Monday, 20 February 2017

Catatonic symptoms and autism

"Catatonic symptoms are more prevalent in young people with autism than previously thought" said the article recently published by Breen and Hare [1]. Continuing a research theme of at least one of the authors [2], the idea that catatonic symptoms - primarily manifesting as stupor, unresponsiveness to light, noise or touch, mutism, etc - might be over-represented when it comes to autism is not a new one by any means.

Breen & Hare set about looking for "the presence and nature of such attenuated behaviours in children and adolescents with autism" based on something called the Attenuated Behaviour Questionnaire. This was delivered to parents/caregivers online alongside looking at information from other measures based on the presence of repetitive behaviour and depression.

"Attenuated behaviour indicative of catatonia was relatively common in young people with autism with up to 20.2% having an existing diagnosis of catatonia and evidence of a relationship between attenuated behaviours and measures of depression and repetitive and restricted behaviours." Such findings as I said, are by no means novel but once again highlight how a diagnosis of autism or autism spectrum disorder (ASD) is seemingly protective of nothing when it comes to comorbidity. To quote another author on this topic: "an unabashed drumroll for increased recognition and treatment of catatonia in autism spectrum disorders (ASD)" [3] is needed.

Catatonia appearing alongside [some] autism leads into a number of areas in relation to the 'closeness' of any relationship (some people have talked about 'autistic catatonia') and the management strategies that may be subsequently indicated. On the issue of management, guidance is available [4] albeit including a strategy - electroconvulsive therapy (ECT) - that is probably not going to win any awards in terms of popularity given its historical basis. Accepting that still today ECT as an 'intervention' option when it comes to autism still courts heated discussion (see here), there is the requirement for much greater study of catatonic symptoms in relation to autism and whether there may be several presentations ripe for more novel intervention [5] (in light of a growing area of research interest). Said intervention might also take into account the plurality of autism too (see here)...

To close, yet another song for my brood and a very proud father who saw some real talent in the karate competition yesterday (those first place trophies are proof that team kata and team kumite are definitely the way forward)...

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[1] Breen J. & Hare DJ. The nature and prevalence of catatonic symptoms in young people with autism. J Intellect Disabil Res. 2017 Feb 1.

[2] Hare DJ. & Malone C. Catatonia and Autistic Spectrum Disorders. Autism. 2004; 8: 183-195.

[3] Dhossche DM. Decalogue of Catatonia in Autism Spectrum Disorders. Frontiers in Psychiatry. 2014;5:157.

[4] Mazzone L. et al. Catatonia in patients with autism: prevalence and management. CNS Drugs. 2014 Mar;28(3):205-15.

[5] Kiani R. et al. Anti-NMDA-receptor encephalitis presenting with catatonia and neuroleptic malignant syndrome in patients with intellectual disability and autism. BJPsych Bull. 2015 Feb;39(1):32-5.

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ResearchBlogging.org Breen J, & Hare DJ (2017). The nature and prevalence of catatonic symptoms in young people with autism. Journal of intellectual disability research : JIDR PMID: 28150394

Saturday, 18 February 2017

Social interaction and autism: it takes two to tango

Psychology experiments are not generally fodder for this blog when it comes to autism. The main reason being that quite a few appearing in the peer-reviewed literature tend to look at quite abstract features perhaps somewhat removed from the daily lives of autistic people and their significant others. A few also seem to struggle with the idea that grand over-arching psychological theories (that seem to inevitably follow psychological findings in particular) are not required when it comes to autism in these days of heterogeneity and plurality.

I am making an exception today however with the paper by Noah Sasson and colleagues [1] (open-access) and their findings suggesting advocating "for a broader perspective of social difficulties in ASD [autism spectrum disorder] that considers both the individual’s impairments and the biases of potential social partners." In other words, it takes two to [socially, interactively] tango. I might add that a doctoral thesis by one of the co-authors on the Sasson paper (Daniel Faso) is also available for further inspection too (see here).

Based on the idea that issues with social interaction "quantity and quality" might not be something exclusively under the control of those diagnosed with autism, Sasson et al devised a series of experiments to test their hypothesis: "three studies conceived and conducted independently by three research groups assessing observers’ first impressions of—and intentions to socially engage with— children and adults with ASD based upon “thin slices” of their real-world social behavior." I'm not going to go into too much detail about the experiments because the paper is open-access and you can read about them for yourselves. 'Thin slices' in the context of the experiments carried out referred to media that were rated pertinent to "observers’ first impressions of individuals with ASD engaging in real-world social behavior."

The results make for some important reading as across the different experiments undertaken the key messages were that: "first impressions of individuals with ASD are significantly less favorable than those of matched TD [typically developing] controls, and are associated with greater reluctance on the part of observers to pursue social engagement." Further: "social interaction difficulties in ASD are not solely an individual impairment but also a relational one, and consideration of both of these factors is necessary for a full understanding of social impairment in ASD." I relay all of that bearing in mind that these were experiments carried out under controlled conditions (I don't know about you, but I don't generally rate people at first contact using a "0-3Likert scale or a "non-graduated slider" on 'how approachable' they were or the likelihood of a friendship developing).

Although important, I don't think anyone should be too surprised by the results reported in the context of how first impressions count and how people are generally quick to judge from "personality and character traits" whether social engagement with a person or group of people is going to be a short or longer-term thing. I say this also bearing in mind that minus any psychobabble, people generally take into account things like context, familiarity and similarity when it comes to their social interaction decisions too [if for example, you happen to be a fan of Star Wars or a Shotokan karateka, I might be more inclined to chat with you than say if you talked about the goings-on on various reality TV shows]. Indeed, the authors note: "these studies present only group-wise comparisons and do not address individual differences among those with ASD, nor whether individual characteristics of the raters (e.g., gender, personality, etc.) affect the results reported here." I'd also forward the idea that they might also include important concepts such as self-monitoring for example when it comes to future studies in this area. Similarly, it would also be handy to see if 'comorbidity counts' when it comes to further investigations on this topic in light of expanding links between different labels and traits (see here).

