Monday, 26 September 2016

On HERV-H, autism, ADHD and methylphenidate?

Today's post is a bit of a mash-up including two paper: the first from Emanuela  Balestrieri and colleagues [1] (open-access available here) talking about "increased HERV-H [Human Endogenous Retroviruses - H] transcriptional activity in all autistic patients" included in their cohort (author's words not mine) and the second from D'Agati and colleagues [2] (open-access available here) describing "the reduction of HERV-H expression and the significant improvement of ADHD [attention-deficit hyperactivity disorder] symptoms after 6 months of methylphenidate treatment."

Taken together, both papers provide some potentially important information on how those fossil viruses that litter the human genome might not be as redundant as we might have first thought. Also how some of the commonly used medications to treat/manage certain psychiatric labels might have quite a few more effects than those listed on the package insert. A shocker indeed.

I've covered HERVs a few times on this blog in relation to quite a few labels (see here and see here and see here). If you've clicked on that first link, you'll know that this is not the first time that Balestrieri et al have talked about HERVs with autism in mind [2]. On that first occasion, they even went as far as proposing that "HERV-H expression be explored in larger samples of individuals with autism spectrum in order to determine its utility as a novel biological trait of this complex disorder." This time around "the transcriptional activity of three human endogenous retrovirus (HERV) families, in peripheral blood mononuclear cells (PBMCs)" was examined in 30 children diagnosed with autism spectrum disorder (ASD) and 30 asypmtomatic controls. Quantitative real-time PCR was the analytical weapon of choice, as "transcriptional levels of env of HERV families were quantitatively evaluated." As I've already mentioned, HERV-H expression showed some interesting trends compared to the not-autism controls. The authors note that this data from Albanian children is pretty much the same as what they found in Italian children diagnosed with autism.

The D'Agati findings - also including Balestrieri on the authorship list - although discussing a case report on what happened to HERV-H expression following use of methlyphenidate (MPH) in relation to ADHD, might also have some implications for [some] autism. Reiterating that this was a case report where both before and after HERV-H expression levels were measured, it potentially offers a road map for how HERV-H expression might be 'affected' by the use of certain medicines. Yes, I know that researchers only measured one variable (HERV-H) and one variable/measurement does not a link make. But given the quite significant overlap between ADHD and autism (see here) and the insinuation that over-expression of HERV-H might not necessarily be a 'good thing', one could see how further [independent] studies might be informative in this area.

Although slightly complicated by the fact that we are only beginning to realise how important HERVs might be to things like stem cells for example or even potentially being involved in the process of genetic deletion (see here), what is becoming clear is that these fossil viruses might be something to watch when it comes to health and wellbeing at different times of development. I've tried not to be too enthusiastic about HERVs and autism / ADHD / other (delete as appropriate) on this blog given our lack of understanding on any connection, specifically the hows and whys of any effect on either aetiology or symptoms. But it is getting harder not to wonder what role these and other mobile elements might play in development and behaviour, particularly in the context of HERVs being implicated in autoimmunity [3] (yes, that might also show a connection to some autism) and a possible role for the still emerging science of epigenetics in both HERV expression [4] and also [some] autism. There is lots more research to be done on this topic.

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[1] Balestrieri E. et al. Transcriptional activity of human endogenous retrovirus in Albanian children with autism spectrum disorders. New Microbiol. 2016 Sep;39(3):228-31.

[2] D'Agati E. et al. First evidence of HERV-H transcriptional activity reduction after methylphenidate treatment in a young boy with ADHD. New Microbiol. 2016 Sep;39(3):237-9.

[3] Tugnet N. et al. Human Endogenous Retroviruses (HERVs) and Autoimmune Rheumatic Disease: Is There a Link? The Open Rheumatology Journal. 2013;7:13-21.

[4] Lavie L. et al. CpG methylation directly regulates transcriptional activity of the human endogenous retrovirus family HERV-K(HML-2). J Virol. 2005 Jan;79(2):876-83.

