidepressants Action. Annu Rev Pharmacol Toxicol. 2013; 53: 59–87.

[9] Ntanasis-Stathopoulos J. et al. Epigenetic regulation on gene expression induced by physical exercise. J Musculoskelet Neuronal Interact 2013; 13(2):133-146

[10] Canli T. Reconceptualizing major depressive disorder as an infectious disease. Biology of Mood & Anxiety Disorders 2014, 4:10.

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Ole Köhler, Michael E. Benros, Merete Nordentoft, Michael E. Farkouh, Rupa L. Iyengar, Ole Mors, & Jesper Krogh (2014). Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects JAMA Psychiatry : doi:10.1001/jamapsychiatry.2014.1611



Snehal M. Pinto Pereira, Marie-Claude Geoffroy, & Christine Power (2014). Depressive Symptoms and Physical Activity During 3 Decades in Adult Life JAMA Psychiatry : doi:10.1001/jamapsychiatry.2014.1240





Toseeb, U., Brage, S., Corder, K., Dunn, V., Jones, P., Owens, M., St Clair, M., van Sluijs, E., & Goodyer, I. (2014). Exercise and Depressive Symptoms in Adolescents JAMA Pediatrics DOI: 10.1001/jamapediatrics.2014.1794

Neurotensin, autism and tail-chasing Bull Terrriers?

I'm not kidding.

The paper by Tsilioni and colleagues [1] (open-access) did indeed look at serum levels of neurotensin and corticotropin-releasing hormone (CRH) in a cohort of children diagnosed with an autism spectrum disorder (ASD) alongside levels in tail-chasing Bull Terrier dogs as compared to unaffected [non tail-chasing] Bull Terriers (BTs) and Labrador Retriever dogs. You may well smirk or even laugh at such research but, as per the recent [preliminary] broccoli chemical - autism study (see here), unusual research may yet offer some interesting insights into some of the biology of at least some of the autism spectrum.

Meg's gravy is famous.

Mention of neurotensin and autism really can only mean the involvement of one researcher: Prof. Theoharis Theoharides and his continuing interest in this area [2]. Indeed, the only thing seemingly missing from the Tsilioni paper is some analysis of another of Prof. Theoharides' interests: mast cells and autism (see here); although I do note that the authors mention how: "NT [neurotensin] is a vasoactive peptide isolated from the brain and is implicated in immunity. It is increased in the skin following acute stress, triggers skin mast cells (MCs) and increases skin vascular permeability in rodents through MC activation".

The Tsilioni paper is open-access but a few pointers might be in order:

• Greek children diagnosed with an ASD (N=40) fulfilling quite a few inclusion criteria provided a fasting blood sample. Similar samples were also provided by "normotypic" controls (I assume this means asymptomatic for ASD).
• "Serum from unaffected (n=18) and affected BTs (n=14) and unaffected Labrador retriever dogs (n=6) was collected at various facilities accessible to the owners and was sent to the senior Author’s laboratory on dry ice". Apparently a behavioural survey was used to classify Bull Terriers into affected and unaffected groups.
• Analysis for NT and CRH levels was completed on samples based on ELISA preceded by some clean-up steps. Results were presented to also include: "whether there is any relationship between the number of ASD children with GI [gastrointestinal] symptoms and high serum NT levels and whether it is more than expected by chance".
• So: group serum NT levels were significantly elevated in the cohort of children with ASD compared to controls (see here). As per the scatterplot shown in that last link however, this elevation was not noted for every child with autism; by my count about 11 children in the ASD group showed results above the upper 95% confidence interval (CI) for that particular group. The presence of GI symptoms also seemed to moderate this relationship: "There is a strong correlation between the number of ASD children with GI symptoms and high serum NT levels".
• Group serum CRH levels were also elevated for the ASD group compared to controls (see here) (12 of which seemed to show a similar pattern to that previously described).
• Bull Terriers affected by that tail-chasing behaviour - "reminiscent of stereotypic spinning exhibited by autistic children" - also showed group elevations in the levels of serum NT and CRH when compared to control dogs. The authors suggest that this: "supports the premise that these dogs could represent at least an autism endophenotype" from an animal model point of view (see this table for further information).

Outside of trying to model autism or more precisely behaviours associated with autism in another animal model other than rodents (see here) or monkeys (see here), the authors provide other clues for their report of a [potential] canine model: "This dog breed may be useful in the investigation of the diagnosis, pathogenesis and treatment of ASD. NTR and/or CRHR-1 antagonists, as well as MC blockers, could provide possible therapeutic approaches for stress-induced ASD. For instance, the natural flavonoid luteolin is known to inhibit mast cell-mediated allergic inflammation, and a dietary supplement containing luteolin was recently reported to significantly benefit children with ASD". That last sentence on luteolin as a potential intervention option for autism comes from other work published by the authors [3] in need of further, controlled study.

