Showing posts with label weight. Show all posts
Showing posts with label weight. Show all posts

Saturday, 19 January 2019

"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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Wednesday, 17 October 2018

"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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Saturday, 23 December 2017

"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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Thursday, 21 December 2017

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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Thursday, 5 October 2017

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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Wednesday, 6 September 2017

Metformin to tackle medication induced weight gain in autism continued

The results of the open-label extension trial on the use of "Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism" reported by Benjamin Handen and colleagues [1] is blogging fodder for today. Continuing a research interest from this group (see here), the idea that weight and related side-effects from certain antipsychotic medicines can be managed by a drug readily used to treat type 2 diabetes receives yet more support.

Last time around [2] researchers showed that under double-blind, placebo controlled conditions, metformin was fairly well-tolerated and did aid in "decreasing weight gain associated with atypical antipsychotic use" in children and young adults diagnosed with an autism spectrum disorder (ASD). This latest publication detailed what happened when everyone - well, 85% of the original cohort - went on metformin in terms of their body mass index (BMI) and "additional body composition and metabolic parameters" for an additional 16 weeks.

Results: well, as would probably be expected, "participants initially taking placebo during the RCT [randomised controlled trial] had reduced BMI z-scores" when metformin was introduced. For those who were already taking metformin during the original trial, prior reductions in BMI were maintained but they "did not experience additional weight loss." I might also add that 'fairly well-tolerated' meant that: "Three participants discontinued treatment due to an adverse event."

These are important findings and add to other preliminary research findings in this area [3]. I know many people (including myself) have some reservations about adding in medicines to treat the side-effects of other medicines (as well as the conditions for prescribing antipsychotics in the first place [4]), but given what elevated BMI scores can mean to physical health and associated health risks, this is one occasion where intervention might be truly life-saving (with appropriate clinical monitoring assumed). Further studies are indicated.

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[1] Handen BL. et al. A Randomized, Placebo-Controlled Trial of Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorder: Open-Label Extension. Journal of the American Academy of Child & Adolescent Psychiatry. 2017. Aug 19.

[2] Anagnostou E. et al. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial.  JAMA Psychiatry. 2016 Sep 1;73(9):928-37.

[3] Wink LK. et al. Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder. J Autism Dev Disord. 2017 Jul;47(7):2290-2294.

[4] Jackel C. et al. Factors Associated with Developmental Behavioral Pediatricians Prescribing Psychotropic Medication to Children with Autism Spectrum Disorder: A Study of Three DBPNet Sites. J Dev Behav Pediatr. 2017 Aug 10.

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Saturday, 5 August 2017

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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Friday, 11 November 2016

"While you're here, I just want to talk about your weight"

The important Doctor-Patient relationship
In a slight departure from the typical material discussed on this blog, I want to briefly direct readers to the paper by (Prof) Paul Aveyard and colleagues [1] and results suggesting that: "A behaviourally-informed, very brief, physician-delivered opportunistic intervention is acceptable to patients and an effective way to reduce population mean weight."

The title of this post comes from some of the media coverage of the Aveyard study summarising how general practitioners (GPs) in particular, might be ideally placed to bring up the topic of 'weight issues' when seeing some of their patients for other health matters.

Minus any charges of plagiarism, I'd like to particularly draw readers attention to the example given in the Aveyard paper of a 'typical physician intervention'. So:

"Physician: While you're here, I just wanted to talk about your weight. You know the best way to lose weight is to go to [Slimming World or Rosemary Conley] and that's available free on the NHS?
Patient: Oh?
Physician: Yes, and I can refer you now if you are willing to give that a try?
Patient: Yes, ok.
Physician: Ok, what you need to do is take this envelope back outside to the person who weighed you and they will book you into the weight loss course now.
Patient: Ok.
Physician: Good, but I'd like to see how you're getting on, so come and see me again in 4 weeks, please. Ok?
Patient: Ok, see you then."

