New in the journal journal Cortex: four shocking cases of practicing medicine while exhausted (Dharia & Zeman, 2016). The authors called this newly discovered syndrome “fatigue amnesia.” Why this is is any different from countless other examples of not remembering things you did while exhausted — I do not know. Except amnesia for performing a complex medical procedure is a lot more disturbing than forgetting you did the dishes the night before.Here are the cases in brief:Case 1: A consultant geriatrician, while working as house officer, treated a patient with chest pain and severe pulmonary oedema in the middle of night. She made an entry in the notes, demonstrating successful initial memory acquisition. She does not remember going to bed that night. On the ward round on the following morning the patient was pointed out to her but she had no recollection of seeing the patient or writing the note.Case 2: A senior house officer, now a consultant neurologist, went to bed in the early hours after a busy shift. She was woken soon afterwards to manage a patient with cardiac arrest. The resuscitation was complex and included an intracardiac adrenaline injection. She documented events in the medical notes immediately, demonstrating successful initial memory acquisition. She returned to bed. She was told on the morning ward round that the patient was well and had his breakfast following the cardiac arrest. She was startled by this information, as she had no recollection of the previous night's events.Case 3: A consultant microbiologist who was working on a night shift as a house officer clerked in a patient at 11:00 pm and continued to work thereafter throughout the night. On the morning ward round when the patient was pointed out to her she had no recollection of seeing or managing him.Case 4: A paediatrician reported memory loss for a complex decision made and instructions given over the phone. While working as a registrar he went to bed in the early hours of morning when on call. He was woken by a call about a complex patient. He went to the ward soon afterwards to find out that the trolley was laid out for Swan Ganz catheterisation. Although he was assured that he had done so, he did not remember giving instructions to prepare the trolley.The incidents were not due to alcohol or drugs. Long hours and sleep deprivation were to blame. And fortunately, the amnesic episodes were isolated and did not recur in any of the doctors. Dharia & Zeman (2016) suggested that:While the resulting memory gaps can reasonably be described as resulting from a ‘transient amnesic state', the evidence from the medical notes suggest that this phenomenon reflects a novel form of accelerated long-term forgetting (Elliott, Isaac, & Muhlert, 2014), whereby a memory for events is acquired normally but then decays more rapidly than usual.By tomorrow, I will have forgotten that I wrote this...ReferenceDharia, S., & Zeman, A. (2016). Fatigue amnesia Cortex DOI: 10.1016/j.cortex.2016.03.001
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Minus any sweeping generalisations, I want to bring your attention to the recent paper by Ashy Rengit and colleagues  today, continuing a theme of case reports discussing autism co-occurring with a substance use disorder (SUD). A SUD is generally defined as where the use of one or more substances (drugs) with psychoactive properties leads to significant impairment or distress for a person. Although some people might envisage the use of illicit drugs as being the only way to receiving a diagnosis like SUD, the label also covers more 'everyday' drugs such as problematic alcohol use for example. Indeed, alcohol use disorder (AUD) has its very own category in DSM-5.I appreciate that this topic is generally neither good dinner-table conversation nor particularly great when it comes to the public image of autism, but as per other discussions overlapping with this topic (see here) it would be folly to ignore it. That some of the characteristics accompanying the diagnosis of autism *might* play a hand in increasing the risk of developing a SUD  provides an important message on the value of screening for risk of SUD and where appropriate, educating and intervening early.Rengit et al provide some useful discussions on the "risk factors which predispose individuals with ASD [autism spectrum disorder] to developing SUD" but I hasten to reiterate that sweeping generalisations are to be avoided, including the ideas of "a positive family history for substance misuse" and the suggestion that autism might be one 'phenotype' "previously reported to be associated with cannabis use"  for example."It is relaxing in general and provides an amount of happiness" is the explanation offered by Mr. A, the participant under inspection, when it came to explaining his history of alcohol use and abuse. His relationship with alcohol, we are told, began after he graduated from high school and thereafter escalated from "one or two beers per week in solitude" to "hard liquor and wine on a daily basis." There is a familiar theme included in the Rengit paper on how a 'vicious cycle' of anxiety and depression are "perpetuated by his psychosocial limitations" and how combined with chronic worry, a pattern related to his alcohol use may be emerging in conjunction with social circumstances "eliminating his motivation to leave the house." That some of the traditional strategies for overcoming depression and anxiety only previously "showed limited benefit" also provides a rationale for how alcohol might be part and parcel of a self-medication strategy in this case. Similar sentiments have been noted in other research on this topic . I might also bring to your attention the history of suicide attempt(s) reported by the authors as a consequence of "feeling overwhelmed by the new environment and social challenges" that college life brought and how it may also be relevant to discussions on the pathway to SUD in relation to autism. This is particularly relevant to some important discussions recently.Accepting that different people have different ways and means bringing them to something like a diagnosis of SUD, the Rengit paper brings to light a potentially important but difficult issue linked to some autism. Given the increasing numbers of people being diagnosed with autism (some of them quite late in life) and how in these times of continued austerity many are being left to fend for themselves, one might appreciate that cases of SUD linked to autism are only likely to increase further. This is on top of the idea that certain comorbidity that is over-represented in cases of autism might also increase the chances of something like SUD . That a SUD may further disadvantage people on the autism spectrum not just in terms of health but also in relation to obtaining and sustaining employment for example - "He was also fired from his job for being suspected of being intoxicated" - requires further study and action on both screening vulnerable populations and also managing/treating such issues quickly as and when they occur . Oh, and don't forget the burden of such additional issues on caregivers too ...---------- Rengit AC. et al. Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A Review and Case Study. J Autism Dev Disord. 2016 Mar 5. Tabata K. et al. Three cases of alcoholism with autism spectrum disorder. Alcohol Alcoholism. 2014 Sep;49 Suppl 1:i54. Stringer S. et al. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium. Transl Psychiatry. 2016 Mar 29;6:e769. Clarke T. et al. Substance use disorder in Asperger syndrome: An investigation into the development and maintenance of substance use disorder by individuals with a diagnosis of Asperger syndrome. Int J Drug Policy. 2016 Jan;27:154-63. Pedersen SL. et al. The Indirect Effects of Childhood ADHD on Alcohol Problems in Adulthood through Unique Facets of Impulsivity. Addiction. 2016 Mar 21. Kronenberg LM. et al. Personal recovery in individuals diagnosed with substance use disorder (SUD) and co-occurring attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). Arch Psychiatr Nurs. 2015 Aug;29(4):242-8. Kronenberg LM. et al. Burden and Expressed Emotion of Caregivers in Cases of Adult Substance Use Disorder with and Without Attention Deficit/Hyperactivity Disorder or Autism Spectrum Disorder. Int J Ment Health Addict. 2016;14:49-63.----------Rengit AC, McKowen JW, O'Brien J, Howe YJ, & McDougle CJ (2016). Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A Review and Case Study. Journal of autism and developmental disorders PMID: 26944591... Read more »
Rengit AC, McKowen JW, O'Brien J, Howe YJ, & McDougle CJ. (2016) Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A Review and Case Study. Journal of autism and developmental disorders. PMID: 26944591
Food for the worms, a dirt nap, kicking the bucket, maybe there are so many euphemisms for death because it is still a taboo in certain cultures. Not so fun fact, my Uncle committed suicide some years back. I’m not going to go into details, but because suicide is looked down on, was his death still considered a “good death”? Trying to qualitatively and quantitatively define a good death, researchers have published a new paper offering help in defining the idea of a good death and have ultimately identified 11 core themes associated with dying well.