The question of what to do about the Sasson findings similarly provide some food for thought. The authors suggest that: "intervention and education approaches that target both those with ASD as well as their TD [typically developing] peers may offer a more comprehensive approach for improving social and functional outcomes in autism." In the context of other studies looking at social interaction and autism particularly in the school setting (see here) I can see how this might work in terms of raising awareness of how people are not always the same when it comes to the presentation of their social persona. Intervening with a wider group (i.e. peers) and taking the onus off 'just the person with autism' is a win-win situation and will no doubt have other positive knock-on effects in terms of self-esteem and helping to remove barriers around the 'disability' framing of autism. I might add that in these days of the potential virality of personality traits, it makes sense to include everyone.

In a wider context - outside of school - and in the big, wide [adult] world however, I'm slightly less sure of how such intervention is going to be achieved. Yes, we would all love people to be more understanding and less 'judgemental' in their first (and subsequent) impressions, but when it comes to influencing aspects such as views on "awkwardness, attractiveness, [and] likability" I'm not so sure that this can be universally achieved. Indeed, facets such as attractiveness and likability are probably going to be influenced by lots of variables outside of those just linked to an autism diagnosis and its presentation (frank or not). By saying all that, I'm not suggesting that we shouldn't try to educate and perhaps even move people away from the whole 'first impressions last' [2] thing, but rather am looking at the realistic prospect of achieving such a societal goal, mindful that it takes two to tango...

And on the topic of first impressions, at least get the handshake right (i.e. let go)...

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[1] Sasson NJ. et al. Neurotypical Peers are Less Willing to Interact with Those with Autism based on Thin Slice Judgments. Sci Rep. 2017 Feb 1;7:40700.

[2] Gunaydin G. et al. Impressions Based on a Portrait Predict, 1-Month Later, Impressions Following a Live Interaction. Social Psychological and Personality Science. 2017. 8: 36-44.

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ResearchBlogging.org Sasson NJ, Faso DJ, Nugent J, Lovell S, Kennedy DP, & Grossman RB (2017). Neurotypical Peers are Less Willing to Interact with Those with Autism based on Thin Slice Judgments. Scientific reports, 7 PMID: 28145411

Friday, 17 February 2017

Vitamin D halting colds and flu?

"Overall, the study said one person would be spared infection for every 33 taking vitamin D supplements. That is more effective than flu vaccination, which needs to treat 40 to prevent one case, although flu is far more serious than the common cold."

That was some of the media interpretation of the paper - "systematic review and meta-analysis of individual participant data" - published by Adrian Martineau and colleagues [1] looking at the collected data on vitamin D supplementation "on risk of acute respiratory tract infection." Including data on approximately 11,000 'randomised' participants reported in 25 studies, authors assessed whether the quite messy data on vitamin d supplementation potentially decreasing the risk of acute respiratory tract infection showed any semi-definitive trends.

Results: "Vitamin D supplementation resulted in a statistically significant reduction in the proportion of participants experiencing at least one acute respiratory tract infection." Further: "Use of vitamin D did not influence risk of serious adverse events of any cause... or death due to any cause. Instances of potential adverse reactions to vitamin D were rare." And finally: "Subgroup analysis revealed that daily or weekly vitamin D supplementation without additional bolus doses protected against acute respiratory tract infection, whereas regimens containing large bolus doses did not."

I note that in the BBC news report on the Martineau paper we are told: "Public Health England (PHE) says the infections data is not conclusive, although it does recommend supplements." This slightly counter-intuitive position follows more general advice from the powers-that-be that perhaps we should all be taking a little more vitamin D (see here) given what is emerging when it comes to the varied functions of the sunshine vitamin/hormone. But bear in mind that supplementation comes with potential risks too (see here) particularly when people forget to treat their vitamins and minerals as what they are: biologically active pharmaceutics. Neither is everyone completely sold on the idea that vitamin D 'could stop colds or flu' as an accompanying editorial to the Martineau paper makes clear [2]: "The results are heterogeneous and not sufficiently applicable to the general population."

What such research does advance however, is that vitamin D is a potentially important nutrient (more so for some groups) and one that we should be [cautiously] dedicating a lot more investigation to for all-manner of possible reasons (see here and see here) outside of just bone health and the English disease. And within that scheme of research, don't forget a few things: (a) there's more to vitamin D metabolism than just 'getting enough' and (b) even today, science is still finding out new things about the chemistry of vitamin D [3]. In short, the scheme of science around vitamin D needs to be broad...

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[1] Martineau AR. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583.

[2] Bolland MJ. & Avenell A. Do vitamin D supplements help prevent respiratory tract infections? BMJ 2017; 356: j456.

[3] Pauwels S. et al. 1β,25-Dihydroxyvitamin D3: A new vitamin D metabolite in human serum. J Steroid Biochem Mol Biol. 2017 Feb 10. pii: S0960-0760(17)30040-7.

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ResearchBlogging.org Adrian R Martineau, David A Jolliffe, Richard L Hooper, Lauren Greenberg, John F Aloia, Peter Bergman, Gal Dubnov-Raz, Susanna Esposito, & et al (2017). Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ : 10.1136/bmj.i6583

Thursday, 16 February 2017

"early medical events are associated with clinical ASD phenotypes"

The paper by Charlotte Willfors and colleagues [1] (open-access) provides some food for thought today and the observation that various individual and cumulative medical events - "early medical events likely to be caused by environmental factors" - may be important to at least some autism.

Researchers "scrutinized the early medical histories of a rare and informative sample of 13 MZ [monozygotic] twin pairs discordant for clinical ASD [autism spectrum disorder]" also including "13 MZ typically developing (TD) control pairs (n=52) matched for sex" as an 'exploratory step. Discordant for autism means that one twin had autism and the other did not.

