Showing posts with label diet. Show all posts
Showing posts with label diet. Show all posts

Wednesday, 12 June 2019

Childhood dietary patterns and ADHD?

The findings of the systematic review and meta-analysis published by Bianca Del-Ponte and colleagues [1] provide the blogging fodder today, and the suggestion that: "a diet high in refined sugar and saturated fat can increase the risk, whereas a healthy diet, characterized by high consumption of fruits and vegetables, would protect against ADHD [attention-deficit hyperactivity disorder] or hyperactivity."

The starting point: "The diet during childhood has been investigated as a factor potentially involved in the ADHD etiology." Yes it has, and Del-Ponte et al managed to find 14 studies looking at this issue published in the peer-reviewed literature. The data were boiled down and results obtained suggesting that "healthy dietary patterns were protective against ADHD (OR: 0.65; 95% CI: 044 – 0.97), while unhealthy dietary patterns were found as risk to ADHD (OR: 1.41; 95% CI: 1.15–1.74)."

The authors admit that the science upon which they made their observation is "weak" insofar as cause and effect not being proved. This is an important point (see here) that follows other research in this area too (see here and see here) together with an understanding that many different variables *might* influence the risk of something like ADHD as a diagnosis or in behaviour (see here and see here for examples).

Still, if there is even the remotest possibility that diet might be something to consider in respect of ADHD, adding it to the intervention arsenal that already exists (see here) can only be a good thing...

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[1] Del-Ponte B. et al. Dietary patterns and attention deficit/hyperactivity disorder (ADHD): A systematic review and meta-analysis. Journal of Affective Disorders. 2019; 252: 160-173.

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Tuesday, 11 June 2019

SHANK3, gut issues and (mouse) autism continued

"We conclude that apart from its well-known role in the CNS [central nervous system], SHANK3 plays a specific role in the GI [gastrointestinal] tract that may contribute to the ASD [autism spectrum disorder] phenotype by extracerebral mechanisms."

So said the findings reported by Ann Katrin Sauer and colleagues [1], and yet more evidence that issues with SHANK3 mentioned in relation to 'some' autism, may well (partly) explain much more than just behaviour (see here and see here).

The Sauer study was yet another mouse study. They specifically focused on the "Shank3αβ KO" mouse, where KO means knock-out, referring to the engineering of this mouse strain to mimic issues with the functioning and availability of SHANK3, "a known scaffolding protein of the postsynaptic density (PSD) of glutamatergic excitatory synapses." Said knock-out mice have been "reported to display ASD-like behavior with abnormal ultrasonic vocalization, repetitive self-grooming, and reduced interest in novel mice." I say this being careful to reiterate that we're talking about a mouse not human beings (see here).

On the basis of the observation that SHANK3 is expressed in the gut as well as brain and that GI issues are no stranger to autism (see here), researchers set about looking at how SHANK3 issues might also manifest as gut issues, and what this *could* mean for some autism. They observed some interesting things:

  • "analysis of the GI tract of Shank3αβ KO mice revealed significantly altered gut morphology" which included, among other things, increased levels of ZONULIN1 ("a modulator of tight junctions and alterations"). Zonulin is something that I'm particularly interested in on this blog (see here and see here) on the basis of its *connection* to intestinal barrier function and the misnomer that is 'leaky gut' (see here).
  • "The Microbiome of Shank3 KO Mice Is Altered." Bearing in mind the increasing importance of the gut microbiome to autism (see here), researchers reported some interesting difference between "Shank3αβ KO mice" and controls with regards to several different bacterial species. 
  • Researchers describe how those gut morphology and gut bacterial differences seemed to be linked to alterations in the "expression of inflammatory markers" too as they talked about "signs of increased immune activation in the periphery and the brain." A familiar cytokine is mentioned - IL-6 - and quite a few avenues for further investigation.

The net result of all this work is to say that, yes, the SHANK3 mouse model *potentially* mimicking some of the behavioural signs and symptoms of autism does also appear to show some significant gut-related issues. No, this does not directly translate into issues for 'all human autism', but it does add further credence to the idea that the gut-brain axis is likely important to at least 'some autism'. Where also SHANK3 issues are identified as coinciding with 'human autism', one might also entertain the idea that gut issues should be screened and treated/managed. And there might be lots of ways to manage them (see here for one example)...


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[1] Sauer AK. et al. Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. Int. J. Mol. Sci. 2019; 20: 2134.

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Wednesday, 30 January 2019

Milk opioid peptides and dipeptidyl peptidase-4 (DPPIV) linked to autism

So: "we have concluded that milk-derived opioid peptides and DPPIV [dipeptidyl peptidase-4 (DPPIV)] are potentially factors in determining the pathogenesis of autism."

That was the quite sweeping statement made in the paper published by Beata Jarmołowska and colleagues [1]. It continues a quite a long running research topic in autism circles (see here and see here) on whether the chemical arrangement of certain dietary components *might* have an important biological effect on at least some people diagnosed as being on the autism spectrum.

The Jarmołowska paper is open-access so there is no real need for me to go over the suggested hows-and-whys of some diets being potentially related to (some) autism. If you need some further reading on the topic, I'll direct you to other posts on this blog where I've discussed this 'gluten and casein' issue (see here) and onward, my professional interest in it for quite a few years.

The aim of the Jarmołowska study was to determine "BCM7 [β-casomorphin-7] influence on DPPIV functioning in children with ASD in comparison to healthy children." 'Healthy children' is the term for the control group used by the authors by the way, not me. They "examined content and activity of serum DPPIV, content of BCM7 in serum and urine, and studied the effect of hydrolysed bovine milk, as a source of opioid peptides, on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in both groups."

Results: "We found that the content of BCM7 in serum was significantly higher (p < 0.0001) in ASD than in the control group." Urine concentrations of BCM7 were not significantly different among those with autism compared with controls. Also: "Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01)."That was about the sum of the differences noted by researchers.