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Meier, E., Gallegos, J., Thomas, L., Depp, C., Irwin, S., & Jeste, D. (2016) Defining a Good Death (Successful Dying): Literature Review and a Call for Research and Public Dialogue. The American Journal of Geriatric Psychiatry, 24(4), 261-271. DOI: 10.1016/j.jagp.2016.01.135
"Descriptive analyses indicated that prenatal exposure to maternal BPA [Bisphenol A] concentrations were related to higher levels of anxiety, depression, aggression, and hyperactivity in children. BPA exposure in childhood was associated with higher levels of anxiety, depression, hyperactivity, inattention, and conduct problems."That was the conclusion reached in the systematic review by Maede Ejaredar and colleagues , that provides one of two studies brought to the blogging table today. With the aim of looking at the current collected peer-reviewed literature on the topic of "prenatal and childhood BPA exposure" and offspring/childhood outcomes, the authors suggest that there may indeed be more to see in this area, but with the important requirement for further "Prospective cohort studies" to clarify any relationship.BPA, by the way, is a chemical of some note in modern society given its quite widespread use in plastics and related materials. Although some agencies have provided current guidance to the effect that BPA is 'safe' and poses no health risk at current levels of exposure, not everyone is so convinced by such sweeping statements about safety.Indeed to make the point, the findings reported by Meda Kondolot and colleagues  add to an existing body of scientific literature suggesting that when it comes to at least 'some' autism, there may be something of an increased biological burden of BPA present. Based on the analysis of 50+ children diagnosed with an autism spectrum disorder (ASD) and an equivalent number of asymptomatic - not autism - controls, a range of metabolites were looked for including "plasma phthalates and BPA" and compounds linked to "oxidant/antioxidant status." The authors reported that: "Plasma BPA levels of children with PDD-NOS [Pervasive Developmental Disorder-Not Otherwise Specified] were significantly higher than both classic autistic children and controls." Combined with some interesting findings potentially reflective of issues with oxidative stress in relation to their participant group, authors speculate that there may be some issues with the metabolism of things like BPA in relation to some autism. I might however also add that the chosen method of analysis of samples used by Kondolot et al - high performance liquid chromatography (HPLC) - is not the most sensitive of methods when used minus it's important detection counterpart, mass spectrometry; particularly when analysing such a complicated medium such as plasma. It implies that further, more technical investigation of samples, is perhaps required.Being careful not the fall into any 'chemophobic' traps ('chemicals' is a word that has received a bad rap in my opinion), I continue to believe that there is more to see in this area of research. I draw back from any sweeping generalisations that have been put forward with other chemicals in relation to autism (see here for example) because I'm not convinced that all autism is due to BPA or any other single compound. Anyone who follows this blog regularly knows about my fascination with plural autisms (see here) and the fact that autism rarely exists in some sort of diagnostic vacuum (see here). That also takes into account the range of 'chemical exposures' that modern-day life brings.I would however like to see further investigation on a few aspects: (i) is autism (some autism) associated with an increased exposure risk to certain chemicals? Y'know, the sort of data that is coming out of Vietnam for example (see here); and (ii) are there genetic and/or biological reasons why some people on the autism spectrum have issues with the metabolism of a range of xenobiotics? Under that last category, there are numerous examples in the literature of various compounds being elevated in terms of biological load (see here for example) combined with quite a bit of discussion about 'issues' with methods/systems for removing such compounds from the body (see here). Such findings could be just epiphenomenal to autism but could also represent something rather more central and important .There is quite a bit more science to do in this area.---------- Ejaredar M. et al. Bisphenol A exposure and children’s behavior: A systematic review. Journal of Exposure Science and Environmental Epidemiology. 2016. March 9. Kondolot M. et al. Plasma Phthalate and Bisphenol A Levels and Oxidant-Antioxidant Status in Autistic Children. Environmental Toxicology and Pharmacology. 2016. March 9. Kardas F. et al. Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder: The Role of Endocrine Disruptors in Autism Etiopathogenesis. J Child Neurol. 2016 Apr;31(5):629-35.-----------Ejaredar M, Lee Y, Roberts DJ, Sauve R, & Dewey D (2016). Bisphenol A exposure and children's behavior: A systematic review. Journal of exposure science & environmental epidemiology PMID: 26956939... Read more »
Ejaredar M, Lee Y, Roberts DJ, Sauve R, & Dewey D. (2016) Bisphenol A exposure and children's behavior: A systematic review. Journal of exposure science . PMID: 26956939
Kondolot, M., Ozmert, E., Ascı, A., Erkekoglu, P., Oztop, D., Gumus, H., Kocer-Gumusel, B., & Yurdakok, K. (2016) Plasma Phthalate and Bisphenol A Levels and Oxidant-Antioxidant Status in Autistic Children. Environmental Toxicology and Pharmacology. DOI: 10.1016/j.etap.2016.03.006
So if you are one of the bodybuilders, powerlifters, marathon runners, or just people who like to binge-eat every now and then — no judgment all you can eat pizza day is a thing I’m told telling myself — there is some bad news. If you like to preload carbs like they are the magic bullet to your workout woes, you may want to rethink it because according to a new study, it can have an acute and detrimental effect on heart function.