This research first step looked at medical events (likely to be caused by environmental factors!) included things like delivery and neonatal variables (e.g. foetal distress, hypoxia), minor and frequent infections (e.g. ear infections), allergy and epilepsy to name a few. Data was acquired from a few sources including medical records and medical history "assessed from a parent reported questionnaire." They examined exposure to the medical events "in relation to either quantitative or qualitative discordance for ASD." Qualitative discordance referred to when "only one twin within a pair meeting the diagnostic criteria of ASD." A 'confirmatory' study was also carried out whereby a larger, independent cohort of 100 twin pairs "quantitatively discordant for autistic traits" were also quizzed and findings cross-validated.

Results: a few non-shared environmental (NSE) events seemed to be important based on their analysis. So: "Single early medical factors, likely to be caused by NSE, that discriminated between twins in qualitative ASD discordant pairs were dysregulation during the first year of life (comprising feeding and sleeping problems, excessive crying and worrying) and birth weight." Authors also reported that cumulatively, the appearance of early medical events were significantly different in MZ twins with autism compared with their non-ASD co-twin. It's worth mentioning that some of those 'dysregulation' events have been talked about in the earliest descriptions of autism (see here). Birth weight too has something of a long-standing connection to [some] autism (see here). When it came to analysis based on autistic traits (the confirmatory study) it seemed that "early dysregulation and the cumulative load of a variety of early adverse medical events" continued to be important variables (although birth weight linked to ASD traits lost its significance).

These are important findings. The focus on MZ twins (who share a common structural genetic blueprint) means that the genetics side of things is to a large extent 'controlled for' and the results are more likely to reflect some environmental or, more accurately, non-genetic influence. There is a caveat to this though, as per the authors recognition: "with the exception of putative post-twinning de novo mutations." I might also add that MZ twins are also not necessarily epigenetically the same too so gene expression can (and does) differ. What causes these epigenetic differences is still the source of some debate but I might chime in with one idea (see here) out of many possibilities.

"Our data indicate that taking into account the cumulative load of early medical factors might strengthen or discourage a suspicion of ASD, at least in a minority of cases." This is an interesting thought provided by the authors based on their findings. It ties in well with the idea that although behavioural presentation is core to autism presentation and diagnosis, behaviour might not be the only important feature present in relation to autism. I do have to express a degree of caution however with such an approach based on the idea that various types of regression have been noted in the peer-reviewed literature to accompany some autism (see here) and with it, the concept of 'acquired autism' should really be properly recognised (see here for example) in these days of the plural 'autisms'. Indeed, there's a research study idea for anyone out there: looking at MZ twins discordant for autism with onset of said autism tied into a regression of skills?

Scientific replication is the name of the [future] game in this area of study, drawing on larger cohorts and perhaps based in other geographical areas outside of Sweden. We also need to find out what mechanisms might be potentially associating something like 'early dysregulation' with the onset of autism, taking into account how factors such as early feeding practices/issues for example, might provide at least one avenue for future study (see here).

To close, in light of some recent media headlines about the 'myth' that autism rates are on the up (and quite significantly so over past two decades), I offer some past posts suggesting that the word 'myth' should be reserved for other [non-peer-reviewed] matters (see here and see here and see here) and not this particular branch of epidemiological science. As to what may be 'causing' the upswing in numbers of diagnosed cases, well, it's likely to be very, very, very complicated (and without any need for sweeping generalisations please)...

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[1] Willfors C. et al. Medical history of discordant twins and environmental etiologies of autism. Transl Psychiatry. 2017 Jan 31;7(1):e1014.

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ResearchBlogging.org Willfors C, Carlsson T, Anderlid BM, Nordgren A, Kostrzewa E, Berggren S, Ronald A, Kuja-Halkola R, Tammimies K, & Bölte S (2017). Medical history of discordant twins and environmental etiologies of autism. Translational psychiatry, 7 (1) PMID: 28140403

Wednesday, 15 February 2017

"Androgens were not associated with autistic traits at 12 months of age"

EARLI - the Early Autism Risk Longitudinal Investigation study - has been mentioned on this blog before (see here) with the aim of the initiative to "examine possible environmental risk factors for autism and study whether there is any interplay between environmental factors and genetic susceptibility."

In this post I'm bringing the paper by Bo Park and colleagues [1] (open-access) to your attention and the observation(s) that umbilical cord blood levels of testosterone and other related androgens were seemingly not associated with autistic traits at 12 and 36 months of age in their cohort. Such findings represent yet another biological research blow (see here) to facets of the Extreme Male Brain (EMB) theory of autism and the suggestion that "ASD [autism spectrum disorder] is an extreme presentation of a typical male cognitive profile where the drive to “systemize” is stronger than the drive to empathize."

So, looking at cord blood samples from 137 children recruited on to EARLI - "a high autism-risk cohort following pregnant mothers with an older child diagnosed with an ASD (autistic disorder, Asperger syndrome, or pervasive developmental disorder not otherwise specified)" - researchers looked at whether measures of various androgens might correlate with scores on the Autism Observation Scales for Infants (AOSI) and Social Responsiveness Scale (SRS). Said schedules were administered at 12 months and 36 months respectively and various potentially confounding variables were taken into account when it came to looking at any associations. It's also worth pointing out that the technology of choice when it came to those measures of cord blood levels of androgens was an old favourite of this blog: liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: well as per the title of this post, and after adjustment for potentially confounding variables - "maternal age, gestational age, and cesarean delivery" - there wasn't a great deal to see in terms of levels of androgens and the presence of autistic traits. Indeed, the title of this post only tells half the story as testosterone was also found not to be associated with the SRS scores at 36 months too. The authors do note that: "Male infants (n=75) showed significantly higher umbilical cord testosterone levels and greater social deficits at 36 months of age" than females, but after adjustment for confounders this observation was left wanting. They also talk about some interesting observations about when a child had an older female sibling diagnosed with autism - "androgen levels and autistic traits may depend on sex of the older affected sibling" - but I'm not so sure about the strength of such findings and whether other mechanisms might also be at work. I might reiterate that autistic traits were the name of the research game in this study not a diagnosis of autism.