Caveats? Well some. So: "ELISA test enabled identification of BCM7 contents in the serum and urine from patients, as well as in tested peptide extract obtained from hydrolyzed bovine milk." Authors do mention how the testing was carried out "in triplicate" following a previously published protocol. I don't dispute the results they got but am not exactly enamoured with the ELISA method used. I'd much rather see the analysis undertaken using something like mass spectrometry or similar technology, given the precision that comes with such methods (see here) based for example, on the use of internal standards. Perhaps if the authors still have their samples, they might consider further analyses if available to them?

Although researchers provide quite a bit of information about their participant groups, I also noted one important detail to be missing: were any of their participants - diagnosed with autism or not - following any special dietary regime? Y'know, they talk about casein (milk) free diets and how such diets are supported by "numerous scientific reports." So I guess in a cohort of 86 children diagnosed with autism, at least a few of them might be following such a dietary intervention? I've searched their paper but couldn't find anything to say that they were or weren't.

Putting such issues to one side, I don't want to take anything away from the Jarmołowska findings. As they end their paper: "this issue requires further investigation." I wouldn't disagree.

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[1] Jarmołowska B. et al. Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders. Nutrients. 2019 Jan 4;11(1). pii: E87.

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Tuesday, 22 January 2019

"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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Tuesday, 13 November 2018

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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Tuesday, 1 May 2018

Pregnancy diet and offspring "hyperactivity-inattention symptoms"?

I appreciate that the findings reported by Cédric Galera and colleagues [1] are potentially a little uncomfortable. Their examination of over 1200 mother-child pairs looking at data from food frequency questionnaires during pregnancy and subsequent offspring 'externalising' behaviours into childhood, could be construed as evidence that poor eating habits during the nine months that made us have the ability to translate into childhood issues. Because food choices are seen as just that - 'choices' - the Galera results *could* potentially fall into the same category as other 'choices' that also seemingly affect offspring development in this area (see here for example). I make no value judgements.

Having also bumped into the Galera paper at the same time as seeing a BBC media report observing that "We learn nothing about nutrition, claim medical students", one might further make an argument for the need for much greater education, guidance, support and potentially 'nudging', when it comes to issues such as 'what to eat during pregnancy'. That however, is another discussion for another day.

Anyhow, the science...

Galera et al report findings based on the EDEN mother-child cohort [2], an initiative set up to examine "the relations and potential interactions between maternal exposures and health status during pregnancy, fetal development, health status of the infant at birth and the child’s health and development." It's interesting that the opening words to the Heude [2] description of the initiative mention the name 'Barker', as in the late David Barker, a man who helped popularise the idea that nutrition in the womb (through maternal diet) might have some important *consequences* for offspring in the short- and long-term. Looking at some of the other research produced by the EDEN mother-child cohort (see here), Barker and others may have indeed been on to something.

As well as looking at offspring externalising symptoms such as conduct problems via use of "the Strength and Difficulties Questionnaire at ages 3, 5, and 8 years", authors also looked at "trajectories of hyperactivity-inattention symptoms." This, on the basis that the SDQ does pretty well at discriminating between ADHD and non-ADHD cases [3]. They concluded that, taking into account infant dietary patterns "at age 2 years" and various other potential influencing variables ("maternal stress and depression, gestational diabetes, and socioeconomic variables"), there was something to see with regards to use of a 'high Western diet' and 'low Healthy diet' during pregnancy in relation to offspring developmental outcome. Specifically: "Maternal diet during pregnancy was independently associated with children's hyperactivity-inattention symptoms."

Of course, one needs to be a little bit careful that *association* is not viewed as 'cause-and-effect' based on such observational studies. That also it is downright unethical to put mums-to-be on a 'healthy diet' vs. 'a non-healthy diet' is also a stumbling block to robust investigations in this area; similar to the fact that one wouldn't put mums-to-be on a tobacco smoking vs. a non-smoking intervention.

But the Galera results are not stand-alone in potentially implicating maternal diet as a factor in relation to offspring hyperactivity-inattention [4] and are therefore deserving of some further investigation. I've already mentioned that perhaps more guidance and 'nudges' need to be provided in the area of pregnancy nutrition, and that I assume, would include looking at the cost and convenience of a healthy diet vs. a not-so-healthy diet in the context of a possible *link* between diagnosed attention-deficit hyperactivity disorder (ADHD) and "socioeconomic deprivation" for example (see here). More than that however is the idea that David Barker and others who talked about 'foetal programming' during the pregnancy months as a result of what is in or perhaps not in a maternal diet may have been a lot more accurate than many people would have perhaps imagined...

And on the topic of 'foetal programming', diet might not be the only factor to consider [5]...

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[1] Galera C. et al. Prenatal diet and children's trajectories of hyperactivity-inattention and conduct problems from 3 to 8 years: the EDEN mother-child cohort. J Child Psychol Psychiatry. 2018 Mar 24.

[2] Heude B. et al. Cohort Profile: The EDEN mother-child cohort on the prenatal and early postnatal determinants of child health and development. Int J Epidemiol. 2016 Apr;45(2):353-63.

[3] Algorta GP. et al. Diagnostic efficiency of the SDQ for parents to identify ADHD in the UK: a ROC analysis. Eur Child Adolesc Psychiatry. 2016 Sep;25(9):949-57.

[4] Rijlaarsdam J. et al. Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. J Child Psychol Psychiatry. 2017 Jan;58(1):19-27.

[5] Andersen SL. et al. Maternal Thyroid Function in Early Pregnancy and Child Neurodevelopmental Disorders: A Danish Nationwide Case-Cohort Study. Thyroid. 2018 Mar 27.

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Wednesday, 18 April 2018

"Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder"

It's been a while coming but the paper by Jim Adams and colleagues [1] detailing the effects of a "comprehensive nutritional and dietary intervention for autism spectrum disorder" has finally seen the peer-reviewed light of day. I say 'a while coming' because as per the ClinicalTrials.gov entry for this research (see here), it was seemingly scheduled to start back in 2011 and be completed by 2013, I assume, without taking 5 years to write up and be published. But better late than never I suppose.

