Colliding spectrums: autism and schizophrenia (meta-analysed)

Consider this post talking about the findings reported by Jorge Lugo Marín and colleagues [1] an extension of previous chatter on this blog about the possibility of overlapping spectrums when it comes to autism and schizophrenia (see here).

I appreciate that there is some 'history' when it comes to moves to separate autism and schizophrenia [2] but the evidence being produced more recently perhaps questions whether the historical 'eagerness' to compartmentalise the labels as separate and independent was more of a socio-political thing over and above a true reflection of the state of any relationship (see here and see here for examples). Indeed, when [peer-reviewed] science for example, starts talking about a possible 'subtype of autism linked to psychosis' (see here) you know that the connections are perhaps not to be under-estimated...

Lugo Marín et al report results following a meta-analysis of the relevant peer-reviewed science done on this topic. Ten papers fulfilled their inclusion criteria. They report that: "The pooled prevalence of SSD [schizophrenia spectrum disorder] in the total ASD [autism spectrum disorder] sample was close to 6%, pointing to a high co-occurrence of the two conditions." Further, that more research is required about the specific hows-and-whys of SSD or symptoms of SSD appearing alongside [some] autism (and vice-versa) and onward, the possibility of preferential screening and intervention.

I've thought about the relationship between autism and schizophrenia quite a bit over the years. Not only because in my own area of research interest - gluten- and casein-free diets and autism - there is history linking autism and schizophrenia (see here) but also because the relationship down the years seemingly plays into the stigmatisation of a label i.e. move autism 'away' from schizophrenia because of the perceived 'dangerousness' connotations attached to schizophrenia for example (see here for a more recent example of this in action [3]). On that point, the evidence is getting clearer that whilst the diagnosis of schizophrenia (plus other factors) is by no means preventative of 'dangerous' acts being committed, people diagnosed with the condition are seemingly far more likely to be victims of something like crime than perpetrators (see here). Sounds familiar doesn't it?

Then also there is the 'identity' perspective to consider when talking about autism and schizophrenia in the same breath. Schizophrenia is considered to be a mental health issue; autism by contrast is primarily viewed as a developmental condition, which, although increasing the risk of developing a mental health issue (see here for example), is not itself described as such per se. I say this acknowledging that support for schizophrenia as being a 'neurodevelopmental disorder' is also growing [4] as words like 'prodrome' become more frequently discussed. Also important in this context, are the possible effects of certain comorbidity being 'over-represented' in cases of autism potentially also impacting on the subsequent risk of a diagnosis of schizophrenia (see here).

Keeping the theme of 'identity' going when discussing autism and schizophrenia, there is another angle to consider in terms of 'ownership' of the labels and perceptions around such a concept. I speak of the movement towards use of terms like 'autistic person' over 'person with autism' preferentially considered by some (see here) and how such a move is seemingly at odds with identity in terms of schizophrenia. The term 'schizophrenic' is considered unsuitable in this day and age (see here - "A person is not the sum total of the symptoms") alongside other 'label-first' terms such as 'manic depressive' and 'psychotic' for example. You can perhaps see how labelling someone as 'autistic' whilst at the same time labelling them has 'having schizophrenia' under circumstances where the two spectrums collide, presents a quandary when it comes to language and identity and perhaps serves to reiterate the gulf between the labels/conditions in terms of perceived stigma for example.

What we can say on the back of the Lugo Marín findings is that, in these days of ESSENCE (see here) and RDoC (see here) the possible reunification of the autism and schizophrenia spectrums in specific cases, should not be seen as something detrimental to either label and could provide some important insights into the genetic and biological nature of both spectrums (see here). I have my views about where the two spectrums might meet on a biological level [5] but no doubt there will be lots of other intersections too. Indeed, once again harking back to the [sadly forgotten] writings of Mildred Creak and colleagues and their "9 key features of ‘schizophrenic syndrome in childhood’", their description is uncannily pertinent to large parts of the autism spectrum when taking into account inclusion of diagnostic items such as "abnormal perceptual experience", "distortion in motility patterns" and "acute, excessive and seemingly illogical anxiety" and the often pronounced effects that such symptoms can have on quality of life.



To close, a picture relevant to today...

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[1] Lugo Marín J. et al. Prevalence of Schizophrenia Spectrum Disorders in Average-IQ Adults with Autism Spectrum Disorders: A Meta-analysis. J Autism Dev Disord. 2017 Oct 4.

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

[3] Sasson NJ. & Morrison KE. First impressions of adults with autism improve with diagnostic disclosure and increased autism knowledge of peers. Autism. 2017 Oct 1:1362361317729526.

[4] Owen MJ. et al. Neurodevelopmental hypothesis of schizophrenia. The British Journal of Psychiatry. 2011;198(3):173-175.

[5] Prata J. et al. Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation. 2017 Sep 4;14(1):179.

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Pregnancy hypertension and offspring autism reloaded

"There is growing awareness that prenatal adversity may increase the risk of autism spectrum disorder (ASD)."

Go on.

"These findings indicate that HDP [hypertensive disorders of pregnancy] exposure may increase the risk of ASD in the offspring."

So said the findings reported by Eileen Curran and colleagues [1] whose results have previously appeared on this blog with hypertension in mind (see here). I'm not altogether sure if this latest publication from this group represents 'new data' or is the same as/similar to that previously published [2]. It doesn't really matter to be honest given that the latest publication also includes a research addition insofar as the examination of "cytokine expression in the serum of women with pre-eclampsia, which is the most common HDP, and whether exposure of foetal neurons to this serum could change patterns of neuronal growth."

Drawing on data from some 13,000 children whose details were included in the Millennium Cohort Study (MCS) researchers, after "adjusting for several potential confounders including maternal alcohol consumption, education, depression, age, and poverty status", observed "a significant association between HDP and a twofold increased risk of ASD." They also reported that: "exposure of foetal cortical neurons to 3% serum isolated from women with an established HDP increased neuronal growth and branching in vitro." The authors have reported similar things with attention-deficit/hyperactivity disorder (ADHD) in mind too [3]; something that might be particularly important in the context of autism and ADHD overlapping in quite a few people (see here).

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[1] Curran EA. et al. Exposure to Hypertensive Disorders of Pregnancy Increases the Risk of Autism Spectrum Disorder in Affected Offspring. Mol Neurobiol. 2017 Oct 3.

[2] Curran EA. et al. Hypertension in pregnancy and autism spectrum disorder in a British cohort: Long term consequences for mother and child. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2016; 6: 153.

[3] Curran EA. et al. The effect of hypertensive disorders of pregnancy on the risk of attention-deficit/hyperactivity disorder in the offspring: Long term consequences for mother and child. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2016; 6: 169–170.