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Arora, P., Wu, C., Hamid, T., Arora, G., Agha, O., Allen, K., Tainsh, R., Hu, D., Ryan, R., Domian, I.... (2016) Acute Metabolic Influences on the Natriuretic Peptide System in Humans. Journal of the American College of Cardiology, 67(7), 804-812. DOI: 10.1016/j.jacc.2015.11.049
Without trying to scaremonger, it is already well known that certain anti-psychotics potentially indicated for some of the more 'challenging behaviours' associated with conditions like autism for example, carry their own important side-effects. Risperidone, one of the more commonly used medicines, has quite an extensive list of possible side-effects, some of which have been previously mentioned on this blog (see here). Increased appetite and weight gain are some of the more commonly observed side-effects.The paper by Lawrence Scahill and colleagues  indeed concluded that weight gain and increased appetite also seemed to be present in their cohort of children with autism (mean age 6.9 years) who were in receipt of risperidone for approximately 30 weeks. Worryingly, the authors reported that there was an average of about 5 kg weight gain among 97 of their cohort with "risperidone exposure" and: "At baseline, 7 patients met conventional criteria for metabolic syndrome; by Week 16, 12 additional patients were so classified." The authors suggested that: "Rapid weight gain with risperidone treatment may promote the cascade of biochemical indices associated with insulin resistance and metabolic syndrome. Appetite, weight, waist circumference, liver function tests, blood lipids, and glucose warrant monitoring."As per other posts on this blog, I'm not adverse to the selective use of medication to manage certain 'challenging behaviours' with autism in mind (see here) bearing in mind appropriate screening and 'detective work' before immediately reaching for such meds (see here). With appropriate medicines management and monitoring procedures in place, medicines such as antipsychotics (even with appropriate adjuvant therapy) can play an important role in managing symptoms and onwards positively affecting quality of life.But it is important to note that there are risks attached to such medication use and the possible benefits to the presentation of certain behaviours have to be balanced with the those risks and specifically the potential role of side-effects. The additional important focus on children - "mean age 6.9 + 2.35 years" - highlighted in the Scahill study also invites quite a lot more scrutiny. I know some people might be a little shocked that young children on the autism spectrum are being medicated in such a fashion, but other evidence has reported on the potential value of such an approach  particularly when quite extreme behaviours are present and are able to be so utterly disruptive. To tie in those findings on the presence of something like metabolic syndrome and the young age of medication recipients however, suggests that moves should continue (at a pace) towards the discovery of new methods and means of managing such behaviours without potentially setting recipients up for a lifetime of possible future health complaints.Indeed, I'll be blogging about the related results from Chen et al  soon enough.---------- Scahill L. et al. Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder. Journal of the American Academy of Child & Adolescent Psychiatry. 2016. March 7. Fung LK. et al. Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis. Pediatrics. 2016 Feb;137 Suppl 2:S124-35. Chen MH. et al. Risk of Developing Type 2 Diabetes in Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Study. Diabetes Care. 2016 Mar 22. pii: dc151807.----------Scahill, L., Jeon, S., Boorin, S., McDougle, C., Aman, M., Dziura, J., McCracken, J., Caprio, S., Arnold, L., Nicol, G., Deng, Y., Challa, S., & Vitiello, B. (2016). Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder Journal of the American Academy of Child & Adolescent Psychiatry DOI: 10.1016/j.jaac.2016.02.016... Read more »
Scahill, L., Jeon, S., Boorin, S., McDougle, C., Aman, M., Dziura, J., McCracken, J., Caprio, S., Arnold, L., Nicol, G.... (2016) Weight Gain and Metabolic Consequences of Risperidone in Young Children With Autism Spectrum Disorder. Journal of the American Academy of Child . DOI: 10.1016/j.jaac.2016.02.016
I'd like to start by making one thing abundantly clear about today's post: I am not insinuating that self-injurious behaviour (SIB) accompanying autism is solely under genetic (or epigenetic) control.As I've discussed before on this blog, there are potentially many, many reasons why SIB under the umbrella of the so-called 'challenging behaviours' occurs (see here). As and when it does happen, the onus is on those significant others to turn detective before anyone immediately reaches for something like the anti-challenging behaviour meds (see here) or indeed makes any sweeping generalisations about it 'just being part of their autism'. I say this mindful that sometimes it can seemingly be the smallest things that can trigger such episodes...The findings reported by Matthew Shirley and colleagues  (open-access) do however require some attention with the idea that certain genetic issues *might* "contribute to the etiology of SIB." The specific genetic issues under the research spotlight were copy number variants (CNVs) and authors were looking at quite a precise cohort of children/young adults diagnosed with "autism and intellectual disability with self-injurious behavior (SIB) resulting in tissue damage" (N=14). I might add that CNVs with autism and learning disability in mind have some history (see here).Based on quite a thorough work-up (including a functional behavioural assessment), researchers zoomed in on 4 children (29%) where they identified "a CNV likely to have a causal role" in SIB. I'm afraid my very limited knowledge of genetics precludes any critical discussion about the nature or role of any individual genetic issues reported but I might backtrack slightly based on something the authors write regarding 'causality': "the present findings are not able to indicate definitively that any of these variants is causal." Apparently we need to wait for more data from additional patients with the same/similar clinical phenotype before much more can be said on this issue. Indeed: "it is likely that exome or genome sequencing will greatly increase the diagnostic yield of the cohort we are studying."Perhaps just as important as the question of whether genetics plays a role in a complex behaviour pattern like SIB are the authors' observations of what might have triggered SIB in their participants. The authors talk about the results of the very important functional behaviour assessments as revealing some common themes: "SIB was multiply maintained by escape from demands and access to preferred toys... SIB was multiply maintained by access to preferred foods and access to attention... Head-banging was found to be maintained by access to preferred foods... Head-hitting, self-biting, and head-banging against hard surfaces were observed to be maintained by automatic reinforcement." What these excerpts tell me is that SIB could potentially be a communicative act, bearing in mind details of language and communication 'level' of participants are fairly scant in the Shirley paper. As I've talked about previously (see here), issues such as fatigue and setting event are also potentially important parameters when getting to the bottom of SIB and other challenging behaviours.The final question, and perhaps an important one when one realises just how extreme an effect SIB can exert (see here), is 'what can be done about reducing levels of SIB' when they present. Well, working out the hows and whys of such behaviour should be the first strategy, and can sometimes yield impressive results. Although I suggested at the beginning of this post that the 'anti-challenging behaviour meds' should be a further-down-the-list resort, there is evidence that they can be helpful for some people in some situations assuming appropriate medicines management and monitoring for potential side-effects (see here). With no medical or clinical advice given or intended, I'd also be minded to direct readers to some research looking at adjuvant therapies such as the use of N-acetylcysteine (NAC) where issues like irritability might show some connection to SIB (see here and see here) or even something of particular interest to me, the use of naltrexone (see here). More research is indicated and indeed, quite a lot more with much greater participant numbers before anyone starts on about having identified the genetics of SIB in autism...---------- Shirley MD. et al. Copy Number Variants Associated with 14 Cases of Self-Injurious Behavior. PLoS ONE. 2016; 11: e0149646.----------Shirley, M., Frelin, L., López, J., Jedlicka, A., Dziedzic, A., Frank-Crawford, M., Silverman, W., Hagopian, L., & Pevsner, J. (2016). Copy Number Variants Associated with 14 Cases of Self-Injurious Behavior PLOS ONE, 11 (3) DOI: 10.1371/journal.pone.0149646... Read more »
Shirley, M., Frelin, L., López, J., Jedlicka, A., Dziedzic, A., Frank-Crawford, M., Silverman, W., Hagopian, L., & Pevsner, J. (2016) Copy Number Variants Associated with 14 Cases of Self-Injurious Behavior. PLOS ONE, 11(3). DOI: 10.1371/journal.pone.0149646
When most of us think maggots, we probably don’t think anything good, but maybe we should start. In a proof-of-concept study, researchers have shown that genetically engineered green bottle fly (Lucilia sericata) larvae can produce and secrete a human growth factor – a molecule that helps promote cell growth and wound healing.