The evidence is starting to stack up suggesting that there may be more to see when it comes to NT and CRH levels in relation to at least some cases of autism (the autisms?). That GI symptoms (which are becoming much more readily accepted as being elevated in frequency when it comes to autism) might be a moderating variable of the presence of those peptide hormones is another potentially important feature in terms of how such pathology seems to interplay with behavioural symptoms (see here). I would like to see a little more focus on how other behavioural signs and symptoms (autism+) might also be affecting NT and/or CRH levels when it comes to cases of autism, and indeed, how this work overlaps with other reports of NT for example, in other conditions [4] potentially acting as "an endogenous antipsychotic drug" and more [5]

Music then. The Sound of Silence by S & G.

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[1] Tsilioni I. et al. Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism. Transl Psychiatry. 2014 Oct 14;4:e466.

[2] Angelidou A. et al. Neurotensin is increased in serum of young children with autistic disorder. J Neuroinflammation. 2010 Aug 23;7:48.

[3] Theoharides TC. et al. A case series of a luteolin formulation (NeuroProtek®) in children with autism spectrum disorders. Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):317-23.

[4] Boules M. et al. Diverse roles of neurotensin agonists in the central nervous system. Front Endocrinol (Lausanne). 2013 Mar 22;4:36.

[5] Boules MM. et al. Elucidating the Role of Neurotensin in the Pathophysiology and Management of Major Mental Disorders. Behav. Sci. 2014; 4: 125-153.

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Tsilioni I, Dodman N, Petra AI, Taliou A, Francis K, Moon-Fanelli A, Shuster L, & Theoharides TC (2014). Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism. Translational psychiatry, 4 PMID: 25313509

(Partly) explaining the increase in the prevalence of autism

"Changes in reporting practices can account for most (60%) of the increase in the observed prevalence of ASDs [autism spectrum disorders] in children born from 1980 through 1991 in Denmark."

Prince of Denmark @ Wikipedia 

That was the headline conclusion reported by Stefan Nygaard Hansen and colleagues [1] based on an analysis of births in Denmark between 1st January 1980 and 31st December 1991 (N=677,915) followed up until 31st December 2011 (or "until ASD diagnosis, death, emigration"). The suggestion being that an update to the ICD (International Classification of Diseases) criteria in 1994 - ICD-8 replaced by ICD-10 - played a significant role alongside "the inclusion of outpatient contacts" and voilà: "the apparent increase in ASDs in recent years is in large part attributable to changes in reporting practices". Some associated media coverage of this study can be found here.

This is certainly interesting data which again taps into those oh-so valuable Scandinavian health registries which are producing all-manner of interesting correlations and results (see here for another example). The question of what factor(s) might be driving the quite astounding increase in cases of autism worldwide (see here) has been a constant source of discussion and argument in certain circles. I have covered some of those debates before on this blog (see here).

Changes to the various diagnostic schedules as being a factor behind the alterations to the autism prevalence rate is by no means a new idea as per discussions about the the rival DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria down the years. Indeed, looking at how the DSM-IV revision (which also came into play in 1994) might have influenced the autism numbers compared against the previous DSM-III criteria tells a similar tale (see here). The most recent DSM-5 revision also looks like it will be playing its own part on the epidemiology of autism at some point (see here) but we wait to see how that eventually pans out.

As per the press release for the Hansen study, there is still a question about the remaining percentage (~40%) of cases of autism not readily attributed to the changes in reporting practices.  A quick trawl through some of the other peer-reviewed work produced by Erik Parner, one of the co-authors on the Hansen paper, provides a few clues as to where researchers have been looking. I've covered some of these variables previously including: shifts in age at diagnosis (see here), the sibling recurrence rate (see here), maternal infection requiring hospitalisation (see here), etc. I might add that this list is not exhaustive as the words 'better autism awareness' are also likely to be banded around (see here for some recent interesting data on this).

I note also one sentence in the press release: "Environmental factors like using certain medications during pregnancy might also contribute, but more research is required to quantify the contribution of hypothesized risk factors" which I suspect ties into some work looking, for example, at prenatal valproate exposure and offspring neurodevelopmental outcomes [2]. Again, this is a topic which has been covered on this blog on more than one occasion (see here and see here) with no medical advice given or intended. I might add that valporate is not the only pharmaceutic which has come under the research spotlight (see here).

