A gluten-free diet for "schizophrenia positive for antigliadin antibodies (AGA IgG)"

Short post alert...

"This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder."

So said the findings reported by Deanna Kelly and colleagues [1] as the conference abstract [2] of their study finally hits the peer-reviewed science literature (see here).

As per my previous musings on this study, this was the "first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA [anti-gliadin antibodies] IgG." Results were interesting insofar as "participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale... and in negative symptoms." Net result: encouraging findings with the need for more study; also with a nice focus on effect sizes too...

'Nuff said.

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[1] Kelly DL. et al. Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019 Mar 27;44(3):1-9.

[2] Kelly D. et al. Randomized double-blind feasibility study of a gluten-free diet in people with schizophrenia and elevated antigliadin antibodies (AGA IgG). Schizophrenia Bulletin. 2018; 44: S190.

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The positive effects of 12 weeks of probiotics and vitamin D in chronic schizophrenia?

The findings reported by Amir Ghaderi and colleagues [1] (open-access) provide the blogging fodder today, and the results of a study looking at a "novel combination of vitamin D and probiotic on metabolic and clinical symptoms in chronic schizophrenia." Said probiotic formulation contained "Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum (each 2 × 109)" and was delivered over a period of 12 weeks alongside a vitamin D supplement - "50,000 IU vitamin D3 every 2 weeks" - utilising a "randomized, double-blind, placebo-controlled trial" design. We are also told that the trial protocol was "retrospectively registered."

The Ghaderi study wasn't solely focused on what their combined intervention might do for the 'clinical symptoms' of schizophrenia despite this being a prominent part of the results obtained. They also wanted to examine things like "biomarkers of oxidative stress and cardiometabolic risk in chronic schizophrenia." This was done via the measurement of marker compounds pertinent to establishing total antioxidant capacity, total glutathione levels and high-sensitivity C-reactive protein (hs-CRP) among other things.

Results: first things first, vitamin D supplementation raised vitamin D levels in those who received the vitamin D + probiotic supplement. Not exactly an unexpected result I grant you, but important from the point of view that any subsequent findings *could* be linked to those increasing vitamin D levels. Further: "Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general... and total PANSS scores." PANSS stands for the Positive and Negative Syndrome Scale and has some important uses in the context of schizophrenia, and the presentation of positive and negative symptoms. That all being said, the authors also mention how their supplementation combination did not seemingly affect scores on another measure included in the study - the Brief Psychiatric Rating Scale (BPRS) - which kinda demonstrates that vitamin D + probiotics is not a panacea for every aspect of schizophrenia.

Researchers also report on how their combined supplement also *correlated* with a some changes in those oxidative stress and cardiometabolic risk measures included for study in line with other study results (see here). There's quite a bit of data so I won't provide details. Suffice to say that some of them might be 'positively' important to those health inequalities that seem to follow a diagnosis of schizophrenia (see here).

What else? Well, I can't seem to find too much in the way of side-effects details in the Ghaderi paper so I'm assuming that it wasn't a significant issue. The fact that participants in the study were "being hospitalized during the intervention" means that they were, I assume, being monitored with greater assiduity than for example if they were in the community, including looking for potential side-effects.

And with that, and the requirement for further study (see here and see here), I say no more...

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[1] Ghaderi A. et al. Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients. BMC Psychiatry. 2019; 19:77.

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Autistic traits in schizophrenia: meta-analysed

"Current findings support that individuals with schizophrenia spectrum disorders have higher autistic symptoms than healthy controls."

So said the meta-analysis findings reported by Franco De Crescenzo and colleagues [1] and their study which "systematically reviews and quantitatively synthetizes the current evidence on the presence of autistic symptoms in individuals with schizophrenia spectrum disorders." I might quibble (again) with the use of the term 'healthy controls' but the findings reiterate something quite important: autistic signs and symptoms are not necessarily exclusively linked to a diagnosis of autism (see here and see here).

The De Crescenzo paper represents a 'let's boil down the existing peer-reviewed science literature into a coherent statement' kinda study; as 13 studies including nearly 2000 participants were included for review and meta-analysis. The primary outcome "was the Autism Spectrum Quotient (AQ)" and its use on those diagnosed with schizophrenia or schizophrenia spectrum disorder (SSD) vs. those with autism or vs. those asymptomatic controls as a total score or scores on the various sub-domains. The results went something along the lines of "individuals with SSDs have significantly higher autistic symptoms than healthy controls and lower autistic symptoms than individuals with autism." That finding followed for the total AQ score and most of the sub-domain scores.

What else is there to say? Well, the De Crescenzo results relied on the AQ for their measurement of autistic signs and symptoms. I've mentioned more than once on this blog how the AQ might show an important connection to autism but is not necessarily the premier (exclusive) autism screener (see here and see here). Applying such logic to the current meta-analysis findings and one has to be a little bit careful about what is being measured by such a scale and whether such overlap is there on the basis of just autistic signs and symptoms.

That all being said I have talked about overlap between scores on the AQ in autism and schizophrenia before on this blog (see here) and the notion of potential 'fuzzy boundaries' between the two labels. Indeed, it makes you wonder whether science and clinical practice were too quick to dismiss the important findings from Mildred Creak and colleagues [2] and the seeming desire to move autism as far away from schizophrenia as possible...

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[1] De Crescenzo F. et al. Autistic Symptoms in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis. Front Psychiatry. 2019;10:78.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013;26(3):3-31.

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On gut bacteria and schizophrenia

Hot on the heels of my discussions about the possible *association* between gut bacteria and depression (see here), the results published by Peng Zheng and colleagues [1] (open-access) entered my Twitter feed recently, extending the gut bacteria 'connection' to schizophrenia.

The Zheng study represents yet more good scientific value for money as researchers initially sought to "compare the gut microbial communities of patients with SCZ [schizophrenia] and healthy controls (HCs) to evaluate whether microbiotal dysbiosis was linked with schizophrenic episodes or the severity of schizophrenic symptoms." They also "transferred gut microbiota from patients with SCZ into GF [germ free] mice to test whether SCZ-relevant behavioral phenotypes were transmissible via their gut microbiome". The study findings have been covered quite a few media outlets (see here).

