"Physical and mental health issues were highly prevalent among children with obesity..."

The quote titling this post - "Physical and mental health issues were highly prevalent among children with obesity" - comes from the findings reported by Stasia Hadjiyannakis and colleagues [1].

Researchers set out to "examine the association between BMI [body mass index] class and EOSS-P [Edmonton Obesity Staging System for Pediatrics] stage" on the basis that measures such as BMI "do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities" [2] and issues like obesity don't typically appear in a "metabolic, mechanical, mental health and social milieu" vacuum.

As you might have already noted, Hadjiyannakis and colleagues have some 'research form' in this area. This time around data on nearly 850 children "with obesity aged 5-17 years" attending one of a number of weight management clinics were the source material. They observed that most of their cohort - about two-thirds of them - were described as having severe obesity according to their BMI score. When it came to their EOSS-P staging scores, 80% fell into the categories of a 2 or 3 denoting moderate to severe issues with regards to health issues such as metabolic complications either requiring pharmacotherapy or being described as "uncontrolled".

Of particular note to this blog and the focus on the intersection between physical and mental health parameters, researchers describe how "mental health concerns were most common" among their participant group. By 'mental health concerns' they specifically talk about anxiety and attention-deficit hyperactivity disorder (ADHD) as being present and "equally distributed across BMI classes." I was particularly intrigued with the ADHD bit because despite the focus on hyperkinetic behaviours in ADHD, the emerging research picture is suggesting that ADHD and obesity *might* actually be connected (see here) under quite a few different circumstances (see here).

What's more to say? Well, the Hadjiyannakis results perhaps imply that preferential screening for various physical and mental / behavioural are indicated when obesity is present. Specifically, and bearing in mind that "mental health risks were high across BMI classes" the results suggest that the possibility of an elevated risk of mental / behavioural diagnoses is not something confined to those with more or less severe obesity but rather, potentially, a universal issue.

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[1] Hadjiyannakis S. et al. Obesity class versus the Edmonton Obesity Staging System for Pediatrics to define health risk in childhood obesity: results from the CANPWR cross-sectional study. Lancet Child Adolesc Health. 2019 Apr 2. pii: S2352-4642(19)30056-2.

[2] Hadjiyannakis S. et al. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity. Paediatr Child Health. 2016;21(1):21–26.

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"no good evidence that time in front of a screen is "toxic" to health"

BBC News January 4 2019

Quite a few days back the BBC here in Blighty ran the headline "Worry less about children's screen use, parents told" as part of their coverage of the paper by Neza Stiglic & Russell Viner [1]. This paper - "a systematic review of reviews" no less - set out to "systematically examine the evidence of harms and benefits relating to time spent on screens for children and young people’s (CYP) health and well-being, to inform policy."

Informing policy is just what the Stiglic/Viner paper did (see here), as the Royal College of Paediatrics & Child Health (RCPCH) concluded that: "Many of the apparent connections between screen time and adverse effects may be mediated by lost opportunities for positive activities (socialising, exercise, sleep) that are displaced by screen time" but parents shouldn't necessarily get too stressed if their offspring find some enjoyment in their computer/tablet and/or phone in amongst their busy lives. Indeed it was refreshing to see that children and young peoples' voices were being heard on the potential benefits of screen time, with comments such as: "Gives you knowledge" and "Provides you with more opportunities to reach a wider community." All those hours of watching You Tubers fooling around or building whatever on Roblox or similar platforms can actually be intermixed with something approaching gaining knowledge; i.e. learning. Who knew!

The Stiglic/Viner review paper drew on data from 13 reviews reporting "associations between time on screens (screentime; any type) and any health/well-being outcome in CYP [children and young people]." All was not however completely rosy when the reviews were boiled down to a consensus, as we are told that authors found "moderately strong evidence for associations between screentime and greater obesity/adiposity and higher depressive symptoms" and "moderate evidence for an association between screentime and higher energy intake, less healthy diet quality and poorer quality of life." I don't think anyone should really be surprised that more screen time *might* mean an increased tendency towards being overweight or obese. If one subscribes to the idea that energy in - energy out is at least partially related to being overweight or being obese [2] it stands to reason that unless people are running around whilst using their tablets or phones, there is likely to be less 'energy out'.

As for the 'higher depressive symptoms', well let's just say that this is something else that is no stranger to the debate about screen time, as other recent research has similarly observed (see here). Whether it is the actual use of tablets, phones and/or television or the type of material being accessed [3] *correlating* with depression is a question that needs further investigation. I might add that the scenario of when screen time turns into an addiction also needs to be discussed in this context (see here), bearing in mind the limitations of observational studies in relation to discerning cause-and-effect.

Also: "There is weak evidence for association of screentime with behaviour problems, anxiety, hyperactivity and inattention, poorer self-esteem and poorer psychosocial health in young children." Bearing in mind that 'weak evidence' does not mean 'no evidence', this part of the Stiglic/Viner review paper is also important. It means that sweeping conclusions that screen time is somehow playing a major role in the rise of behaviour problems in children (young and old) are not yet necessarily backed up by the scientific evidence. Indeed, as per other topics on this blog, I'd advance the position that certain facets of screen time may actually be advantageous to quite a few children and young people (see here) who are perhaps not for example, the social butterflies that other children are.

The Stiglic/Viner review and subsequent RCPCH advice does not say that screen time for children is risk-free. It does not say that parents shouldn't be continually asking questions about how long their children spend using screens and/or what material they are accessing. It does however mean that, on the basis of the currently available evidence, parents shouldn't get too stressed about moderate screen use in their offspring. Balance things out with the odd physically active inclined hobby or two (avoiding any tiger parenting notions) by all means, but don't stress too much about their swiping. See the potential positives as well as the potential negatives of screen use, and remember that screen time is an inevitable part of growing up these days...