As mentioned, the Park findings represent another setback for the generalisability of the role of androgens (prenatal and beyond) in relation to autism and/or autistic traits. I guess that in these days of the plural 'autisms' (see here) it's perhaps not entirely unexpected that grand theories of autism seem doomed to fail when put up to scientific scrutiny. Indeed someone recently has talked about this [2]. I still however remain interested in the discussions around the EMB theory of autism, and although this and other research has not been entirely kind to the hypothesis, it is still perhaps deserving of further study in order to see who it may be most relevant to in these days of plural autisms and subgroupings...

To close, isn't this why Twitter was invented?

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[1] Park BY. et al. Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study. Molecular Autism. 2017; 8: 3.

[2] Müller R-A. & Amaral DG. Editorial: Time to give up on Autism Spectrum Disorder? Autism Res. 2017. Jan 27.

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ResearchBlogging.org Park, B., Lee, B., Burstyn, I., Tabb, L., Keelan, J., Whitehouse, A., Croen, L., Fallin, M., Hertz-Picciotto, I., Montgomery, O., & Newschaffer, C. (2017). Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Molecular Autism, 8 (1) DOI: 10.1186/s13229-017-0118-z

Tuesday, 14 February 2017

Relative age and ADHD medication

"Youngest children in class 'more likely to be given ADHD drugs'" went the NHS Choices headline that led me to the short report produced by Martin Whitely and colleagues [1] (open-access).

ADHD - attention-deficit hyperactivity disorder - is something of interest to this blog; not least the idea that relative age (age relative to peers in the same school year group) might be an important variable when it comes to at least some diagnoses of the condition (see here).

The Whitely paper draws on data from a research favourite place - Western Australia (WA) - and focused on "the proportions of WA children born in the early and late months of a recommended school-year intake who received at least one Pharmaceutical Benefits Scheme [PBS] prescription for an ADHD medication in 2013."

The results: from a starting population of some 300,000 children, about 6,000 of them (~2%) were in receipt of a state-recognised prescription of an ADHD medication. The article does not actually mention which ADHD medication was given but methylphenidate (a.k.a Ritalin) is listed in the PBS directory and is the typically indicated medication used for ADHD (see here). Boys, we are told, were more likely to be prescribed ADHD medication than girls (2.9% vs. 0.8% respectively).

Then to the headline: when splitting the children into two age groups - 6-10 year olds and 11-15 year olds - researchers noted that those born in June (the last birth month influencing year of school intake) were more likely to be prescribed ADHD medication than those born in July. This trend was noted in both age groups. The conclusion being that the youngest children in a year group at school were more likely to be in receipt of prescribed medication for ADHD compared to older children in the year group.

Alongside the caveats linked to the Whitely report made by NHS Choices, there is a need for further investigation in this area and in particular, whether the results generalise to places outside of just WA. I've already linked to my previous discussion about relative age and ADHD diagnosis/medication (see here again) and from comparisons with the Taiwanese data [2] on this topic, including the fact that Taiwan have a different cut-off month for school entry (August 31). On that basis, yes the trend appears to generalise across geographies...

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[1] Whitely M. et al. Influence of birth month on the probability of Western Australian children being treated for ADHD. MJA. 2017; 206: Feb 6.

[2] Chen MH. et al. Influence of Relative Age on Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder in Taiwanese Children. J Pediatr. 2016 May;172:162-167.e1.

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ResearchBlogging.org Martin Whitely, Leanne Lester, John Phillimore, & Suzanne Robinson (2017). Influence of birth month on the probability of Western Australian children being treated for ADHD The Medical Journal of Australia

Monday, 13 February 2017

Depression, SMILES and Modified Mediterranean diet (advice)

SMILES in the title of this post refers to the SMILES trial - Supporting the Modification of lifestyle In Lowered Emotional States - and results recently published by Felice Jacka and colleagues [1] (open-access) pertinent to the idea that "dietary improvement" might be something to consider when a diagnosis of major depressive episode (MDE) is received.

Having previously published their study protocol [2], researchers set about looking at whether under "single blind, randomised controlled" conditions, the application of advice pertinent to a diet - the 'ModiMedDiet' - focused on increasing diet quality along Mediterranean diet lines, might be useful for those diagnosed with MDE. The results (which had already been revealed before peer-reviewed publication) said 'yes', such an intervention might be something to consider based on scoring of the Montgomery–Åsberg Depression Rating Scale (MADRS) after 3 months of "individual nutritional consulting sessions delivered by a clinical dietician."

Looking at two groups, those randomly allocated to dietary advice/intervention (n=31 completing) and those allocated to a control condition (social support) (n=25 completing), researchers noted improvements in the MADRS scores more frequently in the diet intervention group. To quote: "At 12 weeks, 32.3% (n = 10) of the dietary support group and 8.0% (n = 2) of the social support control group achieved remission criteria of a score less than 10 on the MADRS." Similar differences were also noted on other study schedules: the Hospital Anxiety and Depression Scale (HADS)-depression subscale.

Caveats? Well as a seasoned veteran of research looking at how dietary intervention for labels generally thought to be outside of the somatic domain can go, I can testify to the limitations attached to this kind of work associated with a lack of double-blindedness and issues associated with dietary compliance. This was also a study providing dietary support and so was not necessarily making study controlled meals for each participant over the course of the study (lessons from other recent research show that advice and prompts can only go so far in dietary studies). The authors also note that they "recruited participants on the basis of existing ‘poor’ quality diet" and how "this may limit the generalisability of our findings to the wider population of individuals with depression." An important point indeed.

