Monday, 16 January 2017

Autism-like traits and/or autism elevated in psychosis

"Rates of ASD [autism spectrum disorder] and ASD traits are elevated in a psychosis population."

The paper by Debbie Kincaid and colleagues [1] provides yet more [short] blogging material pertinent to the increasing interest in how psychosis may be yet another comorbidity over-represented when it comes to autism (see here) and vice-versa. I know this is another topic that has to be treated with some caution in terms of concepts like stigma but more discussions - science discussions - are needed to ensure that appropriate screening, diagnosis and also management is available to those who might need it.

A systematic review was the name of the research game for Kincaid et al as seven studies "reporting prevalence rates of Autistic-like Traits (ALTs) and ASD in populations with a diagnosis of schizophrenia or other psychotic disorder" were included. The results weren't exactly precise in terms of what was reported as anywhere between 9-61% of those diagnosed with psychosis presented with those ALTs and between 1-52% of those with psychosis were also diagnosed with an autism spectrum disorder (ASD). The authors however are correct when they point out that the "prevalence rates of ALTs and ASD in psychosis populations are much higher than in the general population." Quite a bit higher if one looks at the top end of those prevalence stats.

I'll leave it at that for now.


[1] Kincaid DL. et al. What is the prevalence of Autism Spectrum Disorder and ASD traits in psychosis? A systematic review. Psychiatry Research. 2017. Jan 6.

---------- Kincaid, D., Doris, M., Shannon, C., & Mulholland, C. (2017). What is the prevalence of Autism Spectrum Disorder and ASD traits in psychosis? A systematic review Psychiatry Research DOI: 10.1016/j.psychres.2017.01.017

Saturday, 14 January 2017

No significant difference in circulating cytokines in autism vs controls?

"As compared with 54 typically developing controls, we found no evidence of differences in the blood profile of immune mediators supportive of active systemic inflammation mechanisms in participants with autism."

That was the unexpected research bottom-line published by Carlos Pardo and colleagues [1] (open-access) examining whether various immune-related chemicals - "cytokines, chemokines, or growth factors in serum and cerebrospinal fluid" - might be linked to autism following longitudinal assessment. By longitudinal I mean that: "Up to four serum samples and up to two CSF samples were obtained from participants, at intervals ranging from 9–24 months, and stored until simultaneous laboratory analysis."

"Participants were drawn from a longitudinal study of autism" we are told, the aim of which was 'to learn more about autism and its subtypes'. Indeed, some of the research attached to this cohort has been previously discussed on this blog (see here) and for example, the suggestion that the horror that is a gluten- and/or casein-free diet used in the context of autism might not be as horrible as many people might think [2]. This time around serum samples were available for over 100 children diagnosed with autism and some 54 not-autism controls. Sixty-seven of the children with autism also provided a cerebrospinal fluid (CSF) sample taken via a lumbar puncture. The authors note: "Ethical constraints prevented lumbar punctures in the TYP [control] group" so make of that what you will.

Bearing in mind that no participants had a history of immunodeficiency or autoimmune disorder (important concepts to some autism) but that "Food, environmental, and seasonal allergies were present in a minority of participants, but were more common in AUT [participants with autism]" the results are interesting. First, when comparing results based on the analysis of CSF samples and serum samples researchers noted that there were "striking differences in the expression of selected cytokines, immune-related growth factors, and chemokines in the CSF compartment compared to the circulating bloodstream compartment." So basically what goes on in serum might not necessarily be the same as that going on in CSF in a biochemical sense.

Next and as per the title and headline of this post: "we found no evidence for major differences in the expression of circulating cytokines and chemokines between children with autism and typically developing controls." This contrasts with quite a bit of other research in the area of immune-related compounds and autism (see here for example) but one has to be a little careful with the wording here, specifically the term 'major differences'. I say that because the authors do report that EGF - epidermal growth factor - did come out as 'different' between the groups (greater in the autism group) for example. EGF has been mentioned before in the context of autism but levels of the stuff have tended to be lower in autism not higher (see here). Puzzling.

This is important work not least because of the cautions highlighted by the authors: "about the lack of relationship between central and peripheral immune markers, signaling that caution should be taken when interpreting the available studies implicating current immune dysfunction in the phenomenology of ASD [autism spectrum disorder], as few have included direct measures of CNS [central nervous system] status." Bearing in mind that there were no CFS comparison samples from controls included in this study (quite a big research flaw by all accounts) it is something else to suggest that if one really wants to see what is going on with immune function and autism, one needs to be looking to a far more invasive sample media. That some of this research group have some 'form' when it comes to the immune system potentially being linked to autism [3] and even more invasive tissue types is also worth noting as further investigations are very carefully merited...