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[1] Stiglic N. & Viner RM. Effects of screentime on the health and well-being of children and adolescents: a systematic review of reviews. BMJ Open. 2019;9:e023191.

[2] Malhotra A. et al. It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet. Br J Sports Med 2015;49:967-968.

[3] Kelly Y. et al. Social Media Use and Adolescent Mental Health: Findings From the UK Millennium Cohort Study. EClinical Med. 2019. Jan 4.

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"maternal obesity and overweight were significantly associated with [offspring] increased ASD risk"

The title heading up this brief post - "maternal obesity and overweight were significantly associated with [offspring] increased ASD [autism spectrum disorder] risk" - comes from the results published by Xian-Yang Lei and colleagues [1].

Under systematic review and meta-analysis conditions, researchers basically found what many people had suspected for quite a while, insofar as maternal weight, before or during pregnancy, being a 'risk factor' for an offspring diagnosis of autism or ASD. They arrived at their conclusion based on "13 eligible studies for meta-analysis (involving 943,293 children and 30,337 cases)" which collectively found that "both maternal obesity... and maternal overweight... were significantly associated with ASD, while maternal underweight was not associated with ASD." Researchers also looked at paternal weight as a possible risk factor for offspring autism but found no statistical association between paternal obesity, overweight or underweight based on the available data (limited to only three studies).

Mindful of the potential for 'stigma' to set in with such investigation, and likewise being careful not to generalise too much from such findings, the Lei results point to both the requirement for more research in this area and a possible 'intervention' route towards reducing the risk of offspring autism: "pre-pregnancy weight control is suggested." I've covered this topic numerous times on this blog (see here and see here and see here for examples) and have concluded that whilst correlation is not the same as causation and that pre- and peri-pregnancy weight is often intricately tied into other features of the condition known as metabolic syndrome, immune function and in particular inflammation, are perhaps important areas for further assessment. Research should perhaps head in that direction, and see what further crops up...

And as if to further prove the point [2]...

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[1] Lei XY. et al. Association between parental body mass index and autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2018 Nov 23.

[2] Windham GC. et al. Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain in Relation to Autism Spectrum Disorder and other Developmental Disorders in Offspring. Autism Res. 2018 Dec 21.

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SEED says... risk of overweight/obesity in autism is heightened

SEED - The Study to Explore Early Development - provides yet more discussion fodder today as I bring the findings reported by Susan Levy and colleagues [1] to the blogging table. This time around the focus was on the risk of being overweight and/or obese in relation to a diagnosis of autism and the conclusion that: "Prevention of excess weight gain in children with ASD [autism spectrum disorder], especially those with severe symptoms, and in children with developmental delays/disorders represents an important target for intervention" on the basis of results observed.

It's not exactly a new thing to observe that those diagnosed with autism are perhaps at a greater risk of being overweight and/or obese (see here). There are a multitude of possible reasons behind such statistics covering everything from research showing those on the autism spectrum to typically be more sedentary than peers (see here) (bearing in mind the idea that 'you can't outrun a bad diet'), to a heightened risk of receiving medicines that list weight issues as a side-effect (see here) to a possible role for over-represented comorbidity (see here) with regard to weight issues. The net results however is the same: being diagnosed with an autism spectrum disorder places someone at a heightened risk of being overweight or obese.

Levy et al compared three groups of young children - "2-5 years of age" - classified by a diagnosis of autism spectrum disorder (ASD) or developmental delay/disorder or classed as a general population controls (i.e. asymptomatic). Importantly they describe how height and weight were "measured during a clinical visit" thus removing the reliance on 'at home' or routine records measurements [2] and the risk of bias that they can sometimes bring. Researchers also gathered background information on various co-occurring conditions/diagnoses.

Results: "The odds of overweight/obesity were 1.57 times... higher in children with ASD than general population controls and 1.38 times... higher in children with developmental delays/disorders than general population controls." One needs to be bear in mind the quite young age of participants when putting that last sentence into some context. Also: "Among children with ASD, those with severe ASD symptoms were 1.7 times... more likely to be classified as overweight/obese compared with children with mild ASD symptoms."

There's little more to say about such findings other than autism or autistic traits, yet again, seems to place someone as a quite significant disadvantage when it comes to their physical health and wellbeing. Now, the important question: what can be done about it?

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[1] Levy SE. et al. Relationship of Weight Outcomes, Co-Occurring Conditions, and Severity of Autism Spectrum Disorder in the Study to Explore Early Development. The Journal of Pediatrics. 2018. 9 Oct.

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"maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring"

The results reported by Kandice Varcin and colleagues [1] concluding that "maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring" continue and extend a research theme (see here and see here). A research theme that highlights a potentially important relationship between maternal weight (and/or related parameters) and offspring development across various, potentially intertwined, variables (see here).

Including the notable name of Andrew Whitehouse on the authorship team (see here and see here for some examples of his other research), researchers set about to explore whether "pre-pregnancy weight was related to autistic-like traits among offspring not diagnosed with ASD [autism spectrum disorder]." I added the bold highlight to the word 'not' to emphasise how this work was set slightly apart from the other research that has observed an *association* between maternal weight before or during pregnancy and a risk of a formal diagnosis of autism in offspring. Pregnant women in their second trimester of pregnancy were recruited and "had their height measured." They also "reported their pre-pregnancy weight" which combined with the height measurements to give the measure known as the body mass index (BMI). And also: "At 19-20 years of age, 1238 offspring of these women completed a measure of autistic-like traits, the Autism-Spectrum Quotient (AQ)." Keep those issues in mind for now.