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Fatty acids and autism meta-analysed again (yet again)

"Our preliminary meta-analysis suggests that supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in ASD [autism spectrum disorder] patients."

So said the results of the meta-analysis of randomized controlled trials undertaken by Yu-Shian Cheng and colleagues [1] adding further to this interesting area of nutrition with autism in mind. Before venturing through the results, I'll draw your attention to two other occasions this year when fatty acids use and autism have been given the meta-analysis treatment (see here and see here) albeit coming to slightly different conclusions.

This time around six studies made the grade for inclusion in the meta-analysis covering nearly 200 participants. All pitted an omega-3 fatty supplement against placebo and discussed study periods ranging from 6 weeks to 24 weeks. Various schedules were used to measure the impact (if any) of supplementation and/or placebo but the Autism Behavior Checklist (ABC) seemed to be one of the more frequently used assessment scales.

Results: bearing in mind "the average Jadad score was 4.67 with a standard deviation of 0.52" denoting that the methodological quality of the collected literature was pretty good, authors reported a general skewing trend towards 'better response by omega 3' over that of response to the placebos used by the various studies. This covered various areas of both core autistic behaviour(s) such as stereotypy and other, quality of life affecting parameters such as hyperactivity.

But... the clinical picture was not so clear-cut when it came to other autism-related measures such as the SRS - Social Responsiveness Scale - where "there was only borderline improved response by placebo in SRS total scores than those by omega 3." Taking into account the collected results, I do wonder whether use of something like an omega-3 supplement with autism in mind might actually be more relevant to the presence of co-occurring attention-deficit hyperactivity disorder (ADHD) given that (a) ADHD is very much over-represented in relation to autism (see here) and (b) the evidence base on the use of fatty acid supplements for ADHD seems to show a much more 'clear' positive relationship (see here).

There is another point raised in the Cheng paper that is worth noting: "Meta-analysis demonstrated no significant difference in the rate of discontinuation due to side effects between children receiving omega 3 and those treated by placebo." Although this does not mean that fatty acid supplements are universally 'side-effect' free, it does provide some good evidence that such supplementation was generally well-tolerated by the cohorts included for study. I say this bearing in mind that: "Gastrointestinal discomfort and irritability were most commonly reported side effects in the omega 3 groups" understanding that gastrointestinal (GI) issues are already over-represented when it comes to autism (see here).

Minus sweeping generalisations and keeping in mind the prime directive of this blog - no medical or clinical advice is given or intended - I have to say that the peer-reviewed science base for using omega-3 fatty acid supplements in the context of autism (or autism+ADHD?) is looking rather favourable. I say that in connection to the behavioural data that has so far been produced following supplementation but also more generally, with population evidence that omega-3 supplement seems to be good for aspects of physical health and wellbeing too. Certainly, the risk-benefit profile of fatty acid supplementation seems to favour benefit over risk...

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[1] Cheng Y-S. et al. Supplementation of omega 3 fatty acids may improve hyperactivity, lethargy, and stereotypy in children with autism spectrum disorders: a meta-analysis of randomized controlled trials. Neuropsychiatric Disease and Treatment 2017: 13  2531–2543.

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Vitamin-mineral mix for ADHD part 2

"Although direct benefit for core ADHD [attention-deficit hyperactivity disorder] symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation."

So said the findings reported by Julia Rucklidge and colleagues [1] posting results from their "fully blinded randomized controlled trial" of micronutrients in the context of childhood ADHD. Said study is similar to other research from this authorship group that has been previously covered on this blog (see here). The trial protocol (prospectively registered!) can be seen here and provides further details of the micronutrients in question, study design and various outcome measures employed.

Medication-free children diagnosed with ADHD were assigned to either the micronutrient formulation or placebo for 10 weeks. This was not a study for faint-hearted when it came to pill swallowing as up to 12 capsules a day were required to taken over the course of the study period. Then: "Data were collected from clinicians, parents, participants and teachers across a range of measures assessing ADHD symptoms, general functioning and impairment, mood, aggression and emotional regulation."

Results: well as per the opening sentence to this post, there were some important differences noted across the vitamin-mineral supplement group compared with the placebo arm of the trial. But: "No group differences were identified on clinician, parent and teacher ratings of overall ADHD symptoms." It appeared instead that specific aspects of ADHD presentation and more general issues such as aggression were seemingly affected by the micronutrient supplementation but effects were not necessarily just in universal terms of ADHD.

There are a few other important details to add to this post. First: "no group differences in adverse events and no serious adverse events identified" so taking a vitamin-mineral supplement in the context of paediatric ADHD over 10 weeks is a relatively safe affair we are told. I wouldn't have thought anything different to be honest. Bear also in mind that those diagnosed with ADHD may be at greater risk of vitamin deficiencies according to other research (see here) so there may have been a clinical need here also. Second, vitamin and mineral supplements are pretty widely available for many different age groups so getting hold of them is not likely to be a problem. Looking at the specific formulation used, it appears however that an important class of nutrient(s) are missing: essential fatty acids. I could be wrong, but given the quite large body of peer-reviewed research talking about specific fatty acid supplementation in the context of ADHD (see here) one might have expected to have seen this in the formulation used?

There is apparently more to come from this research initiative so I'll probably be posting a part 3 to complement this and the previous post on this topic. As part of the whole 'nutritional medicine as mainstream in psychiatry' ethos (see here) and bearing in mind the range of adverse outcomes over-represented when it comes to a diagnosis of ADHD (see here for example) I'd like to think that relatively simple and affordable moves to manage [some aspects of some] ADHD involving nutritional tools (see here also) are going to continue to be on the research agenda for some time yet.

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[1] Rucklidge JJ. et al. Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial. J Child Psychol Psychiatry. 2017 Oct 2.

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Mercury levels and autism meta-analysed

"Indeed, if someone is looking for yet another systematic review and meta-analysis topic, there you go - you're welcome." Those are my words on a previous blogging occasion earlier this year discussing yet another peer-reviewed article on the topic of heavy metals and autism (see here). The findings reported by Tina Jafari and colleagues [1] have seemingly done just that with their meta-analysis of the collected science literature up to June 2017 looking at assessing the "relationship between ASD [autism spectrum disorder] and mercury levels in hair, urine, blood, red blood cells (RBC), and brain."

OK, I know that mention of mercury in the context of autism can be a bit of hot potato in terms of the different types of mercury and their potential sources (see here). I don't want to get into any specific debates on wheres-and-hows in this post but rather focus on what the peer-reviewed science currently says (see here). Jafari et al describe how from the 40+ articles they included for analysis, several themes emerged: (1) blood and brain levels of mercury seemed to be generally elevated in cases of autism vs. controls, and (2) hair levels were typically lower in autism vs controls. Urinary mercury levels were described as "not significantly different" comparing autistic and non-autistic groups although I'll draw your attention to some 'technical talk' in this area that could potentially affect any results produced (see here).