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ResearchBlogging.org Balestrieri E, Cipriani C, Matteucci C, Capodicasa N, Pilika A, Korca I, Sorrentino R, Argaw-Denboba A, Bucci I, Miele MT, Coniglio A, Alessandrelli R, & Sinibaldi Vallebona P (2016). Transcriptional activity of human endogenous retrovirus in Albanian children with autism spectrum disorders. The new microbiologica, 39 (3), 228-31 PMID: 27602423


ResearchBlogging.org D'Agati E, Pitzianti M, Balestrieri E, Matteucci C, Sinibaldi Vallebona P, & Pasini A (2016). First evidence of HERV-H transcriptional activity reduction after methylphenidate treatment in a young boy with ADHD. The new microbiologica, 39 (3), 237-9 PMID: 27602426

Saturday, 24 September 2016

Correcting ophthalmic problems in autism

'Does Correction of Strabismus Improve Quality of Life in Children with Autism Spectrum Disorder?' went the title of the paper by Pinar Ozer and colleagues [1]. Yes, it may very well do was the answer (but with certain caveats and the requirement for a lot more research in this area).

Strabismus, a condition where the eyes don't line up in the same direction, can sometime have some quite noticeable effects on a person's vision and indeed, has been linked to various other non-vision related symptoms and outcomes.

Ozer et al looked to identify "the impact of optical or surgical correction of the strabismus on the child using a questionnaire for parents." The published research of this team has been previously discussed on this blog (see here) with ophthalmic findings in mind, and the requirement for quite a few more resources to be put into eye examinations when autism is diagnosed (see here). This time around they were discussing what happens when such eye issues are resolved.

I'm not completely convinced that the Ozer findings this time around reporting 'significant improvements' in areas of "psychosocial interactions" is as it stands, a methodologically firm finding just pertinent to autism. Although no expert on strabismus, from what I gather, the 'cosmetic' side of the condition can have some far-reaching effects on 'psychosocial' functions. I daresay that such effects would be just as prevalent in autism as they are in the general population and hence, correction would likely have similar outcomes.

I am more open to the idea that if strabismus is affecting vision, as in causing something like blurred or double vision, correction of the issue may in some cases have some important 'effects' in relation to autism. Accepting that structural issues with the eye are not necessarily the same as or causative of visual perceptual issues that seem to crop up quite often in the autism research arena, it is not outside the realms of possibility that something like strabismus could be part and parcel of visual effects for some people.

I suppose to reiterate, screening for structural eye/vision issues when it comes to autism remains a pretty important area.

To close, karate gradings for one of my brood today and this is what they will be attempting...

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[1] Ozer PA. et al. Does Correction of Strabismus Improve Quality of Life in Children with Autism Spectrum Disorder: Results of a Parent Survey by Ophthalmologists. Semin Ophthalmol. 2016 Sep 6:1-6.

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ResearchBlogging.org Ozer PA, Kabatas EU, Bicer BK, Bodur S, & Kurtul BE (2016). Does Correction of Strabismus Improve Quality of Life in Children with Autism Spectrum Disorder: Results of a Parent Survey by Ophthalmologists. Seminars in ophthalmology, 1-6 PMID: 27599387

Friday, 23 September 2016

Epilepsy and systemic autoimmune diseases: birds of a feather?

A couple of years back on this blog I talked about some rather intriguing research suggesting that epilepsy and autoimmune disease might not be unstrange diagnostic bedfellows (see here) and that a "potential role of autoimmunity must be given due consideration in epilepsy." [1]

Today, I'm continuing that research theme as the findings from Zhang Lin and colleagues [2] caught my eye concluding that: "There is an association between epilepsy and SAD [systemic autoimmune diseases], which was shown to be stronger at a young age."

Relying on that rather important methodological tool called a meta-analysis, where various study findings are lumped together and conclusions (hopefully) derived from the whole, Lin et al included data from some 25 studies where epilepsy and SAD had been examined together "which included 10,972 patients with epilepsy (PWE) and 2,618,637 patients with SAD."

Aside from those with epilepsy showing "more than a 2.5-fold increased risk of SAD" the authors also observed the opposite too: "patients with SAD were also shown to have a more than 2.5-fold increased risk of epilepsy." When it came to specifics, those diagnosed with epilepsy were observed to show "a 2.6-fold increased risk of celiac disease" and those "patients with systemic lupus erythematosus had a 4.5-fold increased risk of epilepsy."