Results: "Regression analyses identified a positive association between increasing maternal pre-pregnancy BMI and increasing AQ Total Score amongst offspring; this association was maintained even after controlling for a range of variables including maternal/obstetric factors (age at conception, education, smoking, alcohol consumption, hypertensive diseases, diabetes, threatened abortion), paternal BMI at pregnancy, and child factors (parity, sex)." Sorry for the large quote, but the authors said it better than I ever could. Authors also reported that those women defined as being obese before pregnancy, according to their BMI measurement, were quite a bit more likely to "have offspring with high scores (≥26) on the AQ." This then lead them to conclude that "maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring."

Caveats? Well, yes, a few. Height measured in the second trimester but participants "reported their pre-pregnancy weight"? I can see a few complications there in terms of accuracy of recall and perhaps the possibility of some bias creeping in. Having said that, many mums-to-be do have records of their weight during that 'special time' and some probably before as part of their regular clinical care or just as a result of how health conscious everyone is being these days. That and the fact that most people roughly know their typical weight (outside of pregnancy).

But also the AQ... the AQ. Regular readers probably already know that I have some qualms about the AQ and it's 'specificity' when it comes to autism and autistic traits (see here and see here). I know it's often seen as one of the internet's premier 'are you autistic?' instruments, but sometimes I think it's done more harm than good by way of it's probable link to the rise and rise of the 'self diagnosis' (see here) for example. I could go on about this, but I won't. Instead I'll just mention that 'autism-like' behaviours as judged by the AQ is probably the correct phrase to use in the context of the Varcin paper. Indeed, one might easily suggest that in a non-clinical population, AQ might also be tapping into other labels and traits [2]: "Higher AQ scores were associated with higher scores of loneliness, social anxiety, depression, and anxiety, as well as with lower scores of quality of life (QoL)." So unless one accepts that depression and/or anxiety might potentially be core features of autism (see here and see here), AQ might be picking up other things other than autism.

Still, I can't argue with the *association* talked about by Varcin et al, and what it might mean for the quite spectacular rise and rise in the numbers of people being diagnosed with an autism spectrum disorder (see here). No, not by any means the only factor to account for the increase in diagnoses, but potentially an important part of the story...

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[1] Varcin KJ. et al. Maternal pre-pregnancy weight and autistic-like traits among offspring in the general population. Autism Res. 2018 Sep 19.

[2] Reed P. et al. Loneliness and Social Anxiety Mediate the Relationship between Autism Quotient and Quality of Life in University Students. Journal of Developmental and Physical Disabilities. 2016; 28: 723-733.

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Risk of breast cancer in women with schizophrenia: meta-analysed

"In this meta-analysis of 12 cohort studies that included 125 760 women and in which conventional methods of meta-analysis had been used, schizophrenia in women was associated with an increased breast cancer incidence compared with the general population."

That was a primary findings reported by Chuanjun Zhuo & Patrick Triplett [1] following their survey of the peer-reviewed research literature on the topic of breast cancer risk and schizophrenia up to August 2017. The authors caution however that their review of this topic might not be the last word on it - "it is possible that a future study will show a decreased breast cancer risk in women with schizophrenia compared with the general population" - given "substantial between-study variance" among the research literature they examined. Another very good example of how the currency of science is probability and big sweeping generalisations may not necessarily stand the test of time.

"The status of physical health in patients with schizophrenia has become an important topic in health care management research" introduced the the Zhuo/Triplett paper, and with it, important recognition that diagnoses like schizophrenia can lead to an over-emphasis on the psychiatric often to the detriment of the somatic (see here). This, allied to other findings that have suggested that risk of premature mortality from various somatic complaints / diagnoses / issues is potentially heightened in relation to schizophrenia (see here).

Authors located studies fulfilling their study entry criteria, including "schizophrenia identified as exposure at baseline" and "documented incidence of breast cancer on follow-up" and applied their statistical analyses to results. Importantly: "Studies reporting breast cancer–related mortality rather than incidence were also excluded because the mortality outcome may be affected by many factors other than breast cancer incidence, such as comorbidities and treatments." Most of the included studies/data were found to be methodologically sound based on scores on the Newcastle-Ottawa Scale.

Alongside their finding that women with schizophrenia seemed to be at an elevated risk of breast cancer, authors also suggested that "intensive prevention and treatment against breast cancer are warranted for women with schizophrenia." So yes, this means discussing about potentially modifiable risk factors for breast cancer such as alcohol use and obesity (obesity, at the time of writing, being something of a focus for one large cancer charity here in Blighty). But this also means looking at how schizophrenia and its management might also place someone at elevated risk of something like breast cancer as a result of it sometimes being a "hormone-dependent cancer" and, as the authors note, "a significant positive association between plasma prolactin levels and the risk of breast cancer, has been observed." Minus any scaremongering, prolactin elevations have been noted following the use of certain antipsychotic medicines typically indicated for schizophrenia [2] and other conditions (see here). Any additional risk needs to be managed, and managed well.

I don't think anyone should be unduly alarmed by the Zhuo/Triplett results, but rather more mindful of the fact that a psychiatric diagnosis does not disqualify someone from other risks of more somatic conditions / complaints. The key, yet again, is screening and keeping an open mind...

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[1] Zhou C. & Triplett PT. Association of Schizophrenia With the Risk of Breast Cancer Incidence: A Meta-analysis. JAMA Psychiatry. 2018. March 7.

[2] Wu Chou AI. et al. Female schizophrenia patients and risk of breast cancer: A population-based cohort study. Schizophr Res. 2017 Oct;188:165-171.

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An exercise intervention for autism

"Our results provide support for exercise and physical activity, including basic coordination and strength exercises, as important therapeutic interventions for children with ASD [autism spectrum disorder]."