The authors go on to talk about how "detoxification and excretory mechanisms are impaired in ASD patients which lead to accumulation of mercury in the body" which - minus sweeping generalisations - is a conclusion that I've pretty much settled on when talking about some of the findings in this area down the years. There are likely many mechanisms involved in the removal of heavy metals such as mercury from the body but one group in particular, the intersecting "redox and methylation" pathways [2] stand out in view of other research on glutathione levels and autism for example (see here). Other research has pointed to other biological mechanisms that may be worth research consideration [3].

What can and should be done in this area? Well minus any medical or clinical advice given or intended, there are protocols in place as and when mercury poisoning is diagnosed in the general population. There is no reason to assume that these same protocols shouldn't be followed if and when mercury poisoning is diagnosed alongside autism or ASD save any further health inequalities appearing. Autism science needs to also continue it's interest in this area and perhaps make move towards what can be done for example, to 'prop up' biological mechanisms that aid in the detoxification of things like mercury. This may take the form of some rather peculiar research directions (see here) but nonetheless is an area that could potentially be important. Finally, there is the idea that if there are biological issues associated with the removal of several heavy metals including mercury in cases of autism, greater focus on 'avoidance' might also be important. I say this on the basis of findings such as those by Jia Ryu and colleagues [4] who for example, observed that "blood mercury levels at late pregnancy and early childhood were associated with more autistic behaviors in children at 5 years of age." Yes, correlation is not the same as causation, but can we/should we take the chance that the two are connected particularly knowing how detrimental heavy metals can be to human health?

Music to close: Ain't That A Shame by Fats. RIP.

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[1] Jafari T. et al. The association between mercury levels and autism spectrum disorders: A systematic review and meta-analysis. J Trace Elem Med Biol. 2017 Dec;44:289-297.

[2] Hodgson NW. et al. Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman. Exp Biol Med (Maywood). 2014 Jun;239(6):697-706.

[3] Gump BB. et al. Background lead and mercury exposures: Psychological and behavioral problems in children. Environmental Research. 2017; 158: 576-582.

[4] Ryu J. et al. Associations of prenatal and early childhood mercury exposure with autistic behaviors at 5 years of age: The Mothers and Children's Environmental Health (MOCEH) study. Science of The Total Environment. 2017; 605-606: 251-257.

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Generalised joint hypermobility: not so generalised in the non-clinical general population

"Although GJH [generalised joint hypermobility] is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population."

'A normal population' is not exactly the term that I would use to denote a non-clinical population (hands up if you're 'normal') but I was interested in the findings reported by Martin Glans and colleagues [1] (open-access) talking about how GJH does seem to be over-represented in cases of autism (see here), attention-deficit hyperactivity disorder (ADHD) and other ESSENCE-type overlaps (see here) but does not seem to be frequently present in a non-clinical population. To quote: "... in a non-clinical, adult Swedish population comparing individuals endorsing or not endorsing GJH traits (broadly defined), we found no difference in self-reported symptoms of ADHD or ASD, nor self-reported childhood clumsiness."

The suggestion of a link between joint hypermobility disorders and psychiatry has been around for a while now (see here). Joint hypermobility describes an "ability to extend several synovial joints beyond their normal limits" and is a frequent feature of several connective tissue disorders including Ehlers-Danlos syndrome (EDS). There's still quite a bit of debate about hows-and-whys of joint hypermobility rates being elevated in particular neurodevelopmental conditions but I've speculated that other somatic presentations of GJH such as those affecting the bowel [2] might eventually provide some clues for some groups (see here for example) in the context of a proposed gut-brain axis [3].

This time around Glans et al set about asking nearly 900 people about both their GJH symptoms via the 5PQ (Five-Part Hakim-Grahame Questionnaire) and presentations around diagnoses such as autism and ADHD. The AQ-10 was the autism-symptoms measure used, which, as regular readers might know, I've always been a little hesitant about when it comes to it's ability to separate out autism from other potential diagnoses (see here). No mind, after excluding "thirty-two individuals (3.6%) [who] endorsed being diagnosed with ADHD or ASD [autism spectrum disorder] or did not respond to this question" researchers reported that around a third of their sample "endorsed two or more items on the 5PQ, suggesting GJH in accordance with our criteria." When also examining responses pertinent to autism or ADHD, researchers reported no outstanding results linked to the presentation of GJH symptoms. They did observe something of a *possible* link between "extraordinary hypermobile women" and their ADHD symptoms measure for example, but this was based on a very small sample number indeed.

"Contrary to our hypothesis, we did not find any relationship between GJH and neurodevelopmental traits, nor between GJH and clumsiness in our primary analyses." The authors seem to be quite surprised by their findings. Bearing in mind the fact that researchers were exclusively basing their findings on the results of self-report questionnaires (including GJH symptoms) and the like, the observations made are interesting and potentially suggest that "GJH is not a dimensional trait associated with neurodevelopmental symptoms in the general population" but something perhaps more integral to clinically-relevant signs and symptoms. Further, independent replication might shed some more light on this potentially important topic.

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[1] Glans M. et al. Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population. British Journal of Psychiatry Open. 2017; 3: 236-242.

[2] Beckers AB. et al. Gastrointestinal disorders in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: A review for the gastroenterologist. Neurogastroenterol Motil. 2017 Aug;29(8).

[3] Whiteley P. Food and the gut: relevance to some of the autisms. Proc Nutr Soc. 2017 Sep 26:1-6.

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NEET (not in education, employment or training) status and mental health

"NEET [not in education, employment or training] status and negative symptoms are modifiable predictors of illness trajectory across diagnostic categories and are not specific to transition to psychosis."

So said the findings reported by Shane Cross and colleagues [1] (open-access) who set out looking at the "trans-diagnostic study of rates and predictors of early transition from sub-threshold to full syndromal mental disorder" with "sub-syndromal unipolar, bipolar and psychotic disorders" in mind. This work adds to a growing body of research suggesting that "social as well as clinical characteristics of individuals presenting to youth mental health services for the first time (e.g. demography, symptom severity, functional impairment and NEET status) can help to predict the likelihood of and time to early transition across diagnostic groups."

Nearly 250 people aged 15-25 who were deemed to present with "a sub-syndromal presentation of a potentially severe mental disorder" were followed for a year to see if and whether there 'sub-syndromal' status 'transitioned' to a a full syndromal psychiatric disorder. Various measures were employed to assess current symptoms as well as researchers keeping an eye on those social factors including NEET status.