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Linger, R., Belikoff, E., Yan, Y., Li, F., Wantuch, H., Fitzsimons, H., & Scott, M. (2016) Towards next generation maggot debridement therapy: transgenic Lucilia sericata larvae that produce and secrete a human growth factor. BMC Biotechnology, 16(1). DOI: 10.1186/s12896-016-0263-z
Last month, we spoke of our vision of the future of humanity here at the lab. It makes sense that humanity would one-day step away from the static, non-living computer constructs we have designed. Moving us instead towards an organic alternative, one that can be readily repaired, replaced, or changed. While we cannot pretend to know what the future may hold, a new discovery helps bolster the stance we presented.
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Lampa-Pastirk, S., Veazey, J., Walsh, K., Feliciano, G., Steidl, R., Tessmer, S., & Reguera, G. (2016) Thermally activated charge transport in microbial protein nanowires. Scientific Reports, 23517. DOI: 10.1038/srep23517
'The disrupted connectivity hypothesis of autism spectrum disorders: Time for the next phase in research' went the title of the paper by Roma Vasa and colleagues .Disrupted connectivity by the way, refers to the idea that "deficiencies in the way the brain coordinates and synchronizes activity amongst different regions may account for the clinical symptoms of ASD [autism spectrum disorders]." Picture if you will, the brain as a serious of telephone wires all connecting different parts of itself and transmitting information down multiple phone lines. The idea that certain areas might be talking too little or too much to each other kinda simplistically sums up what this theory is all about .I'm not going to spend a lot of time on the Vasa paper because (a) it is an area well outside of my comfort zone (a cobbler should stick to his last and all that) and (b) the sizeable peer-reviewed literature on this topic (see here) is still a little confusing as to which areas are 'under-connected' and which areas are 'over-connected'. If one also takes into account added 'issues' such as the growing moves towards pluralising autism ('the autisms) and the fact that a diagnosis of autism rarely exists in some sort of diagnostic vacuum, the best advice I can give about the 'where next for disrupted connectivity and autism' is to cut out any sweeping generalisations. Y'know, learn from past theories trying to describe/explain autism (see here) and maybe focus in one or more individuals or subgroups, but please don't over-hype the theory. Oh, and bear in mind that whilst it is important to focus on the brain and central nervous system, the body also houses another important 'second brain' where connectivity might likewise be 'disrupted'.Said connectivity issues might not be static also (for various reasons) which opens up the associated question of 'what can be done'  about disrupted connectivity in the 'first brain' as and when identified. Indeed, one wonders whether reports on the promise of transcranial magnetic stimulation (TMS) for example  might require quite a bit more controlled investigation with at least some autism in mind with reference to connectivity. But keep in mind that intervention like TMS might not always work out the way you might want it to...---------- Vasa RA. et al. The disrupted connectivity hypothesis of autism spectrum disorders: Time for the next phase in research. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2016. March 2. Wass S. Distortions and disconnections: disrupted brain connectivity in autism. Brain Cogn. 2011 Feb;75(1):18-28. Fox MD. et al. Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS). Neuroimage. 2012 Oct 1;62(4):2232-43. Oberman LM. et al. Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Res. 2016 Feb;9(2):184-203.----------Vasa, R., Mostofsky, S., & Ewen, J. (2016). The disrupted connectivity hypothesis of autism spectrum disorders: Time for the next phase in research Biological Psychiatry: Cognitive Neuroscience and Neuroimaging DOI: 10.1016/j.bpsc.2016.02.003... Read more »
Vasa, R., Mostofsky, S., & Ewen, J. (2016) The disrupted connectivity hypothesis of autism spectrum disorders: Time for the next phase in research. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. DOI: 10.1016/j.bpsc.2016.02.003
In today’s lexicon, the term mental illness is used pretty widely. It can be used to describe someone suffering from depression, to PTSD, to even someone suicidal. In fact, today it is sort of a catch all term for anyone who is involved in a mass shooting here in the US. We are getting off […]... Read more »
Elkington, K., Teplin, L., Abram, K., Jakubowski, J., Dulcan, M., & Welty, L. (2015) Psychiatric Disorders and Violence: A Study of Delinquent Youth After Detention. Journal of the American Academy of Child , 54(4), 302-31200000. DOI: 10.1016/j.jaac.2015.01.002
Su, J., Chen, J., Lippold, K., Monavarfeshani, A., Carrillo, G., Jenkins, R., & Fox, M. (2016) Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex. The Journal of Cell Biology, 212(6), 721-736. DOI: 10.1083/jcb.201509085
Jacobs, R., Barba, A., Gowins, J., Klumpp, H., Jenkins, L., Mickey, B., Ajilore, O., Peciña, M., Sikora, M., Ryan, K.... (2016) Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder. Psychological Medicine, 1-13. DOI: 10.1017/S0033291715002615
Dowell, N., Cooper, E., Tibble, J., Voon, V., Critchley, H., Cercignani, M., & Harrison, N. (2016) Acute Changes in Striatal Microstructure Predict the Development of Interferon-Alpha Induced Fatigue. Biological Psychiatry, 79(4), 320-328. DOI: 10.1016/j.biopsych.2015.05.015
Li, W., Lai, T., Bohon, C., Loo, S., McCurdy, D., Strober, M., Bookheimer, S., & Feusner, J. (2015) Anorexia nervosa and body dysmorphic disorder are associated with abnormalities in processing visual information. Psychological Medicine, 1-12. DOI: 10.1017/S0033291715000045
Vita, A., De Peri, L., Deste, G., Barlati, S., & Sacchetti, E. (2015) The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies. Biological Psychiatry, 78(6), 403-412. DOI: 10.1016/j.biopsych.2015.02.008
I'm a fan of the idea that the categorical labelling system currently used in psychiatric and psychological circles probably isn't fit for purpose these days. Y'know, the idea that compartmentalising people into diagnostic boxes with an overarching title whilst useful for general identity and statistical classification, does little to inform about individual experiences or the important cross-over in presentation between and across different labels. Don't even get me started on how the use of such all-encompassing labels have probably hindered as much as helped research on these important presentations.The continued moves towards 'pluralisation' with autism (see here) or schizophrenia (see here) in mind reflect the strength of feeling in this area and how reform might be needed. This is probably also why RDoC has continued its rise (and rise).The paper by Katherine Musliner and colleagues  continues the idea that heterogeneity in the presentation of psychiatric or behavioural conditions might be good evidence for plural conditions, this time with depression in mind. With the aim to "characterize patterns and correlates of 10-year course trajectories of MDD [major depressive disorder]" researchers relied on data from one of those oh-so-useful Scandinavian registries - "The Danish Psychiatric Central Research Register (DPCRR)." With participant numbers in the thousand (~11,000) diagnosed with MDD, researchers followed participant records for 10 years after their initial MDD diagnosis. They looked at various variables including "past-year inpatient, outpatient, or emergency contact at a psychiatric hospital" as a primary 'response variable' and other details around "previous record of suicide attempt or self-harm, severity of the initial MDD diagnosis (mild, moderate, severe without psychotic features, severe with psychotic features, and severity unspecified), and parental records of psychiatric diagnoses in the DPCRR (unipolar depression, bipolar disorder, schizophrenia and related disorders, substance abuse, and anxiety or somatoform disorders)." Further reading about the study aims and findings can be found in an accompanying editorial .Results: bearing in mind that researchers excluded individuals with other diagnoses such as bipolar disorder or schizophrenia from the analysis, four primary classes of trajectory were noted based on that primary response variable dealing with contact with psychiatric services: "brief contact (77.0%), prolonged initial contact (12.8%), later reentry (7.1%), and persistent contact (3.1%)." It is perhaps pleasing to see that for the majority of people diagnosed with MDD, their experiences of the condition were either ones of recovery