Saturday, 4 July 2015

A viral 'cause' of obesity?

I must thank Leah Hardy (@LeahFHardy) for bringing to my attention the paper by Qinglong Shang and colleagues [1] (open-access available here) reporting that: "Ad36 [Human adenovirus 36] infection is associated with an increased risk of obesity development."

Based on a meta-analysis of the available research literature examining whether Ad-36 - "a nonenveloped icosahedral virus comprised of double-stranded DNA and is one of 56 serotypes in 7 subgroups of human adenoviruses" - might be linked to obesity, researchers concluded that the weight of evidence from 11 studies did favour "an association between Ad36 infection and a significantly increased risk of obesity development, especially in children." Such findings can be added to other meta-analyses [2] that have also previously suggested that there may be more to see in this 'infectobesity' area [3].

I have to say that I was quite unaware of the links being made between Ad-36 and obesity prior to reading the Shang paper. I've previously tackled the idea that the obesity might have some important microbiological links (see here) before on this blog but never considered the possibility of a viral infection as showing involvement until now. Obviously one has to be a little guarded against making any sweeping statements that for example, Ad-36 is the primary cause of all obesity, because in all likelihood the issue is likely to be rather more complex than that. Appreciating that the old 'energy in, energy out' hypothesis is itself likely to be an over-simplification of why we are faced with growing rates of overweight and obesity, I'm sure that Ad-36 probably fits into a rather large jigsaw puzzle - somewhere. The requirement for a greater understanding of the hows and whys of any viral - obesity link is also strong alongside the idea that even if proved, any viral link should not absolve responsibility for eating and exercising right as part of maintaining a healthy weight.

Research such as that from Berger and colleagues [4] suggesting that "Ad36(+) may be associated with biomarkers implicated in inflammation but not with greater levels of fat mass" offers some cautionary data on why there may be quite a bit more research needed looking at Ad-36 and obesity. If one considers that inflammation seems to be part and parcel of obesity, the whole thing starts to get quite a bit more complicated.

Still, if science does start to get closer to the idea that Ad-36 (or other agents) might indeed heightened the risk of obesity and perhaps even suggest 'transferability' from person-to-person, this may open up new ways of tackling this issue [5] even with the prospect of immunising against infection-induced weight gain [6].

Music: Babies by Pulp.


[1] Shang Q. et al. Serological data analyses show that adenovirus 36 infection is associated with obesity: a meta-analysis involving 5739 subjects. Obesity (Silver Spring). 2014 Mar;22(3):895-900.

[2] Yamada T. et al. Association of Adenovirus 36 Infection with Obesity and Metabolic Markers in Humans: A Meta-Analysis of Observational Studies. PLoS One. 2012; 7(7): e42031.

[3] Valiquette L. et al. A microbiological explanation for the obesity pandemic? Can J Infect Dis Med Microbiol. 2014 Nov-Dec;25(6):294-5.

[4] Berger PK. et al. Association of adenovirus 36 infection with adiposity and inflammatory-related markers in children. J Clin Endocrinol Metab. 2014 Sep;99(9):3240-6.

[5] Esposito S. et al. Adenovirus 36 infection and obesity. J Clin Virol. 2012 Oct;55(2):95-100.

[6] Na HN. & Nam JH. Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36. Int J Obes (Lond). 2014 Nov;38(11):1470-4.

---------- Shang Q, Wang H, Song Y, Wei L, Lavebratt C, Zhang F, & Gu H (2014). Serological data analyses show that adenovirus 36 infection is associated with obesity: a meta-analysis involving 5739 subjects. Obesity (Silver Spring, Md.), 22 (3), 895-900 PMID: 23804409

Friday, 3 July 2015

Vitamin D metabolic gene variants and risk for autism

I was really rather happy to see the "preliminary evidence" reported by Rebecca Schmidt and colleagues [1] when it came to examining whether selected vitamin D metabolic gene variants might show linkage to autism spectrum disorder (ASD) based on data derived from the CHARGE initiative.

For quite a while now I've discussed the various peer-reviewed science on the topic of vitamin D deficiency / insufficiency with autism in mind on this blog (see here and see here for example). Specifically, how a diagnosis of ASD seems to offer little protection against issues with vitamin D appearing and what that could mean for important issues such as bone health (see here) for example.

