Sunday, 17 December 2017

ADHD and risk of injuries meta-analysed (again)

"ADHD [attention-deficit hyperactivity disorderis significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies."

So concluded the "systematic review with meta-analyses" conducted by Maite Ruiz-Goikoetxea and colleagues [1] pertinent to "the association between ADHD and risk of unintentional physical injuries in children/adolescents." The '(again)' mentioned in the title of this post references the findings reported by Amiri and colleagues [2] that were discussed earlier this year on this blog (see here).

Ruiz-Goikoetxea et al do make mention of the Amiri meta-analysis and how post-2014 (the point at which the Amiri systematic review and meta-analysis halted) "several methodological sound studies have been published." They also mention how the Amiri analysis "did not control for gender effects, which are a crucial confounder due to the association of both risk of UPIs [unintentional physical injuries] and ADHD to male gender" nor how they looked at the impact of medications for ADHD on the risk(s) of such injuries.

Splitting their analyses in two (a) a risk analysis looking at the risk of UPIs with ADHD in mind and (b) a medication analysis looking at the role (or not) of medication in terms of UPIs in the context of ADHD, authors report results based on their already published protocols [3]. They reported on "odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries" and cumulatively included participant numbers in the tens of thousands.

Results: "a significantly higher risk of injuries in ADHD compared to children or adolescents without ADHD" was observed. Nothing particularly novel there. Also, based on the finding that: "Methylphenidate was the most frequent drug among children and adolescents with ADHD", researchers reported on "a significant protective effect of the medication" on injury risk. The size of the risk reduction for UPI when medication was used was estimated at about 10%.

Once again, I can't argue with the associations made in terms of how a diagnosis of ADHD does 'up' the risk of physical injury and how medication might be one option out of several to reduce the risk of UPIs in the context of ADHD. Added to other work talking about how medication might also positively affect specific risk of motor vehicle accidents in the context of adult ADHD (see here) for example, it's becoming clearer that intervention helps. I appreciate that there may be some consumer resistance to the idea of 'medicating children' but the data so far on the cost-benefit profile of something like methylphenidate for ADHD is pretty favourable (see here). Certainly, one has to be careful about making too many negative sweeping statements about such medication (see here for example) just for the sake of it.

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[1] Ruiz-Goikoetxea M. et al. Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: a systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews. 2017. Nov 21.

[2] Amiri S. et al. Attention deficit/hyperactivity disorder and risk of injuries: a systematic review and meta-analysis. J Inj Violence Res. 2017 Jun 1;9(2).

[3] Ruiz-Goikoetxea M. et al. Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: protocol for a systematic review and meta-analysis. BMJ Open. 2017 Sep 25;7(9):e018027.

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Saturday, 16 December 2017

Mortality patterns in older adults with learning disability

"Older adults with ID [intellectual disability] in Sweden carry a higher mortality risk compared with the general population, mainly attributable to respiratory, nervous and circulatory diseases."

So said the findings reported by Nawi Ng and colleagues [1] (open-access) looking at the records of some 15,000 individuals diagnosed with an intellectual (learning) disability compared with a similar number of control participants with respect to "patterns and risk of mortality." Researchers observed "a 4-fold higher mortality rate and a shorter median survival time among older adults with ID compared with the general older adult population." Such findings add to a growing body of research literature (see here and see here) suggesting that behavioural, cognitive and/or psychiatric diagnoses seem to be accompanied by some significant health inequalities too.

I could go into the details about the Ng study and the various ins-and-outs of how they arrived at their conclusions but to be honest, I'm just not minded to. I say that on the basis that the figures speak for themselves: "the mortality rate among individuals with ID was three times higher than in the control population" and: "Individuals with DS [Down's syndrome] had an 11-fold higher mortality risk than the control population." Sombre reading, perhaps partially reflecting how modern-day society treats some of its most vulnerable citizens.

The ultimate question should be: is there anything that can be done to improve this situation for those with a learning disability? Yes, is the answer; taking into account how a diagnosis of ID for example, means that some might be "more prone to cardiovascular disease risk factors, morbidity and mortality than the general population." The authors add that: "Cardiovascular disease health promotion and prevention programmes should be tailored for individuals with ID, to prevent or delay cardiovascular diseases and premature mortality in this vulnerable group." Corresponding action in relation to deaths resulting from epilepsy for example, should also (and always) be a priority.

"How a society treats its most vulnerable is always the measure of its humanity" is a phrase attributed to many speakers. On the basis of the research from Ng and other study results, society is seemingly failing many of those diagnosed with a learning disability as it is other vulnerable sections of society (see here).

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[1] Ng N. et al. Mortality patterns and risk among older men and women with intellectual disability: a Swedish national retrospective cohort study. BMC Geriatrics. 2017; 17: 269.

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Friday, 15 December 2017

"patients with CFS/ME do not exhibit insufficient concentrations of circulating total 25(OH)D"

The title heading this post comes from the findings reported by Kate Earl and colleagues [1] (open-access available here), where '25(OH)D' refers to calcifediol, a compound typically used to estimate how much vitamin D is present in the body and CFS/ME refers to Chronic Fatigue Syndrome / Myalgic Encephalomyelitis.

After assaying some 92 people with CFS/ME and an almost equal number of 'age-matched healthy controls' (HCs) for plasma total 25(OH)D and individual vitamin D metabolites - "25(OH)D2 and 25(OH)D3" - researchers concluded that vitamin D deficiency was not rife in their cohort. Indeed we are told that: "total 25(OH)D was significantly higher (p=0.001) in serum of patients with CFS/ME compared with HCs (60.2 and 47.3 nmol/L, respectively)." The authors were also able to report that vitamin D supplementation by the CFS/ME group seemed to be a primary reason for their findings.

There are a few important strengths to the Earl results that are worth mentioning. Not least that vitamin D metabolites were measured by mass spectrometric methods similar to other independent research occasions (see here for example). Mass spectrometry seems to have quite a few advantages over other methods of vitamin D analysis; now labelled as a gold-standard technique. Added to their use of a deuterated standard ("hexadeuterated (OH)D3") and one has some degree of confidence in the analytical results; albeit, as the authors acknowledge: "that only the main marker of vitamin D status, that is, 25(OH)D, was measured" and how "there is a need to assess all of the vitamin D metabolites" of which there are quite a few [2].

At first glance, the Earl findings seem pretty unremarkable. Supplementation with vitamin D, as everyone is being encouraged to do these days (see here), means higher levels of circulating vitamin D. I would be surprised if they didn't. This is also not the first time that vitamin D levels in relation to CFS/ME have been talked about in the peer-reviewed domain either (see here) albeit not always with the same results but again with that caveat about supplementation in mind.