Results: around 15% of the group moved from a sub-syndromal status to "threshold caseness" during the study period: "Eleven per cent (11%) of sub-syndromal depressive cases, 40% of individuals with sub-syndromal psychosis and 22% of individuals with sub-syndromal bipolar disorder transitioned to stage 2 [threshold caseness]." Gender seemed to play a role - more females than males transitioned - and more negative symptoms - blunted affect, emotional withdrawal, motor retardation - as measured using the Brief Psychiatric Rating Scale (BPRS) seemed to show an effect also.

NEET status was also flagged up as a potentially important variable in transition: "26% of those who were categorised as NEET at baseline versus 16% of those who were not NEET had reached threshold caseness." NEET status as a variable also seemed to span various different psychiatric labels too.

What are the implications of such findings? Well, aside from providing a little more data about what factors might move someone from sub-clinical presentation of a mental health condition to full 'caseness' they also provide evidence that social factors might play a role. By saying this, I'm not going all 'biopsychosocal' on you (I think we've had quite enough of that, thank you very much) but rather stressing that both biological and social drivers probably impact on mental health as per other examples in the [growing] peer-reviewed research literature in this area (see here).

Other research from members of the Cross paper have looked at the possible drivers of NEET status [2] and where 'early intervention' might need to focus to offset risk of this social outcome (and potentially then impact on risks to mental health too) bearing in mind that intervention might need to be cross-generational [3].

I however, close with research indicating that any sweeping generalisations about those fulfilling NEET status as being 'unmotivated' to work are not warranted on the basis of the existing peer-reviewed science in this area [4] and what implications this has for mental health issues...

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[1] Cross SPM. et al. Predicting early transition from sub-syndromal presentations to major mental disorders. British Journal of Psychiatry Open. 2017; 3: (5) 223-227.

[2] Lee RSC. et al. A transdiagnostic study of education, employment, and training outcomes in young people with mental illness. Psychol Med. 2017 Sep;47(12):2061-2070.

[3] Alfieri S. et al. Young Italian NEETs (Not in Employment, Education, or Training) and the Influence of Their Family Background. Eur J Psychol. 2015 May 29;11(2):311-22.

[4] Goldman-Mellor S. et al. Committed to work but vulnerable: self-perceptions and mental health in NEET 18-year olds from a contemporary British cohort. J Child Psychol Psychiatry. 2016 Feb;57(2):196-203.

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Shocker alert: gut problems in autism impact on sleep

I don't mean to be sarcastic about the findings reported by Lena McCue and colleagues [1] talking about how gastrointestinal (GI) dysfunction might show an *association* with sleeping problems in the context of autism. There was however, an air of 'inevitability' about such findings that has been discussed previously in the peer-reviewed science literature (see here)...

Researchers drew upon data from the Autism Genetic Resource Exchange (AGRE) research program (something that they've done before) to identify over 600 children and young adults diagnosed with "idiopathic autism spectrum disorder, aged 2-18 years" (idiopathic = autism not secondary to a known genetic condition). They examined data on the presence of GI and sleep issues in order to gauge whether there was any relationship between the two.

Lo and behold: "The adjusted odds ratio for sleep disorder among those with gastrointestinal dysfunctions compared to those without was 1.74 (95% confidence interval: 1.22-2.48)." Results held even when various potentially confounding variables were taken into account. Ergo: "Early detection and treatment of gastrointestinal dysfunctions in autism spectrum disorder may be means to reduce prevalence and severity of sleep problems and improve quality of life and developmental outcomes in this population."

Gastrointestinal (GI) issues are very much over-represented when it comes to autism (see here). I'd say that the evidence is pretty overwhelming for that last statement both when it comes to functional bowel issues such as constipation and/or diarrhoea (see here) and also risk of more pathological conditions too (see here). Indeed, we've had peer-reviewed published guidance on screening and treating bowel issues in relation to autism [2] for some time now. Sleeping issues are also over-represented in relation to autism (see here). Alongside seemingly greater risk for specific sleep issues (see here for example) accompanying a diagnosis of autism, sleeping problems often feature as one of the more 'quality of life draining' aspects in relation to autism [3] (as they also affect significant others too [4]). It strikes me as a win-win situation that detecting and treating GI issues may also have positive implications for sleep issues in autism.

And finally, a small (peer-reviewed) contribution to this area from yours truly [5]...

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[1] McCue LM. et al. Gastrointestinal dysfunctions as a risk factor for sleep disorders in children with idiopathic autism spectrum disorder: A retrospective cohort study. Autism. 2017 Nov;21(8):1010-1020.

[2] Buie T. et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan;125 Suppl 1:S1-18.

[3] Kuhlthau KA. et al. Associations of quality of life with health-related characteristics among children with autism. Autism. 2017 Jul 1:1362361317704420.

[4] Tilford JM. et al. Treatment for Sleep Problems in Children with Autism and Caregiver Spillover Effects. J Autism Dev Disord. 2015 Nov;45(11):3613-23.

[5] Whiteley P. Food and the gut: relevance to some of the autisms. Proc Nutr Soc. 2017 Sep 26:1-6.

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"we found no association between maternal folic acid supplementation and offspring ASD" but...

The findings reported by Marit Strøm and colleagues [1] observing "no association between maternal folic acid supplementation and offspring ASD [autism spectrum disorder]" throw yet another research 'spanner in the works' when it comes to the [very generalised] idea that pregnancy folic acid supplementation might affect risk of offspring autism.

Don't get me wrong, I appreciate all the data suggesting that folic acid supplementation during pregnancy is a useful thing for helping to reduce the risks of neural tube defects (NTDs) for example. But when it comes to pregnancy folic acid (folate) potentially impacting on offspring risk of autism, I've always been a little cautious of the collected data so far and how its been interpreted/generalised in certain quarters (see here and see here for examples).

So, drawing on data from the "entire DNBC [Danish National Birth Cohort]" initially including nearly 100,000 singleton, live born children, researchers set out to find female "users" of folic acid supplements either just before conception or during the earliest stages of their pregnancy. Not just content with folic acid, they also looked at available data on "periconceptional vitamin B12" use too on the basis of some connection between the two vitamins. They then searched connected databases to find those offspring with a diagnosis of autism spectrum disorder (ASD): "identified by International Classification of Diseases (ICD)-10 diagnosis codes F840, F841, F845, F848, and F849; ‘childhood autism’ by diagnosis code F840." Analyses of these collected variables were undertaken, as well as adjusting for potentially confounding variables such as maternal age, parity, education level and the like.