or movement to care from other healthcare providers outside of specific psychiatric services as a consequence of their membership of the grouping 'brief contact'. Although including a much smaller percentage of people, the trajectory described by the grouping 'persistent contact' potentially reflects a type of MDD that is perhaps less treatment responsive and more chronic in terms of its presentation. The authors also suggest that this finding "suggests that a large proportion of specialized MDD treatment goes to a small proportion of cases."Insofar as the other variables potentially linked to the classes of trajectory, a few notable observations emerged from the data. So: "severity of the first diagnosis was most strongly associated with trajectory class membership: the more severe the first diagnosis, the higher the probability of a more severe 10-year trajectory." Sex/gender was also a potential correlate in that: "Female sex was most strongly associated with membership in trajectories characterized by prolonged contact."Familial psychiatric history also revealed some potentially interesting correlates such that: "different psychiatric diagnoses in parents were associated with different MDD trajectory patterns in offspring." Picking out one or two details, researchers observed that those participants with a parental history of depression were for example, more likely to belong to the 'later re-entry' group. A family history of a primary psychotic disorder often led to categorisation in the 'persistent contact' grouping and onwards a more chronic disease course with a greater likelihood of poor treatment response.Cumulatively, these findings provide good evidence that trajectory in MDD is diverse and potentially associated with various different factors including sex and parental experiences of mental illness. Further the authors note: "Different psychiatric disorders in parents are associated with different MDD trajectory patterns in their offspring, which suggests that observable heterogeneity in the course of MDD may reflect differences in the genetic underpinnings of the disorder." I'd be minded to suggest that science should continue to be wide-ranging in light of the 'heritability' aspect indicated (including the idea that structural genomics might not be the be-all-and-end-all of any relationship) but the Musliner findings do perhaps add to the increasingly louder calls for an overhaul of the way we categorise mental health. Oh, and the idea that psychiatric/behavioural diagnoses can be 'remitting' at a clinical descriptive level is something else we should be willing to take on board more generally, even if it does mean challenging dogma (see here).Now, if one assumes that there may be various 'types' of depression, how about entertaining the idea that treatment-wise we might need to look to wider bodily functions such as that related to the immune system at least for some people? It has been mentioned before y'know...---------- Musliner KL. et al. Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder. JAMA Psychiatry. 2016. March 2. Shelton RC. The Course of Illness After Initial Diagnosis of Major Depression. JAMA Psychiatry. 2016. March 2.----------Musliner, K., Munk-Olsen, T., Laursen, T., Eaton, W., Zandi, P., & Mortensen, P. (2016). Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2015.3365... Read more »
Musliner, K., Munk-Olsen, T., Laursen, T., Eaton, W., Zandi, P., & Mortensen, P. (2016) Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2015.3365
"Mental disorders have become the most common cause of receiving benefits, with the number of claimants rising by 103% from 1995 to 1.1 million in 2014. Claimants with other conditions fell by 35%."The findings reported by Sebastião Viola & Joanna Moncrieff  (open-access) provide stark evidence of both how prevalent mental illness is these days, and the financial implications of such illness to both the individual and more generally society.Set within the context of some pretty inflammatory language being used to describe those claiming benefits (see here) and the continued saga that is austerity in the UK (see here), I would hope that the Viola/Moncrieff results might serve to further illustrate the increasing parity (of esteem) between physical illness and mental illness insofar as the burden they can both inflict. For too long now, the focus on physical health has perhaps been at the expense of mental health (see here). I'd also hope that such findings might also serve to help 'de-stigmatise' some of the circumstances leading someone to claim for such benefits.Drawing on data "from the Department for Work and Pensions [DWP] regarding numbers of claimants of all sickness and disability-related benefits in England, Scotland and Wales" (UK), researchers looked at the 'significant' causes for claims recorded. For those not familiar with the UK welfare system, some background can be found here. Taking into account how the benefits system has changed somewhat over recent years, researchers reported on various trends noted from the data including those related to long-term benefit claims (more than 5 years) and claims according to age, gender and regional distribution.Results: the general trend in claiming sickness benefit was one of a decline between 1995 and 2014. When however, breaking down the statistics according to "causal categories of medical condition" the authors reported that 'mental disorders' were by far, the most common cause of claims awarded: "rising by 103.4% over the period examined to over a million in 2014 (from 571 600 in 1995 to 1 136 360 in 2014)." Claims based on the previous most common category - musculoskeletal disorders - dropped by about 40% over the same period. The authors note: "By 2014, almost half of claimants were claiming benefits for a mental disorder, up from 21.4% in 1995 to 46.5%."Analysis of long-term claimants also showed a similar trend insofar as the impact of mental illness. So: "Numbers of long-term claimants for mental disorders rose by 87.4% from 346 770 in 2000 to 649 990 in 2011 and numbers with all other conditions rose by only 0.79% (from 826 910 to 833 480)." Trends by gender (sex) suggested an equalisation between males and females. The authors also noted some geographic changes in the data: "The proportion of mental disorder claims was highest in London and southern regions in 1995, and in Scotland in 2014." Interestingly too: "areas traditionally associated with industrial decline, such as Wales, the North East and the North West, did not show particularly high proportions of mental disorder claims compared with other areas."Drilling down into the details of what constituted a 'mental illness', the authors reveal some interesting trends in relation to claims. Depression or depressive disorder is consistently shown to be the most frequent 'category of disorder' (circling around the 40% mark of total mental illness claimants for 1999 and 2014). Anxiety and related conditions is the second most frequently cited category; between them and depression capturing 65-75% of the total claims with mental disorders mentioned. The authors also make an interesting point about claims appearing under the category of 'learning disability' including "Pervasive Developmental Disorder" (PDD). Although the total number of claims increased in this category - ~87,000 in 1999 and ~125,000 in 2014 - there was only a small change registered as a percentage of the 'total mental disorder claimants' between the years. I know some people might um-and-ah about the descriptors used to code PDD and other developmental disorders (including use of the words 'mental retardation' in the same category) but those are the codings specifically used by the DWP not my own.Viola & Moncrieff provide some important discussions about their findings and the context they are presented in. The ideas, for example, that "regions of high unemployment and economic inactivity" or "the recent economic recession" somehow correlate with claims for state benefits as a result of mental illness don't generally hold true on the basis of the presented data. I would however soften those words by pointing out that austerity may very well exert a psychiatric toll on a person if one accepts that the quite alarming suicide statistics we've seen recently (see here) are not solely down to just social factors."Evidence from the UK suggests a modest increase in the reported prevalence of common mental disorders since the early 1990s, but this is not large enough to account for the increase in disability claims, and may represent increasing recognition and identification of such disorders as much as their actual occurrence." With this statement, the authors tap into how stigma associated with mental health problems might be decreasing, as