A key component that seemed to be missing from the growing volume of research looking at vitamin D and autism was some discussion about whether the genetics of vitamin production and usage might offer some further clues to how vitamin D might more directly be 'linked' to [some] autism. Schmidt et al have started to put some flesh on to the scientific bones in this area following their previous research discussions on vits and SNPs with autism in mind (see here) .

So: "Maternal, paternal, and child DNA samples for 384 (81%) families of children with ASD and 234 (83%) families of TD [typically developing] children were genotyped for: TaqI, BsmI, FokI, and Cdx2 in the vitamin D receptor (VDR) gene, and CYP27B1 rs4646536, GC rs4588, and CYP2R1 rs10741657." In effect, researchers looked for potential genetic 'issues' with the vitamin D receptor (VDR) gene that have previously been linked to various health issues. They found some potentially interesting information including: "Paternal VDR TaqI homozygous variant genotype was significantly associated with ASD in case-control analysis." Homozygous by the way, refers to the concept of zygosity and the fact we have pairs of chromosomes. Further: "A significant association between decreased ASD risk and child CYP2R1 AA-genotype was found in hybrid log-linear analysis."

This is early days research insofar as the genetics of vitamin D and autism only being mentioned once before in the research literature as per the report from Yan and colleagues [2]. I'm excited at the Schmidt data but am not going to go all out on this very preliminary inspection of vitamin D receptor gene functioning without further large-scale replication and validation studies being carried out including discussions on things like cognitive ability in light of other recent data [3]. Whilst we are however, on the topic of vitamin D and its potential extra-skeletal activities, I'm minded to also bring in the paper by Kaneko and colleagues [4] and their results implying that "vitamin D affects brain serotonin concentrations" with mention of autism among other labels. Reporting on a particularly interesting enzyme - tryptophan hydroxylase (TPH)2 - which has an important role in serotonin metabolism (see here) I'll be watching closely on how vitamin D research with autism in mind also develops in this area.

And then there are the Raftery results [5] to bring to your attention putting further scientific flesh on to the bones about the possibility of a relationship between vitamin D levels and intestinal permeability (see here). Given what has been mentioned about 'leaky gut' and autism in the peer-reviewed literature so far (see here) one might also add this to further investigations in this area...

Music: I am the Monarch of the Sea.


[1] Schmidt RJ. et al. Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. Early Hum Dev. 2015 Jun 11;91(8):483-489.

[2] Yan J. et al. Vitamin D receptor variants in 192 patients with schizophrenia and other psychiatric diseases. Neurosci Lett. 2005 May 20-27;380(1-2):37-41.

[3] Jorde R. et al. Vitamin D and cognitive function: The Tromsø Study. J Neurol Sci. 2015 Jun 7. pii: S0022-510X(15)00350-0.

[4] Kaneko I. et al. 1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D. FASEB J. 2015 Jun 12. pii: fj.14-269811.

[5] Raftery T. et al. Effects of vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn's disease: Results from a randomised double-blind placebo-controlled study. United European Gastroenterol J. 2015 Jun;3(3):294-302.

---------- Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Sconberg JL, Schmidt LC, Volk HE, & Tassone F (2015). Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study. Early human development, 91 (8), 483-489 PMID: 26073892

Thursday, 2 July 2015

Acute bipolar depression and immune alterations

"Individuals with acute bipolar depression show immune alterations. Some of the alterations are similar to those found in acute mania."

That was the bottom line reported by Faith Dickerson and colleagues [1] following their analysis of blood samples provided by "82 individuals with acute bipolar depression, 147 with acute mania, and 280 controls." Looking for the presence of various antibodies to "human herpesviruses, gliadin, Toxoplasma gondii, and endogenous retroviruses as well as for C-reactive protein (CRP) and pentraxin-3" in said samples, researchers reported a few potentially important findings.

So: "The levels of CRP and IgG antibodies to an endogenous retrovirus, Mason-Pfizer monkey virus (MPMV), were significantly elevated in the bipolar depressed group." Further: "Levels of pentraxin-3 were reduced in both psychiatric groups." Researchers also reported that for 32 individuals who were hospitalised (and I assume treated) for bipolar depression, they "showed a significant decrease in the levels of MPMV antibodies, but not a change in the other markers."

Looking through the list of antigens included for analysis, without looking at the authorship list, I could have told you that the authors Faith Dickerson and/or Robert Yolken were involved in this study based on what has been discussed before on this blog (see here and see here for example). The work coming out of Johns Hopkins has been particularly interesting with their focus on "the role of infectious and inflammatory processes in complex psychiatric disease such as schizophrenia, bipolar disorder, and autism." Their most recent work on pentraxin-3 looks very interesting indeed (see here) and complements their most recent results.