The Hansen results make a valuable contribution to the discussions about what might have been driving the increase in autism cases at least in Denmark [3]. Given their focus on participants with birth dates between 1980 and 1991 and the reporting changes included between 1994 and 1995, I'd be interested to see how future work from this group following up subsequent birth cohorts goes, assuming no significant changes in diagnostic schedules or other important adjustments to reporting procedures. I'd also rather hope to see a little more data about possible tie-ins with comorbidity for example, given the input of another Scandinavian team on the ESSENCE of autism...

To close: given that today is 'Remember, remember the 5th of November', I'm inclined to provide you yet again with a link to the rousing speech by 'V' from a favourite film of mine bearing in mind I'm not advocating such revolution. Oh, and please do be careful this Bonfire night...

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[1] Hansen SM. et al. Explaining the Increase in the Prevalence of Autism Spectrum Disorders. JAMA Pediatr. 2014. November 3.

[2] Christensen J. et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013 Apr 24;309(16):1696-703.

[3] Parner ET. et al. A comparison of autism prevalence trends in Denmark and Western Australia. J Autism Dev Disord. 2011 Dec;41(12):1601-8.

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Hansen, S., Schendel, D., & Parner, E. (2014). Explaining the Increase in the Prevalence of Autism Spectrum Disorders JAMA Pediatrics DOI: 10.1001/jamapediatrics.2014.1893

Producers and consumers of autism research: never the twain shall meet?

I was interested to read the paper by Elizabeth Pellicano and colleagues [1] (open-access) investigating "the views of community involvement in autism research both from the perspectives of autism researchers and of community members, including autistic adults, family members and practitioners". Quite a few results are reported including the idea that researchers "were skeptical about the possibilities of dramatically increasing community engagement, while community members themselves spoke about the challenges to fully understanding and influencing the research process".

I'm made of wax, Larry. What are you made of?

I believe this research links into a previous study by the same authors [2] which has also been discussed on this blog (see here) asking the question: what should autism research focus upon? The results on that occasion implied that depending on who was asked: "There was a clear disparity between the United Kingdom’s pattern of funding for autism research and the priorities articulated by the majority of participants". As an addition to that work, I'll take this opportunity to direct you to the paper by Jina Jang and colleagues [3] reporting that most autism research seems to be centred on the "younger population".

The most recent Pellicano work is again open-access but a few details are worth mentioning:

• Two instruments/methods were reported on: (i) the results of an on-line questionnaire completed by over 1500 respondents "aged 18 and over who could be divided into four key stakeholder groups: autistic adults, immediate family members, practitioners and researchers", and (ii) focus groups / individual interviews, again including people representative of those key stakeholder groups (albeit much reduced in terms of participant numbers). The idea being to ask "both researchers and members of the autism community about their experiences of engagement in research".
• Several themes are reported based on either researcher views or autism community views. "The majority of autistic adults, parents of children with autism and professionals wanted to be more involved in the research process". A nice position for autism researchers to be in by all accounts, but... "community members felt that researchers aren't proactive enough" when it came to approaching the autism community to take part in research. Even when taking part in autism research there were "largely asymmetric interactions with researchers" according to the autism community in terms of research wanting/needing study volunteers but not much after that in terms of engagement.
• Researchers also had a few issues with the whole research engagement process too. Some wanted a more inclusive relationship when it came to research engagement with the autism community. But, there was also some caution about how far this engagement should go insofar as "they [the autism community] might not be the appropriate people to decide what and how issues should be researched and... it risks “politicizing” scientific issues".
• Perhaps of potential importance to how you are reading about this study was some mention on how some members of the autism community felt that autism research was "indigestible" when it came to writing up in science papers and the use of "scientific jargon". One of the first thoughts that crossed my mind on reading such results was an article I'd read not so long ago by Steven Pinker (see here) and what this could mean for peer-reviewed science writing. That and the value of science blogging...
• Alongside quite a few other snippets of potentially important information, the authors conclude that: "There is no ‘one size fits all’ approach to community engagement" (no real surprise there) but with a little innovation, autism researchers and the autism community can reach some middle ground mutually beneficial to both camps. 

What's more to say on this topic? Well, not a great deal really, aside from that which Pellicano et al cover in their collective papers on this topic and where autism research should perhaps be heading. Of course, I would advocate for more people to get interested and involved in science - autism science - even if this means spending a few hours a week looking through something like PubMed or joining social media sites like Twitter and following those interested in the various autism research being produced. The caveats to that are that: (i) science is all about probability not absolutes, (ii) not all science is equal, and (iii) when it comes to autism, the issues of heterogeneity and all that enhanced risk of various comorbidity, need to be kept in mind when reading about any 'scientific breakthrough' or 'wonder-study' which purports to definitively answer any research question.