I remain intrigued about this topic. Appreciating that within the peer-reviewed literature there is such a thing as autoimmune epilepsy [3] and that even in cases of epilepsy seemingly without the autoimmune encephalitis element to it, there may be antibodies to neuronal tissue involved [4], there are perhaps some further important clinical studies to be done in this area. It is for example, not uncommon to see more than one autoimmune condition appearing at the same time (see here) as various autoimmune overlaps have been noted in the quite voluminous science literature on this topic. The implications perhaps being that if one could find some of the 'causes' behind such autoimmune issues (be that related to molecular mimicry or the presence of a superantigen for examples) one may potentially be able to treat/manage quite a few conditions.

Wearing my autism research blogging hat and extending the possibility of an 'autism link' discussed on my previous post on this topic, I'd like to think there may be some scope for further inquiry with autism in mind too. Not only because epilepsy is one of the prime comorbidites attached to a diagnosis of autism (see here) but also that for some people on the autism spectrum, autoimmunity is also potentially something to contend with (see here). Should we therefore be so surprised at the possibility that autism, epilepsy and autoimmunity could form an important clinical triad for some?

And with full caveats in action about not giving medical or clinical advice on this blog, there is a body of evidence out there supporting immunotherapy for certain types of epilepsy [5] where other interventions have failed. Mmm, I also wonder...

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[1] Ong MS. et al. Population-level evidence for an autoimmune etiology of epilepsy. JAMA Neurol. 2014 May;71(5):569-74.

[2] Lin Z. et al. Association between epilepsy and systemic autoimmune diseases: A meta-analysis. Seizure. 2016 Aug 23;41:160-166.

[3] Britton J. Autoimmune epilepsy. Handb Clin Neurol. 2016;133:219-45.

[4] Wright S. et al. Neuronal antibodies in pediatric epilepsy: Clinical features and long-term outcomes of a historical cohort not treated with immunotherapy. Epilepsia. 2016 May;57(5):823-31.

[5] Bello-Espinosa LE. et al. Efficacy of intravenous immunoglobulin in a cohort of children with drug-resistant epilepsy. Pediatr Neurol. 2015 May;52(5):509-16.

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ResearchBlogging.org Lin Z, Si Q, & Xiaoyi Z (2016). Association between epilepsy and systemic autoimmune diseases: A meta-analysis. Seizure, 41, 160-166 PMID: 27592469

Thursday, 22 September 2016

"Paediatricians are seeing more children with developmental-behavioural conditions"

The findings reported by Harriet Hiscock and colleagues [1] are brought to the blogging table today, specifically that suggestion that paediatricians, at least in Australia, might be encountering an increased number of "developmental/behavioural conditions" as part of their workload.

Looking at the clinical experiences of some 180 paediatricians who took part in the study in late 2013 and comparing them with data from 2008, researchers probed a number of practices relating to "(i) conditions seen; (ii) consultation duration; (iii) imaging and pathology ordered; and (iv) prescribing." The details associated with seeing an increasing number of children "with developmental-behavioural conditions" included: "More paediatricians reported diagnoses of autism spectrum disorder... attention-deficit/hyperactivity disorder... and intellectual disability... in first consultations."

Whilst being slightly careful that 'seeing more children with developmental-behavioural conditions' is not necessarily equated with there 'being' more children with such issues, I'm inclined to suggest that such data is important. Quite a few times in the British media at least, stories have emerged about long waiting times for developmental assessments (see here for one example) and how an already stretched National Health Service (NHS) is seemingly struggling in some parts, to cope with the number of referrals coming through (see here).

As part of a wider peer-reviewed and 'other' evidence base suggesting that (a) the estimated prevalence rates for autism have increased (see here) and (b) there may be a 'real' increase in 'rates of behaviour' associated with an autism spectrum disorder (ASD) (see here) I am becoming more and more convinced that old arguments about 'better awareness' or 'diagnostic switching' are becoming less relevant to the debate about the increasing numbers of cases of autism (see here for example).

I don't doubt that as a society we are far more aware of autism than we ever were (we've even started 'screening for it' during early infancy here in Blighty) and where decades ago someone for example, might have been diagnosed with a learning disability even though they presented with autistic features so things are a little different nowadays. But the sorts of stresses and strains being placed on developmental screening and diagnostic services (particularly paediatric services) in comparison to times gone by are seemingly not comparable anymore. Even taking into account population increases and changes to the organisation of screening and diagnostic services, talk of a growing tide of children being diagnosed, or waiting to be assessed, as being on the autism spectrum is something that really should be prompting a lot more urgency and action. I might also add that arguments about better clinical awareness - did they really miss all those children? - really do a disservice to those who have been skillfully diagnosing autism for many years. Value our experts!