In these days of the 10-minute consultation combined with something of an 'epidemic' of obesity and overweightedness I like the idea that a 30-second chat from an authority figure like a GP with a patient can potentially transform lives, even if only a proportion of the intended market. Despite the fact that only 40% of those offered weight reduction classes actually attended, there are some pretty decent statistics included in the paper to suggest that for this group, weight change was better than for those who weren't offered any additional support ("mean weight change at 12 months was 2·43 kg with the support intervention and 1·04 kg with the advice intervention, giving an adjusted difference of 1·43 kg"). And with decreasing weight, so the risk of various other health complaints also decreases accepting the old/new adage of 'not out-running a bad diet' [2].

In these days of the soundbite and 140-characters or less, it makes me wonder what other health promotion advice might be amenable to a very brief chat from someone like a GP?

To close, lest we forget...

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[1] Aveyard P. et al. Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial. Lancet. 2016. Oct 24.

[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 Aug;49(15):967-8.

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ResearchBlogging.org Aveyard, P., Lewis, A., Tearne, S., Hood, K., Christian-Brown, A., Adab, P., Begh, R., Jolly, K., Daley, A., Farley, A., Lycett, D., Nickless, A., Yu, L., Retat, L., Webber, L., Pimpin, L., & Jebb, S. (2016). Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial The Lancet DOI: 10.1016/S0140-6736(16)31893-1

Monday, 17 October 2016

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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ResearchBlogging.org 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

Wednesday, 12 October 2016

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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ResearchBlogging.org 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

Thursday, 8 September 2016

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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ResearchBlogging.org 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

Thursday, 14 April 2016

Risk of type 2 diabetes in autism

"Adolescents and young adults with ASD [autism spectrum disorder] were more likely to develop type 2 DM [type 2 diabetes mellitus] during the follow-up. In addition, those with ASD using atypical antipsychotics exhibited a high risk. Therefore, further research is necessary to investigate the common pathophysiology of ASD and type 2 DM."

So said the findings reported by Mu-Hong Chen and colleagues [1] as, yet again, Taiwan and their very useful National Health Insurance Research Database (NHIRD) continues to give to autism and related research.

Type 2 diabetes - the one where the pancreas don't produce enough insulin or the body's cells don't react to insulin - was the focus of NHIRD interrogation this time around, following in the scientific footsteps of previous research looking at both type 1 and type 2 diabetes in relation to autism (see here). Enrolling over 6,000 adolescents and young adults diagnosed with an autism spectrum disorder (ASD) and nearly 25,000 age and sex-matched controls "between 2002 and 2009", researchers followed participants until the end of 2011 watching for who and how many would be diagnosed with type 2 DM.

Dividing groups into adolescents and young adults, researchers reported that those diagnosed with autism were at "higher risk of developing type 2 DM than those without ASD" after adjusting for various potential forms of bias including "atypical antipsychotics use, and medical comorbidities." Further: "Short-term... and long-term... use of atypical antipsychotics were associated with a higher likelihood of subsequent type 2 DM." Ergo, yet another important, growing and potentially life-changing comorbidity appears to be 'over-represented' when it comes to the label of autism.

Accepting that it is not necessarily new news that certain pharmaceutical formulations can affect risk of type 2 diabetes [2], these are interesting and potentially important results. The focus on how maternal diabetes 'exposure' might modify risk of autism in offspring (see here) coupled to ideas about how autoimmunity inferred by type 1 diabetes history might link into some autism (see here) have tended to predominate in this area of the autism research landscape. The Chen results tap into a pretty under-appreciated idea that for one reason or another, a diagnosis of autism could potentially raise the risk of something like type 2 diabetes.

There is additional research to do on this topic. So, in these days of greater appreciation that 'autism genes' might not necessarily just be 'genes for autism' (pleiotropy), one could reasonably ask the question of whether there are subtle genetic (or epigenetic) issues influencing risk of type 2 diabetes. As per my use of the word 'epigenetic' in that last sentence, I'm also minded to bring in the work from people like the late David Barker, and the idea that birth weight might also 'program' for a greater risk for type 2 diabetes and related health issues (see here) given what's known about this area with autism in mind (see here).

