"Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD [coeliac disease] onset during childhood, suggesting the role of dysbiosis during early life."Those were some of the rather surprising findings reported by Fredinah Namatovu and colleagues  (open-access) following their pretty well-powered study covering "1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age" living in Sweden. With the aim of exploring "how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood" quite a few variables were thrown into the statistical mix with some rather interesting results. Indeed, researchers also reported that: "High maternal age and high income reduced the risk of CD, which might be due to infant-feeding practices and life style."Aside from the rather large participant numbers included for study "based on the entire child population in Sweden born during between 1991 and 2009" Namatovu et al were also able to accumulate enough cases of CD so as to ensure "high precision in [their] estimates and enabled adjustment for several variables." Said CD cases were also rigorously confirmed, being "identified through the Swedish National Childhood CD Incidence Register reported from all paediatric departments across the country."The idea that although there is a pretty well-defined course of genetic and biological events tied into CD (see here) onset might also be moderated by some impact of those trillions of wee beasties that call us home (the gut microbiome) for example, is not a new one. I've already covered the peer-reviewed idea that antibiotic use potentially 'altering' the gut microbiome might have implications for CD on this blog (see here). I note also that a recent review by Simon Murch  also mentions a possible role for the gut microbiome too, and with it the requirement for greater scrutiny of this important organ . This all falling under the general suggestion that antibiotics during infancy 'might change their gut microbes for years'."In future, preventive strategies could benefit by taking measures to prevent gut dysbiosis." Further: "Reduced prescription of antibiotics is one way that would also work to counteract the enormous problem with development of bacterial resistance to antibiotics. Promoting normal delivery would also be in line with goals in the field of maternal and child health." I, personally, would like to see a little more investigation done on such variables before anyone jumps to too many conclusions. The jury is for example, currently out when it comes to infant feeding and risk of CD  on the basis of the suggestion by Namatovu et al that: "older mothers are more likely to practise prolonged and exclusive breastfeeding." There is slightly more support for the idea that a child's mode of entry into the world might influence the development of CD  but the absolute risk seems to be rather small.---------- Namatovu F. et al. Maternal and perinatal conditions and the risk of developing celiac disease during childhood. BMC Pediatrics. 2016;16:77. Murch S. Recent Advances in Celiac Disease. Indian J Pediatr. 2016 Jun 8. Baquero F.& Nombela C. The microbiome as a human organ. Clin Microbiol Infect. 2012 Jul;18 Suppl 4:2-4. Silano M. et al. Infant feeding and risk of developing celiac disease: a systematic review. BMJ Open. 2016 Jan 25;6(1):e009163. Mårild K. et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology. 2012 Jan;142(1):39-45.e3.----------Namatovu, F., Olsson, C., Lindkvist, M., Myléus, A., Högberg, U., Ivarsson, A., & Sandström, O. (2016). Maternal and perinatal conditions and the risk of developing celiac disease during childhood BMC Pediatrics, 16 (1) DOI: 10.1186/s12887-016-0613-y... Read more »
Namatovu, F., Olsson, C., Lindkvist, M., Myléus, A., Högberg, U., Ivarsson, A., & Sandström, O. (2016) Maternal and perinatal conditions and the risk of developing celiac disease during childhood. BMC Pediatrics, 16(1). DOI: 10.1186/s12887-016-0613-y
Returning to the idea that not every symptom/characteristic present in cases of autism is necessarily 'due to autism' are the findings reported by Heifert and colleagues  and the observations that: "Children with ASD are more likely to be diagnosed with EoE [Eosinophilic esophagitis] compared to controls" and further: "A diagnosis of feeding disorder was strongly associated with EoE."EoE is something that has been discussed before on this blog in relation to the myriad of gastrointestinal (GI) findings that have been reported alongside a diagnosis of autism (see here). Describing an inflammatory state affecting the esophagus (the tube that leads from mouth to stomach), there is still some debate about the exact hows and whys of the condition. As per the name, eosinophils (cells of the immune system) do seem to be involved in pathology of the condition but are likely to be only part of the clinical story. The primary overt symptoms of EoE tend to be based around feeding issues (dysphagia, regurgitation/vomiting and decreased appetite).Heifert et al relied on data from the (US) Military Health System database capturing medical data on some 45,000 children diagnosed with an autism spectrum disorder (ASD) "from Oct 2008 to Sept 2013." Seeking to "evaluate the association of ASD with EoE", they compared records of participants with autism with over 225,000 age- and gender-matched controls and found that, whilst relatively small in frequency, EoE was more commonly reported in children with autism than in controls (0.4% vs. 0.1% respectively). Authors also reported that feeding disorders were associated with EoE in both kids with autism and those asymptomatic (not-autism) controls. They concluded that: "Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE."This is important work. Feeding issues associated with autism are not uncommon. Although various explanations have been put forward down the years about how the symptoms of autism might exacerbate such issues, there is a growing realisation that other clinical diagnoses might also impact on their presentation too and should be screened for. The Heifert data is pretty strong data insofar as the participant numbers included and also the coding and structure of diagnoses like autism and EoE in the database used. Further research is indicated to substantiate the prevalence of EoE in cases of autism and whether, given the focus on immune function in manifestations of both conditions, there may be important overlaps. That treatment for EoE might include 'dietary elimination' linked into the idea that specific foods might trigger EoE also builds on the quite substantial research base looking at elements of diet and [some] autism (see here).The bottom line: when a child (or adult) presents with feeding difficulties, don't just assume that 'it's just part of their autism'...To close, today is about remembering; and perhaps reflecting on a poem: Dulce et Decorum est.---------- Heifert TA. et al. Feeding Disorders in Children with Autism Spectrum Disorders Are Associated with Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2016 Jun 8.----------Heifert TA, Susi A, Hisle-Gorman E, Erdie-Lalena CR, Gorman G, Min SB, & Nylund CM (2016). Feeding Disorders in Children with Autism Spectrum Disorders Are Associated with Eosinophilic Esophagitis. Journal of pediatric gastroenterology and nutrition PMID: 27276430... Read more »
Heifert TA, Susi A, Hisle-Gorman E, Erdie-Lalena CR, Gorman G, Min SB, & Nylund CM. (2016) Feeding Disorders in Children with Autism Spectrum Disorders Are Associated with Eosinophilic Esophagitis. Journal of pediatric gastroenterology and nutrition. PMID: 27276430
"Overall, these data show for the first time that gestational exposure to GBS [Group B Streptococcus] plays an important role in the generation of neurodevelopmental abnormalities reminiscent of human autism spectrum disorders (ASD)."I chose to discuss the findings reported by Marie-Julie Allard and colleagues  on this blog for various reasons. That this research team already have some research 'form' when it comes to looking at GBS  is one; another is the idea that they report "new evidence in favor of the role of a common and modifiable infectious/inflammatory environmental factor in human ASD pathophysiology." With all the focus these days on how there may be some kind of foetal programming going on during the nine months that made us pertinent to the risk of developing autism for some, this line of research also potentially offers up the idea that said programming needn't always be related to the genome we are born with.GBS infection during pregnancy and birth is not something to be taken lightly. As a primary cause of bacterial infections in newborns, this type of infection can in extreme cases lead to septicaemia (blood poisoning) and also meningitis. This all stems from the fact that around 25-30% of healthy human adults carry this bacteria around in their gut and/or genitourinary tract with no apparent issues for the majority. In rare cases however, infants traversing the birth canal of a mother carrying GBS can come into contact with the bacteria and processes are then set in motion...Allard et al started with the hypothesis that "GBS-induced gestational infection/inflammation has a deleterious neurodevelopmental impact on uninfected offspring" and set about looking at this potential issue in a rodent model - "a new preclinical rat model" no less. They reported that placentas exposed to GBS "exhibited chorioamnionitis characterized by the presence of Gram-positive cocci and polymorphonuclear cells, with the latter being significantly more prominent in the labyrinth of male offspring." Whilst interesting, this is not necessarily new news. But... when it came to looking at the brain and behaviour of male rat offspring exposed to GBS, there appeared to be a few features potentially "reminiscent of human autism spectrum disorders (ASD)." So: "autistic-like behaviors, such as abnormal social interaction and communication, impaired processing of sensory information and hyperactivity" were noted in this group. The conclusion being that science may have yet another animal model of autism (is this a good or bad thing?) and that GBS-exposed placentas might have implications for offspring developmental outcome.The previous research paper by this group  had already provided some important details pertinent to this line of investigation. "Surprisingly, only male offspring were affected by these combined autistic-like traits" went one of their conclusions on that previous research occasion, insofar as GBS-exposed placentas and their onward effects. They also suggested that there may be some important effects to be had from the "materno-fetal inflammatory response to GBS" coinciding with quite a lot of peer-reviewed data suggesting immune system and inflammatory signalling involvement when it comes to pregnancy and offspring risk of autism (see here and see here).Stressing that animal models of autism are not necessarily the same as the complexity of autism in it's lived form, the Allard findings are potentially important. Added to something of an important body of research looking at artificial modelling of bacterial infection and its potential importance to offspring outcomes (see here) one can see that the so-called protective cocoon of our mother during the months of our earliest development is not an impenetrable force-field by any stretch of the imagination. Indeed, such an association may go much further than just autism (see here).Insofar as the 'where next?' in terms of research in this area, well, I might suggest that looking at the rates of offspring autism in women positive or negative to GBS could represent a good research start and perhaps taking things from there. Although there may be some way to go in determining the precise mechanism of GBS exposure in-utero in relation to any possible heightened risk of autism, science might also consider other findings from this research group  on how 'intervening' in issues related to inflammation at certain critical periods, might eventually provide some 'protection' for the developing brain...Oh, and I'll be coming to the paper by Jiang and colleagues  in a future post.