Given however that a measure of fatigue - "the Chalder Fatigue Questionnaire" - was also included for all participants in the Earl study, and how nothing very much seemed to be present when looking at any connection between fatigue scores and vitamin D status, this provides a possible clue that vitamin D is probably not a big player specifically in relation to the presentation of fatigue in most cases of CFS/ME. Such a questionnaire does not rule out other potential associations (e.g. post-exertional malaise, PEM) nor that other, potential comorbidity appearing alongside CFS/ME might not have a stronger vitamin D link (see here for example). But for now, it adds to the literature (see here) casting doubt on any direct role for vitamin D in relation to CFS/ME.

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[1] Earl KE. et al. Vitamin D status in chronic fatigue syndrome/myalgic encephalomyelitis: a cohort study from the North-West of England. BMJ Open. 2017 Nov 8;7(11):e015296.

[2] Abu Kassim NS. et al. Simultaneous determination of 12 vitamin D compounds in human serum using online sample preparation and liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2017 Dec 6. pii: S0021-9673(17)31772-7.

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Thursday, 14 December 2017

The inter-pregnancy interval and risk of offspring autism yet again

I'm gonna try and keep this post quite brief starting with the observation that: "ASD [autism spectrum disorder] was increased in second and later-born children who were conceived less than 18 months or 60 or more months after the mother's previous birth."

So said the findings reported by Laura Schieve and colleagues [1] adding to quite a consistent research theme (see here and see here and see here). Based on "data from the Study to Explore Early Development [SEED]" initiative, with "rigorous case-finding and case-classification methods and detailed data collection on maternal reproductive history" researchers were quite confident in their observations. SEED, I might add, is developing quite a good peer-reviewed autism research reputation (see here).

Implications? Well, based on the current collected peer-reviewed research literature in this area it appears that there may be a specific time frame when it comes to potentially modifying the risk of offspring autism. Please don't take this as gospel but an interpregnancy interval (IPI) of somewhere between 12-18 and 60-72 months 'seems' to be emerging as an 'optimal' period based on the collected data currently to hand. I say this bearing in mind that multiple factors associated with pregnancy and birth *seem* to be associated with offspring outcomes (indeed, Schieve and colleagues have examined others too). This probably also includes what happens after birth (see here for example) and factors like parental age at conception/birth too (see here).

Possible mechanisms of effect? Yet again, it is more than likely that multiple factors are going to be influencing risk (or not) of offspring autism. I am drawn to the idea that a depletion of micronutrients associated with pregnancy might be an area for further investigation in relation to the IPI effect on offspring autism risk. This set in the context that pregnancy places some significant physical and biological demands on a mother's body; demands probably not immediately resolved as soon as baby enters the big, wide world. As to which micronutrients might be the more important to replenish, well, take yer pick (see here and see here for examples). Bearing, that is, in mind that no medical or clinical advice is given or intended...

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[1] Schieve LA. et al. Autism spectrum disorder and birth spacing: Findings from the study to explore early development (SEED). Autism Research. 2017. Nov 22.

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Wednesday, 13 December 2017

"A Blood Based Diagnostic Test for Coeliac Disease" (minus dietary gluten?)

The findings reported by Vikas Sarna and colleagues [1] have the potential to excite. Excite because, as the authors note: "A diagnosis of celiac disease based on serologic and histologic evidence and duodenal histology requires patients to be on gluten-containing diets" but a "growing number of individuals adhering to a gluten-free diet (GFD) without exclusion of celiac disease complicates its detection." A diagnostic test therefore, that could confirm/reject a diagnosis of coeliac disease (CD) without someone having to have gluten in their diet for some weeks, might be a rather exciting prospect.

Having previously posted their study aims and objectives on the ClinicalTrials.gov website (see here), authors tested the idea that "multimerized HLA bound to different gliadin-peptides (tetramer) and with the help of a flow-cytometer identify (along with other relevant T-cell-markers) gluten specific T-cells."

If all that sounds a little 'science-y' the long-and-short of it is the suggestion that the specific gene variants linked to CD - HLA-DQ2 and HLA-DQ8 variants - produce molecules -  HLA-DQ8 and HLA-DQ2 molecules - that bind to 'super-charged' gluten peptides to form a more complex molecule (tetramer) that has some rather important effects on components of the immune system, specifically on CD4+ T cells. Looking for such 'gluten specific T-cells' could be done by adding HLA-DQ-gluten tetramers to blood samples from patients with suspected/diagnosed CD. I think...

Anyhow, examining blood samples from a range of people - "62 subjects with celiac disease on a GFD, 19 subjects without celiac disease on a GFD [due to self-reported gluten-sensitivity], 10 subjects with celiac disease on a gluten-containing diet, and 52 presumed healthy individuals [controls]" - researchers put their test to the test. Most samples were analysed blind: "except for samples from subjects with celiac disease on a gluten-containing diet" and results were compared.

"An HLA-DQ-gluten tetramer-based assays that detects gluten-reactive T cells identifies patients with and without celiac disease with a high level of accuracy, regardless of whether the individuals are on a GFD." The sensitivity and specificity figures reported by Sarna are pretty good when authors managed to 'optimise' their results based on the values obtained. Indeed: "The values identified subjects with celiac disease on a gluten-containing diet with 100% sensitivity (95% CI, 1.00-1.00]) and 90% specificity (95% CI, 0.83-0.98) vs controls." Even a couple of the control participants - 'presumed healthy individuals' - were actually found to have unrecognised CD.

More science needs to be done before this potential diagnostic test is rolled out further and potentially across many, many groups. Larger participant numbers and a greater diversity of participants in terms of ethnicity, sex/gender and age need to included for study. I'm also wondering whether those with other autoimmune conditions/diagnoses could also be included in future research plans too, on the basis that birds of an autoimmune feather tend to flock together (see here and see here).

Things do seem to be getting rather interesting when it comes to CD these days. Alongside this rather exciting work, there is also the prospect of preparations that degrade gluten peptides also coming into the mainstream (see here) and how nutrients like vitamin D might also show some potentially important gastrointestinal effects [2] (see here also) pertinent to CD and beyond. No, it's not quite the end of the 'lifelong gluten-free diet' (yet!), but science is seemingly moving just a little bit closer...

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[1] Sarna VK. et al. HLA-DQ-Gluten Tetramer Blood Test Accurately Identifies Patients With and Without Celiac Disease in Absence of Gluten Consumption. Gastroenterology. 2017 Nov 13. pii: S0016-5085(17)36352-7.

[2] Scricciolo A. et al. Vitamin D3 Versus Gliadin: A Battle to the Last Tight Junction. Dig Dis Sci. 2017 Nov 20.