The immune system and autism continues to intrigue.


[1] Pardo CA. et al. Serum and cerebrospinal fluid immune mediators in children with autistic disorder: a longitudinal study. Molecular Autism. 2017. 8: 1.

[2] Graf-Myles J. et al. Dietary adequacy of children with autism compared with controls and the impact of restricted diet. J Dev Behav Pediatr. 2013 Sep;34(7):449-59.

[3] Vargas DL. et al. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005 Jan;57(1):67-81.

---------- Pardo, C., Farmer, C., Thurm, A., Shebl, F., Ilieva, J., Kalra, S., & Swedo, S. (2017). Serum and cerebrospinal fluid immune mediators in children with autistic disorder: a longitudinal study Molecular Autism, 8 (1) DOI: 10.1186/s13229-016-0115-7

Friday, 13 January 2017

Exercise as an intervention for anxiety?

"Our data suggest that exercise is more effective than control at reducing anxiety symptoms."

So said the meta-analysis published by Brendan Stubbs and colleagues [1] who surveyed the peer-reviewed literature "investigating the benefits of exercise compared to usual treatment or control conditions in people with an anxiety and/or stress-related disorders." From the 6 randomised, controlled trials found "from inception until December 2015" exercise (various types of exercise regime) did seem to have something of an effect on anxiety symptoms in adults compared to control conditions.

I'm not going to labour too much on these findings because they really speak for themselves bearing in mind control conditions may not be the same as pitting exercise against something rather more proactive when it comes to tackling anxiety. Allied to the idea that exercise is basically medicine when it comes to various psychological/psychiatric labels as well as more somatic ones (see here) and is one of the more cost-effective interventions proposed (and typically side-effect free), the questions that remain are: (a) what are the mechanisms of effect? and (b) are there specific types of exercise that might be more suited to specific diagnostic labels? At least one of those questions has been touched upon in other papers [2] whereby low to moderate intensity exercise seems to be the way forward for at least some forms of anxiety. I assume that means activities such as walking, swimming and non-competitive cycling might be something to consider for example. A quick trawl of some of the other literature in this area also suggest that activities such as yoga might be useful for trait anxiety when attached to other diagnoses [3] but please, do not read this as medical or clinical advice in any intended form. Speak to your medical physician if you're unsure.

Finally, given my previous discussions on how various types of anxiety disorder seem to be over-represented among many parts of the autism spectrum (see here for example), I can't help but wonder whether the chatter about behavioural outcomes following exercise with autism in mind (see here) might also come into play here. If for example, one accepts that anxiety can not only be an utterly disabling state to exist in but might also 'interact' with more 'core' presentation of autism (see here), future studies may be minded to look at how exercise might impact on both autistic and anxiety-related traits for the benefit of the individual...

And finally, for the 'weekend [exercise] warriors' out there, some good news...


[1] Stubbs B. et al. An examination of the anxiolytic effects of exercise for people with anxiety and stress-related disorders: A meta-analysis. Psychiatry Research. 2017. Jan 6.

[2] Takács J. & Stauder A. The role of regular physical activity in the prevention and intervention of symptoms of anxiety and anxiety disorders. Psychiatr Hung. 2016;31(4):327-337.

[3] Buffart LM. et al. Physical and psychosocial benefits of yoga in cancer patients and survivors, a systematic review and meta-analysis of randomized controlled trials. BMC Cancer. 2012 Nov 27;12:559.

---------- Stubbs, B., Vancampfort, D., Rosenbaum, S., Firth, J., Cosco, T., Veronese, N., Salum, G., & Schuch, F. (2017). An examination of the anxiolytic effects of exercise for people with anxiety and stress-related disorders: A meta-analysis Psychiatry Research DOI: 10.1016/j.psychres.2016.12.020

Thursday, 12 January 2017

On autism risk and immigrant status

"Fifteen studies suggest a higher prevalence rate of ASDs [autism spectrum disorder] among children of immigrants in comparison to native children."

Those fifteen studies formed a large part of the seventeen studies included in the review by Rafal Kawa and colleagues [1] who set out to look at the collected peer-reviewed literature on the topic of the "prevalence and risk for ASD in Europe among immigrants and ethnic minorities." Carried out as part of a European Union (EU) initiative titled 'Enhancing the Scientific Study of Early Autism' the Kawa review was a sort of first step to looking at whether the racial/ethnic disparities noted in autism rates in the United States for example, might also hold true for Europe. Evidently they did.