---------- Allard MJ. et al. A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation. Autism Res. 2016 May 25. Bergeron JD. et al. White matter injury and autistic-like behavior predominantly affecting male rat offspring exposed to group B streptococcal maternal inflammation. Dev Neurosci. 2013;35(6):504-15. Girard S. et al. IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation. J Immunol. 2010 Apr 1;184(7):3997-4005. Jiang HY. et al. Maternal Infection during Pregnancy and Risk of Autism Spectrum Disorders: A Systematic Review and Meta-analysis. Brain Behav Immun. 2016 Jun 7. pii: S0889-1591(16)30154-4.----------Allard MJ, Bergeron JD, Baharnoori M, Srivastava LK, Fortier LC, Poyart C, & Sébire G (2016). A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation. Autism research : official journal of the International Society for Autism Research PMID: 27220806... Read more »
Allard MJ, Bergeron JD, Baharnoori M, Srivastava LK, Fortier LC, Poyart C, & Sébire G. (2016) A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation. Autism research : official journal of the International Society for Autism Research. PMID: 27220806
"Almost 1 in 10 antipsychotic-treated youth were diagnosed with ASD [autism spectrum disorder] and/or ID [intellectual disability], and 1 in 6 youth with ASD received antipsychotics."The findings reported by Su Young Park and colleagues  have not surprisingly garnered some media attention (see here). Meta-analysing the available peer-reviewed data on "the frequency of youth diagnosed with ASDs and/or ID among antipsychotic-treated youth, as well as antipsychotic use in youth with ASD/ID", researchers came to some important conclusions when it came to prescribing patterns for the important class of medicines known as the antipsychotics. The focus was on youths this time around, complementing what is currently known about such medication use when it comes to adults (see here and see here) and a younger cohort (see here).One or two details are worthy of promotion regarding the Park findings aside from the idea that antipsychotic use might not be unfamiliar when a diagnosis of autism is received: "In 5 longitudinal studies, the proportion of antipsychotic-treated youth with ASD did not change significantly from 1996 to 2011." That being said, the authors did note that later 'study time point' did seem to moderate "higher antipsychotic use among patients with ASD" and also among those with ASD/ID combined. This could indicate that reaching for the antipsychotic meds in response to things like 'challenging behaviour' is slowly becoming a little more common in recent times ; something that might have a few implications for corresponding health screening and monitoring for example (see here).Indeed, in the accompanying media about their study, the authors make some interesting points: "Although the increased prescribing of antipsychotics in youth with autism spectrum disorders or intellectual disability cannot be judged as appropriate or inappropriate based on database studies, side effects of antipsychotics can be quite problematic, especially in children and adolescents." Additionally that: "clinicians should consider using psychosocial interventions that are proven to be efficient for behavioral dysregulation such as irritability and aggression, before prescribing antipsychotics to adolescents with autism or intellectual disability."All I will say on the matter (with no medical or clinical advice given or intended) is that, yes, when faced with challenging behaviours, clinicians and others should always be first asking the question 'why' (see here) before immediately reaching for the antipsychotic or other meds. If and when important factors such as pain (see here) are ruled out, there may be grounds for the use of antipsychotic meds appropriate and proportionate to the scale of the behaviour(s) being presented, bearing in mind the name 'antipsychotic' provides the proper basis for such medication use . But, as with any intervention of this type, the words 'time-limited experiment' should always be on the lips of the prescribing physician, allowing for the fact that the technology now exists to monitor things like plasma levels of various antipsychotics  and other important parameters routinely and mindful of what the research literature tells us about risks associated with such medicine use . Said side-effects can include a variety of different issues .Bear also in mind, that antipsychotics for 'tackling' challenging behaviour might not necessarily be the only option in future (see here)...---------- Park SY. et al. Antipsychotic Use Trends in Youth With Autism Spectrum Disorder and/or Intellectual Disability: A Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2016 Jun;55(6):456-468.e4. Satoh M. et al. Prescription trends in children with pervasive developmental disorders (PDD): A claims data-based study in Japan. World J Pediatr. 2016 Jun 10. Marston L. et al. Prescribing of antipsychotics in UK primary care: a cohort study. BMJ Open. 2014 Dec 18;4(12):e006135. Wijma RA. et al. Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry. Biomed Chromatogr. 2016 Jun;30(6):794-801. Yu ZH. et al. Use of Antipsychotics and Risk of Myocardial Infarction: A Systematic Review and Meta-analysis. Br J Clin Pharmacol. 2016 May 16. Shirazi A. et al. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2016, 17(6), 863----------Park SY, Cervesi C, Galling B, Molteni S, Walyzada F, Ameis SH, Gerhard T, Olfson M, & Correll CU (2016). Antipsychotic Use Trends in Youth With Autism Spectrum Disorder and/or Intellectual Disability: A Meta-Analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 55 (6), 456-4680000 PMID: 27238064... Read more »
Park SY, Cervesi C, Galling B, Molteni S, Walyzada F, Ameis SH, Gerhard T, Olfson M, & Correll CU. (2016) Antipsychotic Use Trends in Youth With Autism Spectrum Disorder and/or Intellectual Disability: A Meta-Analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 55(6), 456-4680000. PMID: 27238064
The job of pesticide applicator is one that has been discussed on this blog before (see here). Minus any scaremongering, the conclusion of that post was that under certain circumstances (e.g. a high pesticide exposure event - HPEE), the effects of that particular occupation might be pretty far-reaching for the 'cognitive' as well as physical health of the individual concerned.Today I'm talking about other potential effects "needing confirmation by further studies" related to perhaps one of the most famous pesticides in recent times: glyphosate. The systematic review "of observational studies" by Jessica de Araujo and colleagues  (open-access) provides the starting material and the suggestion that whilst "exposures to GLY [glyphosate] before conception and/or during pregnancy did not increase the risk of adverse reproductive outcomes" there was perhaps more to see when it came to "an excess of risk of ADD/ADHD [attention-deficit disorder/attention-deficit hyperactivity disorder] among the offspring of GLY applicators." The de Araujo paper was a review paper and included the findings reported by Vincent Garry and colleagues  that: "Use of the herbicide glyphosate yielded an OR [odds ratio] of 3.6 (CI, 1.3-9.6) in the neurobehavioral category" including ADD/ADHD.Glyphosate - N-(Phosphonomethyl)glycine or Roundup - has something of a love/hate relationship in many circles. As a herbicide (an organophosphonate), it does a pretty good job killing weeds by interfering with some important biochemistry linked to the aromatic amino acids, and has enjoyed significant commercial success for quite a few years. As with all pesticides however, there are cautions attached to its use, and this preparation seems to catch media attention on a pretty regular basis; more so when organisations such as the World Health Organisation (WHO) come out with statements like the one last year (2015).Before going back to the de Araujo and Garry papers, I think it's worth mentioning that the idea of an 'association' between GLY and ADHD is not without some controversy. I note that at least one attempt has been made to talk about the possibility of a link between the two albeit retracted for various methodological reasons. I therefore tread carefully and note there are some important strengths and weaknesses attached to the idea that offspring ADD/ADHD might specifically be more frequently present in GLY pesticide applicators.Weaknesses, well, Garry et al relied heavily on self-report and interviews with no detailed use of analytical measures in terms of biological load for GLY. Yes, they did survey registered pesticide applicators on the basis of their licencing and the data provided at interview was cross-referenced with other available "medical records examination" but theirs was still a study heavily reliant on recall and association. de Araujo also make the point that "the herbicide was analyzed as a dichotomous (exposed / not exposed) variable" which takes no account of variables such as "wearing protective clothes, the diet, the amount of the pesticide used" and thus, says nothing about any dose-response relationship. Strengths - the Garry paper did cover various different types of pesticides, the metabolites of some have also subsequently been linked to risk of a diagnosis of ADHD for example (see here). They also reported on quite a few other variables that might impact on risk of offspring ADHD and controlled for them. In short, an interesting association which again is: "needing confirmation by further studies."Insofar as the possibility that there may 'associations' between glyphosate use and behavioural outcomes, some people with some knowledge of autism research might have come across some pretty stark warnings about glyphosate exposure and the quite staggering increase in cases of autism being diagnosed around the world (see here). I, myself, am not so convinced that one agent, and one agent alone, plays such an important role in autism rates but am willing to concede that there may be more research to do on the effects of exposure and offspring outcomes (see here). Indeed minus any sweeping generalisations or solely resting any 'blame' at the door of a specific preparation, science really needs to conduct some more detailed analysis on environmental components such as pesticides and behaviour and developmental outcomes (including biochemistry ), if anything else, just to rule out any relationship. And various lawmakers around the world might be aiding efforts to do so...Music to close: Beyoncé plays the SoL tonight. No, I'm not going but I do like some of her music...