But this study represents important work and provides yet more evidence that 'nutritional medicine' should perhaps be part of mainstream psychiatry (see here). You can um-and-ah about whether 'food is medicine' and all that jazz (have you never heard of pharmacognosy?) but I'm firmly with the idea that what we eat might, on occasion and for some people, have some pretty profound implications for things other than our physical health and that includes depression (included in several forms)...

To close, a note to any would-be ageing karateka, middle-aged hips tend to take a little more time to get used to perfecting yoko geri kekomi (pass the ibuprofen please). But practice does (eventually) make perfect...

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[1] Jacka F. et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Medicine. 2017; 15: 23.

[2] O'Neil A. et al. A randomised, controlled trial of a dietary intervention for adults with major depression (the “SMILES” trial): study protocol. BMC Psychiatry. 2013; 13: 114.

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ResearchBlogging.org Jacka, F., O’Neil, A., Opie, R., Itsiopoulos, C., Cotton, S., Mohebbi, M., Castle, D., Dash, S., Mihalopoulos, C., Chatterton, M., Brazionis, L., Dean, O., Hodge, A., & Berk, M. (2017). A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial) BMC Medicine, 15 (1) DOI: 10.1186/s12916-017-0791-y

Saturday, 11 February 2017

Pregnancy exposure to SSRIs and offspring autism risk: debate continues

"It remains unclear whether the association between first trimester SSRI [selective serotonin reuptake inhibitorexposure and child autism that was present in the case-control studies even after adjustment for MMI [maternal mental illness] is a true association or a product of residual confounding."

So said the results of the systematic review and meta-analysis undertaken by Hilary Brown and colleagues [1] looking at a potentially important association between pregnancy use of a class of medicines typically used as antidepressants (albeit with some caveats [2]) and risk of offspring autism. This topic has previously received some airtime on this blog (see here and see here) and specifically, how maternal mental health - as per the question 'why were mothers taking SSRIs during pregancy?' - might be a rather large confounding variable affecting any possible correlation.

Unfortunately even with the Brown paper, the debates will continue as to whether the SSRI-offspring autism correlation is a 'true' correlation or not. Based on the results of 6 studies - "4 case-control studies and 2 cohort studies" - where MMI was adjusted for/restricted to, authors reported some interesting trends. So in their meta-analysis of the data where results from case-control studies were adjusted for a potential impact from MMI, researchers observed that "first trimester exposure remained statistically significant." In "MMI-restricted analyses" covering the same study type, the collected studies did not show any connection between pregnancy SSRI use and offspring autism during either the first trimester or 'any time during pregnancy'. Similar results were found in the cohort studies included in the Brown paper (although both first trimester and 'any point during pregnancy' SSRI use both showed significant correlations to offspring autism in adjusted studies). I might also add that the Brown meta-analysis on this topic is not the only recent addition to the peer-reviewed literature [3]; indeed, there are several [4] others.

"Future studies require robust measurement of MMI prior to and during pregnancy" said Brown et al. I would agree with this sentiment added to the caveat that we may never truly know whether there is a definitive connection between pregnancy SSRI use and offspring autism risk on the basis of observational studies alone. Yes, I know it is unethical to withhold treatment such as SSRIs when clinically indicated even during pregnancy and so investigations utilising this kind of 'interventionist' study design are not likely to be undertaken anytime soon. But it does strike me that we could do quite a bit more modelling any potential effects (or not) in animal studies for example, as per some investigations with fish a while back (see here) as a start.

And finally, although it is not my place to give clinical or medical advice on this blog, I should point out that much like investigations on another medicine prescribed during pregnancy potentially linked to offspring outcomes (see here), SSRIs are not generally given willy-nilly to pregnant women; there are very valid reasons for managing mum's psychiatric health particularly during pregnancy. If anyone is in doubt, please consult your doctor (and not just Dr Google).

To close, before 'fake news' there was The Day Today (and they did it oh so well)...

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[1] Brown HK. et al. The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. J Clin Psychiatry. 2017 Jan;78(1):e48-e58.

[2] Jakobsen JC. et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017; 17: 58.

[3] Kaplan YC. et al. Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. Reprod Toxicol. 2016 Dec;66:31-43.

[4] Kobayashi T. et al. Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reprod Toxicol. 2016 Oct;65:170-178.

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ResearchBlogging.org Brown HK, Hussain-Shamsy N, Lunsky Y, Dennis CE, & Vigod SN (2017). The Association Between Antenatal Exposure to Selective Serotonin Reuptake Inhibitors and Autism: A Systematic Review and Meta-Analysis. The Journal of clinical psychiatry, 78 (1) PMID: 28129495

Friday, 10 February 2017

A few-foods diet for ADHD: a systematic review of meta-analyses of double-blind, placebo-controlled trials

"... the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD [few-foods diet] in subgroups of children with ADHD [attention-deficit hyperactivity disorder], thus offering innovative treatment opportunities for ADHD."

So said the "Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials" published by Lidy Pelsser and colleagues [1] (open-access available here) looking at various dietary interventions that have been studied with ADHD in mind. Pelsser, I might add, is a name not completely unfamiliar to this area of investigation as per other research on elimination diets and ADHD (see here).

The few-foods diet mentioned in the opening sentence of this post, could include a few things but Pelsser et al make specific reference to it consisting of "lamb, chicken, potatoes, rice, banana, apple and brassica: foods chosen as they were unlikely to produce an adverse response." You'll perhaps note that there are a few food groups missing from that list of foods, not least the grains (including the gluten protein), dairy products (containing the casein protein) and those processed foods that we all like to enjoy.

The Pelsser paper is an interesting one insofar as their systematically reviewing meta-analyses that were already conducted on dietary intervention(s) for ADHD. Said meta-analyses included in their paper were only allowed in if they meta-analysed double-blind placebo-controlled trials (the gold-standard of clinical trial design). If one assumes that a meta-analysis - where data from different trials is analysed and condensed into a sort of position statement - sits at the top of the evidence-based science hierarchy, the Pelsser study design perhaps sits on top of the top!