The results: "seminal evidence that SCZ is associated with changes in gut microbiota composition that are both specific to SCZ and correlated with symptom severity." This translated into:

• reduced (alpha) microbial diversity in those with schizophrenia (n=63) compared with "healthy controls" (authors words not mine),
• the identification of certain bacterial differences between the groups: "the most significant deviations between SCZ and HC subjects occurred for the bacterial families Aerococcaceae, Bifidobacteriaceae, Brucellaceae, Pasteurellaceae, and Rikenellaceae",
• a *correlation* between the presence of some bacterial species and the 'severity' of symptoms of schizophrenia,
• behavioural changes in those mice who received a gut bacterial transplant from participants with schizophrenia,
• "Perturbed gut-brain amino acid and lipid metabolism in SCZ microbiota recipient mice." Gut bacteria produce chemicals (for messaging and the like), and those bacteria transplanted into germ-free mice produced a different cocktail of chemicals that showed up "in the SCZ microbiota compared to the HC microbiota recipient mouse samples." In particular: "lower glutamate and higher glutamine and GABA in the hippocampus."

As I said, the Zheng study was pretty good value for money on the basis of the results obtained. The authors note that their findings "provide a novel framework for understanding the mechanisms of SCZ through the MGB [microbiota-gut-brain] axis and may lead to new diagnostic and treatment strategies."

Caveats? Well, fairly small participant numbers is one thing, as was the potential influence of medication being taken by those with schizophrenia. Authors however mention that: "we found that the distributions of global microbial phenotypes did not vary between medicated and unmedicated patients with SCZ." I'll also point out the inherent 'difficulties' when talking about "SCZ-relevant behaviors in GF recipient mice" similar to that noted with regards to other diagnostic labels (see here). People are given labels like schizophrenia not mice.

But it's a good start and complements other work in 'related' areas talking about the gut-brain axis as being potentially pertinent to 'some' schizophrenia (see here and see here). Whether modifying gut bacteria via use of something like diet, probiotics or the horror that is the gut microbial transplant might relieve some of the signs and symptoms of schizophrenia is an area that requires quite a bit more investigation...

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[1] Zheng P. et al. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Science Advances. 2019; 5: 2.

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Gluten, mimicry and schizophrenia

The findings reported by Daniela Čiháková and colleagues [1] provide the rather long blogging fodder today, and some interesting observations on how the immune system 'reacting' to gluten in some cases of schizophrenia might have some pretty far-reaching consequences when it comes to other proteins with a similar chemical structure.

OK, first things first, gluten is a protein. It's made up of long chains of amino acids; the building blocks of proteins. As gluten is digested in the gastrointestinal (GI) tract, various enzymes get to work on the protein to break it down into it's constituent amino acids, forming peptides (short chains of amino acids) along the way. The protein gluten and its components like gliadin has a characteristic shape like every protein has. For reasons that aren't yet completely understood, the immune system of some people can sometimes 'mark' normally fairly harmless proteins like gliadin as something that needs dealing with. It does this via the production of antibodies. Antibodies usually mark pathogens like bacteria or viruses, and by doing so, set off a cascade of biological processes to [try and] ensure that such invaders don't take hold and also to remind the immune system of what to look out for. Marking something like gliadin out (which is neither bacteria nor virus!) probably means that the body is detecting gliadin in places it shouldn't be; something that I'll come back to in a minute.

It's not beyond the realms of possibility that when the immune system marks a specific protein as something to keep an eye on, it can make mistakes. If for example, two proteins 'look' similar to each other in a chemical arrangement sense, despite being different proteins with different functions, the immune system can sometimes become a little confused and start to mark both as being an invader on the basis of one already having 'special interest' status. Several descriptions describe such a process: "cross reactivity or mimicry." This accidental marking can sometimes have important repercussions, where such a process is thought to be a basis for autoimmunity.

Čiháková et al detail findings suggesting that just such a process - mimicry - could well be pertinent to some cases of schizophrenia. As already mentioned, they started with the observation that some people diagnosed with schizophrenia have high levels of specific antibodies to gliadin (see here and see here). This follows quite a lot of history linking gluten and schizophrenia together (see here). They wanted to see if as well as presenting with antibodies to gliadin, a cohort of people diagnosed with schizophrenia might also present with elevated antibodies to something called GRINA - Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1. They focused in on GRINA because it has a "similar protein structure to gliadin representing a potential target for cross reactivity or mimicry." GRINA also links into glutamate system functioning, something which has also already been mentioned with schizophrenia in mind (see here).

There's another detail about the Čiháková study which relates to a point I touched upon earlier, on the possible hows-and-whys of gliadin antibodies being found in cases of schizophrenia: enhanced gut permeability a.k.a leaky gut. Researchers also analysed serum samples for the presence of something called Anti-Saccharomyces Cerevisiae antibodies (ASCA) which they say are "related to gut permeability." This follows other research in a similar vein (see here) and the suggestion that something like abnormal gut permeability *could* be implicated in some cases of schizophrenia.

Results: looking at serum samples of 160 people diagnosed with schizophrenia and 80 not-schizophrenia controls, researchers observed "a higher prevalence of positivity to ASCA IgA... and IgG" in those with schizophrenia. This tallies with the leaky gut hypothesis. They also reported that "GRINA IgG was higher in schizophrenia patients than in healthy controls." Putting these results together, they concluded that the mimicry hypothesis might well be pertinent to some schizophrenia.

There is a lot more work required in this area for sure. This will need to involve further investigation of the hows-and-whys of any such mimicry, and whether such a process could be a potential target for intervention. Indeed, in that intervention vein, I'm wondering whether use of a gluten-free diet for some with schizophrenia who have such antibodies (to gluten and other things like GRINA) might be an option. There's also merit in looking further at the issue of gut permeability and schizophrenia; whether again adoption of a gluten-free diet (which can positively affect gut permeability measurements) might be indicated, perhaps alongside other therapeutic targets.

But this area of research is interesting, and adds to the quite long research history linking food components and some behavioural / psychiatric labels...

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[1] Čiháková D. et al. Gut permeability and mimicry of the Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) as potential mechanisms related to a subgroup of people with schizophrenia with elevated antigliadin antibodies (AGA IgG). Schizophr Res. 2019 Jan 23. pii: S0920-9964(19)30007-6.

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T. gondii infection might be "a contributing causal factor for schizophrenia"

T. gondii mentioned in the title of this post refers to Toxoplasma gondii, a parasite with something of a rather interesting profile and history (see here and see here). I've talked quite a bit on this blog about T. gondii and it's various 'associations', but of particular interest has been the suggestion of a 'connection' between T. gondii exposure and risk of psychiatric diagnoses like schizophrenia (see here).