So said the results published by Chrystiane Toscano and colleagues [1] looking at an important, and sometimes easily overlooked, avenue of intervention with autism in mind: physical activity. I say 'intervention' but as with quite a few other programs/activities described in such terms, it's often more about offering equal access to things that most children (and adults) take for granted. Indeed, to 'intervention-ise' something like exercise in the context of autism kinda follows a pattern where even playing with some well-known connecting blocks is sometimes talked about in 'therapeutic' terms when mentioned alongside autism rather than just being play (see here). One has to be quite careful about the language used...

Anyhow, various parameters were monitored and measured as "a 48-week exercise-based intervention" was put into place looking at the presentation of autism as well as various physical-metabolic variables: "high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol."

Bearing in mind potentially problematic issues such as a lack of blinding - double-blinding - and of course the idea that exercise really needs to make you feel happy in order to keep doing it, researchers reported that many aspects seemed to improve over the quite long study period, more so for the group in receipt of exercise intervention. Not only did physical indicators show improvements, so did autistic features and also "parent-perceived quality of life" too.

Allowing for the fact that there could be 101 different variables impacting on the Toscano results outside of the increase in physical activity, I am happy to see that exercise is a continued focus when it comes to the autism spectrum [2]. There is literally oodles and oodles of research out there talking about how sedentary behaviour(s) do seem to be over-represented in relation to autism (see here for example) and where they could (in part) lead (see here); bearing in mind the sentiment: you can't outrun a bad diet. Anything that gets kids (and adults) up and active has to be a good thing.

Once again, I'm going to draw your attention to one potential exercise option that ticks many boxes when it comes to the autism spectrum and beyond: the martial arts (see here and see here). Physical activity... check. Focus on "basic coordination and strength"... check. Focus on predefined and (sometimes very) repetitive patterns of movement... check. Focus on individual performance set within a social context... check. Regular accomplishment levels - gradings - to boost confidence, pride and self-esteem... check. Something that will make any would-be bullies perhaps think twice or thrice... check.

And of additional importance to any discussions on exercise and physical activity, the data from Flygare Wallén and colleagues [3] highlight the important physiological reason(s) why getting those on the autism spectrum moving more is so damn important...

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[1] Toscano CVA. et al. Exercise Effects for Children With Autism Spectrum Disorder: Metabolic Health, Autistic Traits, and Quality of Life. Percept Mot Skills. 2017 Jan 1:31512517743823.

[2] Najafabadi MG. et al. The Effect of SPARK on Social and Motor Skills of Children with Autism. Pediatrics & Neonatology. 2018. Jan 6.

[3] Flygare Wallén E. et al. High prevalence of diabetes mellitus, hypertension and obesity among persons with a recorded diagnosis of intellectual disability or autism spectrum disorder. J Intellect Disabil Res. 2017 Dec 26.

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"people with a diagnosis of schizophrenia have an increased hazard of being obese"

Warm but not hot on the heels of a previous post potentially turning upside-down our understanding of inflammatory markers in the context of schizophrenia (see here) I'm bringing the paper by Isobel Cameron and colleagues [1] to the blogging table.

What's the link you may ask?

Well, if one assumes that the Hartwig findings [2] on inflammatory markers in schizophrenia could be 'influenced' by the presence of increasing body mass index (BMI) talked about in other research [3] one should, most definitely, be looking at how weight and/or BMI issues manifest in relation to schizophrenia as Cameron et al did.

So with the aim of estimating levels of obesity "in a national population sample by comparing patients with schizophrenia with matched controls" nearly 5000 adult cases of schizophrenia and "19 752 controls matched by age, gender and practice" were initially identified from a database covering Scotland. Further: "Patients with a recorded BMI were classified as obese (BMI ≥30 kg/m2) or not obese (BMI <30 kg/m2)."

Results: bearing in mind that other population statistics point to obesity not being an unfamiliar health issue in Scotland (see here) as in many other parts of the world, authors reported that: "people with a diagnosis of schizophrenia have an increased hazard of being obese when compared with adults matched by age, gender and practice attended." Taking into account occasions where "no BMI, height and weight were recorded in the 3 years before entry into the PCCIU database" researchers presented two different statistics. One where missing data were treated "as not obese following the logic that as there was no weight or BMI recorded the GP saw no clinical need to obtain these measures" and the other where records were excluded when BMI was not recorded. Both ways were associated with "an increased obesity hazard" to a similar sort of degree.

"Our analyses show that even within a nation with a substantial obesity prevalence, patients with schizophrenia are significantly more likely to be obese." This isn't of course the first time that issues with weight (or BMI) have been noted in the peer-reviewed science domain with schizophrenia in mind [3] and I doubt it will be the last.

The question should then be: what can be done about overweight and obesity in the specific context of schizophrenia? For potential answers to that, I'll refer you to some of the collected works of Dr Brendon Stubbs and colleagues (see here) and their very thorough reviews and meta-analyses on all-manner of topics that potentially tie into such a weighty issue...

This is my last post before Christmas, and so includes a traditional(?) song to send best wishes to all (hopefully not from the drunk tank)...

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[1] Cameron IM. et al. Obesity in individuals with schizophrenia: a case controlled study in Scotland. British Journal of Psychiatry Open. 2017; 3: 254-256;

[2] Hartwig FP. et al. Inflammatory Biomarkers and Risk of Schizophrenia: A 2-Sample Mendelian Randomization Study. JAMA Psychiatry. 2017 Nov 1.

[3] Annamalai A. et al. Prevalence of obesity and diabetes in patients with schizophrenia. World J Diabetes. 2017 Aug 15;8(8):390-396.