This is a topic covered before on this blog (see here for example) and so the results come as little surprise. One does have to be slightly cautious about how such data is interpreted, particularly in light of recent European history but outside of any politics there are some intriguing scientific questions posed by such data and some potentially important 'connections' with other independent datasets that could benefit autism research more generally (see here and see here). Given also some emerging research suggesting that autism may not be the only diagnostic label where risk is heightened according to immigrant status (see here), there are some further studies to be undertaken on this topic, in these days of overlapping labels (see here).


[1] Kawa R. et al. European studies on prevalence and risk of autism spectrum disorders according to immigrant status-a review. Eur J Public Health. 2016 Dec 24. pii: ckw206.

---------- Kawa R, Saemundsen E, Lóa Jónsdóttir S, Hellendoorn A, Lemcke S, Canal-Bedia R, García-Primo P, & Moilanen I (2016). European studies on prevalence and risk of autism spectrum disorders according to immigrant status-a review. European journal of public health PMID: 28013245

Wednesday, 11 January 2017

"the patient improved significantly when a gluten-free diet was started"

The quote making up the title of this post comes from the case report described by Albino J Oliveira-Maia and colleagues [1] talking yet again about how coeliac disease - the archetypal autoimmune condition where dietary gluten is the baddie - may have effects well beyond just the physical.

Describing the experiences of a woman who was admitted to a psychiatry inpatient unit on the basis of "suicidal behaviours" who also "developed an agitated catatonic state", a mix of "antidepressants, anxiolytics, antipsychotics and electroconvulsive therapy" seemingly did very little to her state at/during admission we are told. Further, some diagnostic work-up beyond just her psychiatric features "allowed for the diagnosis of coeliac disease" and instigation of a gluten-free diet - the primary management option for coeliac disease - seemed to have something of a 'significant' effect on her psychiatric well-being as per that opening quote.

Am I particularly surprised by all of this? No. Regular readers will know that I've previously talked about gluten and psychiatry quite a few times on this blog (see here and see here for example) and there is other research out there in the peer-reviewed domain pertinent to discussions [2]. Without trying to over-generalise a case report to anything further, there are a number of notable peer-reviewed papers that have suggested that diet can affect psychiatry and this addition merely adds to the haul.

If I did perhaps have to go into further detail on how something like suicidal behaviours might link into gluten and coeliac disease (CD) I would perhaps draw your attention to how gluten does seem to be a 'mood affector' when it comes to at least some cases of CD (see here) and the link between something like depression and suicidality. I'm sure however that this is not the final word on any such link and please, don't generalise with any sweeping suggestions about how all depression is somehow caused solely by gluten. Depression is a very complicated entity.

More research is of course indicated but I do wonder how many more case reports on previously unidentified coeliac disease (or non-coeliac gluten sensitivity even?) and similar psychiatric symptoms there may be out there? Time for more screening of vulnerable populations perhaps...


[1] Oliveira-Maia AJ. et al. Case of coeliac disease presenting in the psychiatry ward. BMJ Case Rep. 2016 Dec 21;2016. pii: bcr2016216825.

[2] Ludvigsson JF. et al. Increased suicide risk in coeliac disease--a Swedish nationwide cohort study. Dig Liver Dis. 2011 Aug;43(8):616-22.

---------- Oliveira-Maia AJ, Andrade I, & Barahona-Corrêa JB (2016). Case of coeliac disease presenting in the psychiatry ward. BMJ case reports, 2016 PMID: 28003229

Tuesday, 10 January 2017

PACE trial recovery data and chronic fatigue syndrome

PACE mentioned in the title of this post refers to the PACE trial [1] which concluded that: "CBT [cognitive behaviour therapy] and GET [graded exercise therapy] can safely be added to SMC [specialist medical care] to moderately improve outcomes for chronic fatigue syndrome, but APT [adaptive pacing therapy] is not an effective addition."

The recent paper by Carolyn Wilshire and colleagues [2] who drew on "relevant normative data and other research" continues a peer-reviewed research theme focused on some of the details included in the original and subsequent PACE trial publications specifically that discussing the topic of recovery [3]. To quote from that 2013 paper [3] on the topic of the PACE trial: "The percentages (number/total) meeting trial criteria for recovery were 22% (32/143) after CBT, 22% (32/143) after GET, 8% (12/149) after APT and 7% (11/150) after SMC."

OK, anyone that knows anything about chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) will probably have seen or heard about the debates around the PACE trial; the trial now having it's own -gate suffix (see here). The ups-and-downs, twists-and-turns, surrounding this trial have rumbled on for years now; merging with more general criticism of the biopsychosocial (BPS) model (see here), moving into debates about data-sharing, including Information Commissioner legal stuff and allowing the word 'vexatious' to be banded around quite a few times. The term 'bad science' has also been used on occasion (see here) albeit not necessarily in the peer-reviewed domain context...