Anyhow, the nutritional and dietary intervention scheduled adopted by Adams et al was rather a complicated affair as per the study description. So: "Day 0: Vitamin/Mineral supplementation begins. Day 30: Essential Fatty Acid supplementation begins. Day 60: Epsom salt baths begin. Day 90: Carnitine Supplementation begins. Day 180: Digestive Enzyme supplementation begins. Day 210: Healthy, casein-free, gluten-free diet [HGCSF] begins." Quite a few of those individual intervention elements have been fodder for this blog before (see here and see here for examples); also reflecting other research interests from Adams and colleagues (see here). Talk about a gluten- and casein-free diet is also music to my [research] ears (see here), as is the welcome inclusion of sulfate / sulphate back into autism research proceedings (see here).

Results of that nutritional and dietary schedule are reported for a starting pool of 67 children diagnosed with an autism spectrum disorder (ASD), where 28 participants completed the 'treatment' arm and some 27 participants completed a non-treatment arm (where no new intervention(s) were reported for the 12 months of the study). Additional findings for 50 not-autism controls (I don't like the word 'neurotypical' and its rather sweeping connotations) are also reported. The study duration was a year, and the sorts of measures examined over the course of the intervention were quite comprehensive, covering both behaviour and cognition and also physiological parameters.

Results: it's always refreshing to see a study first and foremost reports any adverse effects based on the tenet 'first, do no harm'. Authors note that: "A few adverse effects were reported for some treatments" and go on to list what happened over the course of each element of the intervention. They talk for example, how: "One parent reported that implementation of the diet [healthy, gluten- and casein-free diet] in a strict manner resulted in increased aggression towards peers, inability to problem solve, and increased spinning behavior, probably due to frustration in regards to removal of favorite foods." Thankfully, most of the adverse effects noted over the study period were relatively minor and certainly not life threatening. Once again, first, do no harm.

With levels of compliance regarding the various study elements also reported as being quite high, the authors report that across the various behavioural assessments - including the CARS, SRS, VABS, and ATEC - significant effects in favour of intervention were found. Based on blinded evaluations using something called the Reynolds Intellectual Assessment Scales (RIAS), authors reported "a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group." By contrast, blinded use of the gold-standard assessment instrument known as ADOS revealed "no significant change on the ADOS scores for either treatment or non-treatment group." Interestingly, when parents were asked to rate the effectiveness of each part of the intervention, results revealed that: "The highest rated treatments were the vitamin/mineral supplement and the essential fatty acids, followed by the Healthy HGCSF diets, followed by the carnitine, digestive enzymes, and Epsom salt baths."

Adams and colleagues also provide further details on "3 exceptional cases of improvement during the study, all of which occurred in the treatment group." For one participant it appears that the introduction of a carnitine supplement was associated with some quite remarkable improvements in relation to strength and energy levels in particular. The authors note that: "low carnitine seems likely to have contributed to her challenges, and carnitine supplementation seems to have helped." There could be some interesting tie-ups there with regards to previous peer-reviewed results too (see here for example). For another participant it seemed that the introduction of a HGCSF diet *correlated* with the resolution of urination problems, where a dairy-free diet removed the need for "intermittent catheterization" and resolution of associated problems. OK, these examples don't so much focus on the core issues associated with autism, but I'm pretty sure that they were factors that would have influenced quality of life.

There is quite a bit more to see in the Adams paper and I would encourage readers to take the time to read it in its entirety. Despite the fact that not every measure showed significant effects from such an intervention regime, I like the idea that authors didn't just focus on one intervention but rather, in a systematic way, looked at a whole suite of interventions focused on nutritional and dietary factors. I believe this is more 'naturalistic' in terms of what parents/caregivers tend to report. Indeed the authors themselves discuss how: "A limitation of this study is that all participants received all treatments, whereas probably only a subset are likely to benefit from any single intervention (for example, only participants with low carnitine are likely to benefit from carnitine supplementation)." Yup.

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[1] Adams JB. et al. Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder—A Randomized, Controlled 12-Month Trial. Nutrients. 2018; 10(3): 369.

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Friday, 13 April 2018

Violent ideation and behavior in relation to serious mental illness: substance abuse counts

I approach the findings reported by Matthew Roché and colleagues [1] in the same way as I would any other peer-reviewed science results covering the topic of violence in relation to a diagnosis / label / condition: cautiously and minus the need for sweeping generalisations (see here), but without shying away from potentially important findings.

Roché et al discuss results based on their analysis of "intake records of 63,572 patients diagnosed with SMIs [serious mental illness] (i.e., schizoaffective disorder, schizophrenia, bipolar disorder, and unipolar depression), substance use disorders, and non-SMI psychiatric disorders" in relation to the risk of violent ideation and behavior (VIB). As well as looking at the frequency of VIB among their cohort, they also looked for other variables outside of a diagnosis of SMI that may impact on VIB.

Results: "patients with SMI conditions had higher rates of VIB than both patients with non-SMI psychopathology and those with substance use disorders only." No, this does not make for great PR for SMIs but is a reality of their observations. Further: "patients with SMI and comorbid substance use pathology were responsible for the majority of VIB within each SMI condition." This equation - SMI plus substance abuse equals greater risk of violence - is something that is becoming rather important based on the peer-reviewed science literature. It follows other independent findings [2] too and might even link into other areas.

Appreciating that those diagnosed with a SMI are also at greater risk of being a victim of crime (see here) including crime with a violent element attached to it, there are some important lessons to be learned from the Roché data. Not least is the potential focus on reducing comorbid substance abuse in the context of a diagnosis of serious mental illness so as to potentially modify the heightened risk of VIB and also, other less than desirable outcomes [3]. This is not something that can be done easily (see here) but does not mean it cannot be attempted at all.