Although the FFD receives some welcome scientific backing in the review paper, it was not the only dietary intervention looked at the Pelsser and colleagues. To quote: "six supplement meta-analyses—all investigating the effects of poly-unsaturated fatty acids (PUFA)... —and eight elimination meta-analyses, examining respectively the effects of sugar..., AFC [artificial food colour elimination]..., the Feingold diet..., and the FFD... on ADHD" were reported on. The other interventions did not - for various possible reasons - match up to the research success reported with regards to the current standing of the few-foods diet for ADHD. This included the story on fatty acids for ADHD which has been mentioned previously on this blog (see here for example).

I do not make recommendations on this blog when it comes to intervention and the like for anything. I will however, once again quote Pelsser et al based on their very thorough analysis of the peer-reviewed science in the area of dietary intervention for ADHD: "the effect sizes of a few-foods diet are medium to large, justifying implementation of a diagnostic FFD in subgroups of children with ADHD, thus offering innovative treatment opportunities for ADHD". Also: "FFD research should focus on the mechanism of food in children with ADHD." Their words not mine, and based on some rather credible evidence. I might also add that appropriate dietetic input is a must before anyone heads into the FFD willy-nilly and no, this is not about 'clean eating' or any related fad...

And just before you go, how about casting your eye over the observations made by Alejandra Ríos-Hernández and colleagues [2] and their raising the question of "whether low adherence to a Mediterranean diet might play a role in ADHD development"? Food for thought in the context of the Pelsser data, although perhaps minus the [pregnancy] licorice?

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[1] Pelsser LM. et al. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PLoS One. 2017 Jan 25;12(1):e0169277.

[2] Ríos-Hernández A. et al. The Mediterranean Diet and ADHD in Children and Adolescents. Pediatrics. 2017. Jan 30.

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ResearchBlogging.org Pelsser LM, Frankena K, Toorman J, & Rodrigues Pereira R (2017). Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD. PloS one, 12 (1) PMID: 28121994

Thursday, 9 February 2017

On dietary and nutritional therapies for ME/CFS

ME/CFS in case you don't already know refers to Myalgic Encephalomyelitis / Chronic Fatigue Syndrome and, according to the findings reported by Nadia Campagnolo and colleagues [1], is in need of quite a bit more scientific investigation when it comes to the application of dietary changes and nutritional supplements to potentially alter the course of the condition(s).

Surveying the peer-reviewed literature "from 1994 to May 2016" the authors looked for peer-reviewed studies where "CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing)." They found 17 studies that included 14 different interventions. Unfortunately they concluded that: "Many studies did not show therapeutic benefit on CFS/ME" alongside the observation that the methodological quality of the research in this areas 'could do better'.

But it was not all research doom-and-gloom as some approaches seemed to show promise: "Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10." Without wishing to toot my blogging trumpet, some of these approaches have been discussed before on this blog (Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome? and Coenzyme Q10 and NADH supplementation for Chronic Fatigue Syndrome continued) and beyond that, the target organ of something like the use of probiotics for CFS has made an appearance more than once too (see here for example). I might also add that just outside of the search dates used by Campagnolo et al was the suggestion that issues with a staple foodstuff - cows milk - might be over-represented in cases of CFS (see here) and that a milk-free diet could be useful [2] for some at least. By saying all that, I'm not giving any medical or clinical advice...

As science starts to move further away from the the biopsychosocial (BPS) model of CFS/ME (see here) and starts looking at genetics, biology and somatic disease processes with regards to the various presentations included under the banner of ME/CFS (see here) I foresee some interesting developments further down the line. Granted, dietary and nutritional approaches to CFS/ME are probably not considered 'mainstream' in terms of management strategies but that does not mean they aren't important or at least important in the context of a diagnosis of ME/CFS seemingly being protective of nothing. Central to any future studies in this or any related area is the idea that there may be lots going on under the 'plural' diagnostic umbrella of ME/CFS (see here). Indeed, something that even the PACE trial is starting to take on board [3].

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[1] Campagnolo N. et al. Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. J Hum Nutr Diet. 2017 Jan 22.

[2] Rowe PC. et al. Cow's milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8.

[3] Williams TE. et al. Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial. Psychol Med. 2017 Jan 23:1-12.

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ResearchBlogging.org Campagnolo N, Johnston S, Collatz A, Staines D, & Marshall-Gradisnik S (2017). Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association PMID: 28111818

Wednesday, 8 February 2017

On atopic disease and ADHD: 'strong evidence' for an association

"This current systematic review provides strong evidence that ADHD [attention-deficit hyperactivity disorder] is associated with atopic diseases and that individuals have a 30% to 50% greater chance of developing ADHD compared to controls."

So said the results of the systematic review and meta-analysis published by Jurjen van der Schans and colleagues [1] looking at the collected peer-reviewed science literature on how conditions such as asthma, eczema and rhinitis might increase the risk of a subsequent diagnosis of ADHD.

New news? Not to this blog it isn't (see here for example) as the Schans data really just adds the 'cherry on top' to the idea that such somatic conditions might *connect to* behavioural and/or developmental diagnoses. Preferential screening is of course implied but then also comes the million dollar question: what are the biological mechanisms linking atopy to something like ADHD? The answer is likely to be complex - immune system complex for example - but I might suggest that some starting clues may be found in some of the [limited] peer-reviewed literature talking about what happens to ADHD signs and symptoms for some when treatment for atopic disease is initiated (see here).

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[1] van der Schans J. et al. Association of atopic diseases and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses. Neurosci Biobehav Rev. 2017 Jan 19. pii: S0149-7634(16)30359-1.