The findings reported by Kristoffer Sølvsten Burgdorf and colleagues [1] (open-access available here) add further evidence to such a 'psychiatric' connection with their conclusion that: "exposure to T. gondii might be a contributing causal factor for developing schizophrenia." Researchers arrived at their conclusion following the examination of an intriguing initiative called the Danish Blood Donor Study (DBDS). Started in 2010, the DBDS includes records for over 100,000 patients and "contains DNA and EDTA plasma samples, consecutive for all donors returning for blood donation after enrolment." That's a lot of data. So: authors "identified all individuals in the DBDS cohort registered with psychiatric disorders, suicidal behavior, or traffic accidents (N=5,953)." Said participants were matched with 'suitable' controls (N=7,101) and stored samples were analysed for "immunoglobulin (IgG) class antibodies against T. gondii and CMV." CMV by the way, refers to cytomegalovirus. Contact with (congenital) CMV has also been talked about on this blog (see here). CMV (exposure) also shares a potential *link*  with "psychiatric disorders, cognitive deficits, suicidal behavior, and traffic accidents."

Results: "Of the 11,546 studied individuals, 2,990 and 7,020 individuals, respectively, tested positive for IgG class antibodies against T. gondii (25·9%) or CMV (60·8%)." Onward: "We found that individuals with a T. gondii infection had increased odds of being diagnosed with schizophrenia disorders compared to those without infection." Because researchers were also able to access other national databases containing details on outcomes like diagnosis of a psychiatric disorder and 'attempting suicide' and cross-reference them with their participants, they were also able to look at "temporality, with pathogen exposure preceding outcome" as a factor. And when they did, that T. gondii exposure - schizophrenia association was described as "even stronger." The other data on T. gondii or CMV exposure in relation to traffic accidents or suicide attempts was not as statistically strong, and indeed nothing showed significance when temporality was taken into consideration in relation to causation. On that basis, I'm gonna leave that part of the results without further comment.

This was a good study. It drew on data from a well-defined group (those Scandinavian databases 'do it' yet again) and was able to take into account the important issue of temporality. It wasn't a perfect study - "We cannot rule out that socio-economic factors could potentially account for part or all of the observed causal effect" - and said nothing about possible mechanism(s) of effect however. That being said, I'm willing to go along with the conclusions made and the need for a lot more investigation in this area linking T. gondii exposure and subsequent risk of mental illness. In particular whether new or existing treatment methods for T. gondii *might* hold the promise of much more...

And whilst on the topic of T.gondii and the specific input from cats on the spread of T. gondii (see here and see here), I'll state here and now that I am not a great believer in the idea of 'cat eradication' as mentioned by some researchers recently [2]. That being said, a toxoplasmosis vaccines for cats (see here) sounds like a really good idea...

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[1] Sølvsten Burgdorf K. et al. Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders. Brain Behav Immun. 2019 Jan 24. pii: S0889-1591(18)30699-8.

[2] de Wit LA. et al. Potential public health benefits from cat eradications on islands. PLoS Negl Trop Dis 13(2): e0007040

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"Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood"

I want to bring the findings reported by Julie Dreier and colleagues [1] to your attention today and their observation that: "Children with epilepsy and febrile seizures-with and without concomitant epilepsy-are at increased risk of developing a broad range of psychiatric disorders in later life."

Researchers report results based on the examination of one of those ever-so-impressive Scandinavian population registries that have moved science forward in many, many different areas (see here for example). This time around it was the Danish National Patient Register and the inclusion of data from "1 291 679 individuals... born in Denmark and followed up in our population cohort (approximately 15 million person-years)." Over 43,000 individuals showed a history of febrile seizure - "fits that can happen when a child has a fever" - and over 10,000 had epilepsy. Likewise: "83 735 (6%) cohort members were identified with at least one of the psychiatric disorders of interest" including substance abuse disorders, schizophrenia, mood disorder, anxiety, and personality disorder.

Results: "The risk of any psychiatric disorder was raised in individuals with a history of febrile seizures..., epilepsy..., or both disorders." The magnitude of the risk was categorised as statistically significant in terms of elevation but ranged from between a 10-50% increased risk. Further: "Excess risk of psychiatric illness associated with childhood seizures was present across a range of different disorders, most notably schizophrenia but also anxiety and mood disorders." Authors also opine that further research is needed on this topic with regards to mechanisms pertinent to identifying "potential options for prevention."

Although some caution is always required when one variable (epilepsy) is solely correlated with another (history of recorded psychiatric diagnosis), I am interested in the Dreier findings. I'm interested not only because of the *association* being made between a condition that often has life-changing effects on other often life-changing diagnoses but also because this *association* complements other links being made with epilepsy. I speak of the various studies linking epilepsy to diagnostic labels such as autism and attention-deficit hyperactivity disorder (ADHD) of course (see here and see here for examples) whilst pointing out that ADHD and autism are not to be categorised as mental health conditions. Such links between epilepsy and neurodevelopmental diagnoses are all the more interesting because the presence of labels such as autism and ADHD are also known to manifest elevations in other psychiatric diagnoses such as mood disorder, anxiety and schizophrenia (see here and see here and see here for examples). It's not therefore unreasonable to suspect that there may be some 'over-arching' themes when it comes to epilepsy/febrile seizures 'linking' with various developmental and psychiatric diagnoses.

Minus any sweeping generalisations and being careful how I phrase this, one area that requires a lot more investigation is the neurological effect that epilepsy in particular can have. I speak of the idea that seizures can, in some cases, affect the physical nature of the brain [2] and the question of whether such 'damage' might also then affect the presentation of behaviour akin to the signs and symptoms of a neurodevelopmental or psychiatric diagnosis. I know this is not a particularly palatable line of thinking but it does require further scientific exploration. This is also pertinent to the Dreier study focusing in on childhood seizures and by inference, possible effects on the developing brain. Another area of further investigation is whether the presentation of epilepsy or seizures *might* be part-and-parcel of various syndromes also presenting with neurodevelopmental and/or psychiatric features? We do have some examples of this already (see here) and, given that various genetic syndromes are quite regularly being identified day-by-day, it's another area that could yield some important data.

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[1] Dreier JW. et al. Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood: a Danish nationwide cohort study. Lancet Child Adolesc Health. 2018 Dec 6. pii: S2352-4642(18)30351-1.

[2] Bronen RA. et al. The Status of Status: Seizures Are Bad for Your Brain's Health. American Journal of Neuroradiology. 2000; 21: 1782-1783.

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1 in 5 adults with autism diagnosed with non-affective psychotic disorder (NAPD) before the age of 35?

The quote heading this post - "1 in 5 adults with autism diagnosed with non-affective psychotic disorder (NAPD) before the age of 35?" - comes from the findings reported by Schalbroeck and colleagues [1] continuing a research theme from this authorship group [2] on how autism rarely appears in some sort of diagnostic vacuum.