---------- de Araujo JSA. et al. Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies. BMC Public Health. 2016; 16: 472. Garry VF. et al. Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA. Environmental Health Perspectives. 2002;110(Suppl 3):441-449. De Felice A. et al. Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism. Journal of Neuroinflammation. 2016; 13: 149.----------de Araujo, J., Delgado, I., & Paumgartten, F. (2016). Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies BMC Public Health, 16 (1) DOI: 10.1186/s12889-016-3153-3... Read more »
de Araujo, J., Delgado, I., & Paumgartten, F. (2016) Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies. BMC Public Health, 16(1). DOI: 10.1186/s12889-016-3153-3
I tread quite carefully when discussing the paper by Sarah Harris and colleagues  (open-access available here) on the potential causes and effects of 'eating difficulties' when it comes to adolescent chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).Careful because (i) I don't want to confuse eating difficulties with eating disorder (they are not one and the same) and (ii) the suggestion that some of the young adults included for study "recognised how their eating difficulties were exacerbated and maintained by psychological factors of low mood and anxiety" could potentially play into the concept of 'psychosomatic', something that quite a few people are trying to move on from when it comes to ME/CFS. I count myself in the camp describing CFS/ME as a real organic disease (or spectrum of diseases) potentially manifesting in various physiological and [secondary] psychological ways (see here).A few details first: 11 teens were included for study (aged between 13-17 years). All had a diagnosis of CFS/ME but I'm not exactly sure which of the numerous criteria around were used to make that diagnosis. They were all "drawn from a CFS/ME specialist hospital service providing regional support for assessment and treatment of over 300 children a year" so I am assuming that someone, somewhere had confirmed the diagnosis (somehow). Interviews were arranged around the topics of "the adolescents’ experience of eating; the factors they felt caused and exacerbate eating difficulties and what they believed were helpful strategies" and various primary themes were pulled out from the transcripts.Results: some interesting issues emerged, not least that quite a few participants "perceived their eating difficulties were caused by abdominal symptoms." 'Abdominal symptoms' is quite a nebulous term but specifically issues like bloating, indigestion and stomach cramps/pain were frequently mentioned. Also: "Nausea prior to eating often caused the adolescents to perceive that eating would make it worse or induce vomiting." My first thoughts on reading about these symptoms was a previous post on some research suggesting that 'abdominal discomfort syndrome' might be part and parcel of a subgroup of those with ME/CFS (see here). That and a possible role for certain foods  (see here also)...Next: "Seven adolescents noticed a change in smell or taste (or both)" potentially impacting on their eating behaviours. Alongside perceived changes in the sensation of food texture said to accompany the onset of their CFS/ME, this also seemed to tie into some of the eating difficulties described. As odd as it might sound, the sorts of changes being described by this small participant group with CFS/ME to me sounded very similar to what has been talked about with the autism spectrum in mind. Many (many) moons ago I published a small opinion piece on eating difficulties associated with autism  and well, let's just say some not dissimilar themes cropped up. I'm not saying CFS/ME is autism or vice-versa, but it does intrigue me about the possibility of overlap (see here).When it came to the idea of 'intervention' for such eating difficulties, the Harris paper also includes some information. "Adolescents frequently excluded various dietary items such as diary, gluten and sugar, claiming these created greater digestive disturbances, although they had not been given a medical explanation for this." Having already mentioned the Rowe paper on cow's milk protein intolerance, I don't want to stick too long on this aspect of intervention. All I will say is that there is nothing in the peer-reviewed literature at present to say that a diagnosis of CFS/ME is protective against genetic/biological issues with certain foods... and that also includes dietary gluten for example (see here).Insofar as the other techniques possibly helpful with the eating difficulties described in this group, the authors talk about distraction and relaxation strategies as being potentially useful and also the involvement of healthcare professionals such as dietitians to help overcome some of the difficulties experienced. These all sound pretty reasonable intervention options. Again, drawing on some of the autism research literature (again, with no wild claims of association being made) I wonder if there might be some 'connection' between those sensory issues previously described and other clinical aspects such as anxiety as part and parcel of abdominal manifestations for example (see here)?If there is a bottom line from the Harris data it is that a diagnosis of CFS/ME is certainly not protective against eating difficulties when it comes to young adults. I would like to see this research built upon in future in various ways; first and perhaps foremost is the testing of those presenting with abdominal symptoms for various digestion and/or food-related conditions (i.e. coeliac disease and the rather 'shades of grey' borders of non-coeliac gluten sensitivity for example). I don't want to make connections when none might exist but I'd also be minded to suggest that those trillions of wee beasties that call our gut home (the gut microbiota) might also be a target for further inspection too (see here) in light of their potential connection to all-things gut related. The sensory aspects hinted at in the Harris data are also deserving of quite a bit more study too. Without blowing my own trumpet too much, sensory features accompanying 'overlapping fatigue syndromes' is something else I've also discussed in the peer-reviewed literature .In short, don't dismiss eating difficulties and their potential correlates when it comes to CFS/ME...---------- Harris S. et al. A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clin Child Psychol Psychiatry. 2016 May 23. pii: 1359104516646813. Rowe PC. et al. Cow's Milk Protein Intolerance in Adolescents and Young Adults with Chronic Fatigue Syndrome. Acta Paediatr. 2016 May 13. Whiteley P. et al. Feeding patterns in autism. Autism. 2000; 4: 207-211. Whiteley P. et al. Correlates of Overlapping Fatigue Syndromes. Journal of Nutritional & Environmental Medicine. 2004; 14:----------Harris S,... Read more »
Harris S, Gilbert M, Beasant L, Linney C, Broughton J, & Crawley E. (2016) A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clinical child psychology and psychiatry. PMID: 27215228
"Current evidence indicates that HBOT [Hyperbaric Oxygen Therapy] is not an effective treatment for children and youth with autism."That was the conclusion reached by Cynthia Goldfarb and colleagues  following their "systematic review of the literature evaluating the clinical impact of HBOT on behavior and development in ASD [autism spectrum disorder]." Drawing on guidance from the American Academy of Neurology and their "Classification of Recommendations", authors looked at the collected peer-reviewed literature "focusing on clinical outcomes of HBOT in ASD." They determined that the research literature as it currently stands (a review based on 5 articles) does not support HBOT as an intervention option for children and young people diagnosed with an ASD.I appreciate that for some people this will be slightly disappointing news. As per the multitude of other interventions put forward to improve quality of life or ameliorate the more disabling aspects of autism, there are nearly always reports of 'positive changes'  and such over-arching reviews say little about how individuals might be impacted by such intervention. Indeed, in a post a few years back on the topic of HBOT and autism (see here) I was cautiously optimistic about this approach; not least because alongside descriptions of positive changes, side-effects seemed to be few and far between when it came to HBOT ('first, do no harm' and all that).Without trying to second-guess the findings from Goldfarb et al and without coming across as being a supporter of HBOT, I do think it's worthwhile reiterating a few points. The recent review was only based on data from 5 studies. Most of those studies were quite small scale (in terms of participant numbers) and carried out under slightly different conditions in terms of pressures used. The authors rightly make use of the term 'current evidence' as balancing their findings in these respects. Indeed, quite a few of the research 'issues' potentially involved in the study of HBOT have been covered in the review by Dan Rossignol and colleagues . Among other things they suggested that the frequency of HBOT sessions might be an important factor and also: "certain subgroups of children with ASD [respond] differently to HBOT." Autisms people, autisms; and bearing in mind that inflammation seems to be a key target when it comes to the use of HBOT in this context (well, C-reactive protein (CRP) anyway).The message however, based on the currently available evidence, is that HBOT is probably not blanket indicated for all autism...---------- Goldfarb C. et al. Hyperbaric oxygen therapy for the treatment of children and youth with Autism Spectrum Disorders: An evidence-based systematic review. Research in Autism Spectrum Disorders. 2016; 29-30: 1-7. Rossignol DA. et al. The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study. BMC Pediatr. 2007 Nov 16;7:36. Rossignol DA. et al. Hyperbaric oxygen treatment in autism spectrum disorders. Medical Gas Research. 2012;2:16. doi:10.1186/2045-9912-2-16.----------Goldfarb, C., Genore, L., Hunt, C., Flanagan, J., Handley-Derry, M., Jethwa, A., Jones-Stokreef, N., Kirkpatrick, S., Richards, A., Rojnica, L., Schwartz, C., Shawn, D., Superina-Bell, D., Young, E., & Anagnostou, E. (2016). Hyperbaric oxygen therapy for the treatment of children and youth with Autism Spectrum Disorders: An evidence-based systematic review Research in Autism Spectrum Disorders, 29-30, 1-7 DOI: 10.1016/j.rasd.2016.05.004... Read more »