I might also add that violence, as and when it does occur in the context of SMI, is likely to be related to other social and situational factors as well as being influenced by something like substance abuse (disorder). Indeed, in the context that various aspects of life can very much be *altered* by the experience of an SMI (diet, physical activity, etc) I'm minded to direct your attention to other variables potentially important to VIB such as nutritional factors for example (see here and see here). Science might also perhaps look to other diagnoses that potentially complicate the clinical picture in SMI as perhaps also exerting any effect on the risk of VIB (see here) and the [developmental] importance of transitioning risk from one label to another (see here) again, minus any sweeping generalisations. Finally, and minus passing the buck, the findings reported by Patel and colleagues [4] further complicate the clinical picture...

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[1] Roché MW. et al. Prevalence and Risk of Violent Ideation and Behavior in Serious Mental Illnesses: An Analysis of 63,572 Patient Records. J Interpers Violence. 2018 Mar 1:886260518759976.

[2] Fazel S. et al. Schizophrenia, substance abuse, and violent crime. JAMA. 2009 May 20;301(19):2016-23.

[3] Skalisky J. et al. Prevalence and Correlates of Cannabis Use in Outpatients with Serious Mental Illness Receiving Treatment for Alcohol Use Disorders. Cannabis Cannabinoid Res. 2017 Jun 1;2(1):133-138.

[4] Patel RS. et al. Is Cannabis Use Associated With the Worst Inpatient Outcomes in Attention Deficit Hyperactivity Disorder Adolescents? Cureus. 2018 Jan 7;10(1):e2033.

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Tuesday, 23 January 2018

Mediterranean-style diet + fish oils = better diet quality and mental health in depression

"This is one of the first randomized controlled trials to show that healthy dietary changes are achievable and, supplemented with fish oil, can improve mental health in people with depression."

So said the findings reported by Natalie Parletta and colleagues [1] reporting results from a randomised-controlled trial investigating "the impacts of a Mediterranean-style diet intervention for mental health and quality of life (QoL) in people with depression."

Their study, called "HELFIMED (Healthy Eating for Life with a Mediterranean-style diet) Mood Study", drew on various data derived from a starting population of some 180 participants randomised to receive a Mediterranean diet plus fish oil (MedDiet) or a control social group who - "attended fortnightly social groups (e.g. sharing holiday stories, playing games, doing personality tests, watching a movie with discussion, book club)." The focus on 'social' noted in the control group was designed to "control for the social component of the cooking workshops that can help to improve depressive symptoms" used by the experimental (dietary) group. Having said that, I can't ever recall 'doing personality tests' as being something I've ever encountered in any social groups/outings down the years but hey-ho! We are also told that: "Assessments at baseline, 3 and 6 months included mental health, quality of life (QoL) and dietary questionnaires, and blood samples for erythrocyte fatty acid analysis" covering both groups over the intervention period.

Results: bearing in mind the numbers of completers at 3- and 6-months were quite a bit down on the starting numbers, a few important details were observed. So: "Compared to the social group, the MedDiet group reported significantly greater increase in their total Mediterranean diet score from baseline to 3 months... along with a significantly greater increase in consumption of vegetables, fruit, wholegrain foods, nuts and legumes, significantly lower consumption of unhealthy snacks and meat/chicken, and a greater diversity of vegetables." It appeared that quite a bit of 'nutrition education' and cooking classes et al seemed to do the trick in increasing the nutritional quality of participants food intake in this arm of the trial. Importantly too: "These dietary changes were maintained at 6 months" when intervention wasn't as intense as that given in the first 3-months.

Also: "Both the MedDiet and the social group reported significantly improved mental health on all outcome measures (DASS, PANAS, and AQoL-8D subscales) over 3 months (all P < 0.001) except for the AQoL-8D pain value." The authors speculate that this could be "attributed to the social component of the study as both groups were exposed to group workshops (either cooking or social group)." In other words, loneliness and/or lack of social support are important features when it comes to mental health in relation to depression (see here).

But... "Compared to the social group, the MedDiet group reported significantly greater improvement in their DASS depression score... and AQoL-8D mental health score over 3 months." The authors observed that transition to a Mediterranean diet plus fish oil supplement seemed to provide some value-added benefits when it came to self-reported depression scores. Whether it was the dietary change or the fish oil supplementation is not really clear from the data but the findings do invite further investigation.

Allowing for the fact that there were 'limitations' to this study (use of self-report, high attrition rate, single blind study design) I think it's fair to say that moves towards getting those with depression to eat healthier is a win-win situation on the basis of what the peer-reviewed evidence seems to point to [2]. Adding to the results of other similar trials in this area (see here) and there is a picture building up that alongside the physical health benefits a good diet (good insofar as containing fruit, vegetables, nuts, etc) can bring, there may be psychological benefits too [3]. It's not just about diet however, as the Parletta results show, but diet does seem to be quite a useful add-on.

The fish oil supplementing side of things is something else that requires some further investigation. I note that I've already covered other work by authors of this most recent study before on this blog with regards to their investigation on fatty acids and autism among other things (see here). In relation to depression (clinical depression), there is also evidence suggesting that certain types of fatty acid supplementation do seem to be able to act on presented symptoms (see here and see here) for some people at least. The problem, as I've mentioned in this study, is teasing apart fish oil/fatty acid supplements from the role played by the dietary changes.

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[1] Parletta N. et al. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutr Neurosci. 2017 Dec 7:1-14.

[2] Fowles ER. et al. Stress, Depression, Social Support, and Eating Habits Reduce Diet Quality in the First Trimester in Low-Income Women: A Pilot Study. Journal of the Academy of Nutrition and Dietetics. 2012; 112: 1619-1625.

[3] Opie RS. et al. Dietary recommendations for the prevention of depression. Nutr Neurosci. 2017 Apr;20(3):161-171.