Insofar as resources, at least here in the UK, where people can participate in autism research, the National Autistic Society (NAS) hold a directory of research projects looking for participants (I assume other countries have similar resources). I do wonder if any such international database might exist which could act as a central autism research point drawing on resources like the US Clinicaltrials.gov facility and other research databases for those wishing to take part?

Finally, blog. Yes, you heard me correct. People with autism, parents, professionals and even researchers, put pen to paper and start your own blog... it's normally free and pretty easy to do once you get the hang of it. Who knows, perhaps one day, every study will have its own blog or blog entry.

A little song to close... Danke Schoen.

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[1] Pellicano E. et al. Views on Researcher-Community Engagement in Autism Research in the United Kingdom: A Mixed-Methods Study. PLoS ONE. 2014; 9: e109946.

[2] Pellicano E. et al. What should autism research focus upon? Community views and priorities from the United Kingdom. Autism. 2014 Oct;18(7):756-70.

[3] Jang J. et al. What are the ages of persons studied in autism research: A 20-year review. Research in Autism Spectrum Disorders. 2014; 8: 1756–1760.

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Pellicano E, Dinsmore A, & Charman T (2014). Views on Researcher-Community Engagement in Autism Research in the United Kingdom: A Mixed-Methods Study. PloS one, 9 (10) PMID: 25303222

Probiotics to counter heavy metal toxicity?

"In summary, this work has demonstrated the potential value of long-term probiotic-based interventions to counter mercury and arsenic exposure in vulnerable populations, particularly in pregnant women".

Sounds like an '80s man to me...

That was one of the primary conclusions reported by Jordan Bisanz and colleagues [1] (open-access) examining "at-risk populations of pregnant women and in children in Mwanza, Tanzania". The idea being that alongside the use of metal chelating medicines such as dimercaptosuccinic acid (DMSA) and ethylenediaminetetraacetic acid (EDTA) indicated for 'acute' exposure to heavy metals, there may be other ways and means of treating heavy metal exposure over longer periods and where resources may not be as plentiful. Some media about this study can be seen here.

The Bisanz paper is open-access but a few pointers might be in order:

• The study was based on the idea that certain strains of bacteria are known to have "an affinity for many toxic metals, including lead and cadmium" as documented in papers such as the one by Monachese and colleagues [2]. Further, that so-called "probiotic yogurt kitchens that service economically disadvantaged people" as a source of potentially beneficial bacteria are already working at the particular location selected by the study authors.
• So, two studies were implemented: (a) looking at school-aged children (SAC) (initial N=44) randomised to receive either a probiotic yoghurt containing "1 × 1010 CFU Lactobacillus rhamnosus GR-1 per 250 g" or "an equivalent portion of ultra-heat-treated milk as a control devoid of lactic acid bacteria" daily for 24 days; and (b) "60 pregnant women [PW] were recruited, of which 26 received a probiotic yogurt containing 1 × 1010 CFU L. rhamnosus GR-1 per 250 g and supplemented with 4.3 g of Moringa, a micronutrient-rich plant, to enhance maternal nutrition". The study entries in the US National Institutes of Health (NIH) database can be found here and here respectively. 
• Analysis of blood metal levels ("blood lead, total mercury, total arsenic, and cadmium") were undertaken at enrolment and follow-up for all participants across the two studies. Analysis of fecal samples for children in study (a) was also undertaken pre- and post-intervention to test for any differences across the yoghurt vs. milk groups. Local fish were also analysed for heavy metal content to ascertain dietary exposure alongside dietary patterns of participants.
• Results: there were quite a few... levels of heavy metals in SAC and PW studied were elevated compared to "levels present in a developed country (Canada)" somewhere in the order of over 6 times greater for lead and mercury. Children (SAC) were particularly vulnerable to an increased heavy metal burden. The authors noted: "Metal exposure from dietary fish intake likely explains why we saw elevated blood levels of mercury in both the SAC and PW groups".
• "The studies provided the first positive evidence for the use of probiotics to combat toxic heavy metal exposure in vulnerable human populations". Well, sort of, is probably the best way that I can comment on this assertion, as the authors noted: "no statistically significant differences were detected in blood metal levels in SAC receiving the probiotic or milk control, although we noted that there was a weak trend of reduced blood levels of lead and arsenic". They did find that in the control group in receipt of milk, "blood levels of mercury and arsenic increased" between the testing occasions "but remained stable in the probiotic group". So concluding that levels of certain heavy metals didn't get any worse following the use of a probiotic is probably a more accurate way of looking at things.
• Insofar as the gut bacteria analysis side of things: "Administration of the probiotic was not observed to have an effect on the gut bacterial community composition". But the authors did report that: "Elevated blood lead was associated with increases in Succinivibrionaceae and Gammaproteobacteria relative abundance levels in stool".