Goldfarb, C., Genore, L., Hunt, C., Flanagan, J., Handley-Derry, M., Jethwa, A., Jones-Stokreef, N., Kirkpatrick, S., Richards, A., Rojnica, L.... (2016) Hyperbaric oxygen therapy for the treatment of children and youth with Autism Spectrum Disorders: An evidence-based systematic review. Research in Autism Spectrum Disorders, 1-7. DOI: 10.1016/j.rasd.2016.05.004
The UK media today is awash with the result of 'that referendum'.Life however goes on here at Questioning Answers and today the recent opinion piece by Sarah Ashworth  talking about autism being 'underdiagnosed' in the prison population provides the starting material for today's post.Being careful not to generalise nor also 'excusing' the often important reasons why people end up in prison, I'm particularly interested in this area of discussion given what is increasingly being recognised with regards to the levels of attention-deficit hyperactivity disorder (ADHD) in the prison population (see here). So it was that I wanted to talk about the peer-reviewed literature with autism in mind too.OK, let's start from the beginning and how the currently available data has generally concluded that "people with ASD [autism spectrum disorder] do not seem to be disproportionately over-represented in the CJS [Criminal Justice System]."  Indeed, when I've previously covered this topic (see here), on the occasions that people on the autism spectrum have had contact with the CJS, most times this was as a result of spontaneous crimes over pre-meditated ones  and detainment sentences were diverted in all cases (at least in the Cheely cohort). What this tells us is that, no, not every prisoner has autism (or ADHD) - not even close - and that a diagnosis of autism can sometimes be seen in legal terms as a mitigating factor ; a point recently noted in a "very sad case with a sad background narrative."But, and it is an important point, the focus on the Ashworth opinion piece on autism being underdiagnosed in the prison population refers to the fact that formal diagnosis before entering the CJS may not be the whole story. Indeed, I will draw your attention to the paper by Louise Robinson and colleagues  who started from the point of: "concerns that individuals with autism spectrum disorders (ASDs) are over-represented but not recognised in prison populations" in their attempt to looking at possible screening of prisoners for autism. The results? Well, let's just say that their 'screening tool for ASDs' in prisoners needed more work but on the basis of their findings "rather than routinely screen for ASDs in prison, staff should be encouraged to raise concerns about individuals struggling to cope in prison." Make of that what you will, although prison and probation staff can sometimes be surprisingly good at picking up those in potential need of further referral.Moving on, or rather going back to the idea that a diagnosis of ADHD might be over-represented among the prison population, are those findings from Ylva Ginsberg and colleagues . They observed that among the longer-term inmates where ADHD was identified (~40%), an ASD might also be comorbid in about a quarter of these cases. This is perhaps not an entirely unexpected finding given what is known about autism and ADHD comorbidity (see here) and *could* be interpreted in the context of autism underdiagnosis in prisoners just reflecting that ADHD is also underdiagnosed. Without moving 'blame' from label to label, there is quite a strong emerging research base suggesting that a heightened risk of going to prison as one possible  long-term adverse outcome following a diagnosis of ADHD is worthy of a lot more investigation particularly when it comes to trying to mitigate any enhanced risk (see here).What can we conclude about the question of 'autism underdiagnosis in prisoners'? On the basis of the research base so far, yes, it can happen, because not every case of autism is 'picked up' during infancy and individual reports of such undiagnosed persons coming into contact with the CJS are still apparent. But I'm not so sure about the extent to which underdiagnosis of autism in prisoners occurs  and indeed, whether we would necessarily expect large numbers of prisoners to present on the autism spectrum. I say this on the basis that people on the autism spectrum are far more likely to be the victims rather than perpetrators of crime and although some facets of autism might show some possible connections to certain types of unwanted behaviour (see here), generally speaking, one would expect more law abiding citizens on the autism spectrum than less.Oh, and before you pull the old 'empathy' card in relation to offending behaviour on this one, we also need to get away from the view that a universal lack of empathy is somehow characterstic of all autism...The photo included with this post by the way, will contain some familiar faces to most people here in Blighty particular with the EU referendum in mind. For those who might not know, one chap is a comedian and the other a politician... both have, on occasion, had audiences in stitches...---------- Ashworth S. Autism is underdiagnosed in prisoners. BMJ. 2016 Jun 2;353:i3028. King C. & Murphy GH. A Systematic Review of People with Autism Spectrum Disorder and the Criminal Justice System. J Autism Dev Disord. 2014; 44: 2717-2733. Cheely CA. et al. The prevalence of youth with autism spectrum disorders in the criminal justice system. J Autism Dev Disord. 2012 Sep;42(9):1856-62. Berryessa CM. Brief Report: Judicial Attitudes Regarding the Sentencing of Offenders with High Functioning Autism. J Autism Dev Disord. 2016 Apr 22. Robinson L. et al. Evaluation of a Screening Instrument for Autism Spectrum Disorders in Prisoners. PLoS ONE. 2012;7(5):e36078. Ginsberg Y. et al. Attention Deficit Hyperactivity Disorder (ADHD) among longer-term prison inmates is a prevalent, persistent and disabling disorder. BMC Psychiatry. 2010;10:112. Smith E. et al. Preschool hyperactivity specifically elevates long-term mental health risks more strongly in males than females: a prospective longitudinal study through to young adulthood. Eur Child Adolesc Psychiatry. 2016 Jun 13. Underwood L. et al. Autism spectrum disorder traits among prisoners. Advances in Autism. 2016; 2:----------Ashworth S (2016). Autism is underdiagnosed in prisoners... Read more »
This is the fourth post in a series on strange substances accidentally or intentionally added to street drugs. When you're done here, check out the posts on alcohol, meth, opioids, and cocaine.In the autumn of 2007, hospitals near Leipzig, Germany admitted 29 people after they inadvertently smoked weed contaminated with lead. Yep, some dealer or grower decided it was a good idea to drop a bunch of small lead particles into the marijuana they were selling, presumably to increase its weight (lead is super dense) and thus make mad bank. The average lead content of stashes recovered from the poisoned individuals was 10% by weight, translating into an additional ~$1500 per kg of pot sold.It turns out the center of a lit joint can reach temperatures up to 1200°C, sufficient to ensure a bunch of lead particles will end up in the inhaled smoke and so be absorbed via the lungs (particularly if the inhaled smoke is being held in to maximize absorption of non-lead stuff like THC). Those with lead poisoning showed up to the hospitals with stomach cramps, feeling like they were going to barf, lacking sufficient numbers of red blood cells (anemia), and being unreasonably tired. Most had basophilic stippling and exhibited Burton's line (here's a gross photo), which are classic indicators of lead poisoning. One particularly unfortunate person also had their nervous system seriously damaged by lead. In addition to experiencing hallucinations, this individual exhibited wrist drop because a nerve connecting their spine with their arms stopped working properly.Aluminum and small bits of glass have also been found in marijuana sold on the street. The aluminum was attributed to using unreasonably dirty water to grow the plants, while the glass was thought to be intentionally added to make the pot look better (like it has lots of crystals) and increase its weight. Inhaling hot glass fumes isn't pleasant since they can severely burn your mouth and lungs.Claviceps purpurea fungus growing on grain (Source)Very rarely, dropping acid (LSD) can result in ergot poisoning, which is probably one of the worst possible outcomes for a trip. If the LSD is synthesized from lysergic acid obtained from the ergot fungus (Claviceps purpurea), it may be contaminated with other toxic fungal alkaloids. Ergot poisoning (aka St. Anthony’s fire) has been around since we first began harvesting rye and other grains to eat. The fungus grows on these plants, producing a bunch of compounds that aren't very nice to the human body. They act on the intestines to produce diarrhea and on the nervous system to produce seizures. Ergot alkaloids also cause blood vessels to constrict, reducing blood (and thus oxygen) flow to the arms and legs (aka limb ischemia, usually accompanied by burning pain). In severe cases, the reduced blood flow can lead to gangrene, where the ends of one's fingers and toes to die, turn black, and eventually fall off.ReferencesBusse F, Omidi L, Timper K, Leichtle A, Windgassen M, Kluge E, Stumvoll M. 2008. Lead poisoning due to adulterated marijuana. New England Journal of Medicine 358(15):1641-1642. [Full text]Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. 2011. Adulterants in illicit drugs: A review of empirical evidence. Drug Testing and Analysis 3(2):89-96.Raval MV, Gaba RC, Brown K, Sato KT, Eskandari MK. 2008. Percutaneous transluminal angioplasty in the treatment of extensive LSD-induced lower extremity vasospasm refractory to pharmacologic therapy. Journal of Vascular and Interventional Radiology 19(8):1227-1230.... Read more »