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Wednesday, 20 December 2017

MoBa does... maternal pregnancy iodine intake and offspring ADHD symptoms and diagnosis

Yet another 'MoBa does...' post today, reflecting data derived from the Norwegian Mother and Child Cohort Study and the findings reported by Marianne Hope Abel and colleagues [1] (open-access available here).

Maternal pregnancy iodine intake (both calculated from food sources and also as a supplement) was the starting variable, where responses to "a food frequency questionnaire (FFQ)" provided researchers with enough data to categorise mums-to-be in terms of their iodine intake. Iodine, by the way, is something of an important nutrient from many biological reasons; not least for optimal thyroid function. During pregnancy, suitable iodine levels are also seemingly required to ensure that the developing child is able to reach their full potential (see here).. seemingly.

Alongside, researchers also looked at both children diagnosed with attention-deficit hyperactivity disorder (ADHD) and "maternal report of child ADHD symptoms at eight years of age" on the basis of other data talking about "a negative impact on child behavior problems when mothers had inadequate iodine intake from food and initiated use of supplemental iodine in the first trimester of pregnancy." Keep in mind that last part about supplemental use during early pregnancy...

So, including some 77,000 mother-child pairs where "for 27,945 there were data on maternally reported ADHD scores when the child was aged eight years", what did the researchers find?

"Iodine from food was significantly associated with maternally reported child ADHD symptoms at eight years of age... but not with risk of child ADHD diagnosis." Authors expanded on this observing that the 'inattention' side of ADHD symptoms, derived from a questionnaire covered in independent research [2], was the driving force behind the connection being made, not the hyperactivity subscale. They also noted that "maternal iodine intake of less than ~200 µg/day" seemed to be the crucial cut-off point when it came to those maternal reports of ADHD symptoms.

But... I'm sure it can't have escaped your attention that although maternal reports of offspring ADHD symptoms - indeed, inattention - *correlated* with maternal iodine intake, there was little to see when it came to "risk of specialist-diagnosed ADHD in the child." Indeed, the authors also note that they found "no evidence of any beneficial effect of supplemental iodine in pregnancy" and even that "initiating iodine supplement use within the first trimester in mothers with inadequate iodine intake from food (<EAR) was associated with both an increased risk of ADHD diagnosis and higher ADHD symptom score at eight years of age."

Science is [almost] never clear-cut in the conclusions it arrives at and the Abel results just add to that sentiment. Given that this authorship group seemingly having a considerable research interest in all-things iodine and health, I'm assuming that these latest results were quite the talking point. Certainly, just a little bit different from their other recent publication on this topic [3] that concluded: "Maternal iodine intake below the Estimated Average Requirement during pregnancy was associated with symptoms of child language delay, behavior problems, and reduced fine motor skills at 3 y of age" but perhaps not with the supplementation angle in mind: "results showed no evidence of a protective effect of iodine supplementation during pregnancy."

I don't know what and how much to make of the findings as they stand, aside from suggesting that other recent findings [4] also questioning the value of daily iodine supplementation "in mildly iodine-deficient pregnant women" perhaps add to the discussions in this area. MoBA represents a great resource in these days of population science, so one can't blame the findings on a lack of "large sample size, prospective design, extensive collection of data, and the possibility of linking the cohort to national registries." It could, therefore, well be that talk on iodine supplementation during early pregnancy perhaps needs a lot more science behind it before anyone makes any grand, sweeping claims about its usefulness...

To close, in case you're wondering about the photo included in this post, it's all part of the Public Health England 'celebrations' for 100 years of public health marketing (see here).

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[1] Abel MH. et al. Maternal Iodine Intake and Offspring Attention-Deficit/Hyperactivity Disorder: Results from a Large Prospective Cohort Study. Nutrients. 2017 Nov 13;9(11). pii: E1239.

[2] Silva RR. et al. A rating scale for disruptive behavior disorders, based on the DSM-IV item pool. Psychiatr Q. 2005 Winter;76(4):327-39.

[3] Abel MH. et al. Suboptimal Maternal Iodine Intake Is Associated with Impaired Child Neurodevelopment at 3 Years of Age in the Norwegian Mother and Child Cohort Study. J Nutr. 2017 Jul;147(7):1314-1324.

[4] Gowachirapant S. et al. Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Nov;5(11):853-863.

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Friday, 1 September 2017

A third of kids with autism have small intestinal bacterial overgrowth (SIBO)?

"Ninety-six children with autism suffered from SIBO [small intestinal bacterial overgrowth], giving a prevalence rate of SIBO was 31.0%. In contrast, 9.3% of the typical children acknowledged SIBO."

OK, some of the language used by Li Wang and colleagues [1] might not necessarily be (a) completely grammatically accurate or (b) politically or culturally sensitive (i.e. how do you define 'typical'?) but I do think their results are worthy of a lot more scientific investigation.

Focusing in on a curious term - SIBO - characterised by an over-representation of various bacteria in the small intestine, authors set about testing for the presence of SIBO in their cohort of over 300 children diagnosed with an autism spectrum disorder (ASD) alongside over 1200 age- and sex-matched not-diagnosed-with-autism controls. The test of choice for SIBO was a breath hydrogen test where a sugary drink is given and hydrogen content is later examined. The idea being that carbohydrate metabolism is a primary route for hydrogen production in the body and certain types of bacterial species are adapted to feed on sugars and burp out hydrogen under such conditions. As outlandish as it might sound, there is a condition called auto-brewery syndrome where hydrogen production goes one stage further and has been suggested to be linked to the formation of alcohol (ethanol) among other things! I kid you not.

Added to the quite high percentage of children with SIBO described by Wang and colleagues, the authors also reported some differences in the presentation of autism severity according to autism with SIBO compared with controls minus SIBO. They also noted that scores on the ATEC (ATEC rising!) seemed to correlate with a measure of gastrointestinal (GI) symptoms (6-GSI) [2] providing some interesting discussions about the old gut-brain axis thing that has pervaded autism research for decades (see here).