That type 2 diabetes is not a wholly genetic issue is something else to bear in mind as issues such as weight and eating patterns come into the frame. Minus any sweeping generalisations, weight issues and particularly obesity are not uncommon research topics when it comes to autism (see here) and as for eating patterns and habits, well, let's just say there is some science there too (see here). Whether singularly or combined (and with potential added mention of exercise) one might already see how screening for type 2 diabetes should be added to the list of monitoring required when a diagnosis of autism is received. I might also mention some recent research chatter about leptin as being important to type 2 diabetes in kids and where that might go with regards to other autism research (see here). I'm sure there other factors too.

And, if and when type 2 diabetes in diagnosed, there are a number of positive changes that can be made to lifestyle including the idea that 'reversal' is not something totally unheard of...

So:  The Force Awakens and Dark Side of the Moon... synch or no synch?

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[1] Chen MH. et al. Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study. Diabetes Care. 2016 Mar 22. pii: dc151807.

[2] Galling B. et al. Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2016 Mar 1;73(3):247-59.

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ResearchBlogging.org Chen, M., Lan, W., Hsu, J., Huang, K., Su, T., Li, C., Lin, W., Tsai, C., Tsai, S., Lee, Y., Chen, Y., Pan, T., Chang, W., Chen, T., & Bai, Y. (2016). Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study Diabetes Care DOI: 10.2337/dc15-1807

Wednesday, 13 April 2016

Vitamin D deficiency and psychosis

In amongst my various ramblings about how vitamin D - the sunshine vitamin/hormone - might show more than a few connections to conditions/labels outside of just the English disease (see here), I've covered some science on a possible connection with psychosis (see here) and schizophrenia (see here). There are still gaps in terms of the hows and whys of vitamin D insufficiency and deficiency when it comes to this area of psychiatry, but I believe there is enough science in this area to initially warrant screening of vitamin D levels as and when a diagnosis is received. This similarly extends to other labels too (see here and see here).

The paper by Lally and colleagues [1] (open-access) puts a little more scientific flesh on the bones about how vitamin D insufficiency/deficiency might manifest in cases of psychosis, with a particular focus on "increased cardiovascular disease risk factors and in particular metabolic syndrome [MetS]."

With thanks to Brendon Stubbs (one of the authors of the paper) for bringing the findings to my attention, researchers set about looking at "the prevalence of vitamin D deficiency in a cohort of community patients with established psychotic illnesses" (N=324). Given my earlier mention of the 'English disease', the cohort were indeed all living in England and drawn from a larger study initiative. Vitamin D levels were assayed via a chemiluminescence immunoassay based on the examination of serum samples. Various other measures were also included for study around the issue of cardiovascular risk factors including body mass index (BMI), waist circumference, blood pressure, serum cholesterol levels and glucose levels. High sensitivity serum C-reactive protein (HS-CRP) was also included.

Results: "Almost half of the sample (48.8 %, n = 158) were deficient in vitamin D while only 13.9 % (n = 45) had sufficient vitamin D." Ethnicity seemed to play a role in those determinations of deficiency/sufficiency with vitamin D levels generally lower in those who were black African or black Caribbean. Likewise the season of testing showed an effect. When it came to determining whether there was an association between vitamin D status and mental state, researchers reported nothing significant based on the use of the Positive And Negative Syndrome Scale (PANSS) and related measures.

But... there might be quite a bit more to look at when taking into account those cardiovascular disease risk factors and vitamin D levels as the authors reported various significant correlations. So: "those with the highest levels of vitamin D have a lower prevalence of MetS (20.5 %), compared to those in the lowest (39.1 %), second (48.3 %) and third quartile (43.1 %) of vitamin D." Indeed, just about every measure of cardiovascular risk showed an association with measured serum vitamin D levels when controlling for "age, gender, ethnicity and season of 25-OHD blood sampling." The authors also add that: "Those engaging in low intensity physical activity over the week prior to sampling... had significantly lower 25-OHD levels... than those who engaged in moderate or high intensity physical activity."