The finding of elevations in the levels of CRP in the "bipolar depressed group" fits in well with the idea of inflammation being somehow involved in psychiatry (see here) and seemingly crossing diagnostic labels (see here). One might reasonable ask whether the research voices are indeed getting stronger for the potential usefulness of 'treating inflammation' when it comes to something like depression (see here) bearing in mind no clinical or medical advice is given or intended.

Finally, is that "endogenous retrovirus" finding reported by Dickerson et al. Regular readers of this blog might already know that I'm an avid [amateur] follower of the idea that all those fossil viruses that lurk in our genomes might be some much more than just junk DNA. With schizophrenia in mind (see here), with attention-deficit hyperactivity disorder (ADHD) in mind (see here), with autism in mind (see here), even with chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME) in mind (see here), I've covered the topic a few times on this blog. Although never coming across MPMV before, this is not the first time that antibodies to non-human primate viruses have been talked about with psychiatric / behavioural conditions in mind [2]. Indeed a previous paper from Dickerson and colleagues [3] even went as far as suggesting that as part of suite of inflammatory markers, the presence and elevation of MPMV antibodies is likely derived "from the activation of homologous endogenous retroviruses and to be a reflection of immune activation." Similar sentiments seem to carry over to the most recent results too.

Music: Doves - There Goes The Fear.


[1] Dickerson F. et al. Immune alterations in acute bipolar depression. Acta Psychiatr Scand. 2015 Jun 9.

[2] Lillehoj EP. et al. Serum antibodies reactive with non-human primate retroviruses identified in acute onset schizophrenia. J Neurovirol. 2000 Dec;6(6):492-7.

[3] Dickerson F. et al. A combined marker of inflammation in individuals with mania. PLoS One. 2013 Sep 3;8(9):e73520.

---------- Dickerson F, Katsafanas E, Schweinfurth LA, Savage CL, Stallings C, Origoni A, Khushalani S, Lillehoj E, & Yolken R (2015). Immune alterations in acute bipolar depression. Acta psychiatrica Scandinavica PMID: 26061032

Wednesday, 1 July 2015

Offspring autism risk and advancing parental age (differences)

Parental age at offspring conception/birth in relation to offspring autism risk has been a recurrent theme in autism research circles for quite a few years now. I've covered it more than once on this blog (see here for example) and the various suggestions that advancing parental age in particular, might elevate the risk of offspring autism.

Set in this context, the paper by Sven Sandin and colleagues [1] (open-access) (a name not unfamiliar to this blog) adds to the research evidence based on their analysis of some 5.7 million children born between 1985 - 2004 resident in one of five countries (Denmark, Israel, Norway, Sweden and Western Australia). Including data on some 30,000 children diagnosed with an autism spectrum disorder (ASD): "Parental ages, sex and birth year were obtained from birth or civil registers."

After quite a bit of statistical modelling and controlling for various potentially confounding variables, several findings were reported pertinent to the authors' data being "the strongest evidence to date supporting the hypothesis that advanced parental ages at the time of birth are independently associated with risk for ASD in the offspring." Outside of "no support for any modification by the sex of the child" researchers also noted a "combined parental age effect" whereby there "was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages."

A few of the finer details of this study have been covered elsewhere (see here). I'll draw your attention to one or two statistics unearthed during the study:

  • "relative to fathers aged 20–29 years, fathers 50 years or older had a statistically significantly increased risk for offspring with ASD (RR=1.66 95% CI:1.49–1.85)",
  • "Relative to mothers aged 20–29 years, mothers younger than 20 years had a statistically significantly increased risk for offspring with ASD (RR=1.18 95% CI:1.08–1.29)" and 
  • the "lowest risk corresponded to couples that generated the majority of births, specifically, 29–39-year-old fathers and 25–35-year-old mothers.

Those estimates of relative risk (RR) statistics translate into an estimated 66% increased risk for offspring autism if a dad was over 50 years old compared with a dad in their 20s, an 18% increased risk for offspring autism for teen mums compared to 20-something mums and the lowest statistical risk of offspring autism being reported when dads conceive in their 30s coupled with a mid-20 to mid-30 year old mum. The authors also note that "Similar patterns of association, but with slightly higher RRs for the highest parental ages, were evident for AD [autistic disorder]" so completing the message about older parental ages at conception and differing parental ages being relevant across the autism spectrum.