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Maternal obesity and offspring autism meta-analysed (yet again)

I think the findings reported by Sanchez and colleagues [1] make it at least the third time (see here and see here) that a meta-analysis has been conducted on the collected peer-reviewed research asking the question: does maternal weight before and/or during pregnancy affect offspring risk of being diagnosed with autism spectrum disorder (ASD)?

Granted the emphasis this time around was on "the association between maternal pre-pregnancy overweight/obesity status and child neurodevelopmental outcomes" (bold added by me), but the general question is similar to that looking at pregnancy overweight/obesity status, and whether such anthropometric variables might show an effect. The answer: according to the existing literature (see here for example) is yes; for whatever reason(s) "compared with children of normal weight mothers, children whose mothers were overweight or obese prior to pregnancy were at increased risk for compromised neurodevelopmental outcomes." A diagnosis of autism was but one outcome highlighted by the Sanchez results, as attention-deficit hyperactivity disorder (ADHD) also showed a potential *correlation* (see here).

"Of 1483 identified papers, 41 were included in the systematic review, and 32 articles representing 36 cohorts were included in the meta-analysis" indicating that there is some degree of confidence in a possible *correlation* between maternal weight and offspring outcomes.

What do the results mean? Well, being cautious that correlation is not necessarily the same as causation, and understanding that there may be a multitude of variables 'under' the issue of maternal obesity before and during pregnancy, there are a couple of potentially important implications arising from such findings. Pregnant mothers and potential mothers-to-be are already bombarded with quite a lot of information aimed at keeping themselves and their [potential] offspring 'healthy'. Part of that advice talks about how watching what you eat and maintaining a good physical activity schedule are key elements. Evidence like this from Sanchez et al perhaps add another dimension to any advice given; bearing in mind that pregnancy weight is probably not going to be an important factor for all autism or all ADHD. Indeed, the chances are that such findings are probably going to be part of a 'bigger picture' when it comes to risk profiles.

Mechanism(s) of effect? Potentially lots. Once again I'm going to zoom in on the idea that inflammation potentially generated by something like obesity [2] could be an important issue given all the previous chatter about maternal immune activation (MIA) and 'some' autism (see here). I don't doubt that there could be other factors to consider, but that's all I can [reliably] provide at the moment [3].

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[1] Sanchez CE. et al. (2017) Maternal pre-pregnancy obesity and child neurodevelopmental outcomes: a meta-analysis. Obesity Reviews. 2017. Nov 22.

[2] Lumeng CN. & Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011 Jun;121(6):2111-7.

[3] van der Burg JW. et al. The role of systemic inflammation linking maternal BMI to neurodevelopment in children. Pediatr Res. 2016 Jan;79(1-1):3-12.

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Obesity and overweight in autism meta-analysed

So: "The meta-analysis showed a significant association between obesity and ASD [autism spectrum disorder]. However, no significant association was identified between overweight and ASD."

Those were the conclusions reached by Zhen Zheng and colleagues [1] (open-access) who surveyed the pertinent peer-reviewed science literature up to November 2016 on the topic of the prevalence of overweight and obesity in relation to the autism spectrum (see here).

Including some 15 studies in their meta-analysis mix "encompassing 49,937,078 participants and 1,045,538 individuals with ASD" authors observed a connection between obesity and autism (a body mass index - BMI - between 30 and 39 for obesity and 40 and over for severely obese) but not being overweight. Among the many analyses undertaken by the authors, we are told that "the sensitivity analysis showed that removing any study did not change the final results, suggesting that our findings were robust."

Zheng et al have covered many bases when it comes to the interpretation of their findings. Feeding and eating issues potentially making "healthy dietary interventions less effective"... check (see here). Physical activity levels and 'sedentary activities'... check (see here). Potential side-effects of medication - antipsychotic medication in particular - check (see here). Also: "some individuals with ASD have been reported to have 16p11.2 or 11p14.1 microdeletions, which encompass genes related to obesity susceptibility." Yup, some genetic conditions that manifest autism also place that person at a greater risk for weight issues, either directly or peripherally.

Minus any sweeping generalisations, there are some obvious implications from such results. Obesity places a person at some heightened risk for various adverse health outcomes and potentially, early mortality outside of other, more socially-defined adversities. Prevention and treatment are key. Yes, facets of autism may make intervention slightly more complicated than perhaps noted in not-autism populations but that does not mean that one should not try to impact on the variables that lead someone down a pathway to obesity. And such intervention should be multi-faceted and perhaps also take into account a role for comorbidity that seemingly follows autism (see here)...

Oh, and probably relevant to today's posting, the scientific support for the old "healthy at every size" notion is dwindling...

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[1] Zheng Z. et al. Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis. Sci Rep. 2017 Sep 15;7(1):11697.

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Pre-pregnancy weight and risk of offspring ADHD

"Compared to normal weight mothers, the risk of having a child with ADHD [attention-deficit hyperactivity disorder] was significantly increased if the mother was overweight..., obese... or severely obese."

So said the findings reported by Andersen and colleagues [1] examining data from some 80,000 mother and child pairs "participating in the Danish National Birth Cohort (DNBC)." The name of the research game was to look-see whether maternal weight before pregnancy might be an important factor when it comes to offspring developmental and behavioural outcomes specifically with ADHD and/or autism in mind.

The results showing a possible relationship between maternal pre-pregnancy weight and ADHD were to some extent mirrored in relation to offspring autism albeit not showing the 'dose trend' of hazard ratios - overweight, obese, severely obese - noted in relation  to ADHD. Indeed authors noted that: "Regarding ASD [autism spectrum disorder], an increased risk was observed in underweight... and obese... mothers" illustrating a less confident pattern of possible association.