And alongside the talk about children being diagnosed, adult services too are also under a lot more pressure these days...

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[1] Hiscock H. et al. Trends in paediatric practice in Australia: 2008 and 2013 national audits from the Australian Paediatric Research Network. J Paediatr Child Health. 2016 Sep 4.

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ResearchBlogging.org Hiscock H, Danchin MH, Efron D, Gulenc A, Hearps S, Freed GL, Perera P, & Wake M (2016). Trends in paediatric practice in Australia: 2008 and 2013 national audits from the Australian Paediatric Research Network. Journal of paediatrics and child health PMID: 27594610

Wednesday, 21 September 2016

Respite care and parent stress with autism in mind

"While most studies found that respite care was associated with lower stress, several found that respite care was associated with higher stress."

That sentence is perhaps the most important finding recorded in the 'integrative review' published by Kim Whitmore [1] looking at "the relationship between respite care and stress among caregivers of children with ASD [autism spectrum disorder]."

Covering a "final sample of 11 primary research reports" the author provides yet another example of how sweeping generalisations in relation to autism really do no-one no good and how "tailoring respite care services to the unique family needs" is most definitely the way forward.

This is important stuff [2]. I've previously talked about how - again, minus any sweeping generalisations - parental stress in relation to raising a child with autism is one of the more pressing issues when it comes to the health and wellbeing of carers (see here). A steady flow of firsthand accounts also substantiate this finding even in some instances talking about "trauma-related symptomatology" [3]. Respite as one tool in the arsenal to care for the carers is something important; not least because of how such stress can sometimes severely impact on parental quality of life (see here) and potentially onward parent-child (and other) relationships. In amongst all the discussions about autism - how we view it and the implications for the person diagnosed - the effect of a diagnosis on parents/carers can sometimes get a little lost in all the noise.

What's more to say on this topic? Well, I think it is perhaps important to bring in the paper by Southby [4] who brought up an interesting point about how: "Residential respite appears to be the default conceptualization of 'respite' for carers, service users and stakeholders." It's not, and as per the organisation that I'm linked to, something like domiciliary support (otherwise known as home care) can sometimes provide a viable alternative to residential respite/placement. The knowledge that a person does not have to leave the family home, for example, can in some instances have a more positive impact on carer stress, and indeed, most probably will be less cost- and resource-intensive too. I don't also doubt that when it comes to stress for the person diagnosed with autism (an important consideration), for some the familiarity of the home environment is something not to be tinkered with by thoughts of residential respite. But again as per the idea of 'tailoring' resources to individual needs, for some families [5], residential respite every now-and-again should not be discounted.

Finally, it's all well and good talking about the benefits of respite and tailoring respite to meet individual needs, but the cold, hard reality of providing respite in these austere times should not also be forgotten. Indeed, as social purse strings are tightened alongside criteria for eligibility for such services, the factors associated with use and non-use of such services present some difficult choices [6] and are only likely to become even more narrow in future...

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[1] Whitmore KE. Respite Care and Stress Among Caregivers of Children With Autism Spectrum Disorder: An Integrative Review. J Pediatr Nurs. 2016 Aug 31. pii: S0882-5963(16)30150-6.

[2] Dyches TT. et al. Respite Care for Single Mothers of Children with Autism Spectrum Disorders. J Autism Dev Disord. 2016 Mar;46(3):812-24.

[3] Stewart M. et al. Through a trauma-based lens: A qualitative analysis of the experience of parenting a child with an autism spectrum disorder. Journal of Intellectual and Developmental Disability. 2016. Sep 16.

[4] Southby K. Barriers to non-residential respite care for adults with moderate to complex needs: A UK perspective. J Intellect Disabil. 2016 Jul 20. pii: 1744629516658577.

[5] Harper A. et al. Respite care, marital quality, and stress in parents of children with autism spectrum disorders. J Autism Dev Disord. 2013 Nov;43(11):2604-16.