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Tuesday, 12 December 2017

Low birth weight and autism: rise of the population attributable risk

RIP Cheggers.
"LBW [low birth weightaccounted for 6.0% of all ASD [autism spectrum disorder] cases, 2.4% of BCD [behaviour and conduct disorder], and 6.8% of LD [learning disability] among the study population."

Those were the observations made by Sandie Ha and colleagues [1] and with it, another example of the use of the population attributable risk/fraction in the context of autism (see here for another occasion). Published in 2014 but only recently appearing on PubMed, Ha et al report results based on data from the 2011 (US) National Survey of Children’s Health, (NSCH) - a "random-digit-dial phone survey conducted between February 2011 and June 2012" - where data on birth weight and receipt or not of a diagnosis of "attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), behavior and conduct disorder (BCD) and learning disability (LD)" were available. As an aside, I've talked about the other studies arising from the NSCH program before on this blog (see here and see here for examples).

Including data pertinent to around 81,000 children aged between 2 and 17 years of age, researchers reported that around 9% of the cohort were "born with a LBW as reported by their parent" in response to the question: "What was [sampling child’s] birth weight?" There were some interesting correlates alongside those responses regarding LBW status: "children who were female, non-Hispanic black, had single mothers, had less educated mothers, were poorer, lacked insurance, were exposed to in-home smoking, or born prematurely were more likely to have LBW compared to those with normal BW."

Insofar as 'neurobehavioural disorders' (ND) also asked about: "The weighted prevalence of parent-reported ND among children ages 2 to 17 was approximately 9.9% for ADHD, 2.3% for ASD, 4.1% for BCD, and 10.6% for LD." Yes, this was a telephone-based survey where "both exposure and outcome are based on parental reporting, and thus the information may not represent actual diagnoses" but with the size of the participant numbers included, these prevalence/frequency figures still make for important reading.

Then to the main event - the population-attributable risk percentage (PAR%) and the finding headlining this post: "LBW [low birth weight] accounted for 6.0% of all ASD [autism spectrum disorder] cases, 2.4% of BCD [behaviour and conduct disorder], and 6.8% of LD [learning disability] among the study population." The authors caution that "maternal age at delivery, gestational age, and pregnancy complications could be important confounders" and were not taken into account in their analyses and could be "potential reasons for LBW" alongside undetected "congenital anomalies or genetic disorders." Caution is required.

It's not new news that birth weight might impact on something like autism risk (see here and see here). One also has to bear in mind that something like LBW may not necessarily appear in isolation to other pregnancy or birth events (see here) so a wider research agenda perhaps needs to be followed. But the size of the PAR% talked about by Ha and colleagues is not easily ignored. Taking into account that LBW for some may very well have some 'genetic' influences, one is left asking whether those more 'social' variables linked to LBW might be to some degree 'influenced' with a corresponding effect on neurodevelopmental 'consequences' reported. I say this in the context that poverty as a variable, has already been linked to some diagnoses included in the Ha study (see here)...

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[1] Ha SU. et al. Population attributable risks of neurobehavioral disorders due to low birth weight in US children. Adv Pediatr Res. 2014;1. pii: 2.

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Monday, 11 December 2017

On hormonal contraception and suicide risk

I'll freely admit that the material covered in the paper by Charlotte Wessel Skovlund and colleagues [1] suggesting that: "Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide" is (a) slightly outside of the typical remit of this blog and (b) not something that I'm particularly qualified to talk about. I was however minded to discuss this paper in the context that previous work from this research group has *linked* hormonal contraception use with depression [2] (see here for some of the media on this past paper) and in the more general context of blogging occasions where depression and risk of suicide have been discussed here (see here).

Similar to their last research outing where hormonal contraception - 'birth control methods that act on the endocrine system' - was analysed, some of those rather important Scandinavian population registries were the source study material. Denmark was the country of choice and "a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013." You'll note the words 'no psychiatric diagnoses, antidepressant use' were included, illustrating how researchers were already mindful of the role that depression has in such extreme behaviour(s). Researchers collected information "about use of hormonal contraception" and also suicide attempts and completions. This, based on resources such as the Danish National Prescription Register, illustrating once again the long Scandinavian tradition of "creating nationwide administrative and health registries" [3].

Results: "Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85–2.10) for suicide attempt and 3.08 (95% CI=1.34–7.08) for suicide." I should put that in some context in terms of hundreds of thousands of women - "nearly half a million women" - who were tracked over the course of the study, and how nearly 7000 first suicide attempts were recorded and 71 [completed] suicides registered. The numbers were comparatively small; bearing in mind that behind each figure is a person, a life and a family.

Taking into account the tenet 'correlation is not the same as causation' and indeed, appreciating how complex and individual suicidal thoughts and behaviour can be, these are potentially important data minus any scaremongering. Certainly these are findings worthy of quite a lot more study, particularly in light of the large population included for study mimicking the authors' previous chosen study design, alongside the prospective nature of their investigation.

Mechanisms of effect? I don't think anyone is quite there yet with regards to definitive hows-and-whys. I note that others have talked about a possible *correlation* between elevations in progesterone and suicide attempts [4] but such observations need to be treated cautiously at this point, again reiterating how complex and individual the processes leading someone to suicidal thoughts and behaviours are. Skovlund and colleagues did talk about suicide risk potentially differing according to different contraceptive formulations used: "Risk estimates for suicide attempt were 1.91... for oral combined products, 2.29... for oral progestin-only products, 2.58... for vaginal ring, and 3.28... for patch" potentially suggesting that specific products might have differing risk profiles. This is something else that could perhaps help isolate any pertinent mechanisms.

Questions remain, not least: Are there particular groups of women, based on genetics or other biology, that may be at increased risk of depression and/or suicide when taking such contraception? The answer: we don't yet know. Bearing in mind that in this, and their other work on hormonal contraception and depression, age seemed to be an important variable as per the observation: "Adolescent women experienced the highest relative risk" thus representing a good place to start. And on the topic of adolescent women perhaps having an elevated risk, I might also draw your attention to the findings reported by Jean Twenge and colleagues [5] who discussed another potentially important variable to consider: "Since 2010, adolescents spent more time on social media and electronic devices, activities positively correlated with depressive symptoms and suicide-related outcomes." I wonder if this is something that perhaps needs to be controlled for in future studies?

To close, there's always someone to talk to (see here) if needs be, and please, talk to your medical professional (not Dr Google) if you're at all concerned by these latest findings.

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[1] Skovlund CW. et al. Association of Hormonal Contraception With Suicide Attempts and Suicides. Am J Psychiatry. 2017 Nov 17:appiajp201717060616.

[2] Skovlund CW. et al. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016 Nov 1;73(11):1154-1162.

[3] Pottegård A. et al. Data Resource Profile: The Danish National Prescription Registry. Int J Epidemiol. 2017 Jun 1;46(3):798-798f.