This is not the first time that this topic has been discussed on this blog (see here). One still has to be a little careful with such 'observational' research so as not to assume that only pre-pregnancy maternal weight is a risk factor for offspring ADHD or anything else. I'm also minded to suggest that the continued use of the body mass index (BMI) statistic is not without difficulties. That and the fact that we're also no further forward when it comes to talking about possible mechanisms behind any association given the myriad of effects that excess weight can potentially cause to mother and any children to be (see here).

What we can however take from this and other independent data [2] is that the physical health of mothers (and fathers) might be quite important to offspring even when the prospect of children is still a twinkle in the eyes of parents. We're all constantly being told to eat well, exercise regularly and cut out or cut back on certain things to achieve optimal health and wellbeing. This and other research if true, suggest that heeding such advice might have inter-generational implications too, for lots of different reasons [3]...

Music to close, and sorry Your Majesty, but some of my brood find the alternative 'God Save the Queen' much more entertaining than the original...

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[1] Andersen CH. et al. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur Child Adolesc Psychiatry. 2017 Jul 15.

[2] Van Lieshout RJ. et al. Pre-pregnancy and pregnancy obesity and neurodevelopmental outcomes in offspring: a systematic review. Obes Rev. 2011 May;12(5):e548-59.

[3] Jensen ET. et al. The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm. J Pediatrics. 2017. March 21.

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ADHD, obesity and bariatric surgery?

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

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

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

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

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

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

Maternal obesity and offspring autism meta-analysed (again)

Meta-analyses eh? You spend ages waiting for one and two come along in quick succession. Well today I'm posting about yet another meta-analysis of the peer-reviewed scientific literature suggesting that "excessive maternal BMI [body mass index] is associated with an increased ASD [autism spectrum disorder] risk in offspring." [1]

The review by Ying Wang et al follows hot on the heels of the meta-analysis by Li and colleagues [2] (see here for my take) but further looked at "the potential association of different category of BMI including overweight and underweight with ASD risk" among other things. BMI by the way, is a rough and ready way to quantify how much of a person there is according to height and weight. Whilst a useful statistic, it is not without its issues.

After taking into account data from "6 cohort studies and 1 case-control study involving 8,403 cases and 509,167 participants" the authors unsurprisingly came to the same conclusion as Li and colleagues that a higher BMI seems to confer more [relative] risk for offspring autism as an outcome. Authors even included a nice graphic (see here) suggesting something of a dose-response relationship between the two variables (based on data from four of the studies included in their meta-analysis).

What's more to say? Well, 'The maternal body as environment in autism science' returns into the frame and questions about possible mechanisms need to be asked/answered. No, such findings don't mean (a) every mum with a child with autism was overweight or obese before or during pregnancy or (b) every overweight or obese mum will have a child with autism: "Compared with children whose mothers were at normal weight, children born to overweight and obese mothers have a 28% and 36% higher risk of developing ASD, respectively." Such data does however open the door to the idea of foetal programming when it comes to potential offspring outcomes and how elevated BMI as possibly linking to facets of metabolic syndrome for example, might have some role to play for some (see here).

More investigations are indicated.

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[1] Wang Y. et al. Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis. Scientific Reports. 2016; 6: 34248.

[2] Li YM. et al. Association Between Maternal Obesity and Autism Spectrum Disorder in Offspring: A Meta-analysis. J Autism Dev Disord. 2016 Jan;46(1):95-102.

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Wang, Y., Tang, S., Xu, S., Weng, S., & Liu, Z. (2016). Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis Scientific Reports, 6 DOI: 10.1038/srep34248

Obesity in adolescent chronic fatigue syndrome (CFS)

"At 13 years, adolescents who had received a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) who were attending specialist CFS/ME services were more than two times more likely to be obese than adolescents in the general population."

At first reading, I wasn't particularly surprised by the findings reported by Norris and colleagues [1] (open-access) drawing on data partly derived from everyone's favourite UK longitudinal birth cohort: ALSPAC (Avon Longitudinal Study of Parents and Children). If one assumes that those suffering (yes, people do suffer from CFS/ME) might not be engaging in an optimal exercise regime nor eating the best of diets one can perhaps see how the condition might be a susceptibility factor for issues with weight. That being said, and after some further thought, the Norris findings might not be something entirely representative of the effects of CFS/ME either given documented cases of malnutrition and sadly, death (see here). Sweeping generalisations are, yet again, not required.

So, the Norris group findings... well, some of the authors are not completely unknown to the idea that eating habits might be perturbed in cases of CFS/ME as per other entries on this blog (see here). This time around ALSPAC data was joined by "data collected from all National Health Service (NHS) paediatric specialist services that participated in the CFS/ME National Outcomes Database (NOD) between August 2004 and October 2014." The aim was to "obtain prevalence estimates for obesity at two time points during adolescence (ages 13 years and 16 years), in three groups of adolescents representing a continuum of CFS/ME severity (healthy population, CFS/ME based on responses to questionnaires and clinically diagnosed CFS/ME)." In case your a little confused, the CFS/ME by questionnaire response group were derived from ALSPAC. The categorisation of obesity or not was made by clinical height and weight measurements from the ALSPAC data but was a little less 'formalised' for the more detailed diagnosis CFS/ME group (in clinic) including measurement "in the clinic or GP surgery or obtained from parental report." Body mass index (BMI) was calculated from said measurements.

Results: well, aside from that opening sentence on 13 year olds, the authors also reported that for those with CFS/ME: "At 16 years, they were more than 4 times more likely to be obese compared to those in the general population." The authors noted that the association between CFS/ME and obesity was 'driven' in the most part by "those attending the specialist services, thus representing those with CFS/ME severe enough to be referred for specialist treatment."