As there always seems to be, there is a scheme of further investigations required in this area before grand sweeping generalisations are made. I don't think anyone can really argue with the data suggesting that (a) GI symptoms are well and truly over-represented when it comes to autism (see here) with new data emerging all of the time [3] and (b) behind such GI symptoms there is likely pathology; whether something like irritable bowel syndrome (IBS) (see here) or indeed, in some cases, something altogether more novel (see here). The Wang study also points the finger of suspicion at the presence of certain bacteria in a certain part of the digestive system as potentially being something important to this area of study. Indeed, allied to recent discussions on the use of a low carbohydrate diet (a.k.a the ketogenic diet) as being something potentially important to at least some autism [4] (see here for my take), there are some interesting reports that could be particularly relevant to the SIBO findings being described and importantly, their management (see here also).

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[1] Wang L. et al. Hydrogen breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in autism. Eur Child Adolesc Psychiatry. 2017 Aug 10.

[2] Adams JB. et al. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011 Mar 16;11:22.

[3] Prosperi M. et al. Behavioral Phenotype of ASD Preschoolers with Gastrointestinal Symptoms or Food Selectivity. J Autism Dev Disord. 2017. Aug 31.

[4] El-Rashidy O. et al. Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study. Metab Brain Dis. 2017 Aug 14.

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Saturday, 19 August 2017

Omega-3 fatty acids and ADHD meta-analysed (again)

"In summary, there is evidence that n-3 PUFAs [polyunsaturated fatty acids] supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD [attention-deficit hyperactivity disorder], and that these youth have a deficiency in n-3 PUFAs levels."

So said the results of the systematic review and meta-analysis published by JanePei-Chen Chang and colleagues [1] taking in the collected peer-reviewed research literature on the topic of fatty acids and ADHD. This continues a research theme down the years suggesting that said compounds might be beneficial for at least some people diagnosed with ADHD (see here) and screening for signs of omega-3 fatty acid deficiency could be preferentially clinically indicated for those diagnosed or at risk of a diagnosis.

I don't want to dwell too much on the results because (a) they speak for themselves and (b) this is an area of science that has been a talking point for quite a few years. I know there has been a degree of 'over-hype' associated with fatty acids down the ages but as part of a larger scheme of work suggesting that food and nutrition are not so detached from some behavioural/developmental diagnoses (see here for another example) I'm minded to suggest that they are given their due credit. Certainly fatty acid supplements are quite inexpensive and also seemingly useful for various aspects of physical health too.

As to the mode of effect, well, we don't know all there is to know just yet. I note that some of the authors on the Chang paper are not adverse to the idea that something like psychiatry and immune functions are linked (see here). Whether at least some cases of ADHD might be accompanied by more 'inflammatory' issues is still the source of some debate; although I'd be quick to add in the quite voluminous research suggesting that allergy and ADHD might have more than a passing relationship (see here). Is is possible that supplementation with specific types of fatty acids typically labelled as 'anti-inflammatory' [2] could be working as anti-inflammatory agents? Well, possibly, but I daresay there may be other biological processes at work too. More research is indicated but the Chang results provide yet more [strong] evidence that at least some of those with ADHD may benefit from a fish oil or two a day.

And whilst on the topic of fatty acids, I might also direct you to an interesting piece of research recently published by Sheppard and colleagues [3]...

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[1] Chang JC. et al. Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies. Neuropsychopharmacology. 2017 Jul 25.

[2] Wall R. et al. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010 May;68(5):280-9.

[3] Sheppard KW. et al. Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms. J Autism Dev Disord. 2017. July 26.

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Thursday, 3 August 2017

The pharmacological and non-pharmacological treatment of paediatric ADHD

The findings - "systematic review with network meta-analyses" - reported by Ferrán Catalá-López and colleagues [1] (open-access available here) on the topic of treating attention-deficit hyperactivity disorder (ADHD) were expected [2].

Looking at the available peer-reviewed science comparing "the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents" authors identified nearly 200 randomised trials looking at various intervention options. With data from over 26,000 people diagnosed with ADHD to examine, they applied some nifty statistical analyses leading to various conclusions on the basis of their categorisations of the various interventions analysed: "pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity)."

First: "behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo." I don't think this is a particularly novel finding given the intervention options typically indicated for ADHD (see here).

Then: "Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants." This is important insofar as any notion that use of pharmacotherapy alone is going to 'tackle' ADHD. It also suggests that parents, teachers and significant others have a role to play in managing the symptoms of childhood ADHD as per various examples (see here).

Also: "Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed." It should be no surprise to anyone that there is a cost-benefit balance to be struck when it comes to pharmacotherapy for ADHD or anything else. Medicines always have the potential for side-effects. The lack however, of 'serious adverse events' noted by Catalá-López et al is reassuring and adds to other reviews (see here) highlighting a role for regular monitoring and good medicines management with specific regards to medicines indicated for ADHD.

Finally: "There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine." I don't disagree with these findings but do find it a little 'odd' that other systematic reviews/meta-analyses of something like dietary interventions and/or use of fatty acids for ADHD have come to slightly different conclusions (see here and see here respectively). I don't doubt that there are going to be some subtle differences in what studies were included for further analysis and the interpretation of findings, but 'lack of evidence' is, in my mind at least, perhaps not an entirely accurate viewpoint. Indeed, a more recent paper is a further case in point [3].

"An open and honest discussion with parents and older children about uncertainties of available treatments and the balance between benefits, costs, and potential harms should be established before starting treatment." I think a sentence like this should be added to every article trying to arrive at a coherent statement for many different behavioural and psychiatric labels. It tells us that whilst scientific progress is being made when it comes to the important management of ADHD (see here), there typically is no one-size-fits-all 'silver bullet' that will vanquish all of the challenging symptoms of ADHD and onward improve current and future quality of life. Added to the idea that a multi-pronged approach to managing ADHD is typically better than any one single intervention option, and the Catalá-López article might turn out to be something rather important for many different people with various degrees of interest in ADHD and beyond.