Relying on longitudinal data from the Netherlands ("from Dutch psychiatric case registers"), authors sought to capitalise on their previous findings from Sweden to "to assess the risk of NAPD or BD [bipolar disorder] among individuals with ASD [autism spectrum disorder], and compared the results to those obtained for the Dutch population in earlier studies." NAPD in this case refers to a grouping of labels covering schizophrenia, delusional disorder and acute and transient psychotic disorder. Bipolar disorder was previously called manic depression, reflecting mood swings between depression and mania. Both labels have some research history when it comes to autism (see here and see here for examples).

Based on the longitudinal analysis of participant records in the thousands, over 17,000, all diagnosed with ASD, researchers set about calculating the risk of NAPD and BD in their cohort. They observed that: "Of the individuals with ASD, 23.50%... were diagnosed with NAPD and 3.79%... with BD before age 35 years." Such percentages contrasted with general population figures of 0.9% and 0.1% for NAPD and BD respectively. Further study based on around 8,000 people "diagnosed with ASD before age 16 years" also showed elevated levels of NAPD and BD being diagnosed before 25 years of age (1.8% and 0.5% respectively) compared with general population figures (0.6% and 0.1%); albeit to a lesser extent.

Aside from concluding that the risk of NAPD and BD in relation to autism "is likely not the result of diagnostic or selection bias", the Schalbroeck findings reiterate again that autism seemingly rarely exists in some sort of diagnostic vacuum (see here). They reiterate that psychiatric comorbidity, some of which can often be both serious and quality-of-life destroying, is not uncommon in the context of the label of autism. They also reiterate that timely screening, diagnosis and yes, treatment for such comorbidity, are basic human rights that are as relevant to someone with autism as they are to someone not on the autism spectrum.

Oh, and given the quite significant overlap between autism and such psychiatric comorbidity, it is perhaps all the more reason to keep on studying a group where autistic and psychiatric issues seemingly were but are no more (see here)...

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[1] Schalbroeck R. et al. Risk of non-affective psychotic disorder or bipolar disorder in autism spectrum disorder: a longitudinal register-based study in the Netherlands. Psychol Med. 2018 Nov 21:1-8.

[2] Selten JP. et al. Risks for nonaffective psychotic disorder and bipolar disorder in young people with autism spectrum disorder: a population-based study. JAMA Psychiatry. 2015 May;72(5):483-9.

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"Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia"

The paper published by Guillaume Fond and colleagues [1] concluding that: "Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia" provides the blogging fodder today. Hypovitaminosis D is just another way of saying vitamin D deficiency (or perhaps insufficiency) and follows a number of previous research findings (see here) concluding that schizophrenia seems to be one of a number of conditions/diagnosis/labels where tested vitamin D levels show sub-optimality.

Fond report results based on their examination of the "national FondaMental Expert Center (FACE-SZ) Cohort", something that has been talked about on this blog before (see here). So: "A comprehensive 2 daylong clinical and neuropsychological battery was administered in 140 SZ subjects included between 2015 and 2017" including vitamin D testing and analyses looking for the signs and symptoms of depression and anxiety.

Results: about one in five of the study participants were in a state of hypovitaminosis D. Looking at the accumulated behavioural data - "Depressive symptoms were assessed by the Positive and Negative Syndrome Scale depressive subscore and current anxiety disorder by the Structured Clinical Interview for Mental Disorders" - I was particularly struck by the *link* between vitamin D deficiency and 'current anxiety disorder' ("aOR = 6.18 [2.15-17.75], p = 0.001"). Further: "Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms... and lower rate of current anxiety disorder... compared to patients with hypovitaminosis D."

These are interesting results. They reiterate that a diagnosis of schizophrenia does not seem to be protective against the development of vitamin D deficiency/insufficiency. They also highlight that schizophrenia perhaps should not be considered as a stand-alone diagnosis; something that is beginning to be realised across various different behavioural labels (see here). The suggestion of an *association* between anxiety and/or depression in the context of vitamin D is also important (perhaps even relevant to other studies that have suggested a direct link between vitamin D and schizophrenia). And then there is the 'already supplemented' finding that seems to fly in the face of quite a lot of other evidence suggesting that correcting vitamin D deficiency in the context of something like depression might not be directly applicable to improvement in depressive symptoms (see here). Research questions remain but the Fond results look interesting...

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[1] Fond G. et al. Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort. Psychiatry Res. 2018 Sep 13;270:104-110.

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Autistic traits assessed between 5 and 8 years old are 'primarily stable'

The findings reported by Hideyuki Haraguchi and colleagues [1] (open-access available here) provide the [brief] blogging fodder today and their conclusion that: "total and two subdomain-related autistic trait scores remained primarily stable in males and females" in the general population. Further that "assessing autistic traits before school entrance may aid in predicting later autistic traits as well as other co-occurring social and emotional problems."

Autistic traits were measured "by a mother-reported quantitative measure, the Social Responsiveness Scale, at age 5 and 8 years." The Social Responsiveness Scale or SRS has some good history with autism in mind both from a research and clinical perspective. In this case the Japanese version of the SRS was used, and data from total scores and "Social Communication and Interaction (SCI)" and "restricted and repetitive behaviors (RRBs)" domains also reported on in approaching 170 "Japanese community-based children."

Results: "We found that although autistic traits assessed by the SRS decreased slightly from age 5 to 8, the extent of this change did not reach statistical significance in this sample, indicating that autistic traits are primarily stable during this transition period at the group level."

This is an important finding. Whilst one has to be careful of any sweeping generalisations that for example, the expression of autistic traits by individual children or smaller subgroups might not be as stable as you think (see here and see here), the results do have implications for various areas. Not least those areas connected to the idea that autistic traits might have some subsequent important 'influence' on later psychopathology (or indeed, a subsequent diagnosis of autism). I say this in several important contexts covering the presence of depression and anxiety (see here) and also in relation to other 'overlapping' spectrums (see here and see here) and what this *could* mean for some potentially life-threatening risks (see here and see here).

The next stage of such research? Look beyond the late childhood years and into adulthood with autistic traits in mind.


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[1] Haraguchi H. et al. Stability of Autistic Traits from 5 to 8 Years of Age Among Children in the General Population. J Autism Dev Disord. 2018 Oct 5.

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Colliding spectrums again: autism and schizophrenia meta-analysed (again)

"The systematic review and meta-analysis showed a significant association between schizophrenia and ASD [autism spectrum disorder]."