The findings reported by Ming-Tao Yang and colleagues  make for some brief blogging fodder today and the idea that: "Higher ADHD [attention-deficit hyperactivity disorder] scores in children with AR [allergic rhinitis] compared with healthy controls decreased significantly with AR treatment." Said AR treatment consisted of "nonpharmacologic intervention, oral antihistamines, and topical steroids."I know furrowed brows and eye-rolling might be the response of some people to this work but consider however the [peer-reviewed] data already published on how the presentation of allergy or atopic disease might go well beyond just somatic presentation (see here for example). Given also that Yang et al are based in Taiwan, it is useful to mention how 'big data' from Taiwan has been instrumental in pushing the relationship between immune function and behavioural outcomes (see here).This time around researchers looked at a small-ish participant group diagnosed with AR; evaluating both their physical AR symptoms and also symptoms scores according to ADHD criteria. After treatment for their AR, their AR symptoms improved (not unexpectedly) but alongside changes to their ADHD scores were noted too. Indeed: "Significant predictors for the improvement of ADHD scores included age, AR drugs, AR subtypes, and multiple atopic diseases." The authors make quite a forthright assertion from their data: "For children with AR and borderline ADHD symptoms, who do not meet full ADHD diagnostic criteria, we recommend initially treating their AR and monitoring improvement of ADHD symptoms."Just before anyone assumes that I'm pushing oral antihistamines for ADHD, I'm not. Accepting that there are still some research gaps in how ADHD is managed pharmacologically (see here) I do however think that there could be a further research study or two to do on this topic; not least including a placebo element to it. If you need a template for how this might play out, well, there is some mention in the related autism research literature about allergy symptoms potentially affecting autistic symptoms (see here). The case report included in that previous blog post was from Harumi Jyonouchi  and went a little further in terms of how AR was treated, but the idea that behaviour could be impacted by such intervention is there and perhaps further stretches the whole 'immune function is related to behaviour' hypothesis.And yes, autism and ADHD may share a lot more than perhaps previously recognised (see here).To close, it's news here in Blighty but I'm not so sure elsewhere, but the question 'should I stay or should I go?' will be resolved one way or another today regarding the UK's membership of the European Union. Depending on your point of view, you'll be happy/sad to know we will still be able to take part in Eurovision and the EUROs no matter what...---------- Yang MT. et al. Attention-deficit/hyperactivity disorder-related symptoms improved with allergic rhinitis treatment in children. Am J Rhinol Allergy. 2016 May;30(3):209-14. Jyonouchi H. Marked improvement of neuropsychiatric symptoms following control of allergy symptoms with the use of humanized murine anti-IgE antibody (omalizumab) in 2 patients with severely limited expressive language. Allergy, Asthma & Clinical Immunology. 2015; 11: 38.----------Yang MT, Chen CC, Lee WT, Liang JS, Fu WM, & Yang YH (2016). Attention-deficit/hyperactivity disorder-related symptoms improved with allergic rhinitis treatment in children. American journal of rhinology & allergy, 30 (3), 209-14 PMID: 27216352... Read more »
Yang MT, Chen CC, Lee WT, Liang JS, Fu WM, & Yang YH. (2016) Attention-deficit/hyperactivity disorder-related symptoms improved with allergic rhinitis treatment in children. American journal of rhinology , 30(3), 209-14. PMID: 27216352
Consider this short-ish entry a sort of extension of other discussions on this blog on the topic of lead (Pb) (see here). As per the blog title, the systematic review published by Maryam Daneshparvar and colleagues  (open-access available here) adds to the quite voluminous peer-reviewed literature indicating that lead exposure, particularly during infancy and childhood, seems to be associated with nothing but adverse outcomes in terms of development and behaviour.Surveying the research literature "on the role of lead exposure in children with ADHD [attention-deficit hyperactivity disorder] symptoms" up to May 2014 - including some sources that I've not come across before e.g. IRAN Medex - the authors eventually boiled down the current research landscape to 18 articles "selected and entered into the data synthesis." It appears that some important guidance was followed when it came to study selection and interpretation and, all in all, some 12,000 participants were included in the selected research literature included for analysis.Results: well as perhaps expected, nothing good seems to come from lead exposure. The authors reported that even at quite small concentrations in blood (blood lead levels, BLLs below 10µg/dL), lead is potentially linked to the presentation of ADHD in one form or another. In 16 of the 18 studies included in their analysis: "a significant association was found between BLL and one of the types of ADHD."What's more to say on this topic? Well, as the authors note, the vast majority of the studies analysed included only one measure of BLL so one perhaps has to be a little cautious about the 'snapshot' nature of the data included. They also make some comment on how the symptoms of ADHD were a focus over and above a 'diagnosis' so that could also be considered a methodological weakness.That all being said, and knowing what we know about 'lead being a strong poison' I'm yet again convinced that keeping kids in particular away from sources of possible lead contamination is of vital importance. I say that not just from the point of view of risk of ADHD-type behaviours or any other label (see here), but simply because nothing good comes from exposure to the stuff. When also we talk about lead exposure, we might also be inclined to note that ambient levels of the stuff might also show some interesting correlations too  (yes, correlation is not the same as causation).Finally, in amongst all the doom and gloom about lead exposure and developing brains, there may also be a ray of hope...---------- Daneshparvar M. et al. The Role of Lead Exposure on Attention-Deficit/ Hyperactivity Disorder in Children: A Systematic Review. Iran J Psychiatry. 2016 Jan;11(1):1-14. Dickerson AS. et al. Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic. Environ Monit Assess. 2016 Jul;188(7):407.----------Daneshparvar M, Mostafavi SA, Zare Jeddi M, Yunesian M, Mesdaghinia A, Mahvi AH, & Akhondzadeh S (2016). The Role of Lead Exposure on Attention-Deficit/ Hyperactivity Disorder in Children: A Systematic Review. Iranian journal of psychiatry, 11 (1), 1-14 PMID: 27252763... Read more »
Daneshparvar M, Mostafavi SA, Zare Jeddi M, Yunesian M, Mesdaghinia A, Mahvi AH, & Akhondzadeh S. (2016) The Role of Lead Exposure on Attention-Deficit/ Hyperactivity Disorder in Children: A Systematic Review. Iranian journal of psychiatry, 11(1), 1-14. PMID: 27252763
This is the third post in a series on strange substances accidentally or intentionally added to street drugs. When you're done here, check out the posts on alcohol and meth.Opioids are drugs that affect the human body by binding to a group of related proteins conveniently known as opioid receptors. By connecting to these receptors in a certain manner, they convince receptor-bearing cells in the brain, spinal cord, and intestine to do useful things like reduce the sensation of pain (while making you feel warm and fuzzy), suppress coughing, and prevent an onslaught of diarrhea. In addition to opiates such as morphine and codeine that are naturally produced by the opium poppy, we've figured out how to put together a whole slew of opioids both by modifying opiates, as is done to make heroin (from morphine) and oxycodone (from thebaine), or synthesizing entirely new drugs such as fentanyl from scratch.Desmethylprodine, also known as 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP), was invented by a pair of drug company scientists in 1947. Structurally, it's very similar to meperidine (pethidine, Demerol), another entirely synthetic opioid. Seeing as it wasn't any more effective than meperidine at killing pain, the drug company decided to nix its production. Nearly thirty years later, a chemistry grad student by the name of Barry Kidston read about MPPP and decided to try making some of it for personal use. While the first couple of batches yielded a successful means of getting high, the situation soon devolved into an imaginary TV show I'm calling Breaking Sad. Kidston got sloppy. He apparently started to rush the reactions used to make MPPP and then didn't isolate the drug properly. As a result, an impurity called 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ended up in the final product. If you put MPTP in your body, it's converted into a neurotoxic substance with a fine-tuned appetite for destruction. It specifically annihilates dopamine-releasing neurons in a part of the brain responsible for controlling muscle movements, resulting in permanent symptoms resembling those seen in people with Parkinson's disease (parkinsonism). Kidston ended up hospitalized with acute parkinsonism after unwittingly dosing himself with MPTP. Although doctors eventually figured out they could treat his condition with a L-DOPA, which boosts dopamine levels in the brain, Kidston shortly passed away after overdosing on cocaine and codeine. A couple of other folks subsequently ended up in hospital after using poorly made MPPP and having their brains partially wrecked by MPTP. In at least two cases, the drug was tested and found to consist mostly of MPTP with only trace amounts of MPPP!MPTP brings about destruction of neurons in the substantia nigra (Photo source)Heroin, a suped-up version of morphine, is sold on the street mixed with an assortment of materials