Music: and when Mars Attacks...

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[1] Catalá-López F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials. PLoS One. 2017 Jul 12;12(7):e0180355.

[2] Catalá-López F. et al. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: protocol for a systematic review and network meta-analysis of randomized controlled trials. Systematic Reviews. 2015;4:19.

[3] Chang JC. et al. Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies. Neuropsychopharmacology. 2017 Jul 25.

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Monday, 10 July 2017

Rare genetic condition manifesting as autism and its management

"We report the case of a young boy with nonverbal autism and intellectual disability, with a rare de novo 1q21.3 microdeletion."

That was the starting point of the article published by Cora Cravero and colleagues [1] (open-access available here). Researchers describe in some detail how a diagnosis of autism spectrum disorder (ASD) was made "on communication and social interaction impairments and restricted, repetitive patterns of behaviour and interests" and what followed: "The patient had early and extreme self-injurious behaviours that led to blindness, complicated by severe developmental regression."

Detailing how "comparative genomic hybridization array identified a de novo 1.4 Mb microdeletion of chromosome 1q21.3" and various associated physiological findings, the Cravero report provides some rather intriguing evidence that the sentence 'science does not know what causes autism' might not necessarily ring true for everyone (see here for other examples). As the authors note: "The 1q21.3 microdeletion seems associated with ID [intellectual disability], dysmorphic features, and early SIB [self-injurious behaviour] and can be a cause of syndromic autism."

One or two particular details are noteworthy in the Cravero findings outside of the idea that the N=1 might be an important concept in relation to the autism spectrum.

First, is the quite extreme effects that self-injurious behaviour (SIB) in the context of autism can have on a person. This child was blinded by their extreme SIB: "intense and repeated mutilations of cheekbones and eyes, culminating in a bilateral blindness at the age of 4 years by intumescent white cataract after numerous surgical complications." As I've mentioned before on this blog, SIB can in some cases lead to some very complicated adverse health outcomes (see here) that are not uncommon to the autism spectrum (see here). There is however a brighter note to add to the SIB experienced by this child as the authors noted that a range of interventions seemed to help alleviate some of the challenging behaviours linked to such actions. I note for example that naltrexone - the opiate antagonist - was utilised to "decrease the endorphin sensation seeking procured by SIB and diminish SIB." This follows something of a resurgence in interest in this medicine (see here) and is music to my own research ears (see here).

Second, is a little detail mentioned about the eating habits of this child: "a diet almost exclusively made up of dairy products." Alongside some accompanying details on how "intestinal transit was altered, with episodes of diarrhoea (false constipation), encopresis, and coprophagia" and I'll just say that this is something I've heard quite a bit down my years of autism research. Alongside the use of lactulose to aid the bowel issues and the anti-opioid effect of naltrexone (yes, the protein in dairy products does break down into opioid-like compounds), I'm wondering whether some of the research I've been involved with down the years looking at casein-free diets might also be relevant too (see here)?

Finally, I need to draw your attention to the increasingly popular idea that regression is a part of quite a few cases of autism (see here). Indeed the pattern of autism + ID particularly being over-represented when it comes to regression in the context of autism (see here) seems to be borne out by the case report detailed by Cravero et al.

It is good to hear that after "a year of hospitalization" the outcomes reported on this child were quite a bit more favourable than where he began. So: "His mood was stable, without tantrums or irritability, and he felt pleasure without crippling stereotypes. The SIB were limited to small low intensity fists against his helmet or his cheekbone, occurring from time to time." Further: "During the best of times he wandered half-days without helmet, smiling and exploring his environment using tactile gestures."

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[1] Cravero C. et al. Management of Severe Developmental Regression in an Autistic Child with a 1q21.3 Microdeletion and Self-Injurious Blindness. Case Rep Psychiatry. 2017;2017:7582780.

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Wednesday, 14 June 2017

Autism and phenylketonuria: a double syndrome

I want to briefly talk about the letter to the editor from Esra Demirci [1] (open-access) today and a continuation of some rather important research/clinical chatter about the inborn error of metabolism called phenylketonuria (PKU) intersecting with cases of autism (see here).

The author describes a case report of a child who was diagnosed with an autism spectrum disorder (ASD) "after performing a clinical assessment that included the Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS)" and then subsequently diagnosed with PKU following some important metabolic investigations. They also highlight how instigation of a low phenylalanine diet - the treatment of choice for PKU - seemed to impact on the presentation of autism: "Eight months after the phenylalanine intake diet was initiated, he began to make eye contact, look when his name was said, and form two word sentences. His ABC scores fell from 57 to 46, and his CARS scores fell from 48 to 42."

The 'double syndrome' mentioned in the title of this post refers to the idea that there may be those on the autism spectrum who also have "an already described medical condition" and findings of autism and PKU comorbid fall into that category. I have to say that I'm a fan of this kind of thinking given the range of particularly metabolic conditions that do see to have 'an autistic element' to them (see here for another example). Screening is yet again implied (bearing in mind that PKU is already fairly routinely examined in all newborns in many countries). The idea, also yet again, that use of a low phenylalanine diet might also affect some of the signs and symptoms of autism in such cases remains a point for further investigation into hows and whys...

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[1] Demirci E. Autism Spectrum Disorder and Phenylketonuria: Dyzygotic Twins with Double Syndrome. Noro Psikiyatr Ars. 2017 Mar;54(1):92-93.

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ResearchBlogging.org Demirci E (2017). Autism Spectrum Disorder and Phenylketonuria: Dyzygotic Twins with Double Syndrome. Noro psikiyatri arsivi, 54 (1), 92-93 PMID: 28566968

Wednesday, 24 May 2017

Irritable bowel syndrome (IBS) as a risk factor for bipolar disorder

"Only irritable bowel syndrome (IBS) emerged as a risk factor for BD [bipolar disorder] supported by convincing evidence."