There are some important results to be derived from the Bisanz paper but not necessarily in the way that I think the authors hoped, bearing in mind this was a very short study limited to one specific probiotic strain. That being said, the idea that probiotics might have some kind of protective effect - "probiotic administration may be especially advocated at peak exposure times" - is an interesting one, worthy of quite a bit more investigation. 

I know discussions in certain quarters about the use of chelation therapy for certain conditions have the ability to furrow brows (see here). This despite the fact that when clinically indicated, chelation can provide some powerful results as demonstrated in the recent paper by Thurtle and colleagues [2] (open-access) on the use of oral DMSA for severe lead poisoning in Northern Nigeria. If we are to assume that certain types of bacteria might potentially be able to prevent or reduce uptake of something like heavy metals in the gastrointestinal (GI) tract from oral sources (i.e. food), I'd be minded to say that such inexpensive and potentially safer methods protecting against heavy metal poisoning, might be something to explore. And hopefully I'm talking out of turn when I mention some of the literature on lead and mercury exposure when it comes to autism (see here) as another possible avenue for more formal investigation.

Next up: probiotics and influenza anyone? (With the need for a lot more research and certainly nothing like medical or clinical advice given or intended by me on this topic).

Music then. Domino by Jessie J.

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[1] Bisanz JE. et al. Randomized Open-Label Pilot Study of the Influence of Probiotics and the Gut Microbiome on Toxic Metal Levels in Tanzanian Pregnant Women and School Children. mBio. 2014. 7 October.

[2] Thurtle N. et al. Description of 3,180 Courses of Chelation with Dimercaptosuccinic Acid in Children ≤5 y with Severe Lead Poisoning in Zamfara, Northern Nigeria: A Retrospective Analysis of Programme Data. PLoS Medicine. 2014; 11: e1001739.

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Jordan E. Bisanz, Megan K. Enos, Joseph R. Mwanga, John Changalucha, Jeremy P. Burton, Gregory B. Gloor, & Gregor Reid (2014). Randomized Open-Label Pilot Study of the Influence of Probiotics and the Gut Microbiome on Toxic Metal Levels in Tanzanian Pregnant Women and School Children mBio : 10.1128/mBio.01580-14

Early childhood atopy and autism risk

De profundis clamo ad te, domine

Regular readers will probably have heard something like this before so I'm sorry if I'm repeating myself: "The presence of any atopic disease in early childhood increased the risk of developing ADHD [attention deficit hyperactivity disorder]... and ASD [autism spectrum disorder]... in later life".

So said Mu-Hong Chen and colleagues [1] with yet another 'big data' paper coming out of Taiwan.

There is little point in me turning this research into some sort of mega-post given that this topic has featured so heavily on this blog. In case you missed them, here are some of the relevant posts:

• Allergic and autoimmune diseases and autism (2012) (see here)
• Asthma increases risk of ADHD? (2013) (see here)
• Asthma as a risk factor for autism? (2014) (see here)
• Autism, ADHD and allergy: Taiwan and big data (again) (2014) (see here)

Lazy? Yes, I am being a bit lazy in this post by just supplying older links but what more can I say apart from that there seems to be a complicated relationship between immune function and behaviour. Oh, and other research from this group might also be worthwhile looking at as per studies linking epilepsy and atopic dermatitis [2] and major depression and/or bipolar disorder and asthma [3] knowing about the various comorbidity relationships with autism (see here and see here).

And here is some lazy music to accompany my lazy post...

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[1] Chen MH. et al. Is atopy in early childhood a risk factor for ADHD and ASD? A longitudinal study. J Psychosom Res. 2014 Oct;77(4):316-21.

[2] Chen MH. et al. Risk of epilepsy among patients with atopic dermatitis: a nationwide longitudinal study. Epilepsia. 2014 Aug;55(8):1307-12.

[3] Chen MH. et al. Higher risk of developing major depression and bipolar disorder in later life among adolescents with asthma: a nationwide prospective study. J Psychiatr Res. 2014 Feb;49:25-30.

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Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, Pan TL, & Bai YM (2014). Is atopy in early childhood a risk factor for ADHD and ASD? A longitudinal study. Journal of psychosomatic research, 77 (4), 316-21 PMID: 25280829