That was the conclusion made by Zhen Zheng and colleagues [1] following their trawl through the peer-reviewed science literature with a view to examining "the association between schizophrenia and ASD."

This is not the first time that Zheng et al have featured in the autism meta-analysis arena (see here and see here and see here) so one could perhaps see them as seasoned professionals when it comes to this type of science. It's also not the first time that the relationship between autism and schizophrenia has been subjected to such analyses either (see here) continuing quite a long relationship between the labels and/or spectrums [2] (see here also).

So: "The meta-analysis of the prevalence of schizophrenia in individuals with ASD encompassed 1,950,113 participants and 14,945 individuals with ASD." From such numbers/data, authors were quite confidently able to determine that schizophrenia was more frequent in cases of autism than in control participants. Indeed, this was described as a 'robust' finding and the magnitude of the risk was not to be sniffed at: "odds ratio = 3.55, 95% confidence interval: 2.08-6.05, P < .001."

In relation to the "prevalence of ASD in individuals with schizophrenia", the authors relied on a smaller number of participants but concluded that: "The prevalence of ASD in individuals with schizophrenia ranged from 3.4 to 52%." Ergo, schizophrenia occurring alongside autism and autism occurring alongside schizophrenia both show over-representation.

As I mentioned on a previous blogging occasion when these labels were discussed in an overlapping sense, there are many implications from such findings. There are implications related to the preferential screening for schizophrenia and/or autism (also including other related issues too) when one or other label is diagnosed and for timely and appropriate intervention for such issues when detected (see here). There are implications for the idea that, biologically-speaking, there may be some shared mechanisms at work covering both (heterogeneous) labels (see here and see here for examples). There are also implications in relation to the social impact of such an association; bearing in mind the often very negative image portrayed of schizophrenia in certain quarters of the media and the rise and rise of 'autistic identity' in other circles. There is lots to think about.

And finally and quite timely, the paper from Giacomo Deste and colleagues [3] talking about the PANSS Autism Severity Score (PAUSS) as a "simple, fast and reliable tool for the identification of autistic features in adult patients with schizophrenia" looks rather interesting...

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[1] Zheng Z. et al. Association Between Schizophrenia and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Autism Res. 2018 Oct 3.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. History of the human sciences. 2013;26(3):3-31.

[3] Deste G. et al. Looking through autistic features in schizophrenia using the PANSS autism severity score (PAUSS). Psychiatry Research. 2018. Oct 29.

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"C-Reactive Protein as a Peripheral Biomarker in Schizophrenia"

The results of the 'updated systematic review' published by Guillaume Fond and colleagues [1] looking at the "relationships between elevated blood C-reactive protein (CRP) levels and schizophrenia (SZ) onset risk, illness characteristics and treatments, cognition and physical health" provides the blogging fodder today.

Fond (a name not unfamiliar to all-things schizophrenia) et al dip into a topic with more than its fair share of research 'uncertainty' (see here and see here for examples) on whether or not C-reactive protein (CRP), a marker of systemic inflammation, shows a connection to schizophrenia. On this particular research occasion, no new data is added to the debate, but rather authors looked at the collected peer-reviewed data (up to November 2017) to see if any 'general opinions' could be discerned from the collected works.

Results: based on over 50 studies included in their review, authors concluded that it was 'reasonable' to assume that high-sensitivity CRP (hs-CRP) may be a marker for 'schizophrenia onset risk'. The caveat to that statement is that CRP is probably not something 'schizophrenia-specific' in terms of elevations of CRP being indicative of a inflammatory state. So increased hs-CRP may well be a risk factor for "increased positive symptoms, cognitive impairment, hypovitaminosis D, microbiota disturbances, cardiovascular and metabolic syndrome risk in SZ subjects, and increased nicotine dependence in SZ smokers."

I'm pretty happy with the Fond results and interpretation as they stand. They suggest that CRP probably does show some sort of connection to schizophrenia and onward, points to an immune system connection to at least some cases (see here and see here). At the same time, they also imply that certain other observations around schizophrenia - such as a link with certain physical health issues (see here) and/or vitamin D deficiency (see here) - probably also contribute to the elevations of CRP noted in relation to cases of schizophrenia. They also imply that moves to reduce levels of CRP in relation to schizophrenia may well have various other 'knock-on' effects on those other risk factors associated with the condition/diagnosis. This 'double hit' effect could be quite useful.

And with that last sentence in mind, and accepting that consistently high levels of CRP are probably good for no-one, the next question: what can we do about elevated CRP levels in relation to schizophrenia and further, the immune system issues also being co-expressed? Lots, is my impression; perhaps also learning from other labels where immune function (and dysfunction) has been noted [2] and intervention is similarly indicated.

And there's more to come from this authorship group on this blog soon...

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[1] Fond G. et al. C-Reactive Protein as a Peripheral Biomarker in Schizophrenia. An Updated Systematic Review. Front. Psychiatry. 2018. Aug 23.

[2] Marchezan J. et al. Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy. Neuroimmunomodulation. 2018 Sep 5:1-20.

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The FACE-SZ initiative: inflammation and latent Toxoplasma infection in schizophrenia

The FACE-SZ initiative mentioned in the title of this post refers to the National FondaMental Expert Center (FACE-SZ) Cohort, a French collaboration designed to further knowledge about schizophrenia (SZ). The year 2018 has already been quite a year for peer-reviewed publications stemming from this initiative (see here), previously covering some really important topics.

Today I'm discussing two papers from the FACE-SZ scheme: the first from Guillaume Fond and colleagues [1] covered the issue of latent Toxoplasma infection and schizophrenia, and the second also from Fond and colleagues [2] observed that peripheral low-grade inflammation seemed to be something over-represented when it came to "ultra resistance to treatment in schizophrenia (UTRS)." The common ground between the papers is the immune system and how 'activation' of the immune system *might* have some important connections to the presentation of schizophrenia (see here).

Toxoplasma infection is a topic that has been mentioned in the context of schizophrenia before (see here). The causative agent of such infection - Toxoplasma gondii - is most definitely one of Nature's survivors; even to the point of potentially 'making' mortal enemies 'attracted' to waste products of the other (see here). There's still some debate about the hows-and-whys of T.gondii and Toxoplasma infection in relation to schizophrenia, but the collected data is not easily ignored when it comes to an over-representation of infection in the context of schizophrenia and its symptoms (see here and see here).