intended to do some combination of (1) cheaply bulking up the drug so it can be sold for more money, (2) deceiving buyers into thinking the quality of the drug is better than it really is so it can be sold for more money, (3) altering its effects in a desirable way, and (4) making it easier to use. Inexpensive materials used to dilute heroin include sugars, flour, and talc. Black tar heroin, a heroin-containing mixture named for its appearance and consistency, has been known to be bulked up by adding dirt or ground up paper previously soaked in black shoe polish. Quinine, a plant-derived alkaloid used to treat malaria, is used to dilute heroin in part because it also has a bitter taste and apparently produces a sensation in the lungs resembling what you feel after injecting heroin. Another bitter heroin mimic is paracetamol (acetaminophen, Tylenol), which has the added bonuses of also being painkiller, albeit a way weaker one, and having a similar melting point. Fentanyl is an incredibly strong opioid sometimes added to low quality heroin to increase its potency. Caffeine and procaine, when mixed with heroin, cause the latter to vaporize at a lower temperature, making it easier to smoke. Additionally, procaine is a local anesthetic (a numbing agent) and so can reduce any pain caused by injecting heroin.By far the nastiest accidental addition to heroin has to be people-eating bacteria such as Bacillus anthracis (causes anthrax) and Clostridium botulinum (causes botulism). They produce spores capable of surviving being heated up within a spoonful of heroin before it's injected into a vein or under the skin. In fact, the heat can cause the spores to germinate, priming them for action. Injection means instant access to the human buffet. Heroin can become contaminated with harmful bacteria during its production, shipment, sale, or use. Cases of anthrax in heroin users living in Western Europe have been explained as being the result of Bacillus anthracis spores getting into the drug as it's moved from Afghanistan via Turkey, possibly from the animal skins in which the drug is smuggled (livestock in the Middle East are occasionally killed by the bacterium) or because bone meal contaminated with spores is used to bulk up the drug prior to selling it. Spores of Clostridium botulinum, naturally found in soil, are thought to get into heroin via the materials added to bulk it up or from dirty tools used to administer the drug. Although C. botulinum requires an environment lacking in oxygen in order to flourish, and the tissues of the human body are typically well-supplied with oxygen via the blood flowing to and from them, a heroin user can inadvertently create oxygen-poor pockets within their body where the bacterium can grow and pump out toxins. Heroin doesn't dissolve well in water, so people looking to inject it into them typically use a solution of citric acid, heated gently, to facilitate dissolution. Repeatedly introducing citric acid into the body results in tissue damage and scar formation, reducing blood flow and thus the local level of oxygen. That's how you become infected with C. botulinum.ReferencesBrett MM, Hallas G, Mpamugo O. 2004. Wound botulism in the UK and Ireland. Journal of Medical Microbiology 53(Pt 6):555-561. [Full text]Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. 2011. Adulterants in illicit drugs: A review of empirical evidence. Drug Testing and Analysis 3(2):89-96.Fahn S, Sulzer D. 2004. Neurodegeneration and neuroprotection in Parkinson disease. NeuroRx 1(1):139-154. [Full text]Price EP et al. 2012. Molecular epidemiologic investigation of an anthrax outbreak among heroin users, Europe. Emerging Infectious Diseases 18(8):1307-1313. [Full text]... Read more »
Fahn S, & Sulzer D. (2004) Neurodegeneration and neuroprotection in Parkinson disease. . NeuroRX, 1(1), 139-154. DOI: 10.1602/neurorx.1.1.139
At the end of 2013 there was some media interest in the presentation of interim data at the 2013 Annual Meeting of the American College of Neuropsychopharmacology from a couple of studies being run by Prof. Eric Hollander.It's life Jim but not as we know it... @ CDCThe abstracts for the studies 'Trichuris Suis Ova (TSO) as an Immune-inflammatory Treatment for Repetitive Behaviors in ASD' and 'Hyperthermia and the Improvement of ASD Symptoms' can be found here (look under abstracts T177 and T231).Whilst the media headlines citing 'worms and hot baths' as potential intervention approaches for autism generated quite a nice soundbite and are probably enough for most people to click on the story to read more, I personally did not think they did justice to how potentially important these areas might be to at least some cases of autism. Indeed hot baths as a way of mimicking fever took me back to the article by Curran and colleagues  who "documented behavior change among children with autism spectrum disorders during fever."Sweeping generalisations about hot baths, fever and autism aside, today I'm discussing the paper by Liu and colleagues  who, following a review of "the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians" reported that over half of those 'self-treating' had a diagnosis of autism. Helminths by the way, are parasitic worms, and whilst some are rather unpleasant in terms of their detrimental effects to health, others have been used in a more therapeutic capacity. Insofar as the idea of 'self-treatment', well, let's just say that this is may not be unusual...Liu et al describe how: "Five physicians monitoring more than 700 self-treating patients were interviewed" and how: "These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use." Although one has to be slightly cautious about this type of 'clinical experiences' methodology ('the plural of anecdote is not data' and all that) adopted in the study, it was interesting to note that: "Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis." We are also importantly told that about 1% of paediatric patients using H. diminuta "experienced severe gastrointestinal pains" suggesting that any future studies should also be observant for side-effects.I am still in two minds about this area of study and the 'palatability' of the proposed intervention. I note the full trial by Hollander and colleagues looking at the use of Trichuris Suis Ova in the context of autism has kinda fallen off the radar a little bit judging by the status of the trial entry in ClinicalTrials.gov at the time of writing. Aside from that proposed trial and some other speculations about the use of helminthic therapy potentially applied to autism  there is little else in the peer-reviewed research literature on this topic in terms of effects or some further details about any proposed mode of action. With my speculating hat on, one could perhaps see the logic around helminthic therapy with regards to the suggested augmentation of an abnormal immune response thought to involve the Th1/Th2 response (see here  for more details about this). With autism in mind, certainly there has been some research chatter about this immunological balancing act being potential important for some .I'm sure also that some readers who've encountered this post are either (a) thinking WTF (apologies for my bad language) or (b) potentially thinking about how unethical this study and intervention sounds. Worms after all, are not generally regarded as a great therapy for anything, particularly when people are talking about eradication of such parasites rather than supplementing with them (see here). I'm certainly not going to stand up and suggest helminthic therapy is the be-all-and-end-all for autism intervention by any means even in the context of inflammatory process being potentially involved in many behaviourally-defined conditions The thing is though, that our prejudice against all parasites is similar to our prejudice against all bacteria. Not all parasitic worms are the same, just as not all bacteria are the same (he says drinking from his probiotic yoghurt). Indeed, helminthic therapy has found a place in medicine, particularly when it comes to various conditions with an immune system element to them as exemplified by papers such as this one . The review article by Wammes and colleagues  kinda summarises the mixed feelings that science has about such intervention and how "a paradox exists between efforts to deworm populations with helminth-associated morbidities, and initiatives to test helminthic therapy on patients with hyperinflammatory diseases". If I remember correctly, I think Dr Michael Mosley also had something to say about swallowing parasites...Added also to the words of caution about proposed side-effects from helminthic therapy, I will draw your attention to the paper by Bager and colleagues  who reported that "gastrointestinal reactions" were quite significantly elevated during the early days of quite a long administration period (every 21 days for 168 days) of pig whipworm in their particular trial and cohort. With all that science now knows about gastrointestinal (GI) issues in relation to autism, one probably doesn't want to compound any existing problems in that particular area of comorbidity.Palatability aside, there is however more science to do in this area including looking further at potential mechanisms  and specifically, how swallowing worm eggs might one day be replaced by swallowing pills with a similar mode of biological action...---------- Curran LK. et al. Behaviors associated with fever in children with autism spectrum disorders. Pediatrics. 2007 Dec;120(6):e1386-92. Liu J. et al. Practices and outcomes of self-treatment with helminths based on physicians' observations. J Helminthol. 2016 May 31:1-11. Siniscalco D. & Antonucci N. Possible use of Trichuris suis ova in autism spectrum disorders therapy. Med Hypotheses. 2013 Jul;81(1):1-4. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003 Aug;8(3):223-46. Gupta S. et al. Th1- and Th... Read more »
Liu J, Morey RA, Wilson JK, & Parker W. (2016) Practices and outcomes of self-treatment with helminths based on physicians' observations. Journal of helminthology, 1-11. PMID: 27240605
Researchers have identified a new genetic candidate for testing therapies that might affect fear learning in people with PTSD or other conditions. Individuals with trauma- and stress-related disorders can manifest symptoms of these conditions in a variety of ways. Genetic risk factors for these and other psychiatric disorders have been established but do not explain the diversity of symptoms seen in the clinic - why are some individuals affected more severely than others and why do some respond better than others to the same treatment?