"Health professionals should be aware of this association to encourage appropriate screening for obesity and its possible complications when assessing patients with CFS/ME." I agree with the authors conclusions stemming from their findings but I think a word of caution also needs to be applied too.

For those who've followed the CFS/ME research scene for the past few years, you'll probably already have heard about the PACE trial and the 'suggestion' among other things that graded exercise therapy (GET) might be something to consider "to gradually increase how long you can carry out a physical activity." PACE has stumbled in recent times following a long and drawn out (and expensive) 'battle' to access the data behind the headlines; having already seen a 'downgrading' of effect from some agencies. Now, think to yourself what would be a health professional's response to being presented by a patient who is obese? Change your diet? Maybe do a little more exercise? Hmm...

I'm not saying that young people with CFS/ME who present with weight issues shouldn't be provided with the same appropriate medical advice and care as everyone else with such issues. I'm not saying that every health professional would be prescribing pounding the treadmill or anything related given the quite unique issues associated with CFS/ME. I do however think that set within the research history created partly as a result of initiatives such as the PACE trial, there are sensitivities that need to be observed before sweeping healthcare advice is provided en-masse. That also 'not out-running' a bad diet is gaining some traction is an important point to make as other areas of research could yet be explored bearing in mind how exercise might impact on the gut microbiome of some CFS/ME (see here) for example. That might also includes the gut virome [2] too...

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[1] Norris T. et al. Obesity in adolescents with chronic fatigue syndrome: an observational study. Arch Dis Child. 2016 Sep 21. pii: archdischild-2016-311293.

[2] Giloteaux L. et al. A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition. Am J Case Rep. 2016 Oct 10;17:720-729.

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Norris T, Hawton K, Hamilton-Shield J, & Crawley E (2016). Obesity in adolescents with chronic fatigue syndrome: an observational study. Archives of disease in childhood PMID: 27655658

Metformin to tackle medication induced weight gain in autism?

"Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD [autism spectrum disorder]."

So said the paper by Evdokia Anagnostou and colleagues [1] (open-access) tackling an increasingly important health issue related to the pharmacological 'management' of some aspects of some autism.

Metformin is the treatment of choice when it comes to the management of type 2 diabetes (the one where "the pancreas doesn't produce enough insulin or the body's cells don't react to insulin"). It is thought to work by helping the liver to stop producing new glucose and also helping insulin carry more glucose into muscle cells more effectively. Alongside, an increasing body of research has also suggested that metformin might be a useful intervention measure to offset one of the quite well-known side-effects associated with various antipsychotic agents: weight gain.

So Anagnostou et al set about looking to "assess the safety, tolerability, and efficacy of metformin to decrease weight gain associated with the use of atypical antipsychotic medication in children with ASD." They did this using the gold-standard in clinical trial designs: the "double-blind, placebo-controlled, randomized clinical trial" where some 60 children and young adults diagnosed with an ASD and receiving a stable dose of an atypical antipsychotic received either metformin (Riomet) or a placebo over the course of 16 weeks. "The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables." The study protocol was also registered with ClinicalTrials.gov.

As per the opening sentence, there were some important differences in body mass index (BMI) z-scores suggestive that compared with a placebo, those prescribed metformin saw decreases in weight gain. The range of decrease in BMI were in some cases between about 8-9% over the course of the 16 week study period (most of the benefits seemed to be apparent after about 8 weeks of metformin use). Insofar as those secondary variables also examined during the course of the study (glucose levels, insulin, triglycerides, etc.) no significant differences were noted across the study. When it came to the important issue of side-effects, the authors noted that gastrointestinal (GI) effects seemed to be more apparent in the group taking metformin during treatment days. Aside from that, short-term side-effects seemed to be few and far between.

The authors note that their trial "did not address the question of whether coadministration of metformin at the onset of atypical antipsychotic use prevents initial weight gain" but rather whether metformin use after weight gain associated with antipsychotic use could be effective. In that light, these are important results that very much require further independent investigation.

Quite a few times on this blog I've talked about how the physical health of those on the autism spectrum is sometimes neglected as a function on the focus on mental health or behaviour. There is a growing recognition that autism, or at least some of the important comorbidities associated with autism, might somehow predispose to a more sedentary lifestyle and the accompanying health issues that this can bring. Throw into the mix the possibility that some of the pharmacotherapy used in autism might also contribute to something like weight issues [2], and you have a recipe for some pretty severe health issues potentially building up in later life. These latest findings are therefore welcomed as a way to potentially lower the burden of an elevated BMI in cases where such medication is prescribed.

I do have questions however about this approach and how one perhaps needs to be slightly cautious about slipping into the old 'medication to tackle medication side-effects' routine with autism in mind (something noted in an accompanying editorial to the Anagnostou study). Metformin, whilst a very useful drug, is not without side-effects as was noted in the Anagnostou study and given the quite high rates of GI issues noted in cases of autism (see here), one really does not want to make this any worse. I would also like to see more data on the use of metformin in antipsychotic-induced weight gain in autism with a focus on other parameters thought to be altered by such antipsychotic use such as the issue of prolactin levels for example (see here). Yes, there is data to suggest that metformin might more generally work on prolactin levels too [3] but does this similarly apply to children on the autism spectrum? And then also there is the issue of sleep [4]...

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[1] Anagnostou E. et al. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder. JAMA Psychiatry. 2016. Aug 24.

[2] Shedlock K. et al. Autism Spectrum Disorders and Metabolic Complications of Obesity. Journal of Pediatrics. 2016. Sept 2.

[3] Krysiak R. et al. The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia. Eur J Intern Med. 2016 May;30:94-8.

[4] Kajbaf F. et al. The relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes referred for potential sleep disorders. Diabet Med. 2014 May;31(5):577-80.