[4] Mousavi SG. et al. Recurrent suicide attempt and female hormones. Advanced Biomedical Research. 2014;3:201. doi:10.4103/2277-9175.142046

[5] Twenge J. et al. Increases in Depressive Symptoms, Suicide-Related Outcomes, and Suicide Rates Among U.S. Adolescents After 2010 and Links to Increased New Media Screen Time. Clinical Psychological Science. 2017. Nov 14.

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Sunday, 10 December 2017

From limp to scurvy in the context of autism

"A panel of nutritional markers was sent, and a presumptive diagnosis of scurvy was made."

So said the case report detailed by Adam Yan and colleagues [1] as, yet again (see here and see here), the topic of scurvy in the context of autism appears in the peer-reviewed science literature. Scurvy, a condition affecting various tissues of the body, comes about as a result of a lack of adequate vitamin C in the diet. It's thought of as a rare disease nowadays, following on from some 'limey' historical observations (see here).

I say that scurvy is a rare disease, but as per the other blogging occasions when it's received attention, for those diagnosed on the autism spectrum it's not as rare as it should be. Indeed, even Yan et al note that "scurvy is increasingly identified in children with ASD [autism spectrum disorder] and developmental delay who consume restrictive diets, often lacking in fruits and vegetables." Their case report highlights how clinicians need to be observant...

The subject of the Yan case report was a young boy diagnosed with autism who was described as non-verbal. He came to clinical attention following "a 2-week history of limp and oral mucosal bleeding." Unfortunately, his first contact with medical professionals resulted in less-than-revealing typical test results that meant he was discharged with "a referral to dentistry to address the oral mucosal changes." Things did not improve. He presented again to hospital, this time "with new onset of fevers for 1 week, ongoing limp that had progressed to complete refusal to weight bear, and persistent bleeding from his oral mucosa." This second time a few more investigations were ordered and a very (VERY) low level of vitamin C (ascorbic acid) was detected: "The low ascorbic acid level confirmed the diagnosis of scurvy with a concomitant diagnosis of anemia." Treatment in the form of vitamin C and an iron supplement (alongside a multivitamin) did the trick in terms of the limp/leg problem and bleeding gums.

What are the lessons from this case report? Well, yet again, the realisation that issues such as those related to feeding problems present quite widely in relation to autism (see here) and can very much impact on health is paramount. Indeed, it should really be part of standard medical care to monitor and keep monitoring children in particular, with a diagnosis of autism to ensure that their nutritional needs are being met in many areas (see here). If they're not, supplement (under appropriate medical guidance) and don't be afraid to do so, keeping in mind that each person/child is different (see here).

I'm also minded to mention that when medical and other allied healthcare practitioners are faced with a child/adult with autism that is non-verbal and presenting with 'symptoms', the onus really should be on medicine to turn investigator to find out 'hows-and-whys' rather than discharging with a 'we don't know' sentiment. I say this in the context that a diagnosis of autism is seemingly not protective against any other condition/label/disease occurring, and noting other, more catastrophic, examples where this has happened (see here). And minus any sweeping generalisations, a few correctly framed questions can sometimes be enlightening [2] for all-manner of different issues pertinent to autism...

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[1] Yan A. et al. Limp in a Child With Autism Spectrum Disorder. Global Pediatric Health. 2017. Nov 30.

[2] Cohen S. et al. Sleep patterns predictive of daytime challenging behavior in individuals with low-functioning autism. Autism Res. 2017 Dec 1.

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Saturday, 9 December 2017

Inflammatory bowel disease and autism (again)

"Children with ASD [autism spectrum disorder] were more likely to meet criteria for Crohn’s disease (CD) and Ulcerative colitis (UC) compared to controls."

So concluded Maunoo Lee and colleagues [1] following their "retrospective case-cohort study" of the US Military Health System database. Having previously published their findings as a conference abstract [2], authors gave their data the full peer-reviewed publication treatment covering nearly 300,000 people: ~48,000 children diagnosed with ASD and ~240,000 matched (not-autism) controls.

Alongside gathering data on the frequency of ICD-9 diagnostic codes for CD and UC - both defined as inflammatory bowel diseases (IBDs) - researchers also examined prescription data for treating/managing such bowel conditions. They observed differences in the prescription rate ratio (PRR) *potentially* reflective of either a more severe or more difficult to control form of IBD in children diagnosed with ASD. In short, and hopefully without making too many sweeping generalisations, IBDs are seemingly over-represented when it comes to a diagnosis of autism, and may be more likely to have an atypical pathological course.

Of course all of this is not new news. I've talked about other research that has reported similar things in relation to IBDs and autism (see here) alongside the 'now-not-questioned-so-much' data on the over-representation of functional bowel problems in relation to autism (see here). There's still a way to go in research and clinical terms to try and answer questions about how such bowel issues come about in relation to autism and whether one might consider some IBDs as being potentially 'novel' in relation to 'some' autism (see here). But the days of bowel problems in autism being some sort of fringe issue seem to well and truly gone, as perhaps 'suffering' as a result of such bowel issues can hopefully start to be addressed and other potential 'effects' (see here) investigated further minus hype, generalisation and/or fear...

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[1] Lee M. et al. Association of Autism Spectrum Disorders and Inflammatory Bowel Disease. J Autism Dev Disorders. 2017. Nov 23.

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Friday, 8 December 2017

Big data Taiwan on risk of "major psychiatric disorders" in kindreds of those with schizophrenia

'Big data' Taiwan listed in the title of this post refers to the wide range of findings emerging from the resource known as the National Health Insurance Research Database (NHIRD) based in Taiwan. Seriously people, this is population-wide science at it's very, very best (see here)...

Today I present yet another example of how the NHIRD is being put to good use and, as reported by Cheng and colleagues [1], how NHIRD derived data supports "the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD [autism spectrum disorder] and ADHD [attention-deficit hyperactivity disorder]." In other words, how lots of seemingly individual and specific behavioural and psychiatric labels may well 'club' around each other in affected families.

So, the starting point: "A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes." Yes, several studies have talked about possible genetic 'relationships' between these labels (see here); accepting that structural genetics may only be a part of the story. Researchers specifically examined "whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders" and the extent of any enhanced risk.

The NHIRD harboured details for some 150,000 people diagnosed with schizophrenia and some 225,000 people with FDRs diagnosed with schizophrenia. Authors crunched the data to come up with relative risks (RRs) statistics using schizophrenia as the diagnostic starting point.

Results: "The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population." You'll notice the sliding scale of RRs, where an index case of schizophrenia most significantly raises the RR of schizophrenia being diagnosed in first-degree relatives, down to a slightly lower RR in relation to something like ADHD among FDRs. It's probably to be expected that a diagnosis of schizophrenia might raise the risk of schizophrenia in FDRs too. Indeed, this is precisely what other NHIRD derived data has previously suggested (see here).