Results: well, as per the title of this post, researchers reported finding very little when it came to pre-pregnancy or early pregnancy folate use: "There was no detectable association between maternal folic acid supplementation in the periconceptional period and offspring ASD" and: "Results from the analyses using midpregnancy exposure data were similar: there was no association with ASD/childhood autism neither for folic acid supplementation nor for dietary folate intake." Such results held when various 'corrections' were made for variables such as "sex specific effects" and cases where intellectual (learning) disability was present for example.

I have to say that the authors do seem genuinely surprised that their results did not tally with other large, population studies on this topic: "At present we are not able to present any viable explanation for these discrepant results." They do mention one particularly important point insofar as the usefulness of looking at small changes to something called the methylenetetrahydrofolate reductase (MTHFR) gene in the context of autism and folic acid as other authors have done [2]. This, on the basis that MTHFR plays an important role in folate metabolism (see here) and issues with this gene are no stranger to the autism research landscape (see here). I'm also minded to refer readers back to another potentially important issue identified in relation to some autism that might also affect folate metabolism: folate receptor autoantibodies (FRAAs) (see here).

I still think there is a place for further investigations on folic acid use during pregnancy and offspring autism risk. But like many things in the context of the plural 'autisms' (see here), it perhaps makes more sense to zoom in on potentially relevant sub-groups on the autism spectrum rather than treating all autism as being homogeneous in either aetiology or presentation. I might add that folic acid use as part of wider range of nutritional supplements potentially used during early pregnancy remains an important area of research attention in the context of offspring autism [3].

And also just to complicate things even further, the results from Wang and colleagues [4] add: "this comprehensive meta-analysis suggested that maternal use of folic acid supplements during pregnancy could significantly reduce the risk of ASD in children regardless of ethnicity, as compared to those women who did not supplement with folic acid." I don't think the debate is finished yet on this topic.

Music to close, and since my brood and I are competing again today, Sia (again) and some brilliant kata (hopefully our Heian Sandan will be as good).

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[1] Strøm M. et al. Research Letter: Folic acid supplementation and intake of folate in pregnancy in relation to offspring risk of autism spectrum disorder. Psychol Med. 2017 Sep 26:1-7.

[2] Schmidt RJ. et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr. 2012 Jul;96(1):80-9.

[3] DeVilbiss EA. et al. Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort study. BMJ 2017; 359: j4273.

[4] Wang M. et al. The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis. Molecular Autism. 2017; 8: 51.

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Completing the set: features of ADHD in childhood epilepsy

'Completing the set' used in the title of this post refers to the idea that a diagnosis of epilepsy rarely(?) seems to exist in some sort of diagnostic vacuum as per previous discussions whereby features of autism (see here) and dyspraxia / developmental coordination disorder (DCD) (see here) seem to be over-represented in cases of epilepsy.

This time around the focus was on attention-deficit hyperactivity disorder (ADHD) and the findings reported by Isabell Brikell and colleagues [1] suggesting that: "Individuals with epilepsy had a statistically significant increased risk of ADHD." Researchers arrived at their conclusions on the basis of examining some of those wonderful Scandinavian population registries that are providing all-manner of interesting details on possible trends and patterns in various areas: "We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers..." Said data were actually used to look at "the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence" but also served the purpose of looking at ADHD prevalence alongside epilepsy. Indeed it was also interesting to note the authors' conclusions about familial liability to the "cross-disorder overlap": "The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors." Mmm...

Such research - although requiring quite a bit more independent investigation [2] - follows an important trend in recent times observing how stand-alone developmental and/or psychiatric diagnoses often 'clump together' in seemingly at-risk patient groups. I've for example, talked about the important concept of ESSENCE - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations [3] on this blog and how "co-existence with other conditions was the rule" (see here) rather than the minority perspective in the area of childhood psychiatry. Now we seem to be able to add ADHD to the list of comorbidity potentially over-represented alongside a diagnosis of epilepsy (bearing in mind that epilepsy covers quite a lot of diagnostic ground).

Mechanisms? Well, far be it from me to speculate too much, but an important starting point is the nature of epilepsy and how it affects brain function. It's not inconceivable that particular alterations to the functioning of the brain as a result of epilepsy (or even during some prodromal phase) might be enough to *induce* other behaviours/symptoms to be pronounced. Equally, one might subscribe to the the idea that changes to brain function due to other events or factors that may be connected to conditions such as autism or ADHD or DCD could be enough to induce the onset of epilepsy (this hypothesis draws support from the onset patterns typically seen in cases of autism and epilepsy). I don't doubt that relationships are likely to be complicated.

Much more needs to be done on this topic, not least in ensuring appropriate screening services when cases of epilepsy are diagnosed, particularly in childhood. With no medical or clinical advice given or intended (don't mess with epilepsy), I do wonder whether some of the peer-reviewed data talking about dietary changes being used to manage certain types of epilepsy also potentially impacting on presented symptoms of *some* other labels (see here) might also provide some clues as to potential shared mechanisms between epilepsy and other developmental/psychiatric labels?

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[1] Brikell I. et al. Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study. Biol Psychiatry. 2017 Aug 12. pii: S0006-3223(17)31858-9.

[2] Caplan R. ADHD in Pediatric Epilepsy: Fact or Fiction? Epilepsy Curr. 2017 Mar-Apr;17(2):93-95.

[3] Gillberg C. The ESSENCE in child psychiatry: Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. Res Dev Disabil. 2010 Nov-Dec;31(6):1543-51.

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Weighing up genetics and environment in autism - reanalysed

Consider this post a sort of add-on to a previous entry (see here) published on this blog talking about the relative contributions of genetics and environment when it comes to autism. On that previous blogging occasion, the findings reported by Sven Sandin and colleagues [1] were the source material and the observation: "Heritability of ASD [autism spectrum disorder] and autistic disorder were estimated to be approximately 50%." The press release accompanying those results was titled: "Environment as important as genes in autism, study finds."

Now the same data has been though a bit of a re-analysis [2] and a slightly different conclusion and media headline - "Autism is mostly genetic, suggests study" - has been created. The reason for the quite different conclusions reached: "Instead of looking at just one time point when both members of a sibling pair had been diagnosed, they incorporated the fact that not all siblings would be diagnosed at the same time. They may start as being undiagnosed, then one would get diagnosed and, later, another might be determined to have autism" according to another media take on the findings (see here). I can't argue with the logic.

The data - 37 570 twin pairs, 2 642 064 full sibling pairs, 432 281 maternal and 445 531 paternal half sibling pairs - were now analysed in the context that diagnoses of autism/ASD among siblings are, for many reasons, not always uniform in timing. The influence of genetics or more specifically, heritability was subsequently boosted up to 83% (previously suggested to be 50%) and with it, 'nonshared environmental influence' relegated to an estimates 17%.