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Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, Brian J, Arnold LE, Capano L, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Hadjiyannakis S, Peleg N, Odrobina D, McAuliffe-Bellin S, Zakroysky P, Marler S, Wagner A, Wong T, Macklin EA, & Veenstra-VanderWeele J (2016). Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA psychiatry PMID: 27556593

Lactobacillus reuteri rescuing [mouse] social behaviours: relevance to autism?

Continuing a recent 'probiotic theme' on this blog I've decided to talk a little about the study results reported by Shelly Buffington and colleagues [1] on how a "single species of gut bacteria can reverse autism-related social behavior in mice." I say 'talk about' but my conversations on this topic should be viewed in light of what others have also said about this study (see here for example) including the lead author (see here).

To summarise the findings: authors started from the idea that maternal obesity during pregnancy might have some implications for offspring in terms of their risk of "neurodevelopmental disorders including autism spectrum disorder (ASD)." It's something that has been covered before on this blog (see here) including the idea that inflammation or response to inflammation in-utero might be an important part of any risk mechanism (see here).

Conversations then progressed towards the possibility that the gut microbiome might play a role in that elevated risk of offspring autism following pregnancy obesity. To test this theory out, researchers fed female mice a high fat or 'normal diet' for 8 weeks, paired them for mating and gave all their offspring a regular diet. They studied social behaviour of offspring mice and observed that "MHFD [maternal high-fat diet] offspring had impaired sociability and showed no preference for social novelty."

To examine whether those mouse social behaviours were linked to the gut microbiome, researchers looked at the "bacterial composition and community structure in the feces" of offspring mice to ascertain any differences. They did find differences; indeed in one write-up of the study the authors note: "We found a clear difference in the microbiota of the two maternal diet groups." Could such bacterial differences account for the social differences noted between the groups? Quite possibly as Buffington et al reported that "co-housing one MRD [maternal regular diet] with three MHFD offspring was sufficient to rescue both the social behaviors and microbiota phylogenetic profile of MHFD offspring." Further, researchers transplanted the faecal microbiota from the MRD and MHFD offspring into germ-free mice providing "causal evidence that an imbalanced microbial ecology in the mice born to mothers on a high-fat diet is responsible for their social deficits."

Then came a big question: what was it about the maternal high-fat diet offspring microbiome that might be 'responsible' for the social issues observed? The answer or at least one answer: "L. reuteri [Lactobacillus reuteri] was the most drastically reduced (>9-fold) in the MHFD microbiota population, compared to the MRD microbiota." Subsequent addition of L. reuteri to the drinking water of MHFD offspring was instigated and: "Remarkably, treatment with L. reuteri significantly improved sociability and preference for social novelty in MHFD offspring."

As if all that wasn't enough researchers also looked at the old gut-brain axis and subsequently noted that: "L. reuteri treatment restores oxytocin levels, VTA [ventral tegmental area] plasticity and social behaviors." Oxytocin has something of an interesting possible connection to [some] autism (see here).

And rest.

As you can perhaps appreciate, this piece of research is fairly comprehensive both in terms of the methodologies used and also the findings in relation to maternal pregnancy obesity, offspring social behaviour, gut microbiome and the gut-brain axis. Certainly quite compelling evidence for some kind of effect including the concept of foetal programming allied to the idea of possible intervention.

Of course you'd be right to question whether the processes described in this mouse model would necessarily map on to the human experience and indeed the very heterogeneous autism spectrum characterised by [variable] issues with social affect for example. Similar questioning is asked of all animal studies trying to model the complexities of autism (see here). But added to other research where mouse modelling of autism 'deficits' has been to some degree 'changed' as the result of the addition of a particular bacterial species (see here) there is some reason for potential excitement. More so when one considers other research on the gut microbiome in relation to specific preparations potentially modifying the risk of 'neurospychiatric disorder' (see here) for example, and potentially affecting mood and/or behaviour (see here). Don't even get me started on toddler temperament being linked to the inner workings of the gut (see here) minus any hype.

But just before sales of Lactobacillus reuteri increase markedly there is further research to be done. Not least is the translation of elements of the Buffington research into studies of humans. Set within the idea that mapping exactly what kinds of wee beasties are residing in the gut is now fairly commonplace and has already stretched into autism research (see here) I would have thought that looking for the presence or absence of L. reuteri in certain groups (and sub-groups) on the autism spectrum and beyond should be fairly easy to do. If and when issues are found with this particular species, supplementing could be indicated bearing in mind some of the potential effects [2] noted already on this bacterium might already show indication in some cases of autism (see here). One might also see a way to look at this and other bacteria in conjunction with levels of oxytocin and possibly other important compounds too as part of that gut-brain axis. Given also that the Buffington study was a study of offspring of obese mice in terms of their sociability, does this also mean that kids born to overweight or obese mums are less likely to have age-appropriate social skills outside of any talk of autism?

There is still a research journey to be travelled in this area of investigation and, I might add, potentially linking various areas together including the idea that not all fats in a high-fat diet are necessarily the one and the same (see here)...

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[1] Buffington SA. et al. Microbial Reconstitution Reverses Maternal Diet Induced Social and Synaptic Deficits in Offspring. Cell.2016; 165: 1762-1775.

[2] Coccolrullo P. et al. Lactobacillus reuteri (DSM 17938) in Infants with Functional Chronic Constipation: A Double-Blind, Randomized, Placebo-Controlled Study. J Peds. 2010; 157: 598-602.

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Buffington, S., Di Prisco, G., Auchtung, T., Ajami, N., Petrosino, J., & Costa-Mattioli, M. (2016). Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring Cell, 165 (7), 1762-1775 DOI: 10.1016/j.cell.2016.06.001