... Read more »
Knoll, A., Halladay, L., Holmes, A., & Levitt, P. (2016) Quantitative Trait Loci and a Novel Genetic Candidate for Fear Learning. Journal of Neuroscience, 36(23), 6258-6268. DOI: 10.1523/JNEUROSCI.0177-16.2016
By Maranda CardielA photograph of Culex pipiens, the species of mosquito that the researchers used in their experiment. Source: David Barillet-Portal at Wikimedia Commons.Everybody hates mosquitoes. They are annoying, persistent, and make us itch like crazy. Sometimes there are so many of them that we are afraid to go outside unless we want to risk getting covered in spots and scratching ourselves all over for the next week. And if that wasn’t enough, they can also carry dangerous diseases with the potential to kill us. However, just like us, mosquitoes don’t like to be bugged by parasites that can make them sick either. Research shows that they may even avoid interacting with hosts that might pass along parasites to them. A group of researchers - Fabrice Lalubin, Pierre Bize, Juan van Rooyen, and Philippe Christe from the University of Lausanne in Switzerland and Olivier Glaizot from the Lausanne Museum of Zoology – wanted to see if mosquitoes would show a preference for feasting upon birds that were infected with malaria (a blood parasite) or uninfected birds. Mosquitoes find animals to snack on by sensing odors and carbon dioxide in the air that animals give off, along with using their senses of vision, hearing, and touch. In order to figure out if mosquitoes use these senses to specifically choose their unlucky victims, the researchers did an experiment with mosquitoes, malaria, and great tits (a type of bird with a funny name).For their experiment, the researchers collected mosquito eggs that they hatched and raised in a lab. Only female mosquitoes suck blood, so only female mosquitoes were used in the experiment. The mosquitoes had never been exposed to birds before and were starved of sugar for one day to make sure that they would be hungry. The researchers also caught wild adult great tits, and they took small blood samples from each bird to test for malaria before and after the experiment.Next it was time to see if the mosquitoes would find some birds to be more appealing than others. A special Y-shaped wind tunnel allowed the mosquitoes to choose between the odors of two birds: one that was infected with the malaria parasite and one that was not. But don’t worry, the mosquitoes could not directly contact the birds. The researchers set up the lab so that it was completely dark to mimic the natural settings of when mosquitoes feed in the wild. This also meant that the mosquitoes were blind and could only choose a bird based on the chemicals in the air. Randomly-chosen pairs of birds and new mosquitoes were used for each round of the test.A cartoon depicting the experiment setup. A hungry female mosquito hones in on the odors of a healthy great tit and a great tit infected with malaria parasites. Source: Maranda CardielThe results of the study showed that the mosquitoes had a strong preference for birds that were not infected with the malaria parasite. This was true even when the researchers took into account the body sizes and sexes of the birds. Previous studies with different kinds of birds, mosquitoes, and malaria or malaria-like parasites have found similar results. The researchers think that this may be because the malaria parasite somehow causes changes in the chemical processes in the birds’ bodies that the mosquitoes can pick up on. Infection with malaria might change what the birds smell like to the mosquitoes or how much carbon dioxide the birds give off. There is also evidence that birds who are more susceptible to malaria infections have a different odor than birds with stronger immune systems. But why should mosquitoes be picky and choose to bite healthy birds? They certainly don’t seem like they care whose blood they suck when they are swarming around us!Previous research has shown that mosquitoes infected with malaria parasites have problems developing their eggs and can have trouble sucking up blood from their victims. Female mosquitoes use blood to nourish their eggs, so if they don’t drink as much blood, they will not be able to lay as many eggs. This means that female mosquitoes carrying malaria parasites are less likely to produce as many healthy offspring. Thus, it makes sense for female mosquitoes to want to avoid feeding on birds that are infected with malaria.This probably has not changed your thoughts about mosquitoes. They are still a nuisance that we all squish - or at least attempt to squish - upon sight. It might be ironic, but mosquitoes don’t like to have parasites bothering them either. Even though we hate them, maybe now you can find some solace in mosquitoes finding you attractive. It might be a sign that you are actually healthier than your peers. Source:Lalubin, F., Bize, P., van Rooyen, J., Christe, P., & Glaizot, O. (2012). Potential evidence of parasite avoidance in an avian malarial vector Animal Behaviour, 84 (3), 539-545 DOI: 10.1016/j.anbehav.2012.06.004 ... Read more »
Lalubin, F., Bize, P., van Rooyen, J., Christe, P., & Glaizot, O. (2012) Potential evidence of parasite avoidance in an avian malarial vector. Animal Behaviour, 84(3), 539-545. DOI: 10.1016/j.anbehav.2012.06.004
Continuing a recent 'probiotic theme' on this blog I've decided to talk a little about the study results reported by Shelly Buffington and colleagues  on how a "single species of gut bacteria can reverse autism-related social behavior in mice." I say 'talk about' but my conversations on this topic should be viewed in light of what others have also said about this study (see here for example) including the lead author (see here).To summarise the findings: authors started from the idea that maternal obesity during pregnancy might have some implications for offspring in terms of their risk of "neurodevelopmental disorders including autism spectrum disorder (ASD)." It's something that has been covered before on this blog (see here) including the idea that inflammation or response to inflammation in-utero might be an important part of any risk mechanism (see here).Conversations then progressed towards the possibility that the gut microbiome might play a role in that elevated risk of offspring autism following pregnancy obesity. To test this theory out, researchers fed female mice a high fat or 'normal diet' for 8 weeks, paired them for mating and gave all their offspring a regular diet. They studied social behaviour of offspring mice and observed that "MHFD [maternal high-fat diet] offspring had impaired sociability and showed no preference for social novelty."To examine whether those mouse social behaviours were linked to the gut microbiome, researchers looked at the "bacterial composition and community structure in the feces" of offspring mice to ascertain any differences. They did find differences; indeed in one write-up of the study the authors note: "We found a clear difference in the microbiota of the two maternal diet groups." Could such bacterial differences account for the social differences noted between the groups? Quite possibly as Buffington et al reported that "co-housing one MRD [maternal regular diet] with three MHFD offspring was sufficient to rescue both the social behaviors and microbiota phylogenetic profile of MHFD offspring." Further, researchers transplanted the faecal microbiota from the MRD and MHFD offspring into germ-free mice providing "causal evidence that an imbalanced microbial ecology in the mice born to mothers on a high-fat diet is responsible for their social deficits."Then came a big question: what was it about the maternal high-fat diet offspring microbiome that might be 'responsible' for the social issues observed? The answer or at least one answer: "L. reuteri [Lactobacillus reuteri] was the most drastically reduced (>9-fold) in the MHFD microbiota population, compared to the MRD microbiota." Subsequent addition of L. reuteri to the drinking water of MHFD offspring was instigated and: "Remarkably, treatment with L. reuteri significantly improved sociability and preference for social novelty in MHFD offspring."As if all that wasn't enough researchers also looked at the old gut-brain axis and subsequently noted that: "L. reuteri treatment restores oxytocin levels, VTA [ventral tegmental area] plasticity and social behaviors." Oxytocin has something of an interesting possible connection to [some] autism (see here).And rest.As you can perhaps appreciate, this piece of research is fairly comprehensive both in terms of the methodologies used and also the findings in relation to maternal pregnancy obesity, offspring social behaviour, gut microbiome and the gut-brain axis. Certainly quite compelling evidence for some kind of effect including the concept of foetal programming allied to the idea of possible intervention.Of course you'd be right to question whether the processes described in this mouse model would necessarily map on to the human experience and indeed the very heterogeneous autism spectrum characterised by [variable] issues with social affect for example. Similar questioning is asked of all animal studies trying to model the complexities of autism (see here). But added to other research where mouse modelling of autism 'deficits' has been to some degree 'changed' as the result of the addition of a particular bacterial species (see here) there is some reason for potential excitement. More so when one considers other research on the gut microbiome in relation to specific preparations potentially modifying the risk of 'neurospychiatric disorder' (see here) for example, and potentially affecting mood and/or behaviour (see here). Don't even get me started on toddler temperament being linked to the inner workings of the gut (see here) minus any hype.But just before sales of Lactobacillus reuteri increase markedly there is further research to be done. Not least is the translation of elements of the Buffington research into studies of humans. Set within the idea that mapping exactly what kinds of wee beasties are residing in the gut is now fairly commonplace and has already stretched into autism research (see here) I would have thought that looking for the presence or absence of L. reuteri in certain groups (and sub-groups) on the autism spectrum and beyond should be fairly easy to do. If and when issues are found with this particular species, supplementing could be indicated bearing in mind some of the potential effects  noted already on this bacterium might already show indication in some cases of autism (see here). One might also see a way to look at this and other bacteria in conjunction with levels of oxytocin and possibly other important compounds too as part of that gut-brain axis. Given also that the Buffington study was a study of offspring of obese mice in terms of their sociability, does this also mean that kids born to overweight or obese mums are less likely to have age-appropriate social skills outside of any talk of autism?There is still a research journey to be travelled in this area of investigation and, I might add, potentially linking various areas together including the idea that not all fats in a high-fat diet are necessarily the one and the same (see here)...---------- Buffington SA. et al. Microbial Reconstitution Reverses Maternal Diet Induced Social and Synaptic Deficits in Offspring. Cell.2016; 165: 1762-1775. Coccolrullo P. et al. Lactobacillus reuteri (DSM 17938) in Infants with Functional Chronic Constipation: A Double-Blind, Randomized, Placebo-Controlled Study. J Peds. 2010; 157: 598-602.----------... Read more »
Buffington, S., Di Prisco, G., Auchtung, T., Ajami, N., Petrosino, J., & Costa-Mattioli, M. (2016) Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell, 165(7), 1762-1775. DOI: 10.1016/j.cell.2016.06.001
Mothers of children with autism and were diagnosed with metabolic conditions during pregnancy, particularly gestational and type 2 diabetes, were more likely to have anti-fetal brain autoantibodies in their blood compared to healthy women of children with autism. The presence of these anti-fetal brain autoantibodies has been previously found to be specific to some mothers of children with autism and rare among mothers of children without autism.