I've perhaps been a little unfair by using the word 'relegated' in the context of non shared environmental influence in relation to autism. There are plenty of examples out there whereby such influences might impact on autism risk: prenatal valproate exposure, congenital rubella syndrome, various types of encephalitis being linked to autistic symptoms onset (see here and see here for examples), etc and these are not to be downplayed. Environmental factors can be pretty important.

But it's critical to also mention that genetics do seem to play quite a significant role in many instances of autism too. Yes, the idea of an 'autism gene' is already a distant memory replaced by something altogether a lot more complicated, but when taking into account notions such as the broader autism phenotype (BAP) for example, one cannot discount that particularly in multiplex families, heritability is probably [mostly] driven by genetics and science still needs to continue looking at the specific hows-and-whys (see here for one example). I might add that looking at gene expression over just structural genetics is probably going to be useful in these days of epigenetics and the like.

And whilst the research of Sven Sandin is being discussed today, another recent paper where the name has appeared [3] has suggested that "little or no maternal genetics contribution" is the order of things when it comes to heritability and autism...

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[1] Sandin S. et al. The Familial Risk of Autism. JAMA 2014; 311: 1770-1777.

[2] Sandin S. et al. The Heritability of Autism Spectrum Disorder. JAMA. 2017; 318(12): 1182-1184.

[3] Yip BHK. et al. Heritable variation, with little or no maternal genetics contribution, accounts for recurrence risk to autism spectrum disorder in Sweden. Biological Psychiatry. 2017. Sept 21.

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Tobacco smoking and psychiatric illness

"The prevalence of smoking has remained alarmingly high among individuals with schizophrenia and bipolar disorder, and the disparity with those without psychiatric disorders and with the general population is increasing."

So said the findings reported by Faith Dickerson and colleagues [1] who surveyed nearly 2000 people "about their cigarette smoking at enrollment into a research study for which they were selected without regard to their smoking status." Their findings make for important reading in the context that tobacco smoking is not exactly a healthy activity (see here) and could potentially contribute to some of the health inequalities already recognised when it comes to serious mental illness (SMI) (see here).

The sorts of figures of smoking prevalence observed by Dickerson et al are not to be ignored: "62% of individuals with schizophrenia, 37% with bipolar disorder, and 17% of participants without a psychiatric disorder (control group) reported that they were current smokers." This set in the context of falls in the rates of smoking in the general population. It's also worthwhile noting that being a 'current smoker' with reference to a diagnosis of schizophrenia or bipolar disorder typically meant smoking "more cigarettes per day" than the control cohort.

There are other implications from this work. Without generalising (or stigmatising) if one draws on other work talking about a possible connection between prenatal nicotine exposure and offspring [heightened] risk of schizophrenia for example (see here), a complex pattern of *association* seems to emerge. No, I'm not saying that every woman with schizophrenia who is pregnant will smoke through their pregnancy (despite evidence of some increased risk [2]) but greater focus and education on the need to restrict tobacco smoking during that critical period is perhaps warranted. Such discussions may also have implications for the whole nature-nurture debate with regards to such psychiatric diagnoses too.

Although there are many (many!) good reasons for encouraging those with a SMI to quit smoking, I do feel it is important also to understand why so many are smokers. The findings reported by Li and colleagues [3] offer something of a perspective on this issue where for example: "Smokers had a higher mental QOL [quality of life] than non-smokers... in MDD [major depressive disorder]." Similarly, Mallet and colleagues [4] discussed results that suggested that "some therapeutics may improve daily smoking behavior in smokers" in the context of schizophrenia (as others seemed to be associated with 'not improving' smoking behaviours). In short, the roads that lead to, and perpetuate tobacco smoking in the context of SMI are likely as complex as the ones needed to lead people away from such habits...

And aside from the health reasons to quit smoking particularly among those diagnosed with a SMI, the grand review, meta-analysis and meta-regression paper by Cassidy and colleagues [5] lists tobacco smoking as one potentially important (and modifiable) correlate when it comes to risk factors for suicidality in schizophrenia...

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[1] Dickerson F. et al. Cigarette Smoking by Patients With Serious Mental Illness, 1999-2016: An Increasing Disparity. Psychiatr Serv. 2017 Sep 15:appips201700118.

[2] Nilsson E. et al. Women with schizophrenia: pregnancy outcome and infant death among their offspring. Schizophr Res. 2002 Dec 1;58(2-3):221-9.

[3] Li XH. et al. Prevalence of smoking in patients with bipolar disorder, major depressive disorder and schizophrenia and their relationships with quality of life. Sci Rep. 2017 Aug 16;7(1):8430.

[4] Mallet J. et al. Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):332-339.

[5] Cassidy RM. et al. Risk Factors for Suicidality in Patients With Schizophrenia: A Systematic Review, Meta-analysis, and Meta-regression of 96 Studies. Schizophr Bull. 2017 Sep 23.

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"What are the sex-specific recurrence rates of autism spectrum disorder among siblings?"

The paper by Nathan Palmer and colleagues [1] attempted to shed some light on the question posed in the title of this post: "What are the sex-specific recurrence rates of autism spectrum disorder among siblings?" The topic of sibling recurrence rates with regards to autism has been discussed for quite a few years (see here for example).

Already covered by Spectrum (see here), the Palmer data was derived from the records of a US health insurance organisation covering the period between 2008 and 2016 and some 3 million+ children. Researchers specifically looked at those in receipt of an autism diagnosis and onward to "estimate high-confidence sex-specific recurrence rates of ASD [autism spectrum disorder] among siblings." In other words, how many boy and girl younger siblings of children with autism were also diagnosed with autism or an ASD and whether the gender/sex of the older diagnosed sibling was an important variable in recurrence risk.

The answers: well, first it's worth noting that that prevalence of ASD came out at ~2%. This was based on administrative health insurance records remember, so is probably quite accurate given that such schemes have to 'pay out' for certain services/provisions as and when autism is diagnosed. Such a figure also adds to other data highlighting this upward trend in cases diagnosed (see here and see here).

Then: "When a male was associated with risk in the family, ASD was diagnosed in 4.2%... of female siblings and 12.9%... of male siblings. When a female was associated with risk in the family, ASD was diagnosed in 7.6%... of female siblings and 16.7%... of male siblings."

You can perhaps see that there were some subtle differences in the autism/ASD recurrence rate according to the sex/gender of the child first diagnosed with autism in a family. The Spectrum review of this paper quotes the lead author saying: "For a girl to emerge with [autism] in the first place indicates that that is a high-risk family" indicating that the appearance of females with autism might mean a greater genetic load is already present in relation to autism risk for example, which then affects subsequent recurrence risk for autism in later born siblings. That is, if one assumes that genes are the be-all-and-end-all of autism risk (see here)...