[6] Preece D. & Jordan R. Short breaks services for children with autistic spectrum disorders: factors associated with service use and non-use. J Autism Dev Disord. 2007 Feb;37(2):374-85.

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ResearchBlogging.org Whitmore KE (2016). Respite Care and Stress Among Caregivers of Children With Autism Spectrum Disorder: An Integrative Review. Journal of pediatric nursing PMID: 27592275

Tuesday, 20 September 2016

First trimester maternal vitamin D status and offspring autism risk?

Vitamin D - the sunshine vitamin/hormone - is seemingly everywhere these days in research terms. At the time of writing this post we have news that vitamin D might cut the risk of severe asthma attacks if taken alongside prescribed asthma medication. The week before that it was the suggestion that vitamin D might be part of the explanation as to why childhood learning difficulties were more commonly found in children conceived during the winter months. Vitamin D is seemingly shouldering quite a bit of responsibility when it comes to health and wellbeing.

Today I'm adding to that research responsibility by introducing the paper by Jianzhang Chen and colleagues [1] who suggested that: "Lower first trimester maternal serum levels of 25(OH) D were associated with increased risk of developing autism in offspring." 25(OH)D by the way, is calcifediol, and refers to the typical metabolite assayed for to provide a measure of ones vitamin D status.

Chen and colleagues accessed archived maternal blood samples taken during the first trimester of pregnancy - "11–13 weeks gestational age" - for some "68 children diagnosed with ASD [autism spectrum disorder] and 68 sex and age matched typically-developing children." Not only was vitamin D status examined in those samples but various other potentially useful metabolites: "unmetabolized folic acid (FA), vitamin B12, homocysteine (HCY) and High Sensitivity C Reactive protein (CRP)" that may have some important autism-related links for some (see here and see here for example).

Their report on this occasion focused on the vitamin D results and the finding that mums of children diagnosed with autism/ASD were as a group more likely to present with lower levels of 25(OH)D than control (not-autism) mums. Indeed, when it came to the percentages of who were and weren't vitamin D deficient, some 55% of mums with a child with autism fell into this category compared with less than 30% of control mums. I might add that vitamin D deficiency is typically only one 'banding' when it comes to looking at vitamin D status. With the caveats that this was a study of maternal vitamin D and autism offspring risk in China (so not necessarily translatable to other parts of the world; see discussions shortly) authors also observed a possible correlation between maternal vitamin D status and autism 'severity' in their cohort.

Bearing in mind my recent discussions on the maternal body as 'an environment in autism science' (see here) and the potential pitfalls this presents, the data from Chen et al are interesting. Accepting also that I have a bit of a research 'thing' for vitamin D when it comes to autism on this blog (see here and see here for examples), this work seemingly fits in pretty well with the idea that nutritional factors at critical periods may indeed play a role in the development of at least some autism. Indeed, when one talks about season of conception as potentially being associated with offspring risk of behavioural or developmental issues [2], vitamin D levels look like an attractive research target. The next stage in this research process would be independent replication and perhaps, looking at other populations too.

In fact, on the topic of other populations similarly studied with maternal vitamin D status and offspring autism or autistic traits in mind, the research path previously trodden might not be all one-way. Take for example research coming out of Australia [3] a few years back that observed little in the way of connection between maternal vitamin D levels and offspring development (see here). OK, they used the Autism Spectrum Quotient (AQ) as their behavioural diagnoser (something that might not be cutting the appropriate mustard in recent times) but all-in-all they found little in the way of any relationship in contrast to the Chen findings. The fact that the Raine study data used in the Australian paper also included quite a few more participants also offers a significant advantage to the smaller Chen study.

But I don't think we can just discount the Chen results as they stand, as more and more vitamin D is thrust onto the [autism] research stage. Combined with the recent guidance from the Government here in Blighty suggesting that vitamin D supplementation perhaps needs to be a lot more widespread than it is (see here and see here) throughout the population as a whole, research opportunities aplenty present themselves in this area of growing importance...

Oh, and that includes with regards to the genetics of vitamin D metabolism too (see here).

To close, if you are easily offended by bad language, please stay away from this advert for a cookbook (probably not the language you're likely to hear on Bake Off whatever channel it's on).

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[1] Chen J. et al. Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring. Journal of Psychosomatic Research. 2016; 89: 98-101.