Teasing apart what might actually be doing what is a difficult task in such studies where various outcome measures might be implicated. The authors do speculate on how for example, their finding of "raised CRP and vitamin D deficiency in established psychosis" might tie into other research on inflammation or inflammatory processes with both variables in mind (see here and see here). Indeed, this might also tie in with calls for further integration of immunopsychiatry with psychotic disorders in mind [2]. But there remains more to do, including the intriguing question: "would the supplementation of vitamin D in psychosis prevent and/or ameliorate cardiovascular and metabolic risk?"

I do have some small points to make about the study that might also require attention in follow-up work, not least the idea that immunoassay for determining functional vitamin D levels might not be the most accurate method [3]. Indeed, the authors make this point in their conclusions. One might also hope that comparisons with other patient groups might offer some further information about how specific the findings are to just psychosis or other psychiatric groupings. If found in a more general sense, the idea that vitamin D is related to variables affecting cardiovascular risk in such groups could make lots and lots of waves.

For now however, this research extends the ideas that: (a) preferential screening for vitamin D might be indicated for this group/label, and (b) the focus on psychiatric presentation should not be made at the expense of somatic presentation. Parity of esteem and all that; or rather just making sure that health inequality does not follow from receipt of a psychiatric label...

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[1] Lally J. et al. Clinical correlates of vitamin D deficiency in established psychosis. BMC Psychiatry. 2016; 16: 76.

[2] Leboyer M. et al. Is it time for immunopsychiatry in psychotic disorders? Psychopharmacology (Berl). 2016 Mar 18.

[3] Yang Y. et al. High-throughput measurement of 25-hydroxyvitamin D by LC-MS/MS with separation of the C3-epimer interference for pediatric populations. Clin Chim Acta. 2016 Feb 15;454:102-6.

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ResearchBlogging.org Lally, J., Gardner-Sood, P., Firdosi, M., Iyegbe, C., Stubbs, B., Greenwood, K., Murray, R., Smith, S., Howes, O., & Gaughran, F. (2016). Clinical correlates of vitamin D deficiency in established psychosis BMC Psychiatry, 16 (1) DOI: 10.1186/s12888-016-0780-2

Thursday, 10 March 2016

Omega-3 fatty acids, 'antibiotic exposure-induced gut microbiota dysbiosis' and obesity

The findings reported by Kaliannan and colleagues [1] provide food for thought today and the suggestion that in mice at least: "elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver, and dyslipidemia resulting from early-life exposure to azithromycin (AZT)."

Azithromycin is an antibiotic quite commonly used for treating a number of bacterial infections. The idea that antibiotic use, and specifically the effects on the trillions of wee beasties that call our gut home (the gut microbiome), might impact on weight is not a new one. The precise mechanism(s) are still a point of some speculation. Evidence from various sources however (see here for example) seems to indicate that there may be something about the gut microbiome that seems to have an important bearing on weight gain and obesity.

Kaliannan et al started with the premise that "increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life." I know some people might be a little puzzled as to why supplementing a fat might actually stop someone (or at least something) from 'becoming fat', but these are times where the sweeping notion that 'fat makes you fat' is being re-analysed (see here). Using a specific type of mouse - "the fat-1 transgenic mouse model" [2] - that is "capable of producing n-3 fatty acids from the n-6 type, leading to abundant n-3 fatty acids with reduced levels of n-6 fatty acids in their organs and tissues, without the need of a dietary n-3 supply", researchers exposed mice to AZT during their earliest days. They found that this particular type of mouse that is able to synthesize its own omega-3 fatty acids, potentially showed some important effects as a result of its naturally high levels of omega-3 fatty acids in tissues. Further: "These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice."

Reiterating that this was a mouse study focused on a very specific type of mouse, these are interesting findings. It's not necessarily new news that "dietary lipids affect specific populations of gut microbes and their metabolic end products" [3] or that specific types of bacteria might also affect fat composition of host tissues [4] but more scientific flesh needs to be put on the bones of the relationship. Insofar as how these results might transfer outside of the fat-1 transgenic mouse, well, the authors speculate about "the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics." I would however be minded to suggest that quite a bit more investigation is needed before fish oils are routinely prescribed alongside/following antibiotics in early childhood to 'prevent' microbiota-associated obesity. That also agricultural methods used might be a relevant factor is food for thought [5] as is the focus on fish oils and Akkermansia muciniphila (see here) among other things.