Accepting that this was a huge study in terms of participant numbers and spanning different geographical locations, the authors rightly offer a few words of caution about their methods and data. So: "we lack information about potentially confounding variables such as SES [socio-economic status] and parental psychiatric history" is something to keep in mind [2]. Further: "We cannot rule out the possibility that other factors associated with parental age (for example, length of marriage or partnership, obstetric complications, gestational age and birth weight) have an important role in explaining our results" and "We did not have individual level information on co-morbid ID [intellectual disability] in ASD cases." I'd also suggest that given the growing emphasis on autism or ASD not existing in some sort of diagnostic vacuum (see here) one might reasonably ask whether other comorbidity outside of ID might also play a role in risk estimates.

As to the possible mechanism(s) of effect, well, the authors go through the usual older parents - older sperm and eggs mantra although perhaps bypassing an emerging area outside of just de novo mutations based on the role of epigenetic mechanisms (see here). They do suggest that the 'difference in parental age' factor might suggest "that the increase in risk is not attributable to advancing parental age per se, and that the risk increase cannot be explained solely by an accumulation of point mutations or other genomic alterations in the parents" but say little more on the basis of their collected data.

I might be wrong but I also didn't seem too much in the way of discussion of how parental nutrition might impact on offspring autism risk as per the proposed factor from other work by authors on the Sandin paper in relation to the inter-pregnancy interval (IPI) and autism risk (see here and see here). Although the idea that parental age might affect autism offspring risk, I'd be minded to suggest that this is only the first stage in a journey towards elucidating the particular mechanisms of any effect.

Music: The Pixies - Gigantic.


[1] Sandin S. et al. Autism risk associated with parental age and with increasing difference in age between the parents. Mol Psychiatry. 2015 Jun 9.

[2] Lehti V. et al. Maternal socio-economic status based on occupation and autism spectrum disorders: A national case-control study. Nord J Psychiatry. 2015 Mar 3:1-8.

---------- Sandin S, Schendel D, Magnusson P, Hultman C, Surén P, Susser E, Grønborg T, Gissler M, Gunnes N, Gross R, Henning M, Bresnahan M, Sourander A, Hornig M, Carter K, Francis R, Parner E, Leonard H, Rosanoff M, Stoltenberg C, & Reichenberg A (2015). Autism risk associated with parental age and with increasing difference in age between the parents. Molecular psychiatry PMID: 26055426

Tuesday, 30 June 2015

Low glycemic index diet reduces symptoms of mouse autism

A quote to begin: "Overall, the manuscript supports the idea that ASD [autism spectrum disorder] results from gene–environment interactions and that in the presence of a genetic predisposition to ASD, diet can make a large difference in the expression of the condition."

The manuscript in question was by Antonio Currais and colleagues [1] reporting some rather interesting results based on the 'dangermouse' that is the BTBR mouse model of autism. Researchers from the Salk Institute for Biological Studies showed that "the dietary glycemic index has a significant impact on the ASD phenotype." The dietary glycemic index (GI) by the way, is concerned with how particular foods / foodgroups affect blood glucose levels and the crux of the research was to see what happened to pregnant mice when fed either a high GI or low GI diet in terms of offspring outcomes. Offspring also followed the same diet diet post weaning.

To quote from the paper and some associated media: "The two groups of animals consumed the same number of calories and were identical in weight. But mice that ate a high-glycemic index diet showed all of the expected behavioral symptoms of autism. Their social interactions were impaired, they repeated actions that served no apparent purpose, and they groomed extensively."

Various other differences were present across the different dieting mice as per the findings that: "diet modulates plasma metabolites, neuroinflammation and brain markers of neurogenesis in a manner that is highly reflective of ASD in humans." This included the finding that "the brains of the high-glycemic index diet mice appeared to have greater numbers of activated microglia, the resident immune cells of the brain" and various inflammation-related genes being more readily expressed in comparison to the low-glycemic index diet mice. Microglia and autism remains a complex topic (see here) but with the advent of recent research findings [2] complete with headlines such as ''Missing link' between brain and immune system discovered' I dare say that we'll be hearing more about this is times to come.

The compound doublecortin also receives a mention in the Currais results as per the suggestion that those mice living on the high-glycemic diet had less of the stuff and the significance of this finding given the link between doublecortin and neurogenesis for example [3]. Bearing in mind the BTBR mouse model of autism might already be more prone to reductions in the levels of doublecortin [4] it might be useful to see how this finding pans out when applied to real people in the real world.