The first Fond paper [1] reports data from a cohort of some 250 people diagnosed with schizophrenia and "included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort." Alongside looking for the presence of Toxoplasma infection - "Latent Toxoplasma infection was defined by T. gondii IgG ratio ≥0.8, equivalent to ≥10 international units" - researchers also looked for signs of peripheral inflammation as per their measurement of everyone's favourite pentraxin: highly sensitive C reactive protein (CRP). I should also mention that CRP also has quite a peer-reviewed publication history when it comes to schizophrenia (see here) albeit not always in agreement (see here).

They reported that almost three-quarters of their cohort (184/250) showed signs of latent Toxoplasma infection, equating to Toxoplasma being "almost 3 times more frequent in SZ population compared to general population in France." Not only that but such infection seemed to correlate with some important clinical measurements of schizophrenia, and "Treatments with Anti-Toxoplasmic Activity (TATA)" also correlated with lower depressive symptoms.

The second Fond paper [2] focused on 'chronic low-grade peripheral inflammation' as again, high sensitivity CRP (hs-CRP) was the analyte of choice. The focus this time around was on a sub-group classified as showing "ultra resistance to treatment in schizophrenia (UTRS)" and to see if the such inflammation was *associated* with such cases. Including a starting participant number of over 600 people all diagnosed with schizophrenia, researchers reported that about 10% fell into that UTRS grouping. Among this 10%, they reported something of important relationship between UTRS and levels of CRP as a marker of inflammation. Such a relationship also held when taking into account other, potentially influential variables: "adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption." The authors opine that further studies should be directed to look at whether 'treating' such low-grade inflammation *might* have an important effect on some of the presented symptoms of schizophrenia.

Taken together, I'm hoping that readers can see the value of the FACE-SZ initiative, and what it could mean for research looking at the possible aetiology and pathology of at least some cases of schizophrenia. Yes, I appreciate that genetics and environment are going to be important to schizophrenia (as they seem to be for just about every behavioural/psychiatric label) but with that immune system 'connection' there could be lots of research opportunities including some potentially novel treatments to be examined. Once again, the immune system seems to be doing an awful lot more than just playing protector against various pathogens...

To close, and noting the mention of T.gondii in today's post, the news doesn't seem to be all that great when it comes to cat ownership...

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[1] Fond G. et al. Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort. Schizophr Res. 2018 May 27. pii: S0920-9964(18)30265-2.

[2] Fond G. et al. Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort. Eur Arch Psychiatry Clin Neurosci. 2018 May 28

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The [estimated] global prevalence of schizophrenia in 2016... 0.28%

The findings reported by Fiona Charlson and colleagues [1] looking at the "GBD [global burden of disease] 2016 estimates of schizophrenia prevalence and burden of disease with disaggregation by age, sex, year, and for all countries" provide the brief blogging fodder today.

As per the title of this post, when all the data were captured (from a "total of 129 individual data sources") and numbers crunched, the "global age-standardized point prevalence of schizophrenia in 2016 was estimated to be 0.28%."

Authors talk about schizophrenia as a "low prevalence disorder" highlighting also how there were no sex differences noted and how: "Age-standardized point prevalence rates did not vary widely across countries or regions." Schizophrenia it appears, does not care if you are a man or a woman or where you live. What it does seem to do, quite generally, is affect your quality of life and other life chances, as per another quote from the Charlson findings: "Schizophrenia contributes 13.4... million years of life lived with disability to burden of disease globally." Oh, and it appears to be increasing in frequency too: "Globally, prevalent cases rose from 13.1... million in 1990 to 20.9... million cases in 2016."

I personally, found the Charlson estimate - 0.28% - to be lower than I would have expected. Having talked for example, about schizophrenia prevalence rates in specific countries on this blog (see here) and mention of figures such as 0.83% [2], the global figure seems someway behind. Interestingly also, in the United States, there has been some 'discussion' about the revision of the prevalence estimates of schizophrenia there too (see here), where a quite long-standing 1.1% estimate - "1-year prevalence of schizophrenia in adults in the US" - was recently revised down to 0.3% (a figure not a million miles away from the Charlson estimate).

I guess, there's more to do when it comes to the establishing a precise prevalence of schizophrenia...

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[1] Charlson FJ. et al. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull. 2018 May 12.

[2] Chan KY. et al. Prevalence of schizophrenia in China between 1990 and 2010. Journal of Global Health. 2015;5(1):010410.

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Borna disease virus antibodies and autism: baseline data setting the scene

The findings reported by Tomoyuki Honda and colleagues [1] setting out a baseline prevalence rate of antibodies against bornavirus in children diagnosed with an autism spectrum disorder (ASD) provides the blogging fodder today. Whilst the Honda findings might not exactly sound like 'exciting science' I would perhaps beg to differ...

Although no expert on Borna disease or Borna disease virus (BDV), I am an interested amateur. Borna disease was named after the town of Borna in Germany, where a fatal neurological (encephalitic) disease affected certain livestock including sheep, cattle and horses. The causative agent was found to be BDV. As well as being characterised by a "meningoencephalomyelitis" state, the symptoms of Borna disease also stretch to certain behaviours. This includes stereotypical behaviours (animals travelling in circular movements or standing in peculiar positions and poses) as well as ataxia affecting coordination and balance. Presentation in some animals has led to the name 'Staggering disease' being used.

Although predominantly seen as a disease affecting animals and livestock, there has been a gradual shift towards the idea that Borna disease virus can also infect humans too. Quite a lot of scientific resources have, for example, concluded that BDV might show an important connection to human psychiatric diagnoses/conditions such as schizophrenia [2]. This, on the basis of serological evidence for recent or continued viral exposure. Following on from a previous case report from Honda and colleagues [3] describing antibodies against BDV in a child with autism and her mother, the authors seem to have developed an interest in all-things BDV and autism. There has also been discussion about a BDV rodent model of autism from other research groups [4] including from the now [sadly] non-functioning research tag-team that was Hornig and Lipkin [5].

On this latest research occasion, Honda et al observed a few things. First: "The prevalence of antibodies against bornavirus-specific speckles, N, and P proteins were 22%, 48%, and 33%, respectively, in the ASD children." For discussions on 'Bornavirus-specific speckles, N, and P proteins' I'll refer you to some other work including Honda on the authorship title [6] on the viral nitty-gritty details. Second: "According to our criteria, the prevalence of antibodies against bornaviruses was 7.4% in the ASD children." Bearing in mind a dearth of investigations on the estimated prevalence of Borna virus more generally, particularly in children, and the various ways and means that immunological contact with the virus can be assayed by, that percentage did seem quite high. Other work [6] for example, has talked about a figure of 2% 'exposure' rate in non-clinical populations. I suppose the 'baseline data' from Honda is trying to make in-roads into this prevalence issue.