[2] Zerbo O. et al. Month of conception and risk of autism. Epidemiology. 2011 Jul;22(4):469-75.

[3] Whitehouse AJ. et al. Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord. 2013 Jul;43(7):1495-504.

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ResearchBlogging.org Chen, J., Xin, K., Wei, J., Zhang, K., & Xiao, H. (2016). Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring Journal of Psychosomatic Research, 89, 98-101 DOI: 10.1016/j.jpsychores.2016.08.013

Monday, 19 September 2016

Constipation in schizophrenia

"Constipation and dyspepsia are disturbing gastrointestinal symptoms that are often ignored in research on physical comorbidities of schizophrenia."

Go on.

"The prevalence of constipation was 31.3%, and of dyspepsia 23.6%."

So said the findings reported by Tomi Virtanen and colleagues [1] who assessed "dyspepsia and constipation in a sample of outpatients with schizophrenia spectrum psychoses." Alongside the general practitioner assessment of such functional bowel complaints, researchers also "assessed the possible contribution of several sociodemographic, lifestyle, and clinical variables" including gender/sex and medication use.

As per the sentence above, functional bowel issues such as constipation and dyspepsia might not be unstrange bedfellows alongside a diagnosis of schizophrenia spectrum disorders. There were however some important potential 'correlates' associated with such bowel issues, not least that certain types of medication might exert some effect(s). So for example: "Clozapine use markedly increases the risk of constipation and may lead to life-threatening complications." Even something like the (not-so) humble medicine called paracetamol might also show some relationship to bowel symptoms according to the Virtanen data.

Glancing through the other peer-reviewed literature on the topic of bowel issue prevalence and schizophrenia, I was struck by how little there seems to be at present. Yes, there are various papers talking about the comorbidity of certain bowel diseases and schizophrenia [2] but when it comes to the question of 'how prevalent are functional bowel disorders (i.e. constipation, diarrhoea, etc) in cases of schizophrenia?' there appears to be something of a bit of a research gap. This is perhaps a more important topic than many might realise given the suggestion that 'the gut might matter' when it comes to at least some schizophrenia [3]. Yet another example of the gut-brain axis at work eh?

The very important effect that something like medication might have on the presentation of bowel issues in schizophrenia is not to be sniffed at either. When words like: "Constipation associated with antipsychotic treatment is frequent in patients with schizophrenia. It can be severe when early detection fails." one really would think that a lot more would be done to further quantify such risk and importantly, start providing viable options to reduce any risk from such potentially severe functional bowel effects. On this matter, and minus any charges of me providing clinical and/or medical advice (I'm not), I might draw your attention to the data suggesting that the use of probiotics in cases of schizophrenia with bowel issues [4] (see here for further discussion) might be something to look further at. More so if one assumes that such something like constipation might be more readily described in terms of irritable bowel syndrome (IBS) for some, and the growing moves towards using probiotics as an intervention aid with that label in mind (see here). Dietary advice could also be something that could be utilised a lot more assuming that a diagnosis of schizophrenia (spectrum disorder) might confer some enhanced risk for a poor diet and nutrition [5].

Who knows, treating such bowel issues as and when they present might also have some interesting knock-on effects for other areas of functioning too...

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[1] Virtanen T. et al. Dyspepsia and constipation in patients with schizophrenia spectrum disorders. Nord J Psychiatry. 2016 Aug 26:1-7.

[2] Mäkikyrö T. et al. Comorbidity of hospital-treated psychiatric and physical disorders with special reference to schizophrenia: a 28 year follow-up of the 1966 northern Finland general population birth cohort. Public Health. 1998 Jul;112(4):221-8.

[3] Severance EG. et al. Gastroenterology issues in schizophrenia: why the gut matters. Curr Psychiatry Rep. 2015 May;17(5):27.

[4] Dickerson FB. et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. 2014;16(1). pii: PCC.13m01579.

[5] Teasdale SB. et al. A nutrition intervention is effective in improving dietary components linked to cardiometabolic risk in youth with first-episode psychosis. Br J Nutr. 2016 Jun;115(11):1987-93.

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ResearchBlogging.org Virtanen T, Eskelinen S, Sailas E, & Suvisaari J (2016). Dyspepsia and constipation in patients with schizophrenia spectrum disorders. Nordic journal of psychiatry, 1-7 PMID: 27564411