Quite a few of the authors on the Wilshire paper have been central to many of the discussions around the PACE trial, also including the respondent who is credited with getting the raw trial data released alongside the UK Information Commissioner. They set out to examine the recovery definition used in that 2013 PACE trial add-on paper and "whether these recovery claims are justified by the evidence". Their answer: "None of the changes made to PACE recovery criteria were adequately justified. Further, the final definition was so lax that on some criteria, it was possible to score below the level required for trial entry, yet still be counted as ‘recovered’." The sorts of recovery figures they arrived at were "only single-digit rates of “recovery” for all four groups in the study" according to another write-up of the study in comparisons to the 22% offered in the 2013 paper. Whilst this is important research, this is not the first time that the recovery criteria included in the PACE trial has been discussed. Indeed, this latest publication really just gets the whole thing into the peer-reviewed domain.

"The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments." Strong words indeed from the authors and I expect there will eventually be a reply from the original PACE authors on this matter too. PACE-gate is set to rumble on into 2017...


[1] White PD. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36.

[2] Wilshire C. et al. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior. 2016. Dec 14.

[3] White PD. et al. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med. 2013 Oct;43(10):2227-35.

---------- Wilshire, C., Kindlon, T., Matthees, A., & McGrath, S. (2016). Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial Fatigue: Biomedicine, Health & Behavior, 1-14 DOI: 10.1080/21641846.2017.1259724

Monday, 9 January 2017

T. gondii and OCD?

It's been a while since I've talked about Toxoplasma gondii on this blog; the parasite that more than most, has been linked with all-manner of different psychiatric labels (see here for example). Although still the topic of some discussion, I'm swayed towards the possibility that there may be some important *associations* to be seen when it comes to this survivor and human behaviour(s) outside of just making rats attracted to cat urine (see here) to improve reproduction chances.

Indeed, in that context I offer up the findings reported by Flegr & Horáček [1] who presented results pertinent to "earlier reports of the association between toxoplasmosis and OCD [obsessive compulsive disorder]." OK, the first thing to note about this study is that: "Examined subjects provided the information about their toxoplasmosis and OCD statuses themselves, which could result in underrating the strength of observed associations." Most people probably wouldn't falsely admit to being toxoplasmosis positive but I can imagine that a few people might not want to share such sensitive information for various reasons.

Researchers examined data from over 7400 volunteers (participants), asking about their toxoplasmosis status and also whether they had been diagnosed with OCD, a condition characterised by obsessive thoughts and compulsive behaviours, or one or more of a variety of other neuropsychiatric labels. The symptoms of OCD were also characterised on the basis of the use of the Obsessive-Compulsive Inventory-Revised (OCI-R) (self-completed).

They observed the incidence of OCD to be present in approximately 2% of their cohort. They also observed that where toxoplasmosis was reported, these participants were quite a bit more likely to also report being diagnosed with OCD. A similar relationship also held when it came to the presence of a learning (intellectual) disability too. When researchers also took into account those self-report scores on the OCI-R, they noted that in those with toxoplasmosis "even the OCD-free subjects, scored higher on the OCI-R." Ergo, something of a relationship between T. gondii and OCD (diagnosed or symptoms) may exist.

Accepting the methodological failings of the Flegr / Horáček study, their data do indeed seem to tally with other independent study [2] in this area, albeit still quite limited in quality and amount. Such research also potentially ties into other investigations on other behavioural/psychiatric labels where the gondii has been implicated (see here for example) that might overlap with cases of OCD. There are however still questions to answer, not least which came first, psychiatric presentation or infection with the gondii? Could a behavioural or psychiatric diagnosis increase the risk that someone is more likely to become infected by the gondii? I suppose given what OCD encompasses - "fear of contamination by disease, infection or an unpleasant substance" - one could argue that OCD is not exactly a great template for coming into contact with T. gondii and becoming infected. But before I, or anyone else, jumps to conclusions, more investigation(s) are implied on the nature of the relationship and onward any pertinent biological mechanisms...


[1] Flegr J. & Horáček J. Toxoplasma-infected subjects report an Obsessive-Compulsive Disorder diagnosis more often and score higher in Obsessive-Compulsive Inventory. Eur Psychiatry. 2016 Dec 16;40:82-87.

[2] Miman O. et al. Is there any role of Toxoplasma gondii in the etiology of obsessive-compulsive disorder? Psychiatry Res. 2010 May 15;177(1-2):263-5

---------- Flegr J, & Horáček J (2016). Toxoplasma-infected subjects report an Obsessive-Compulsive Disorder diagnosis more often and score higher in Obsessive-Compulsive Inventory. European psychiatry : the journal of the Association of European Psychiatrists, 40, 82-87 PMID: 27992837