Obviously, there's a way to go yet on this topic before any sweeping generalisations are made. The impact of viral infection/illness in relation to [some] autism has quite a long peer-reviewed research history; be that the effect of congenital cytomegalovirus (CMV) (see here) or the work looking at rubella and autism (see here) for examples. The more contemporary research base examining various encephalitis conditions also presenting as autism or autistic-like disorder(s) (see here and see here) is also important. With regards to any specific possible connection between Borna disease virus and autism, future work needs to establish lots of things (infection route, exposure characteristics, etc.). We also need to know whether behavioural symptoms/traits are actually 'caused' by such viral exposure or perhaps more generally linked to immune responses as per the whole 'immune system does more than just fight infection' bit. If a link is shown beyond reasonable doubt, there could be some real scientific advances possibilities on the back of what is already emerging [7]. But at the moment, it's still 'a big if'...

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[1] Honda T. et al. Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder. Microbiol Immunol. 2018 May 22.

[2] Azami M. et al. The association between Borna Disease Virus and schizophrenia: A systematic review and meta-analysis. Asian J Psychiatr. 2018 Apr;34:67-73.

[3] Honda T. et al. Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother. Jpn J Infect Dis. 2017;70(5):599.

[4] Pletnikov MV. et al. Developmental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism. Behav Brain Res. 1999 Apr;100(1-2):43-50.

[5] Hornig M. et al. An infection-based model of neurodevelopmental damage. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12102-7.

[6] Matsumoto Y. et al. Bornavirus Closely Associates and Segregates with Host Chromosomes to Ensure Persistent Intranuclear Infection. Cell Host & Microbe. 2012; 11: 492-503.

[7] Honda T. et al. Neuropathogenesis of persistent infection with Borna disease virus. Uirusu. 2015;65(1):145-54.

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'Artistic creativity' and risk of hospitalisation for schizophrenia, bipolar disorder and unipolar depression

"Students of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood."

So concluded the findings reported by James MacCabe and colleagues [1] who set about examining whether studying a creative subject at high school or university placed someone at an enhanced risk of later hospitalisation for a mental disorder such as schizophrenia, bipolar disorder or depression. The rationale behind the research was the 'long-standing idea' that "mental disorders are associated with enhanced creativity, intelligence or artistic talent."

To test the hypothesis, researchers employed some of those fabulous Scandinavian population registries (yet again), this time covering the population of Sweden. Based on the "unique registration number carried by all Swedish residents" they were able to look at educational records, results of intelligence tests (via testing during military service) and details of any psychiatric hospitalisations for nearly 4.5 millions people. A creative subject studied at high school or University was defined in both a broad sense - "which included a wider variety of creative or artistic subjects corresponding to ‘Art and Media’... but excluding ‘Science and History of Art, Music, Dance, Film and Theatre’" and also following a narrower definition: "comprising visual arts, music, dance, theatre and drama, film, radio and TV production, and fashion design." As I said, a fabulous population resource.

Results: about 5% of the population studied (~194,000) were deemed to have studied an artistically creative subject by the broad definition, falling to just over 1% (50,000) when the narrow criteria were followed. As per that opening sentence of this post, there did seem to be something in the idea that studying an artistically creative subject was *associated* with hospitalisation for schizophrenia, bipolar disorder and unipolar depression. Authors also noted that: "The associations remain when the analyses are restricted to sibling pairs, indicating that family-level factors alone cannot explain the association."

The possible reasons for this association are also explored by MacCabe et al. The ‘balancing selection’ hypothesis is mentioned whereby "the genetic variants conferring risk for psychosis also carry a biological advantage, such as enhanced intelligence or creativity, and this translates into reproductive advantage in the relatives of those with psychoses; thus maintaining the frequency of risk alleles in the population." Similar to the idea that the genetics of autism are probably not just 'genes for autism' (see here) so the genetics potentially linked to psychiatric disorders such as schizophrenia, probably also affect other areas of functioning (positively and negatively). Authors also entertain more 'psychological theory' (here we go) where, for example: "certain cognitive styles may be associated with artistic creativity and psychosis." Personally, I'd be more inclined to believe the first explanation over the second on the basis that 'cognitive styles' tends to make rather sweeping generalisations (see here for an example) and are rather difficult to confirm/refute from a scientific perspective.

Despite the results obtained by MacCabe, I am not totally convinced of any universally general connection between artistic creativity (or any other kind of creativity) and psychiatric disorder. I say this on the basis of other, independent findings (see here) that have not been so kind to the hypothesis. I'm also a little cautious that making such sweeping generalisations could potentially detract from the often very significant effects that such psychiatric disorders have on a person's life; many of which can lead to issues such as 'hospitalisation' (where hospital records were an important data source for the authors in this study).

Still, these are interesting results and have grabbed some media attention...

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[1] MacCabe JH. et al. Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case–control study and sib-pair analysis. British Journal of Psychiatry. 2018. April 26.

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A gluten-free diet for schizophrenia "with elevations in antigliadin antibodies (AGA IgG)"

Although published on 1st April, the study abstract published by Deanna Kelly and colleagues [1] as part of the 6th Biennial Schizophrenia International Research Society conference is no joke.

Discussing some preliminary results based on the use of a gluten-free (GF) diet with a small participant group diagnosed with schizophrenia and also registering "elevations in antigliadin antibodies (AGA IgG)", authors reported a few things potentially significant to see in terms of the impact of such dietary intervention on presented symptoms.

Such a research topic might be 'new news' to some people but not to me. I've covered the topic of schizophrenia and gluten a few times on this blog (see here and see here for examples), and how names like Curt Dohan and Kalle Reichelt (rest in peace Tiny) really were pioneers of the idea that cereal based foods *might* have quite a few effects on both body and mind. Quite a bit of this early work on gluten and schizophrenia has also 'drifted' over to other diagnostic labels too (see here) (including stretching more generally to a 'secure ward' population [2]) and continues to make some peer-reviewed science waves (see here).

On this research occasion, Kelly et al  - who are not strangers to this area of scientific research - reported initial results based on the use of a randomised, double-blind trial where 16 participants were all assigned to a gluten-free diet and either given "10 gm of gluten flour or 10 gm of rice flour daily in a protein shake" in an inpatient setting for 5 weeks. Various schedules were used to assess symptoms at baseline and again at 5 weeks. Importantly, authors noted that: "The study was not powered to find a treatment effect, but designed to examine the feasibility of conducting an inpatient gluten removal study and examine trends in treatment."