The range (and risks) of other diagnoses present in FDRs of someone diagnosed with schizophrenia is probably of little surprise to anyone who's surveyed the peer-reviewed literature in this area (see here) or indeed works in psychiatric circles. Although contemporary psychiatric science goes to some lengths to 'compartmentalise' specific diagnoses/labels, there's always been a strong undercurrent that labels are likely to be linked or at the very least, overlap. I've talked quite a lot for example, about the links between autism and schizophrenia on this blog (see here and see here). How, minus the [important] societal implications and politics, people such as Mildred Creak and colleagues [2] probably reached a closer 'definition' of some modern-day autism than we have now with their inclusion of "distortion in motility patterns" and "acute, excessive and seemingly illogical anxiety." Yes, they headed it "schizophrenic syndrome in childhood" and autism has been moved away from this description. But with all the emphasis on gait and motility patterns coming back into fashion together with increasing recognition of the truly disabling effect that anxiety can have in the context of autism, I think they were closer that many people thought to hitting the diagnostic mark.

Other implications from the Cheng results? Screening, enhanced screening. So when schizophrenia is diagnosed in the family, greater resources are put into preferential screening of first-degree relatives also for schizophrenia and the range of other labels mentioned in the current study. I'd also add that given the ever-growing relationship between the behavioural/psychiatric and the somatic, a greater consideration of some other health-related conditions (see here and see here for examples) might also be useful...

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[1] Cheng CM. et al. Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study. Mol Psychiatry. 2017 Nov 7.

[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.

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Thursday, 7 December 2017

Cytokines and chemokines in depression point to immune system involvement: meta-analysed

Two papers are presented for your reading pleasure today, both covering a topic of growing importance on how at least some types of depression very much seem to show some immune system involvement whether causative or as part of the illness/condition course.

The first paper is by Leighton and colleagues [1] and provides results based on a systematic review and meta-analysis of the literature pertinent to the role of inflammation or chemicals involved in inflammatory processes ("chemotactic cytokines (chemokines)") in relation to depression. The authors begin their paper abstract with the words "Inflammatory illness is associated with depression" and concluded that their collected results "finds evidence linking abnormalities of blood chemokines with depression in humans."

The second paper is by Köhler and colleagues [2] and, although published slightly earlier this year (2017), similarly set about examining "measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs)" also using a systematic review and meta-analysis. Their results similarly concluded that "a cytokine/chemokine profile [was] associated with MDD."

Combined these two review papers (and other research) provide a compelling case for immune system involvement in at least some cases or classes of cases of depression. Alongside other research [3] asking where the inflammation comes from in potential cases of 'inflammatory depression', there is still much to do in this promising area of interface between immune system/function and psychiatric/behavioural presentation (see here). Then also comes another potentially important implication from such studies: attend to the cytokine/chemokine profile and treat the depression? (see here). I say this with no medical advice given or intended and also acknowledging that the immune system is a mighty, mighty complex thing (see here)...

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[1] Leighton SP. et al. Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis. Molecular Psychiatry. 2017. Nov 14.

[2] Köhler CA. et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017 May;135(5):373-387.

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

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Wednesday, 6 December 2017

'Physical signs' to aid the diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)?

I have to say that I wasn't completely au fait with the Perrin technique mentioned in the article by Lucy Hives and colleagues [1] or the exploration of whether "the five physical signs of the Perrin technique can assist in the screening of patients with CFS/ME, which could then subsequently lead to quicker treatment" but I was interested.

Interested because CFS/ME remains a condition diagnosed on the basis of observable symptoms. As a result, it is still subject to quite a few 'debates' on what the best fitting criteria might be (see here). Anything that might potentially help that diagnostic position is therefore welcomed. Indeed, anything that might provide something approaching an objective diagnosis could potentially open up a whole new world of treatment and intervention...

Accepting that talk of 'Perrin's point' "lymphatic drainage" and "the principle that toxins within fluid in the brain or spine column do not drain away as they should" are probably not everyone's cup of 'science' tea, the authors set about testing the Perrin technique for potentially diagnosing CFS/ME. Also whether "newly trained allied health professional (AHP) with no prior experience of CFS/ME" had the same diagnostic accuracy as more expert AHP. I'm not actually sure what specific disciplines those AHPs were actually following, but looking at the text - "One had 10 years of experience of using the Perrin technique and working with patients with CFS/ME (experienced AHP)" - and the affiliations of the authorship list (see here) - it looks to me like something between physiotherapy and osteopathy as a rough guess.

Approaching 100 participants were recruited for study - "52 patients with CFS/ME and 42 non-CFS/ME controls" - all adults and for those diagnosed with CFS/ME, all with "a prior formal diagnosis of CFS/ME at a National Health Service (NHS) hospital specialised clinic" and displaying various core features of CFS/ME (i.e. persistent fatigue and "the fatigue should feel worse after physical activity"). I note that they also required "a clear starting point to the fatigue." Assessments - "standard clinical neurological and rheumatological" - were also carried out and CFS/ME diagnosis was pitted (blind) against the Perrin technique. Indeed: "A priori, the Perrin technique required all five symptoms to be present for a patient to be diagnosed as CFS/ME." Not to copy too much text from the Hives paper, the five symptoms were: "(1) postural/mechanical disturbances of the thoracic spine... ; (2) breast varicosities... ; (3) tender Perrin’s point... ; (4) tender coeliac plexus... ; and (5) dampened cranial flow."

How did the Perrin technique do? Well, not bad at all: "Results show that, on average, the experienced AHP was most accurate (86%) at correctly diagnosing participants. This was followed by the newly trained who correctly diagnosed 77% and the physician who correctly diagnosed 69% of participants." I reiterate that the clinical team were "blinded to the groupings" (whether or not they were seeing a patient with CFS/ME or not).

Hives et al also provide some data on the specificity and sensitivity of the Perrin technique in relation to CFS/ME diagnosis, as well as some initial chatter about whether all the five symptoms together represent the most efficient grouping. They concluded that: "accuracy for both AHPs, overall, is highest when using only tests of tender coeliac plexus and postural/mechanical disturbance of the thoracic spine" potentially suggesting that "not all of the five physical signs may be necessary."

Whilst pretty interesting results, there is a need for further independent replication before anyone gets too excited about a possible objective test for CFS/ME. The authors similarly note that this was a straight 'yes you're diagnosed with ME/CFS' vs 'no diagnosis of CFS/ME' but also in future need to take into account other conditions potentially overlapping with CFS/ME such as fibromyalgia (FM) and whether the diagnostic waters are still so clear with such comparisons in mind. As I've mentioned in other posts (see here), the tendency in some quarters to conflate CFS/ME with 'chronic fatigue' also perhaps needs some further investigation too.