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ResearchBlogging.org Schans JV, Çiçek R, de Vries TW, Hak E, & Hoekstra PJ (2017). Association of atopic diseases and attention-deficit/hyperactivity disorder: A systematic review and meta-analyses. Neuroscience and biobehavioral reviews PMID: 28111269

Tuesday, 7 February 2017

Psychiatric disorders among male juvenile detainees in South Korea

"Juvenile detainees evidence high rates of psychiatric disorders and comorbidities. Assessment of and intervention in psychiatric disorders, especially alcohol use disorder and comorbid alcohol use disorder with disruptive behavior disorders, may help prevent further offenses."

So concluded Johanna Inhyang Kim and colleagues [1] (open-access) following their investigation into the prevalence of DSM-IV psychiatric criteria in a sample of 173 male juvenile detainees aged between 15-19 years old held at a "male juvenile detention center in Seoul, South Korea, during the period of December 2015 to January 2016." Most of the detainees were held in relation to crimes against property (49%) but violent crimes (39%), traffic offences (24%) and sexual offences (19%) also featured in offending patterns.

The presence of a psychiatric diagnosis was made using the Mini International Neuropsychiatric Interview (MINI) screening for various groups of disorders: disruptive behavioural disorders (DBDs), substance use disorder (SUD) and "any anxiety disorder." Researchers also looked for the presence of psychotic disorder and major depression too, alongside collecting various demographic data and information about recidivism (repeat offending).

Results: "In total, 157 (90.8%) participants had at least one psychiatric diagnosis" is the standout figure from the paper compared with other independent data from this part of the world "of 15–38% among the general adolescent population.Alcohol use disorder was the most frequently mentioned label mentioned in the study, but 'comorbidity seems to be the rule' as we are told that: "Alcohol use disorder with DBDs was the most common combination, accounting for 46.2% of the detainees, followed by DBDs with anxiety disorders (22.5%)."

When it came to the important issue of repeat offending, researchers also report some interesting patterns. Dropping out of school, present in about a quarter of the total cohort, was reported to be a factor in relation to recidivism (present in about 90% of detainees). The presence of two psychiatric disorders also showed a notable connection to repeat offending particularly where an alcohol use disorder was one of them. The message seems to be that keeping kids/young adults in school and away from alcohol might be an important combination in relation to affecting repeat offending rates.

There is quite a lot of other data included in the Kim study and I would encourage interested parties to take a more detailed look. One thing that struck me about the Kim data was the apparent lack of results when it came to attention-deficit hyperactivity disorder (ADHD) in relation to offending and repeat offending outcomes. Minus any sweeping generalisations, I've talked before on this blog about how a diagnosis of ADHD might elevate the risk of contact with law enforcement agencies (see here) for whatever reason(s) and how a combination of ADHD and conduct disorder in particular, might be tied into a range of long-term adverse outcomes including 'risk of criminality' (see here). Kim and colleagues paint a slightly different clinical picture whereby a different combination of psychiatric factors might be specifically related to this group of people in this part of the world.

More investigations are implied including reference to what potential nutritional changes might do to [some] behaviour in this population (see here).

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[1] Kim JI. et al. Prevalence of psychiatric disorders, comorbidity patterns, and repeat offending among male juvenile detainees in South Korea: a cross-sectional study. Child Adolesc Psychiatry Ment Health. 2017 Jan 18;11:6.

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ResearchBlogging.org Kim JI, Kim B, Kim BN, Hong SB, Lee DW, Chung JY, Choi JY, Choi BS, Oh YR, & Youn M (2017). Prevalence of psychiatric disorders, comorbidity patterns, and repeat offending among male juvenile detainees in South Korea: a cross-sectional study. Child and adolescent psychiatry and mental health, 11 PMID: 28115987

Monday, 6 February 2017

Natural course of "chronic disabling fatigue" in adolescents

"We use the term 'chronic disabling fatigue' (CDF) because CFS/ME [chronic fatigue syndrome / myalgic encephalomyelitis] was not verified by clinical diagnosis."

That was one of the important details included in the findings reported by Tom Norris and colleagues [1] (open-access) who "aimed to describe the epidemiology and natural course of CFS/ME in adolescents aged 13–18 years." Relying on data derived from The Avon Longitudinal Study of Parents and Children (ALSPAC) (something this research group have previously used in their peer-reviewed research), information on some 6700 adolescents at 13 years old, 5700 at 16 years old and 4200 at 18 years old were available to researchers.

At those ages (13, 16 and 18 years old) the estimated prevalence rates of CDF - chronic disabling fatigue - ascertained slightly differently at different ages were: "1.47% (95% CI 1.05% to 1.89%) at age 13, 2.22% (1.67% to 2.78%) at age 16 and 2.99% (2.24% to 3.75%) at age 18." I say that CDF was ascertained slightly differently at each age point because mothers of participants reported on "fatigue lasting >6 months that was associated with absence from full-time school or that had prevented them from taking part in activities ‘quite a lot’ or ‘a great deal’" at aged 13 years which then moved to mothers and participants reporting at aged 16 and finally at aged 17-18 years a computer-based interview being used. The key point of all of this is that CDF is assumed to be a proxy for CFS/ME but is not an actual diagnosis of CFS/ME bearing in mind how complicated that side of things already is (see here for example).

Insofar as the 'natural course' of CDF, the authors paint a picture where "the prevalence of CDF increased with advancing age" but also that around 8% of those diagnosed with CDF at aged 13, held on to the 'diagnosis' at 16 and 18 years old. The authors note: "These adolescents may represent a group who were experiencing a more severe form of the disease, characterised by increased persistence or recurrence of the disease." Personally, I would be careful with the word 'disease' in that context because it seems to me that CDF is describing a symptom not necessarily a condition and a symptom that could be present for all manner of different reasons.