What else would I like to see in future investigations? Noting the name Isaac Kohane as part of the authorship group of this paper and acknowledging his past contributions to the autism research landscape with a focus on comorbidity and autism (see here) I do wonder if more could be done on that topic with autism recurrence in mind. Y'know, accepting that various psychiatric and somatic comorbidity are 'over-represented' following a diagnosis of autism (see here), a little more information on what else might be recurring alongside autism could provide some important clues about hows-and-whys, particularly bearing in mind that 'autism genes' aren't necessarily just genes for autism (see here)...

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[1] Palmer N. et al. Association of Sex With Recurrence of Autism Spectrum Disorder Among Siblings. JAMA Pediatrics. 2017. Sept 25.

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Vitamin A supplementation and autistic symptoms: hidden away but no significant effect...

I used the words 'hidden away' in the title of this post because I had a bit of a time deciphering the findings reported by Juan Liu and colleagues [1] (open-access) investigating "the role of VA [vitamin A] in the changes of gut microbiota and changes of autism functions in children with ASD [autism spectrum disorder]." Vitamin A by the way, is a fat soluble vitamin involved in various process such as immune function and vision health. There is a darker side to vitamin A however, as safe upper limits have been in place for quite a few years, particularly for pregnant women as a result of potential teratogenic effects.

Suffice to say that after 6 months of VA supplementation - "participants with an insufficient plasma retinol status (<1.05 μmol/L) received VAI [vitamin A intervention?] with a dose of 200,000 IU once orally" - the authors reported seeing no significant changes in autistic signs and symptoms as measured before and after using the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). They did however report changes in retinol status (a marker for vitamin A availability) coinciding with supplementation: "The plasma retinol level increased from 0.59 ± 0.19 μmol/L to 0.72 ± 0.20 μmol/L in the group of 64 after 6 months of VA supplementation" and changes in the percentages of vitamin A levels (typical, marginal deficiency, deficient) across their group. I say this however, based on their use of high performance liquid chromatography (HPLC) with photodiode-array detection for assaying for retinol; state-of-the-art about 30 years ago and now superseded by better detection technology such as mass spectrometry...

No mind, Liu et al also looked at "CD38 and acid-related orphan receptor alpha (RORA) mRNA levels" as "autism-related biochemical indicators’ changes" following supplementation. RORA - retinoic acid-related orphan receptor-alpha - has some research history discussed before on this blog (see here). Authors reported that: "After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased" despite the seeming lack of effect on presented autistic symptoms.

Further: "Fresh stool samples were collected from participants who did not receive supplemental probiotics or prebiotics and who were not treated with antibiotics for the previous 1 month." Said poo(p) samples - pre and post-vitamin A supplementation - were analysed alongside food diaries and food frequency behaviours. Authors observed that bacterial species showed changes between the baseline and post-intervention samples; specifically settling on "significant increases in the proportion of Bacteroidetes/Bacteroidales and decreases in Bifidobacterium after the VAI, accompanying significant increases in autism biomarkers, while no significant changes were observed in autism symptoms."

What can we make of these collected findings? Well, whilst vitamin A deficiency is something to look out for among children with autism [2] (see here too) and previous research has indicated "an empirical basis for the development of a pharmacological ASD treatment strategy based on retinoids" [3] the lack of a significant behavioural effect from vitamin A supplementation in this case cannot be just glossed over. Yes, this was an open-trial - "we aimed to conduct a placebo-controlled intervention study, but all the participants showed an insufficient VA status and were thus enrolled into the VAI group" - and so has shortcomings but the findings of a lack of significant change across any and all of the autism-related behaviour schedules used is notable. The biological results are a little more interesting; particularly the bacterial findings. But again it wouldn't be difficult to say 'so what?' to such bacterial results given that no corresponding changes in autistic behaviour(s) were noted...

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[1] Liu J. et al. Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders - a pilot study. BMC Microbiology. 2017; 17: 204.

[2] Chiu M. & Watson S. Xerophthalmia and vitamin A deficiency in an autistic child with a restricted diet. BMJ Case Rep. 2015 Oct 5;2015. pii: bcr2015209413.

[3] Riebold M. et al. All-trans retinoic acid upregulates reduced CD38 transcription in lymphoblastoid cell lines from Autism spectrum disorder. Mol Med. 2011;17(7-8):799-806.

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Bullying and autism: stating the bleedin' obvious...

A short post today to reiterate the 'bleedin' obvious': children diagnosed as being on the autism spectrum are far more likely to be the victim of bullying than perpetrator (see here for a previous blog post on this topic).

This conclusion comes from the paper by Hwang and colleagues [1] based on responses to the Behavior Assessment System for Children: Second Edition (BASC-2) (parental report version). The authors initially reported that "children with ASD [autism spectrum disorder] showed significantly increased risk for bullying involvement compared to community children" potentially indicating that a diagnosis of autism does not somehow shield someone from either being bullied or indeed, participating in bullying behaviour (perpetrator). But... "after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated." Said 'comorbid psychopathology' included aggression and conduct problems as well as the signs and symptoms of depression potentially accompanying a diagnosis of autism. Indeed, aggression was pretty much linked to every type of bullying behaviour in both autism and control groups...

What's more to say on this topic? Well, further recognition that school in particular, can be a significant source of stress and anxiety for children on the autism spectrum is one thing (and potentially contributory to the stats on school refusal in the context of autism). Indeed, without trying to armchair diagnose nor artificially inflating the seriousness of bullying, I wonder whether quite a few more children on the autism spectrum need to be screened for possible post-traumatic stress disorder (PTSD) in the context of how traumatic bullying can be for a person (see here). In relation also to the point made about aggression being a common variable predicting bullying across the Hwang cohort, I wonder whether more needs to be done more generally in relation to reducing aggression in places like school and thus potentially reducing bullying behaviour more generally?

And whilst on the topic of bullying, it appears that some of the longer term effects of bullying for some might be countered by some kind of resilience (whatever 'resilience' might mean)...

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[1] Hwang S. et al. Autism Spectrum Disorder and School Bullying: Who is the Victim? Who is the Perpetrator? J Autism Dev Disord. 2017 Sep 21.

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Quarter of kids with autism with iron deficiency but...

Iron (Fe) is something that I've always been a little bit interested in on this blog with specific regards to autism (see here). Outside of the typical 'helping to produce red blood cells' bit, I've always been intrigued by the potential behavioural and cognitive effects following issues with suitable iron supplies. My particular interest in an enzyme that relies on iron as a co-factor (see here) is also worthwhile noting...