Although not necessarily looking for a treatment effect at this stage, there were some potentially important changes noted between baseline and endpoint as a function of a GF diet. So: "During the clinical trial, participants receiving the gluten free diet had an improvement in negative symptoms as compared to placebo (treatment difference) with an ES=0.53." ES stands for effect size and negative symptoms form part of the clinical profile of schizophrenia. Likewise, scores on one scale (attention) of a cognitive battery also pointed to something potentially to see as a function of dietary intervention. I'll reiterate that this was a pilot trial and the participant number was low... but these results are interesting. And, perhaps as expected, strict adoption of a GF diet affected those antigliadin antibody levels too: "The AGA IgG levels decreased by 35% in the five weeks in the gluten free diet group relative to a 17% decrease in the gluten containing group."

"The feasibility study provided data to design the now ongoing fully powered confirmatory double-blind trial in people with schizophrenia with negative symptoms using a higher gluten amount (30 grams daily) and with aims to examine associated mechanisms, with targets of inflammation, neuroimaging and gut permeability." I'll be keeping my research eyes open for the results of that one on the basis of the presented Kelly results and some other previous research gems (see here and see here)...

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[1] Kelly D. et al. Randomized double-blind feasibility study of a gluten-free diet in people with schizophrenia and elevated antigliadin antibodies (AGA IgG). Schizophrenia Bulletin. 2018; 44: S190.

[2] Vlissides DN. et al. A double-blind gluten-free/gluten-load controlled trial in a secure ward population. Br J Psychiatry. 1986 Apr;148:447-52.

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Autistic traits in adult schizophrenia

"Results of this study indicate the existence, in a sample of patients with a diagnosis of schizophrenia, of a distinct group of subjects with ASD [autism spectrum disorder] features, characterized by specific symptomatological and cognitive profile."

So said the findings reported by Stefano Barlati and colleagues [1] continuing a research theme from this group [2] looking at the potential overlap between autism spectrum disorder and schizophrenia.

Reiterating my interest in how the autism and schizophrenia spectrums can and do collide (see here) both at a condition and trait level, the Barlati findings provide some pretty in-depth analysis of what autism *might* look like in the context of schizophrenia. They report evaluation of their cohort - "Seventy-five schizophrenia patients (20 females, mean age 42 ± 12)" - with two of the gold-standard autism assessment instruments: the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) alongside other "clinical, neuropsychological, and psychosocial functioning measures."

It's important to say that, in these days of pluralisation of behavioural and/or psychiatric labels (see here and see here), quite a few participants (47/75) assessed as part of the Barlati study turned up "negative to all the autism scales administered." This tells us that it's not necessarily a straight-forward nor universal relationship when it comes to autism and schizophrenia (and vice-versa). More likely is the possibility that there either may be subgroups within the diagnosis of schizophrenia that present with significant autistic traits or possibly even that the timing or severity or grading of schizophrenia and its symptoms may predispose to autistic traits being more or less likely to be presented. That last point relies on the idea that various traits or characteristics of labels like schizophrenia and autism might not be as immutable as many people believe...

For however the participants diagnosed with schizophrenia who turned up clinically significant autistic traits in one or other or total domains/scores using the ADOS and ADI, further research is indicated. Further research on what this phenotype might look like longitudinally, how frequent it might manifest, and whether there may be unique challenges associated with it. It also might have some implications for intervention too (see here).

And yet again, such findings provide more fodder for the idea that autistic traits are not exclusively just part and parcel of a diagnosis of autism (see here), and the pressing need for formal, professional assessment when autism is suspected...

Oh, and then there's more...

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[1] Barlati S. et al. Autistic traits in a sample of adult patients with schizophrenia: prevalence and correlates. Psychol Med. 2018 Mar 20:1-9.

[2] Barlati S. et al. Autism Spectrum Disorder and Schizophrenia: Do They Overlap? International Journal of Emergency Mental Health and Human Resilience. 2016; 18: 760-763.

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Low grade inflammation in acute psychiatric inpatients

I was interested to read the findings reported by Emanuele Osimo and colleagues [1] (open-access available here) recently, and their observation that: "Evidence of low-grade inflammation was present in all major diagnostic groups, with prevalences ranging from 12 to 40% depending on the measure."

'Major diagnostic groups' included in the Osimo paper, included "acutely unwell psychiatric inpatients from all major ICD-10 diagnostic groups" covering labels such as psychotic disorder, schizophrenia, mood disorders, personality disorders and organic mental disorders.

Authors - including the notable name of Golam Khandaker who has published work previously covered on this blog (see here and see here for examples) - conducted an "anonymised search of the electronic patient records" for those hospitalised in a specialist mental health department for the treatment of a mental health / psychiatric condition between 2013 and 2016. Alongside, they had to have "a blood test result for CRP [C-reactive protein] or for WBC [total white cell count] [that] had been recorded on the electronic medical notes system within 14 days of admission" yielding almost 600 participants. In effect, a blood test pertinent to the measurement of compounds reflective of immune system processes such as inflammation.

As per the opening sentences to this post, and using CRP and/or WBC as a measure of inflammation, authors identified some quite notable prevalences of low-grade inflammation in their patient group. So: "The prevalence of inflammation in the major ICD-10 diagnostic groups of psychotic disorders (F20–29), mood disorders (F30–39), neurotic disorders (F40–48) and personality disorders (F60–69) was 32%, 21%, 22% and 42%, respectively." Various other variables also seemed to be *associated* with the presence of such inflammation too. Authors note for example that: "Patients with medical comorbidities were more likely to be inflamed" alongside various other factors also potentially exerting an effect: "older age, black ethnicity, being single, self-harm, diagnoses of schizophrenia, bipolar disorder, current treatments with antidepressants, [and] benzodiazepines" were all associated with low-grade inflammation.

Such findings add to the ever-growing amount of research that suggests a role for the immune system in relation to various psychiatric / behavioural diagnoses (see here). Further, that with a little more focus on the somatic as well as the psychiatric (see here) when it comes to such conditions, potentially relevant clues may emerge pertinent to treatment options. I might finally also draw your attention to some work previously discussed on this blog dealing with the idea that inflammation *might* have the ability to affect social cognitive processing (see here). Such a finding, focused on symptoms rather than labels, could offer a few alternative directions for intervention given the widespread nature of social cognitive issues across a wide variety of psychiatric conditions.

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[1] Osimo EF. et al. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study. Psychoneuroendocrinology. 2018 Mar 1. pii: S0306-4530(17)31581-0.

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