This is interesting data but I have to say I did feel a little 'misled' by the title of the Norris paper - "Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents" - because of the use of the CDF definition as a proxy for the real thing. I refer you to other instances where ALSPAC has used/formulated measures as a proxy for diagnosis (with autism in mind) but even in that other case, authors used the term 'behavioural traits of autism spectrum disorder' [2] over and above calling it 'autism'. Surely it would have been better for Norris et al to say something like 'a trait of CFS/ME' rather than insinuating that they were examining defined cases of ME/CFS? Peer reviewers, please take note...

To close, The Golden Girls and chronic fatigue syndrome. Ground-breaking.

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[1] Norris T. et al. Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents. Arch Dis Child. 2017 Jan 19. pii: archdischild-2016-311198.

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ResearchBlogging.org Norris T, Collin SM, Tilling K, Nuevo R, Stansfeld SA, Sterne JA, Heron J, & Crawley E (2017). Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents. Archives of disease in childhood PMID: 28104625

Saturday, 4 February 2017

ADHD, obesity and bariatric surgery?

"The findings suggest that a considerable number of patients before and after bariatric surgery screened positive for ADHD [attention-deficit hyperactivity disorder]. It can be hypothesized that some core ADHD symptoms improve after surgery."

Bariatric surgery, where several surgical options are available to aid weight loss in those who present with 'dangerous' obesity, was the topic of the paper by Nielsen and colleagues [1] (open-access available here) who set out to compare "pre- and post-bariatric surgery patients using the internationally used Conners' Adult ADHD Rating Scale (CAARS™) to screen for ADHD" among other measures. The authors came up with some interesting details. They reported that the rate of 'probably ADHD' (defined using the CAARS and also the Wender Utah Rating Scale Short Version (WURS-k) cut-off scores) were 8.3% in their pre-surgery sample (n=120) and 6.3% in their post-surgery sample (n=128).

When looking at the behavioural profiles of those pre- and post-surgery, there were some not entirely unexpected differences when it came to items related to depression and eating-related psychopathology - both scoring lower in the post-surgery participants. But also those post-surgery reported some potentially important information in relation to generally better attention and memory compared to pre-surgery participants. I was intrigued by the authors explanation of this: "The finding of a better attention and memory function in the post-surgery sample is in line with the results of longitudinal studies demonstrating improvements in cognitive functioning following bariatric surgery." Further: "It is reasonable to assume that postoperative cognitive improvement in attention and memory might have impacted the self-report on the respective CAARS subscale." Does this imply that bariatric surgery might act as some kind of nootropic for [some of] those with obesity?

In these days of ADHD being 'linked' to obesity (see here), the Nielsen results fit nicely. Alongside the idea that weight loss surgery might link into improved cognitive functioning and onwards, impacting on facets of ADHD I'd have to question what the biological mechanism(s) might be. Does the restriction of food intake as a consequence of surgery indicate a role for food in some cognitive processes? Does such surgery potentially impact on the trillions of wee beasties that populate our gut and then onwards exert an effect of cognitive processes? There are several questions that still need answering...

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[1] Nielsen F. et al. Attention Deficit Hyperactivity Disorder Prevalence and Correlates Pre- and Post-Bariatric Surgery: A Comparative Cross-Sectional Study. Obes Facts. 2017 Jan 20;10(1):1-11.

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ResearchBlogging.org Nielsen F, Georgiadou E, Bartsch M, Langenberg S, Müller A, & de Zwaan M (2017). Attention Deficit Hyperactivity Disorder Prevalence and Correlates Pre- and Post-Bariatric Surgery: A Comparative Cross-Sectional Study. Obesity facts, 10 (1), 1-11 PMID: 28103594

Friday, 3 February 2017

"Schizophrenia confers a high endogenous risk for diabetes"

"Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics."

So concluded Anto Rajkumar and colleagues [1] who relied on participant data in the thousands derived from several of those very helpful Scandinavian population registries (this time in Denmark) to add some further science to the idea that psychiatric diagnoses like schizophrenia seem to carry an elevated risk for all-manner of somatic conditions.

From a total population of 2.7 millions people born in Denmark between 1977 and 2013, researchers reported that: "14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years)." When looking at the risk of developing diabetes (bearing in mind there is more than one type of diabetes) in those with schizophrenia not following any antipsychotic medication regime, researchers reported that: "The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71–5.41) in antipsychotic-naive schizophrenia compared with the general population." In other words, compared with those without a diagnosis of schizophrenia, there was something of an increased risk of developing diabetes in those diagnosed with schizophrenia.

Then to the potential effect of antipsychotic medication, and as the authors note: "The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95–6.82) than the risk in antipsychotic-naive schizophrenia." The use of an adjusted hazard ratio means that researchers took into account potentially confounding variables such as a family history of diabetes known to potentially elevate the risk of the condition. The focus on medication is also perhaps the side of the whole schizophrenia-diabetes story that people might more readily recognise.

If all that wasn't enough to convince you that schizophrenia - medicated and unmedicated - might show a rather important relationship with diabetes, perhaps the results reported by Pillinger and colleagues [2] might ease your scepticism and the suggestion (from the authors) that "higher levels of insulin, and increased levels of insulin resistance" are a facet of quite a few cases of schizophrenia alongside demonstrating that "people with schizophrenia had higher levels of glucose in the blood." On the basis of these and various other studies, the onus is on regular screening for diabetes and its symptoms alongside other related measures (see here for example) when it comes to schizophrenia under multiple 'medicated or not' conditions.

Music to close, and having bumped into the excellent film 'Stand By Me' again recently, the song of the same name...

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[1] Rajkumar AP. et al. Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study. Am J Psychiatry. 2017 Jan 20:appiajp201616040442.

[2] Pillinger T. et al. Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2017 Jan 11.

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ResearchBlogging.org Rajkumar AP, Horsdal HT, Wimberley T, Cohen D, Mors O, Børglum AD, & Gasse C (2017). Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study. The American journal of psychiatry PMID: 28103712