"The new study found that the diet might directly influence the ecosystem of bacteria in the gut." It perhaps goes without saying that any sort of dietary change is likely to affect the composition of those trillions of wee beasties that call our gastrointestinal (GI) tract home. This also applies to mice and probably every other type of animal. "'We were really surprised when we found molecules in the blood that others had reported could only be generated by gut bacteria,' Maher says. 'There were big differences in some of these compounds between the two diets.'" Metabolites of gut bacteria found in general circulation... does this imply intestinal permeability (leaky gut) might be part and parcel of any effect? If so, would that perhaps also tie into the findings reported by Elaine Hsaio and colleagues a while back on leaky mice guts, gut bacteria and autism? Add in also the idea that high glycemic index foods tend to include things like wheat and various other grains and we start to get something looking rather familiar to autism research that may well show some relationship [5].

"The group plans to analyze the gut bacteria, and its potential link with features of autism, more directly. They also hope to better understand the role of inflammation in the ability to generate new neurons." I'm very much looking forward to seeing these results, bearing in mind that mice are mice not people [6] and autism (or rather the autisms) is/are [a] very complicated condition(s).

Music: The Jesus And Mary Chain - Just Like Honey.


[1] Currais A. et al. Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder. Molecular Psychiatry. 2015. June 9.

[2] Louveau A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jun 1.

[3] Couillard-Despres S. et al. Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci. 2005 Jan;21(1):1-14.

[4] Stephenson DT. et al. Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis. Mol Autism. 2011 May 16;2(1):7.

[5] Lammers KM. et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3.

[6] Wong AH. & Josselyn SA. Caution When Diagnosing Your Mouse with Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders. Biol Psychiatry. 2015 May 6. pii: S0006-3223(15)00361-3.

---------- Currais A, Farrokhi C, Dargusch R, Goujon-Svrzic M, & Maher P (2015). Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder. Molecular psychiatry PMID: 26055422

Monday, 29 June 2015

Fermented foods and social anxiety?

Stumbling across a headline that reads: 'Study Finds Decreased Social Anxiety Among Young Adults Who Eat Fermented Foods' was bound to pique my blogging interest. When I eventually tracked down the source paper behind the headline I became more and more intrigued as today I bring to your attention the study findings reported by Matthew Hilimire and colleagues [1].

Implementing "a cross-sectional approach to determine whether consumption of fermented foods likely to contain probiotics interacts with neuroticism to predict social anxiety symptoms" researchers asked over 700 students - psychology students - to self-report on "fermented food consumption, neuroticism, and social anxiety." Fermented foods by the way, cover a range of foods "that contain probiotics" including yogurt and sauerkraut (a particular favourite of mine). Researchers also enquired about various other variables such as fruit and vegetable intake and the amount of exercise taken over the past 30 days.

Bearing in mind that this was a study based on self-report and that psychology students might not be entirely representative of the population in general, the results of an "interaction model, controlling for demographics, general consumption of healthful foods, and exercise frequency" did seem to suggest that there may be more to see when it comes fermented food consumption and social anxiety: "Fermented foods should be further investigated as an intervention for social anxiety."

I'm not falling hook, line and sinker for these results - correlation is not the same as causation - despite my continuing interest in the science of psychobacteriomics (my word creation) and the idea that those trillions of wee beasties that inhabit our deepest, darkest [gut] recesses might be doing so much more than just helping to digest food and making the odd nutrient or two. I do however think that we need to dedicate quite a few more resources to the idea that psychology and behaviour might not be solely rooted in the grey-pink matter floating in our skull [2] as recent news articles seem to imply.

Finally, and without wishing to make too many sweeping generalisations from the Hilimire results, I did think about whether such findings may be particularly 'useful' for certain groups of people where social anxiety might be over-represented. Autism is an obvious label given the suggestion that at least a quarter of those on the autism spectrum might also fulfil the diagnostic criteria for social anxiety disorder (see here). That such anxiety might also have knock-on effects to the presentation of more core autism symptoms (see here) is also noteworthy bearing in mind that a diet rich in fermented foods might not be for everyone and that social anxiety with or without autism is bound to be a very complicated process.

We await further research in this area.

Music: The Flaming Lips - Do You Realize??


[1] Hilimire MR. et al. Fermented foods, neuroticism, and social anxiety: An interaction model. Psychiatry Res. 2015; 228: 203-208.