more people feel comfortable talking to others about their issues and how this might be reflected in the claimant figures. They also take a bit of a jab at the 'effectiveness' of pharmacotherapy used to treat/manage such mental health issues: "The increasing use of all types of drugs for mental disorders, and especially antidepressants, in England since the 1990s does not appear to have ameliorated the rising trends in disability claims for these conditions." I'll say nothing more on this point.The final words of this rather long post are reserved for what potentially might impact on disability benefit claims in the context of mental health issues, specifically with employment in mind. The authors note that "the provision of suitable employment opportunities where health and mental health-related limitations are accommodated" might be one model to look to with further research required. I'd agree that a caring workplace should be an important part of the strategy to reduce the numbers of claimants and provide the various positive opportunities that accompany work. I am however a little cautious about any 'one-size-fits-all' approach to accomplishing this, as lessons from specific labels covered by the Viola/Moncrieff paper come to mind (see here). And on the topic of employment and autism, I might also divert your attention to a much needed piece on why we perhaps shouldn't get too excited about 'autism employment initiatives' just yet (see here)...Finally, although not wishing to mix science and politics too much, the recent news that a certain gentleman (quiet man?) has quit his post here in Blighty because of "pressure to make cuts to disability benefits" seems to be oddly relevant to discussions today.---------- Viola S. & Moncrieff J. Claims for sickness and disability benefits owing to mental disorders in the UK: trends from 1995 to 2014. British Journal of Psychiatry Open. 2016; 2: 18-24.----------... Read more »
Viola, S., & Moncrieff, J. (2016) Claims for sickness and disability benefits owing to mental disorders in the UK: trends from 1995 to 2014. British Journal of Psychiatry Open, 2(1), 18-24. DOI: 10.1192/bjpo.bp.115.002246
It was a clear case of a false alarm, toxoplasmosis, a parasite that infects mice and cats was thought to have an effect on humans. However, after a thorough review of the data it was off the hook, or so we thought. Individuals with a psychiatric disorder involving recurrent bouts of extreme, impulsive anger--road rage, for example--are more than twice as likely to have been exposed to a common parasite than healthy individuals with no psychiatric diagnosis.
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Coccaro, E., Lee, R., Groer, M., Can, A., Coussons-Read, M., & Postolache, T. (2016) Toxoplasma gondii Infection: Relationship With Aggression in Psychiatric Subjects. The Journal of Clinical Psychiatry, 334-341. DOI: 10.4088/JCP.14m09621
"The present study shows that intragastric treatment of mice with an antibiotic mix impairs novel object recognition, but not spatial memory. This behavioral change is associated with a disruption of the microbial community in the colon, distinct alterations of the colonic and circulating metabolite profile and particular changes of neurochemical brain activity."Those were the headlines attached to the paper published by Esther Fröhlich and colleagues  (open-access available here) who put further scientific flesh on the bones of the suggestion that those trillions of wee beasties (the gut microbiota) that call our gastrointestinal (GI) tract home, might be doing some much more than helping us digest our food or producing the odd nutrient or two. I say 'our' but should however point out that this was a study of mice not people.Not content with the current evidence pertinent to establishing "causality in gut microbiota-brain relationships", researchers devised a plan to study various aspects of the effects of "antibiotic-induced gut dysbiosis" looking at the effects of an antibiotic mix on "(i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior." All this carried out in adult mice, some of whom were given an antibiotic mix consisting of "ampicillin..., bacitracin..., meropenem..., neomycin... and vancomycin" who were then put through their paces with regards to a series of mouse cognitive tests before being sacrificed and further investigations carried out on their brain, blood and GI tract. I'll hasten to point out that I can't think of many typical occasions when such a combination of antibiotics together would be administered to people, so bear that in mind.Results: well, first and foremost, authors were largely able to rule out any direct effect from the antibiotics themselves on brain function as a consequence of not detecting any metabolites of the antibiotics in the brains of those brave mouse participants. This despite the fact that "ampicillin had some oral bioavailability." Next, and as expected, the antibiotic mix "vigorously changed the microbiome." If you want some background on this, have a look at the interesting discussion piece on 'swallowing a grenade' from a while back (antibiotics not real grenades!). Researchers also reported that as a consequence of the disruption of normal gut bacterial service following antibiotic use, there was a shift in the types of metabolites produced by the surviving gut bacteria. So: "the levels of the short-chain fatty acids (SCFA) acetate, butyrate and propionate as well as of trimethylamine, adenine and uracil were significantly diminished by antibiotic treatment." This harks back to my opening sentiments about gut bacteria doing more than just helping digest food.Next: "Antibiotic-treated mice had a significantly lower memory index than vehicle-treated mice."Vehicle-treated refers to those who did not receive the antibiotic mix. But, whilst one aspect of memory - novel object recognition - seemed to have been affected by antibiotic receipt, other aspects were seemingly not. The authors go on to report that various "neurochemical alterations" might be linked to the cognitive results reported including changes to "tight junction proteins, brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 2B, serotonin transporter, NPY system and corticosterone."These are interesting findings and, as the authors conclude: "add to the understanding of the microbiota-gut-brain axis and highlight the potential and limitation of antibiotic-induced gut dysbiosis as model system to probe causality in the interaction between gut microbiota and brain." Accepting that there is a significant level of 'hype' around the possibility of a bacteria-gut-brain axis, this type of science is a welcome addition to the peer-reviewed literature and cries out for further independent replication.Ideally, I would like to see a lot more research looking at the potentially important links between gut bacteria and behaviour in human participants. Obviously I'm not talking about dissecting people in the same way that Fröhlich et al sacrificed their mice, but I'm sure other study designs and methodologies could be introduced minus the need for death. Certainly the application of metabolomics to antibiotic use research could be quite revealing. Harking back to other research talking about toddler temperament potentially *correlating* with gut bacteria (see here) or even the extremes of psychosis appearing alongside acute urinary tract infection (see here), there are plenty of research avenues to pursue. The suggestion that recurrent antibiotic exposure might play some role in the experience of depression and/or anxiety (see here) would also seem to be as good a starting point if any when it comes to moving from mouse studies to human studies. Oh, and I'd minded to say that we might also want to look at gut barrier function too (see here)...---------- Fröhlich EE. et al. Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication. Brain Behav Immun. 2016 Feb 23. pii: S0889-1591(16)30040-X.----------Fröhlich EE, Farzi A, Mayerhofer R, Reichmann F, Jačan A, Wagner B, Zinser E, Bordag N, Magnes C, Fröhlich E, Kashofer K, Gorkiewicz G, & Holzer P (2016). Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication. Brain, behavior, and immunity PMID: 26923630... Read more »
Fröhlich EE, Farzi A, Mayerhofer R, Reichmann F, Jačan A, Wagner B, Zinser E, Bordag N, Magnes C, Fröhlich E.... (2016) Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication. Brain, behavior, and immunity. PMID: 26923630
Think your DNA is all human? Think again. And a new discovery suggests it’s even less human than scientists previously thought. Nineteen new pieces of non-human DNA — left by viruses that first infected our ancestors hundreds of thousands of years ago — have just been found, lurking between our own genes.