So said the results of the umbrella review of systematic reviews and meta-analyses by Beatrice Bortolato and colleagues [1] looking at the various environmental risk factors potentially linked to the diagnosis of bipolar disorder. I might add that this is a topic that has been discussed before on this blog (see here and see here for examples).

If the systematic review / meta-analysis represents the top of the research methodology hierarchy, a review including a number of systematic reviews and meta-analyses represents the cherry on top. Indeed, there is a growing trend of this kind of research (see here).

The authorship names included on the Bortolato paper are not unfamiliar to this type of study methodology (see here) and specifically, the focus on psychiatric and somatic variables often being intertwined. This time around attentions turned to bipolar disorder, previously called manic depression, and a survey of 16 research publications identified listing over 50 "unique environmental risk factors for BD." The report of a possible link (with 'convincing evidence') between IBS and BD consolidates the idea of a gut-brain axis. Authors also detailed a few other factors as showing weaker but not necessarily less important connections to BD including childhood adversity, obesity and asthma. Focusing in on asthma in particular - a condition again previously talked about in the context of BD - I am wondering whether there are quite a few more generalisations connected to this diagnosis within the context of psychiatric labels (see here and see here)?

Of course, more science is indicated on the hows-and-whys of connections such as the one between IBS and BD and the tantalising prospect of new intervention avenues if such a relationship is further confirmed. Minus any medical or clinical advice, I'm specifically thinking about how alterations to the gut microbiome accompanying cases of IBS might mean that talk of things like probiotics affecting the symptoms of IBS (see here) could be applicable to the presentation of [some] BD too. That and the idea that certain dietary elements might also be important to cases (see here and see here)...

To close, I know that the past few days have not exactly been ones for smiling, but if some smiles and laughter are what you need, then the animal kingdom can provide them...

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[1] Bortolato B. et al. Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta-analyses. Bipolar Disord. 2017; 00: 1–13.

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ResearchBlogging.org Bortolato, B., Köhler, C., Evangelou, E., León-Caballero, J., Solmi, M., Stubbs, B., Belbasis, L., Pacchiarotti, I., Kessing, L., Berk, M., Vieta, E., & Carvalho, A. (2017). Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta-analyses Bipolar Disorders DOI: 10.1111/bdi.12490

Monday, 22 May 2017

"a gluten-related subgroup of schizophrenia"?

A quote to begin this post: "this preliminary study demonstrates that altered AGDA [antibodies against gliadin-derived antigen] levels in the circulation are associated with schizophrenia and could serve as biomarkers for the identification of a schizophrenia subgroup that may need an alternative therapy or precision treatment."

So said the findings reported by McLean and colleagues [1] (open-access) looking at an area of some interest to this blog (see here) on how dietary gluten might show something of an important relationship to at least some cases of schizophrenia. Just in case you weren't aware, there is quite a history when it comes to gluten and schizophrenia (see here) as per the very forward-thinking of people such as Curt Dohan and Karl Reichelt.

Researchers on this latest occasion set about looking in a little more detail at the suggestion that circulating anti-gliadin antibodies (AGAs) reflective of an immune response to a component of dietary gluten might show some connection to schizophrenia. Indeed they note that "all the tests for circulating AGAs in schizophrenia have been developed with mixtures of full-length native gliadins consisting of ~300 amino acid residues" suggesting that such a scatter gun approach may have included epitopes "that are unlikely to survive digestion in the gut." So, they instead "measured plasma levels of IgG and IgA against indigestible peptide fragments derived from γ- and α-gliadins" in archived plasma samples from "169 patients with schizophrenia and 236 control subjects."

The results - based on the use of an "In-house ELISA for antibodies against gliadin-derived antigens" - were rather intriguing. So: "There was no significant difference in the levels of plasma antibodies against native gliadins between the patient group and the control group." If I'm reading this right, this finding is in contrast to other independent research occasions [2]. Indeed, when it came to looking at both IgA and IgG plasma anti-gliadin antibodies, there was no significant difference between the schizophrenia and non-schizophrenia participants as groups.

But... when it came to a specific gliadin (γ-Gliadin) derived fragment  - AAQ6C - with the amino acid sequence HPKCSIMRAPFASIVAGIGGQYRD - researchers reported on something potentially important to see: "patients with schizophrenia had significantly higher levels of plasma anti-AAQ6C IgG than control subjects." Importantly too, authors also noted that anti-psychotic medication did not appear to influence their antibody results. This was important given that seemingly all of the participants diagnosed with schizophrenia were taking one or more of this class of medicine. In line with the opening quote to this post, the authors make a preliminary foray into the possible 'biomarker' usefulness of the various anti-gluten antibodies for schizophrenia. I have to say on this point however, that the data is not that impressive as things currently stand.

There is more to do when it comes to the possible effects of dietary elements containing gluten (and casein) in relation to cases of schizophrenia. This work adds something to the idea that diet can affect psychiatry/behaviour/development but what is perhaps missing is the recognition that schizophrenia is probably a heterogeneous and plural condition (see here and see here for examples) and as such, not every case is going to be gluten and/or casein-related. I do agree with the authors that more research is needed in this area alongside the idea that intervention via either dietary changes [3] and/or other options might also be on the research agenda...

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[1] McLean RT. et al. Differential antibody responses to gliadin-derived indigestible peptides in patients with schizophrenia. Translational Psychiatr. 2017. May 9.

[2] Dickerson F. et al. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry. 2010 Jul 1;68(1):100-4.

[3] Jackson J. et al. A gluten-free diet in people with schizophrenia and anti-tissue transglutaminase or anti-gliadin antibodies. Schizophrenia Res. 2012;140(0):262-263.

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ResearchBlogging.org McLean RT, Wilson P, St Clair D, Mustard CJ, & Wei J (2017). Differential antibody responses to gliadin-derived indigestible peptides in patients with schizophrenia. Translational psychiatry, 7 (5) PMID: 28485731