But speaking of our microbial masters, I might also draw your attention to the paper by Laura Blanton and colleagues [6] talking about the other extreme of weight and gut bacteria. Feed the world eh?

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[1] Kaliannan K. et al. Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity. Int J Obes (Lond). 2016 Feb 15.

[2] Kang JX. Fat-1 transgenic mice: a new model for omega-3 research. Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):263-7.

[3] Shen W. et al. Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem. 2014 Mar;25(3):270-80.

[4] Wall R. et al. Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am J Clin Nutr. 2009 May;89(5):1393-401.

[5] Średnicka-Tober D. et al. Composition differences between organic and conventional meat: a systematic literature review and meta-analysis. Br J Nutr. 2016 Feb 16:1-18.

[6] Blanton LV. et al. Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016. Feb 19.

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ResearchBlogging.org Kaliannan K, Wang B, Li XY, Bhan AK, & Kang JX (2016). Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity. International journal of obesity (2005) PMID: 26876435

Tuesday, 24 November 2015

Secondary conditions impacting on obesity stats in autism?

"Decision makers, clinicians, and researchers developing interventions for children with ASDs [autism spectrum disorders] should consider how secondary conditions may impact obesity and related activities."

That was the conclusion reached in the study by Kathryn Corvey and colleagues [1] looking to: "examine obesity, overweight, physical activity, and sedentary behavior among children and youth with and without ASD using nationally representative data and controlling for secondary conditions, including intellectual and learning disabilities, ADHD, developmental delay, and other mental, physical, and medical conditions, as well as medication use."

Detailing results based on information gathered from the 2011-2012 National Survey of Children's Health whereby households of some 65,000 children between the ages of 6 and 17 years were quizzed about various physical and emotional health related matters, researchers specifically focused on some 1300 children with a reported diagnosis of ASD. Various confounding variables including those 'secondary conditions' were taken into account in their quite detailed analyses.

Results: following a trend noted in other peer-reviewed research (see here), the authors reported that a diagnosis of ASD was associated with elevated odds of being obese. But... when it came to adjusting their analyses for the presence of some of those secondary conditions "ASD diagnosis was no longer associated with obesity."

This is interesting stuff. In line with some of the shifts in thinking about autism these days - including plurality, comorbidity clusters and the idea of differing developmental trajectories - the Corvey results imply that more care is needed before making sweeping generalisations about how 'all' autism is linked to obesity or related issues. This comes at a time when other research has talked about the timing of weight issues when it comes to autism [2]. Allied to previous research more generally looking at obesity in learning disability [3] the message is becoming a little clearer that a variety of factors 'around' autism might be the important risk issues for something like obesity or being overweight including various social factors linked to physical activity levels too (see here).

Quite recently I've also become rather interested in the peer-reviewed research related to ADHD (attention-deficit hyperactivity disorder) and obesity (see here) and some of the clues emerging there that are potentially relevant to some autism. Allied to what is known about the 'anthropometric' effects of certain types of medication used by some on the autism spectrum (see here), and it appears that risk of obesity and being overweight in relation to autism is at last getting the 'no sweeping generalisations needed' handling that it truly deserves.

Music: Pick A Part That's New - Stereophonics.

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[1] Corvey K. et al. Obesity, Physical Activity and Sedentary Behaviors in Children with an Autism Spectrum Disorder. Matern Child Health J. 2015 Oct 29.

[2] Hill AP. et al. Obesity and Autism. Pediatrics. 2015. Nov 2.

[3] de Winter CF. et al. Overweight and obesity in older people with intellectual disability. Res Dev Disabil. 2012 Mar-Apr;33(2):398-405.

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ResearchBlogging.org Corvey K, Menear KS, Preskitt J, Goldfarb S, & Menachemi N (2015). Obesity, Physical Activity and Sedentary Behaviors in Children with an Autism Spectrum Disorder. Maternal and child health journal PMID: 26515467