[2] Dinan TG. et al. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015 Apr;63:1-9.

---------- Hilimire MR, DeVylder JE, & Forestell CA (2015). Fermented foods, neuroticism, and social anxiety: An interaction model. Psychiatry research, 228 (2), 203-8 PMID: 25998000

Saturday, 27 June 2015

Probiotics, schizophrenia and inflammation

I have to say that I was initially pretty interested to read the paper by Jakub Tomasik and colleagues [1] (open-access available here) discussing results examining the "possible immunomodulatory effects of probiotic supplementation in chronic schizophrenia patients."

Interested because not only was this a partnership paper including Robert Yolken and Faith Dickerson on the authorship list (names who have appeared a few times on this blog) but also because of the subject matter extending some research interest into how gastrointesinal (GI) 'functions' may very well have some important implications for at least some cases of schizophrenia (see here) particularly linked to the concept of inflammation. This area of research on a 'gut-brain connection', also links into a body of work with autism in mind (see here) and with that autism connection, mention of one Sabine Bahn as a co-author and some research she has published [2] is also worth noting.

In the current paper, Tomasik et al describe work following on from a previous study by Dickerson and colleagues [3] suggesting that adjuvant probiotic use may "help to prevent severe bowel difficulty in patients with schizophrenia" even if not significantly affecting the behavioural presentation of schizophrenia on that research occasion. With no endorsement given or intended, the probiotic preparation in question was called Bifiform Balance and contained "the probiotic organism L. rhamnosus GG and... colony forming units of the probiotic organism Bifidobacterium animalis subsp. lactis BB12 (Ferrosan).Lactobacillus rhamnosus GG has appeared before on this blog (see here) so I was intrigued as I always am when it comes to gut bacteria and health / behaviour.

Authors describe how blood samples from 58 participants who completed the previous Dickerson trial ("31 in the probiotic arm and 27 in the placebo arm") were collected pre- and post-trial (after 14 weeks) and serum samples analysed by immunoassay "targeting selected inflammatory markers, including cytokines, chemokines, and acute-phase reactants."

Results: "Probiotic add-on treatment significantly reduced levels of von Willebrand factor (vWF) and increased levels of monocyte chemotactic protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), RANTES, and macrophage inflammatory protein-1 beta (MIP-1) beta with borderline significance (P ≤ 0.08)." Actually, the only significant effect was noted for vWF (p=0.047) for which levels seemed to drop following probiotic use. Also interesting was the finding that within the group taking the placebo (although I'm not altogether sure what this contained) there were significant pre- and post-intervention differences for compounds such as vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1); both showing reductions.

The authors note that the significant reduction in levels of vWF within the context of probiotics as an add-on treatment alongside more commonplace pharmacotherapy for schizophrenia might have some important implications for "certain cardiovascular risk parameters" for example. This statement is rooted in the idea that vWF has some research history when it comes to schizophrenia both outside [4] and inside this connection [5]. Certainly, vWF shows a link to inflammation and with mention of the words adhesion too. In the context of schizophrenia, inflammation is of growing interest...

"We conclude that probiotics have immunomodulatory effects in schizophrenia patients, affecting molecules that do not respond to standard antipsychotic therapy." If one goes by the statistical book, I'm not entirely sure that the current findings are completely in line with that last statement. Yes, vWF showed something of a 'relationship' to the probiotic use but the other results with "borderline significance" and the fact that authors "were not able to detect all targeted cytokines in [their] clinical samples", I'd be a little cautious about saying too much more.

Music: House Of Love - Destroy The Heart.


[1] Tomasik J. et al. Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. Biomark Insights. 2015 Jun 1;10:47-54.

[2] Schwarz E. et al. Sex-specific serum biomarker patterns in adults with Asperger's syndrome. Mol Psychiatry. 2011 Dec;16(12):1213-20.

[3] Dickerson FB. et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. 2014;16(1). pii: PCC.13m01579.

[4] Hope S. et al. Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor. Bipolar Disord. 2009 Nov;11(7):726-34.

[5] Dieset I. et al. Cardiovascular risk factors during second generation antipsychotic treatment are associated with increased C-reactive protein. Schizophr Res. 2012 Sep;140(1-3):169-74.

---------- Tomasik J, Yolken RH, Bahn S, & Dickerson FB (2015). Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. Biomarker insights, 10, 47-54 PMID: 26052224