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Wildschutte, J., Williams, Z., Montesion, M., Subramanian, R., Kidd, J., & Coffin, J. (2016) Discovery of unfixed endogenous retrovirus insertions in diverse human populations. Proceedings of the National Academy of Sciences, 201602336. DOI: 10.1073/pnas.1602336113
Some poisons are better known than others.Arsenic, for example, is famous for its participation in many a murder and suicide from the Middle Ages through to the mid-19th century (after which it became easier to detect and more difficult to acquire). Even to this day, the malicious metalloid remains in the public eye as a contaminant of groundwater in parts of South Asia and of soil in old orchards.A decidedly more obscure poison is a gooey industrial derivative of coal tar (leftovers from converting coal to coal gas) by the name of tricresyl phosphate (TCP). Over the course of the 20th century, up to 60,000 people across the globe ended up with nerve damage after ingesting foods, drinks, or medicines laced with this toxic substance. It's historically been added to plastics such as PVC to ensure their plasticity, to lubricants and hydraulic fluids to boost their effectiveness at high temperatures and pressures, and to gasoline to help ensure any engines it fuels will run smoothly.Other things you can make with coal tar (Source)While its name specifically refers to three similar compounds (isomers), which contain the same number of atoms but are arranged slightly differently, industrial preparations of TCP tend to be mixtures of many different aryl organophosphates. Some of these are toxic to our nervous system. Back in the day, the isomer tri-ortho-cresyl phosphate was thought to be the principal neurotoxic constituent, but it's now known other parts of the mixture are just as good at making people ill.If it gets inside your body, TCP sets about inhibiting ester-breaking enzymes associated with your nerves, causing them to malfunction. Insecticide and nerve gas organophosphates (e.g. parathion and sarin) harm people by turning off the enzyme acetylcholinesterase, flooding nerve endings with overwhelming amounts of the neurotransmitter acetylcholine and thus disrupting our ability to control when our muscles contract and relax. Although constituents of TCP are known to inhibit acetylcholinesterase, their toxicity is primarily due to them inhibiting another esterase known as neuropathy or neurotoxic target esterase. By inactivating this enzyme, a bunch of biochemical changes take place over a week or two via which damage is inflicted on the brain, spinal cord, and peripheral nerves. This is known as organophosphorus-induced delayed neuropathy.Ingesting a liquid contaminated with TCP initially results in an upset stomach (nausea, vomiting, diarrhea, and abdominal cramping). I'm guessing this is due to the inhibition of acetylcholinesterase and subsequent stimulation of acetylcholine receptors in the smooth muscle of the small intestine, causing it to ramp up peristalsis. After a delay of a week or two, a poisoned person's arms and legs start to ache and feel numb and weak (this usually starts in the feet, then moving up to the lower legs and forearms/hands). Within another week or so, this can progress to paralysis. Complete recovery is possible for mild cases, but usually takes several years. Some people end up with permanent nerve damage.Our poisoning journey begins at the very end of the 19th century. French doctors, seeking an effective treatment for pulmonary tuberculosis (still one of the major causes of death in Europe at the time), decided to try giving their patients a substance called phospho-creosote. Instead of helping to fight the bacterial infection in their lungs, the liquid caused some of the patients to develop peripheral nerve inflammation (polyneuritis). It turns out phospho-creosote contains many of the same neurotoxic compounds found in TCP.Moving forward a couple of decades, the largest ever outbreak of TCP poisoning bloomed across the Midwestern and Southwestern United States in the spring of 1930. This was well into the time of Prohibition (it ended in 1933), so black market alcoholic beverages were all the rage. One of the popular spirits was Jamaica ginger extract (also known as fluid extract of ginger or jake), a medicine that conveniently happened to be a >50% solution of ethanol. Tragically, a portion of the 1930 batches somehow became adulterated with TCP. Up until that time, jake had been prepared using, among other things, castor oil. It's thought a manufacturer out of Boston decided to swap the castor oil with TCP (specifically a preparation known as Lyndol), perhaps to save money. As the year drew to a close, some 15-20 thousand people had been affected by the bad booze (the vast majority survived), their illness having acquired the name 'Jamaica ginger paralysis'.Only a year later, several dozen cases of paralysis were reported in the Netherlands among women who took a substance called apiol in an attempt to terminate their pregnancies. Apiol is an extract (essential oil) of parsley with a long history of use as an abortifacient and a treatment for menstrual cramps. Testing revealed the apiol taken by the women contained a substantial amount (28-50%) TCP. It's not known why it was there, but perhaps it was used to water down the apiol. Similar poisoning cases were also reported at the time (1931-32) in Germany, France, Switzerland, and Yugoslavia.A pot of parsley (Source)In 1937, TCP was responsible for an outbreak (68 people affected) of nerve damage in Durban, a port city in South Africa. This was traced back to a soybean cooking oil (Bestol superfine cooking oil, to be precise), which had been shipped from England in large drums previously used to store an industrial liquid containing TCP. The contaminated cooking oil also made its way on board a cargo ship, the Jean LD, which stopped in at Durban for a week. It caused three-quarters of the ship's crew to become ill. A second smaller outbreak affecting 11 people occurred in 1955. In this instance, poisoning resulted from the storage of drinking water in drums formerly filled with TCP. The drums had been obtained from a paint factory by some of the people employed there.During WWII, a shortage of animal- or plant-derived edible fats and oils in Germany caused some of its citizens to make the unfortunate decision to cook their food using industrial oils derived from fossil fuels. These included torpedo oil and machine gun oil, both of which contained substantial amounts of TCP. As an example, factory workers in Münster became ill after bringing home oil from work and using it to fry up potato pancakes. It's not known just how many people were affected in Germany, but the Nazis did appear to be concerned about the problem, instructing factory medical officers to educate workers about the dangers of cooking with industrial oils. Similar poisonings also occurred in Switzerland and England during the war. The illness only went away once edible oils and fats again became widely available.Fifty years after it transpired, a mysterious outbreak of paralysis in WWII-era Italy was attributed to TCP. In 1942, several dozen people living or working at a farm in Saval (on the outskirts of Verona) became ill. At the time, this illness was suspected to be the work of an infectious virus. Then, in 1994, a paper was published in which the authors reported they had examined still-paralyzed survivors of the outbreak and concluded it was likely the result of TCP poisoning. After talking to survivors and sifting through the literature, they proposed that exposure occurred via the consumption of vegetables grown in contaminated soil on the farm. At the time of the outbreak, farm workers collected old drums and tins for recycling. Some of these likely came from a nearby military truck depot, and so included residual amounts of TCP-containing engine oil. As part of the recycling process, the containers were emptied out onto the ground before being pressed into blocks, which contaminated the soil.Olive oil adulterated with TCP struck down 10,000 people over three weeks in Morocco in the autumn of 1959. Most of those who were poisoned were in the city of Meknes. They inadvertently consumed the world's worst cooking oil: A mixture of olive oil and a jet engine lubricant co... Read more »