Still, there are reasons to be optimistic about the Hives findings. How, even alongside more traditional ways and means of diagnosing CFS/ME, the Perrin technique (in whatever form) *might* serve as a useful accompaniment to aiding the diagnostic process and perhaps even further distancing CFS/ME from the whole biopsychosocial model of disease (see here)...

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[1] Hives L. et al. Can physical assessment techniques aid diagnosis in people with chronic fatigue syndrome/myalgic encephalomyelitis? A diagnostic accuracy study. BMJ Open. 2017; 7: e017521.

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Tuesday, 5 December 2017

Methylphenidate as a 'suicide risk reducing agent' in ADHD: implications for other labels?

Don't get me wrong, I'm not falling hook, line and sinker for the findings reported by Sophie Hsin-Yi Liang and colleagues [1] observing that "among ADHD [attention-deficit hyperactivity disorder] youths, reduction of suicide risk was observed in patients prescribed MPH [methylphenidate] for duration 90 days and longer."

I've read too much on how complex something like suicide - ideation, attempts and completion - is to ever believe that there is some single magical answer to universally reducing or eliminating suicidal behaviours and the wide-ranging effects they have. Yes, there are some compounds that have a pretty good evidence base for being an 'anti-suicidal agent' (see here) but even with something like lithium, further investigations are required on their universal applicability and important details like their cost-benefit ratio.

Having said all that, I am drawn to the findings reported by Liang et al for a few very good reasons. First, is the continued reliance on 'big data' Taiwan and the use of the National Health Insurance Research Database (NHIRD) as a research resource. Second, is the continued focus on suicide and possible factors/predictors of suicide based on examination of NHIRD data [2]. Third, is the idea that "rates of suicide ideation, self-injury and suicide attempts are significantly increased in untreated ADHD populations" and how something like MPH use potentially (positively) affecting ADHD symptoms might have other effects. Finally, there is also the tantalising prospect that other conditions/labels where ADHD might be over-represented where also alongside there is a growing focus on suicidal behaviours, the Liang findings might also be relevant...

So what did Liang and colleagues do and find? Well looking at the records of some 85,000 children and young people where ADHD was diagnosed, researchers looked for evidence of recorded suicide attempts as a function of whether MPH was being used or not (where "MPH is the only stimulant approved for the treatment of ADHD in Taiwan"). They found that "100 (0.1%) youths met the criteria for suicide attempts during the surveillance period" and perhaps a little contrary: "37 (0.2%) in the group without any MPH use and 63 (0.1%) in the group with MPH use."

But the devil is in the detail, as authors then factored in a few pertinent, potentially confounding variables (gender, age, other diagnoses, other medication) and length of time of taking MPH (1-90 days, 91-180 days, over 180 days) into models of risk. They concluded that there was actually a 'risk reducing effect' from MPH use following such analyses: "We observed a 59% suicide attempt risk reduction among ADHD youths prescribed between 90 and 180 days and a 72% risk reduction in those prescribed more than 180 days of MPH."

This is not the first time that MPH use for ADHD and suicide risk has been discussed in the peer-reviewed science literature. The paper by Man and colleagues [3] talked about how the incidence of suicide went up before and at the beginning of MPH initiation in their cohort of around 25,000 children and young adults, but importantly risk "returned to baseline levels during continuation of methylphenidate treatment." They account for their findings by suggesting that: "The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment." I put this in the context that ADHD does seem to be a risk factor for various other psychiatric diagnoses (see here and see here). Other independent data [4] has also talked about "a potential protective effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs." There seems to be a case for MPH as potentially affecting [some] suicide risk in relation to [some] ADHD...

I want to now take you back to the title of this post, and specifically the 'implications for other labels?' bit. How ADHD and specifically, MPH use for ADHD symptoms, might offer some important 'lessons' for conditions where for example ADHD is over-represented as a comorbidity. Of course I speak of autism and autism spectrum disorder (ASD) where it is fast becoming accepted that the risk of receiving a diagnosis of ADHD is pretty significantly heightened (see here). Alongside, quite a lot of attention is also being paid to the issue of suicide risk and autism (see here) and specifically, what factors might predispose to an elevated risk of suicide in cases of autism (see here) (hint: it's probably not all just down to depression or indeed, any one factor in isolation). Adding in the Liang findings to autism is, I think, quite a sensible thing to do. No, it's not about shifting 'blame' for suicidal behaviours from one label to the next, but instead realising that for some people on the autism spectrum, ADHD does present an additional 'feature' and such a feature might very well carry with it some increased risk for suicidal behaviours. The other strand of evidence that is probably relevant to this is the idea that the risk of various psychiatric diagnoses seem also to be elevated alongside a diagnosis of autism. The prospect therefore that MPH used to manage ADHD occurring alongside autism might reduce any risk of suicidal behaviours is something that requires quite a bit more investigation.

And while I'm mentioning MPH in the context of [some] autism, the recent Ccohrane review of MPH for kids and young people diagnosed with autism [5] suggests something quite positive when it comes to issues such as "symptoms of hyperactivity and possibly inattention" (albeit with more research required)...

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[1] Liang SHY. et al. Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: A Taiwan nationwide population-based cohort study. Research in Developmental Disabilities. 2018; 72: 96-105.

[2] Lin YW. et al. Influential Factors for and Outcomes of Hospitalized Patients with Suicide-Related Behaviors: A National Record Study in Taiwan from 1997-2010. PLoS One. 2016 Feb 22;11(2):e0149559.

[3] Man KKC. et al. Association of Risk of Suicide Attempts With Methylphenidate Treatment. JAMA Psychiatry. 2017 Oct 1;74(10):1048-1055.

[4] Chen Q. et al. Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study. BMJ. 2014 Jun 18;348:g3769.

[5] Sturman N. et al. Methylphenidate for children and adolescents with autism spectrum disorder. Cochrane Database Syst Rev. 2017 Nov 21;11:CD011144.

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Monday, 4 December 2017

Is the word 'comorbid' accurate when describing emotional and behavioural issues occurring alongside autism?

The findings reported by Per Normann Andersen and colleagues [1] observing that: "The amount of autism symptoms and degree of attention problems at baseline significantly predicted EBP [emotional and behavioral problems] at follow-up" potentially taps into a wider discussion in the context of autism.

EBP refers to feeling "anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, and aggressive behavior." The wider discussion is framed around a question on whether use of the term 'comorbid' - comorbid EBP for example - is accurate when it comes to such 'issues' appearing alongside the core features of autism? Should instead we be thinking and talking about comorbid issues/symptoms such as depression and anxiety as being something rather more central to at least 'some' autism? Y'know, is there a lot more than just the the triad/dyad of core features for some at least?