... Read more »
Krakowiak, P., Walker, C., Tancredi, D., Hertz-Picciotto, I., & Van de Water, J. (2016) Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Research. DOI: 10.1002/aur.1657
Scientists propose the creation of a synthetic human genome as a follow-up of the Human Genome Project... Read more »
Happy as a pig in...Assuming that I'm still around as and when published, I'd like to think that the final product of the study protocol from Elisa Santocchi and colleagues  will eventually find it's way on to this blog when the peer-reviewed results are finally in.Alongside it's ClinicalTrials.gov entry (see here), authors describe an interesting double-blind, placebo-controlled study where the aim is to "determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD [autism spectrum disorder] children not only on specific GI [gastrointestinal] symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity."Detailing how researchers *might* be able to put a little scientific flesh on the to the bones of the whole 'gut-brain' relationship with autism in mind (see here), the focus will be on how manipulation of the gut microbiome *might* have various impacts for at least some on the autism spectrum. Indeed with mention of words like 'inflammation' and 'leaky gut', I'd be quite interested to read their eventual findings given other (mouse) research in this area (see here for example) and some more recent investigation  on a possible role for Lactobacillus reuteri currently garnering media headlines - blog post to follow soon.You will of course have picked up all the *might* parts of this post as the various subgroups ("Group 1) GI symptoms and probiotics, Group 2) GI Symptoms and placebo, Group 3) Non-GI symptoms and probiotics, Group 4) Non-GI symptoms and placebo") are followed over the 6-month study period. It is entirely conceivable that the Santocchi trial will reveal no effect from probiotic use on the facets of autism under study. Indeed, I'll be the first one to question whether, despite all the gut bacteria findings in relation to autism, we can actually 'change' the constitution of the gut microbiome long-term by such methods. Even some of our strongest antibiotics seem to only have a time-limited effect when it comes to autism and the deepest, darkest recesses of the gut (see here) and there is also the possibility of a 'critical window' for such supplementation use to also contend with.But studies such as this do fill a rather large research gap for at least some on the autism spectrum and perhaps even beyond (see here). "We will watch your career with great interest" to coin a phrase...---------- Santocchi E. et al. Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry. 2016 Jun 4;16(1):183. Buffington SA. et al. Microbial Reconstitution Reverses Maternal Diet Induced Social and Synaptic Deficits in Offspring. Cell.2016; 165: 1762-1775.----------Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella F, Calderoni S, Grossi E, Morales MA, & Muratori F (2016). Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC psychiatry, 16 (1) PMID: 27260271... Read more »
Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella F, Calderoni S, Grossi E, Morales MA, & Muratori F. (2016) Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC psychiatry, 16(1), 183. PMID: 27260271
"Individuals with epilepsy are at increased risk of ASD [autism spectrum disorder], especially if epilepsy appears in childhood. Further, ASD is more common in the siblings and offspring of individuals with epilepsy, suggesting shared etiology."That was the research bottom-line from Heléne Sundelin and colleagues  reporting results based on examination of the "Swedish Patient Register" with regards to the "risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives." Including one Jonas F. Ludvigsson, PhD on the authorship list (yes, he of 'gluten and autism: probably not coeliac disease but...' fame), researchers identified some 85,000 individuals diagnosed with epilepsy "as well as all their siblings (n = 80,511) and offspring (n = 98,534)." With some nifty statistical analysis including matching cases 5:1 with control participant data, they were able to conclude that around 1.6% of those with epilepsy were diagnosed with an ASD compared with 0.2% of controls. Those percentages are seemingly quite small both in real terms and also in differences between the groups but given the huge participant numbers included for study came out with a hazard ratio (HR) around 10.49 "confidence interval [CI] 9.55–11.53)." To put that HR of 10.49 in context, other work by Ludvigsson on epilepsy coinciding with coeliac disease for example, with a participant number in the tens of thousands came out with a HR of 1.42.When also looking at what happened to siblings and offspring of those diagnosed with epilepsy, the authors also observed something of a potentially increased risk of autism being also diagnosed, although quite a bit less than risk to those themselves diagnosed with epilepsy. The results did however suggest that: "The risk in the offspring was particularly high in mothers with epilepsy." And just for good measure, the Sundelin results also noted that risk of epilepsy was "also associated with a prior diagnosis of ASD" confirming what many others have reported over the years (see here).Although making some headlines I wasn't particularly shocked by the bi-directional associations reported by Sundelin and colleagues. Quite a few times on this blog I've talked about autistic features being potentially over-represented in cases of epilepsy (see here and see here) so to see some of those features crossing diagnostic thresholds into an actual autism diagnosis is perhaps not unsurprising. Continuing that line of thought I do wonder what might happen if the broader autism phenotype (BAP) was also analysed with epilepsy in mind (even the new DSM-5 categorisation of social communication disorder?)Insofar as the hows and whys of the association between epilepsy and autism, well, we're still in guessing mode at the current time. I've talked about some of the various genetic syndromes that tend to include autism and epilepsy together as a diagnostic package (see here) as evidence for the more plural 'autisms'. Such syndromes suggest that mechanisms linking the two conditions are likely to be multiple and not necessarily the same for everyone. The issue of GABA and autism might also show some connection in some cases as per what is starting to be known about this neurotransmitter (see here) and where it might fit with some autism (see here) on top of epilepsy. Assuming also that epilepsy in pregnant mothers for example is being managed by medication, it is also not outside of the realms of possibility that certain preparations could also exert an effect on offspring autism risk (see here). I say this with no scaremongering intended.I might also (speculatively) advance the idea that another research area might also be a connecting feature for some autism and some epilepsy: diet. Don't just click away yet as I will first bring your attention to the increasing peer-reviewed literature talking about the use of a ketogenic diet and autism (see here); said dietary intervention more typically indicated in 'some' cases of epilepsy. It's still early days but it strikes me that quite a bit more research is required in this area. Allied to the use of a ketogenic diet (see here) and also perhaps linking back to that other important research area frequently examined by Dr Ludvigsson (coeliac disease) I'm also inclined to ask whether some autism and some epilepsy might show a more specific connection to dietary gluten too. No, I'm not saying that a gluten-free diet nor a ketogenic diet is some sort of 'cure-all' for autism and epilepsy (please don't mess with epilepsy) but rather there may be overlapping genetics or biology potentially linked to facets of gluten metabolism that might be important for some on the autism spectrum with epilepsy. Certainly much more research on this and other less-traditional areas is indicated .There are many questions that remain unanswered in this area of research. With regards to the here and now, well, the Sundelin and other data perhaps suggest that as and when epilepsy is diagnosed, preferential screening for autism could and should be offered particularly in infancy; and perhaps even offered family wide.---------- Sundelin HEK. et al. Autism and epilepsy: A population-based nationwide cohort study. Neurology. 2016. June 15. Frye RE. et al. A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Front Public Health. 2013 Sep 13;1:31.----------... Read more »
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