A new paper by Serkan Gunes and colleagues [1] (open-access) continues the important theme of iron and autism suggesting that various iron-related parameters might be sub-optimal in relation to the autism spectrum but also with a possible confounding effect of comorbidity in relation to the presence of iron deficiency anemia (IDA) and autism.

Looking at 100 children and young adults diagnosed with an autism spectrum disorder (ASD) and 100 not-autism (I hate the term "healthy controls") controls, researchers surveyed both blood samples and behaviour using a variety of measures. Alongside just having a diagnosis, participants with autism were also subject to various measures covering autistic behaviours, "intellectual evaluation" and various behavioural schedules in-between. Various iron-related parameters were studied: serum ferritin ("as an indicator for ID [iron deficiency] since it is a precursor for ID and represents iron levels in body tissues including brain") and then hemoglobin, hematocrit, iron, ferritin, MCV (mean corpuscular volume), and RDW (red blood cell distribution width).

Results: as per the title of this blog post, 25% of participants fell into the range of iron deficiency (ID). Perhaps a little more seriously, some 13% also presented with iron deficiency anaemia (IDA). This compared with 15% and 6% of the control group respectively. The 'but...' in the title of this post reflects the fact that saying a quarter of children with autism might have ID sounds dramatic but perhaps not so dramatic when it compares with that 15% of controls; hence the lack of significant difference between the groups. Having said that, it is worthwhile noting that controls in this study were not necessarily children and young adults just plucked at random: "For the control group, 100 children (an equal number with patients), who referred to the department [child and adolescent psychiatry department] for counseling about child development, school adjustment and performance, teenage problems, family and friend relations, were recruited."

Then: "Hemoglobin, hematocrit, iron, and MCV (p < 0.05) levels were found to be lower in children with ASD."

Finally, taking into account age (comparing those with autism under 6 years (n=46) with those over 6 years (n=54)) and the presence of learning (intellectual) disability (n=58) vs. those with none (n=42) and autism severity (mild-moderate ASD (n=50) vs. severe ASD (n=50)), some other interesting trends were observed. "Hemoglobin, hematocrit, and MCV (p < 0.05) levels were found to be significantly lower in preschool ASD patients" and "Hemoglobin and hematocrit (p < 0.05) levels were significantly lower in ASD patients with intellectual disability."

What can we conclude from the Gunes paper? Well, I don't want to belittle the various issues with iron detected in either group included for study. If ID or more seriously IDA is detected, remedial measures need to be adopted to correct such issues irrespective of a diagnosis of autism or anything else. Insofar as the relationship(s) between iron parameters and autism, the Gunes papers reiterates that this is likely to be complex and not necessarily just exclusive to autism. Perhaps the most accurate thing I can say is that yet again, a diagnosis of autism or ASD is seemingly protective against nothing when it comes to comorbidity and [preferential] screening is once again implied. Oh, and when it comes to trying to predict those people on the autism spectrum who might be at greatest risk of iron deficiency et al, the findings published by Sidrak and colleagues [2] offer some possible variables: "problems sucking, swallowing or chewing...; poor eating behaviour...; and inadequate amounts of meat, chicken, eggs or fish."

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[1] Gunes S. et al. Iron deficiency parameters in autism spectrum disorder: clinical correlates and associated factors. Italian Journal of Pediatrics. 2017; 43: 86.

[2] Sidrak S. et al. Iron deficiency in children with global developmental delay and autism spectrum disorder. J Paediatr Child Health. 2014 May;50(5):356-61.

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Severe mental illness translates into "more sedentary behavior and significantly less physical activity"

The title of this post reflects the findings reported by Davy Vancampfort and colleagues [1] (open-access) who concluded that various diagnoses - "schizophrenia, bipolar disorder or major depressive disorder" - under the label of severe mental illness were associated with decreased physical activity and increased sedentary behaviour(s).

Under the auspice of a "global systematic review and meta-analysis", authors settled on some 70-odd studies that met their search criteria comprising over 35,000 people diagnosed with one of the conditions described and nearly 3000 asymptomatic (asymptomatic for severe mental illness) controls. Vancampfort et al describe assessing for "co-primary outcomes" that "were the mean time (min) per day that people with severe mental illness and healthy controls (in case-control studies) engaged in physical activity, or were sedentary." They found "23 study estimates of physical activity were based on objective measures, three utilized objective and subjective measures and 57 were based on self-report questionnaires"; something important in the context of the technology available to measure activity these days.

Results: Those diagnosed with a severe mental illness (SMI) were "more sedentary than age- and gender-matched controls from the general population, spending a mean of 476 min per day (or almost 8 hours) during waking hours in sedentary behavior." Further: "people with severe mental illness are significantly less physically active and spend only an average of 38.4 min per day in moderate or vigorous physical activity." When tweeting about this article, one of the authors - Brendon Stubbs - also linked to another important paper [2] published on the same day as their own, observing that: "Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD [cardiovascular disease] in middle age." It's not difficult to see the connection(s) between the two findings.

"Our data documented that higher body mass index, lower cardiorespiratory fitness, and antidepressant or antipsychotic prescription might constitute barriers for engaging in physical activity." One of the value-added bits to the Vancampfort data were the discussions on some of the barriers to engaging in physical activity in those with SMI. Combined with observations such as: "Those who are single or unemployed, those with a low educational level and men are less physically active" it's not too difficult to see what areas might need to be 'tackled' if physical activity levels are to be improved. Indeed, other data (see here) has even talked about what types of exercise might be best suited to what labels (minus any sweeping generalisations).

And since I've mentioned the topic of depression in this post, I might also draw your attention to another paper recently published by Joseph Firth and colleagues [3] - one of the authors on the Vancampfort paper - talking about how technology might provide a useful backdrop to intervention for depressive symptoms. Specifically how the delivery of smartphone apps might be something useful to consider in the context of depression. Indeed, if one assumes that physical activity levels might also be lower in relation to something like depression, one could forsee a time when one or more smartphone apps might either prompt the need for more physical activity or even potentially offer a tailor-made physical activity schedule complementary to other intervention options...

Music to close and Sammy singing Mr Bojangles...

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[1] Vancampfort D. et al. Sedentary behavior and physical activity levels in people with schizophrenia, bipolar disorder and major depressive disorder: a global systematic review and meta-analysis. World Psychiatry. 2017. Sept 21.

[2] Lear SA. et al. The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study. Lancet. 2017. Sept 21.

[3] Firth J. et al. The efficacy of smartphone-based mental health interventions for depressive symptoms: a meta-analysis of randomized controlled trials. World Psychiatry. 2017 Oct;16(3):287-298.

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