It's a discussion that has emerged before on this blog (see here and see here) and continues in the peer-reviewed science arena [2]. It has some potentially profound implications for things like autistic identity, the distinction between autism as a developmental condition as opposed to a psychiatric disorder, talk about the 'disabling aspects' of autism (and 'where they potentially come from') and the often polarised topic of intervention specifically 'for autism'...

Andersen et al report results based on analysis of children and adolescent diagnosed with autism - 'high-functioning' autism (HFA) (their term not mine) - where "levels of EBP, autism symptoms, inattention problems, and verbal IQ" were assessed at baseline and 2 years later.  The aim was to see whether symptoms such as autism "can predict EBP 2 years later."

Interestingly, the authors opted for the use of the Autism Spectrum Screening Questionnaire (ASSQ) as one of their study instruments, [partly] devised by a researcher who I have a lot of time for on this blog (see here) and his equally pertinent concept of ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations). This was complemented by "the Schedule for Affective Disorders and Schizophrenia for School Age Children/Present and Lifetime version-2009 (K-SADS-PL)" covering questions on possible "affective disorders, psychotic disorders, anxiety disorders, behavioral disorders (ADHD), substance abuse disorders, eating disorders, tic disorders and ASD [autism spectrum disorder]" and the ADHD rating scale IV among others research tools.

Results: "the level of autism symptoms at baseline were the best predictor of EBP in our group of children with HFA." The authors also observed that "attention problems had an independent impact on EBP" but noted that whilst autism and attention issues correlated at baseline, the role of attentional issues on EBP was "considerably less compared to the level of autism symptoms." Authors also stated that verbal IQ did not seemingly predict EBP, which is perhaps at odds with other independent research on a similar topic (see here). They conclude by suggesting that "interventions aimed at improving ASD symptoms may positively affect the prevalence of EBP in children with HFA."

Of course the Andersen study was not perfect and one has to be careful not to extrapolate too much. As the authors note, their study: "focused on symptoms of autism and attention, and we cannot generalize these findings to those with ASD and clinical diagnoses of ADHD" representing one important limitation. They add that their focus on those with an IQ above 70 and their investigating a very 'male-orientated' sample group also limited the generalisability of their findings to the entire autism spectrum; particularly some of the 'under-studied' people of the autism spectrum (see here). And before you mention it, yes, IQ still needs quite a bit more research work done on it when it comes to autism...

Nevertheless, I believe that these findings do add to an increasingly vocal peer-reviewed research evidence base suggesting that the term 'comorbidity' might not be the most 'useful' description when it comes to chatter about a range of labels/conditions/symptoms that are seemingly over-represented in relation to autism. Indeed, as per more historical mentions - yes, Mildred Creak yet again - set within the context of the plural 'autisms' (see here), many issues described today as 'comorbid' may eventually turn out to be rather more central to [some] autism...

The idea also discussed by Andersen et al about 'intervening' in/on the traditional 'core symptoms' of autism as potentially 'offsetting' some of the effects of those EBP is, no doubt, going to be a bit of a hot potato. We do have a few other examples showing how a reduction/dissipation of core autism symptoms does seem to impact on 'comorbid' signs and symptoms as per some of the discussions on the term 'optimal outcome' (see here). In the example recorded by Gillberg et al [3] observing that "The minority of the AS [Asperger syndrome] group who no longer met criteria for a full diagnosis of an autism spectrum disorder were usually free of current psychiatric comorbidity", we see how there could be quite a bit more to a diagnosis of autism (AS) than has traditionally been recognised. Other research from Andersen and colleagues [4] talking about the same cohort as being discussed today with depression and autism presentation again in mind likewise adds to such 'intervening' sentiments.

I have one final point to make just in case the idea of intervening does not sit well with some: if one assumes that something like depression is in fact, a core part of some autism and could be 'modified' by intervention(s) targeting core autism symptoms, there is a potentially important impact to be made on one of the primary issues affecting the autistic population: risk of suicide. I say that on the basis that depression or related psychiatric disorder (see here) is an all-too-frequent companion when it comes to suicidal behaviour(s) and therefore represents a potentially modifiable variable. Exactly how and where intervention on core autism symptoms is done is another question for another day; also bearing in mind that 'current' core autism symptoms themselves, might be an important risk factors when it comes to suicidal thoughts/behaviours (see here).

Lots more research is indicated, minus hype and minus too much politics...

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[1] Andersen PN. et al. Severity of Autism Symptoms and Degree of Attentional Difficulties Predicts Emotional and Behavioral Problems in Children with High-Functioning Autism; a Two-Year Follow-up Study. Frontiers in Psychology. 2017; 8: 2004.

[2] Nah Y-H. et al. Brief Report: Screening Adults with Autism Spectrum Disorder for Anxiety and Depression. J Autism Dev Disord. 2017. Dec 2.

[3] Gillberg IC. et al. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis. J Autism Dev Disord. 2016 Jan;46(1):74-82.

[4] Andersen PN. et al. Associations Among Symptoms of Autism, Symptoms of Depression and Executive Functions in Children with High-Functioning Autism: A 2 Year Follow-Up Study. J Autism Dev Disord. 2015 Aug;45(8):2497-507.

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Sunday, 3 December 2017

Vitamin D for schizophrenia? No but...

The results published by Amir Krivoy and colleagues [1] talking about "no significant effect of vitamin D on psychotic, depressive or metabolic parameters" in a cohort of people diagnosed with schizophrenia, make for interesting reading.

Interesting, not only because authors reported very little effect of supplementation on the symptoms of schizophrenia, but also because such 'negative' findings kinda follow a theme in vitamin D - psychiatric research circles: low levels of vitamin D (insufficiency and/or deficiency) being associated with a condition (see here) yet little [experimental] evidence that supplementation does anything more than correct the vitamin D availability issues (see here for another example). Certainly the quite significant speculation that vitamin D might have lots and lots of 'extra-bone' related actions do not yet seem to have been borne out by the currently available experimental data in this area...

Krivoy et al describe the methodology and results of their "eight-week, randomized, double-blind, placebo-controlled clinical trial" focused on some 47 patients "age between 18 and 65 years old, diagnosis of schizophrenia according to DSM-IV-TR criteria confirmed by two senior psychiatrists, treated with clozapine for at least 18 weeks and being on a stable clozapine dose for at least four weeks prior to enrollment, serum 25(OH) vitamin D level below 75 nmol/L (30 ng/ml) and total severity of psychopathology score, as measured by the Positive and Negative Symptom Scale (PANSS) total score above 70." Vitamin D supplementation - 14,000 IU [international units] per week - was pitted against a placebo formulation, although I can't seem to find what exactly the placebo contained (N=24 vs. N=23 respectively). Various outcome measures were used to determine any effect or not.

Results: as per the opening line of this post, there was little to see between the vitamin D and placebo receiving groups when compared on the basis of PANSS scores. Both groups showed a trend towards a decreasing total and sub-scale psychopathology scores over the course of the experimental period indicative of some modest improvement in psychiatric symptoms. At the same time, authors report that vitamin D levels did change amongst those in receipt of the vitamin D supplement: "The 25(OH) vitamin D serum levels increased significantly in the drug group... while essentially unchanged in the placebo group" so we can be pretty sure that there was both compliance with the experimental regime and that vitamin levels were increasing in the supplemented group as expected.

There was one small 'ray of hope' when it came to supplementation that has been hinted at in the research literature previously: "A beneficial effect of vitamin D supplementation was noted on cognitive performance, as reflected in an increase in MoCA [Montreal Cognitive Assessmenttotal score." I say 'hinted at' because although it is a little premature to talk about vitamin D as a nootropic (cognitive enhancer), there is evidence that low levels of the stuff *might* under certain circumstances, negatively affect certain cognitive abilities (see here for example). Whether supplementation with vitamin D is a more general cognitive 'affector' remains to be seen but the Krivoy results suggest further inspection is indicated.

There is more to do in this area before the vitamin D - schizophrenia link is branded completely spurious. The authors mention the relatively small sample sizes included for study and how the nature of schizophrenia as a condition potentially means that "patients with extreme presentation are less likely to consent to participate in a randomized controlled trial due to their paranoid and suspicious attitudes" as being something important. It's also interesting that at least one of the supplemented participants seemed to show little response to vitamin D in a physiological levels sense: "This patient, despite attending all assessments and dosing visits, showed vitamin D level of 22 nmol/L at baseline and 17 nmol/L at endpoint due to unclear reasons." Assuming that vitamin D testing was accurate i.e. using something like mass spectrometric methods over older, potentially less reliable assays (see here) I wonder if there could be other components required in future studies in this area, such as also looking at the genetics of vitamin D metabolism as per other, unrelated research (see here).

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[1] Krivoy A. et al. Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial. EBioMedicine. 2017. Nov 29.

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Saturday, 2 December 2017

US National Health Interview Survey (NHIS) on autism rates and beyond

The US National Center for Health Statistics (NCHS) has recently released a data brief [1] covering the topic of diagnosed developmental disabilities and specifically: "the latest prevalence estimates for diagnosed autism spectrum disorder, intellectual disability, and other developmental delay among children aged 3–17 years from the 2014–2016 National Health Interview Survey (NHIS)."

The figures show a number of trends in relation to various diagnoses; not least that the prevalence of autism spectrum disorder (ASD) rose year on year between 2014 and 2016, albeit not significantly. In 2014, the percentage of positive responses to the question: "Has a doctor or health professional ever told you that [sample child] had Autism, Asperger’s disorder, pervasive developmental disorder, or autism spectrum disorder?" was 2.24%; in 2015 it was 2.41% and in 2016 it was 2.76%. I might add that we already knew what the 2014 data showed given other publications (see here).

When it came to the categorisation of developmental disability - "A composite measure of children with a diagnosis of autism spectrum disorder, intellectual disability, or any other developmental delay" - the figures were rather more significant. So: "During 2014–2016, the prevalence of children aged 3–17 years who had ever been diagnosed with a developmental disability increased from 5.76% to 6.99%." The categorisation 'other developmental delay' seemed to be the main driver of the [statistically significant] increase in that composite measure (2014: 3.57%; 2015: 3.56%; 2016: 4.55%).

There are a few additional details to mention about the report by Benjamin Zablotsky and colleagues. Boys, yet again, were the over-represented group when it came to all and total categories and race/ethnicity seemed to show some important differences such as a typically lower percentage estimate being present for most diagnoses in Hispanic children compared to other groups.

What can we make of these recent statistics? Well, it's pretty evident that, for whatever reason(s), there is still an upward trend when it comes to a diagnosis of autism and various other developmental labels. It's worthwhile pointing out that the current report used "a more restrictive definition for a developmental disability that does not include conditions such as attention-deficit/hyperactivity disorder or learning disabilities" so the figures might also not be entirely reflective of the 2014-2016 situation. I also had a question in mind about what the difference was between 'intellectual disability' (shown) and 'learning disability' (not shown) given their interchangeable meaning at least here in Blighty (see here).

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[1] Zablotsky B. et al. Estimated prevalence of children with diagnosed developmental disabilities in the United States, 2014–2016. NCHS Data Brief, no 291. Hyattsville, MD: National
Center for Health Statistics. 2017

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Friday, 1 December 2017

"a pooled ASD prevalence of 6.3% in individuals with epilepsy"

The quote heading this short-ish post came from the findings reported by Lauren Strasser and colleagues [1] who systematically reviewed and meta-analysed the collected data pertinent to "the prevalence and risk factors for autism spectrum disorder (ASD) in epilepsy."

Bearing in mind that epilepsy is quite a comprehensive term, authors estimated that some 6-7% of those diagnosed with epilepsy or a condition manifesting epilepsy will also present with an ASD. Further that specific types of epilepsy might confer a specific risk for ASD: "When divided by type, the risks of ASD for general epilepsy, infantile spasms, focal seizures, and Dravet syndrome were 4.7%, 19.9%, 41.9%, and 47.4% respectively."

The relationship between autism and epilepsy has been known about for many years (see here). We know for example, that age and intellectual functioning level play a role in the risk of developing epilepsy in the context of autism but are careful with sweeping generalisations (see here). We also know that a growing number of genetic conditions manifest both as autism or autistic traits and epilepsy (see here for example). We even have 'colliding' research areas talking about options for treating some 'difficult to treat' cases of epilepsy as perhaps also impacting on some of the features of autism too (see here) (with no medical or clinical advice given or intended).

What's also being recognised a little more in the peer-reviewed research literature and beyond is that being diagnosed with certain types of epilepsy also potentially impacts on the risk of autism or ASD also being diagnosed or presenting with 'significant' autistic traits (see here and see here). This to me has quite a few important implications, not least that this data "may help clinicians in early screening and diagnosis of ASD in this population." It also cements the relationship between autism and epilepsy / epilepsy and autism and further asks whether for some people at least, 'comorbidity' in relation to the presence of both terms should be replaced with something rather more core and fundamental?

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[1] Strasser L. et al. Prevalence and risk factors for autism spectrum disorder in epilepsy: a systematic review and meta-analysis. Dev Med Child Neurol. 2017 Nov 9.

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