Craig PH, & Barth ML. (1999) Evaluation of the hazards of industrial exposure to tricresyl phosphate: A review and interpretation of the literature. Journal of Toxicology and Environmental Health Part B, 2(4), 281-300. PMID: 10596299
Very possibly, is the answer to the question that titles this post on how the diagnostic borders between mitochondrial disease and chronic fatigue syndrome (CFS) might be blurred. I bring to your attention the case report published by Fernando Galán and colleagues  (open-access available here) as an example.Detailing the experiences of a 30-year old male who "appeared to meet the CDC-1994/Fukuda criteria for CFS [chronic fatigue syndrome]" and for whom 1 year of "cognitive behavioral therapy, graded exercise therapy, and antidepressants" resulted in only 'very slight improvement', authors eventually "considered the possibility of mitochondrial myopathy in this patient."Screen and you may find, is the primary lesson offered by Galán et al, as "a severe deficiency of activity in complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase) and IV (cytochrome c oxidase) below 42% and 70% of the minimum reference of control value normalized to citrate synthase activity, respectively" is reported. Combined with several variants noted in the mitochondrial genome, and "adult-onset mitochondrial myopathy, with clinical manifestation of peripheral sensory neuropathy, autonomic symptoms, and occipital neuralgia" was the eventual diagnosis. Treatment, consisting of riboflavin (100 mg 3 times per day) and thiamine (300 mg/day) was begun, and coincided with "a marked and sustained improvement." Further clinical improvement was also noted following the use of pregabalin.In these days of continued questioning about whether the suggested blanket psychological 'treatment' of CFS is actually cutting the scientific mustard (see here) I'm minded to reiterate how Galán et al were able to diagnose a biological reason as to potentially why this man was presenting with the symptoms he was. As far as I'm aware, cognitive behaviour therapy (CBT) is not normally indicated for treating mitochondrial disease and probably why it had such little effect in this case.Yes this is a single case report and it would certainly be unwise to suggest that every case of CFS or ME is due to mitochondrial issues. That being said, the work from Sarah Myhill and colleagues - 'mitochondria, not hypochondria' - has been discussed before on this blog (see here). Combined with other preliminary results (see here) and I think quite a good case for screening for mitochondrial issues is being formed as and when CFS is diagnosed. Certainly following "the appearance of new symptoms and signs" one might consider putting additional screening resources in place, and indeed probably better to do said screening before any psychosomatic explanations are assumed or acted upon.Oh, and without medical or clinical advice given or intended, the peer-reviewed literature 'around' this topic also has some other potential 'placebo-controlled' lessons to offer any interested ears (see here)...---------- Galán F. et al. Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. J Investig Med High Impact Case Rep. 2015 Sep 24;3(3):2324709615607908.----------Galán F, de Lavera I, Cotán D, & Sánchez-Alcázar JA (2015). Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. Journal of investigative medicine high impact case reports, 3 (3) PMID: 26904705... Read more »
Galán F, de Lavera I, Cotán D, & Sánchez-Alcázar JA. (2015) Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. Journal of investigative medicine high impact case reports, 3(3), 2147483647. PMID: 26904705
Why humans and other animals sleep is one of the remaining deep mysteries of physiology. One prominent theory in neuroscience is that sleep is when the brain replays memories "offline" to better encode them ("memory consolidation"). A prominent and competing theory is that sleep is important for rebalancing activity in brain networks that have been perturbed during learning while awake.
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Hengen, K., Torrado Pacheco, A., McGregor, J., Van Hooser, S., & Turrigiano, G. (2016) Neuronal Firing Rate Homeostasis Is Inhibited by Sleep and Promoted by Wake. Cell. DOI: 10.1016/j.cell.2016.01.046
"People with autism 'die younger', warns charity" went the very stark BBC headline recently.Today I'd like to bring your attention to the recent report published by Autistica titled: 'Personal tragedies, public crisis' making the headlines, highlighting how people with autism face a considerably enhanced risk of early mortality compared with the general population  (see here for my take).Although making quite sober reading and rightly using some very emotive language, I think most people would welcome this report in highlighting an issue that for too long has seemingly been 'brushed under the carpet'. I've talked about early mortality and autism a few times on this blog (see here) and how it potentially intersects with other issues such as wandering/elopement (see here) and access to appropriate medical care that takes into consideration the manifestation(s) of autism (see here). The bottom line being that for some people, autism and/or the 'effects' of autism for whatever reason, can be life-limiting as well as life-changing. I know that last sentence might not make a great autism awareness message but lives are being needlessly lost. Indeed, I wonder whether with World Autism Awareness Day approaching, that should be a primary message this year and every year...I appreciate the calls for further research on the issue of premature mortality and autism highlighted in the Autistica report and how for example, we do need to know more about the prevalence of early mortality in relation to autism here in the UK. I'm fearful however that potentially spending years (and precious monetary resources) waiting for such prevalence data to be forthcoming does little for those at risk here and now. Indeed, the more important issue of how to reduce (eradicate) the early mortality risk in relation to autism, is something that I would particularly champion and what this might mean for the way we think about autism in terms of the provision of screening and intervention and providing greater social and health support for those on the spectrum (and their families and loved ones).Epilepsy and suicide are discussed as important causes of death when it comes to autism in the published report but are not then only ones. Accepting that suicide - ideation or completed - is a complex act with many potential roads bringing a person to such a final decision (see here), one of the primary opportunities for reducing suicide risk has to be to screen for comorbid symptoms/diagnoses that might enhance such risk. Y'know, things like depression (see here) in light of where that can potentially lead; taking into account that the label depression covers quite a bit of diagnostic ground and might not always appear as expected in relation to autism (see here). Treating and/or managing symptoms of depression should then be indicated, accepting that talking- and the traditional pharmaco-therapies might not be the only tools in the intervention arsenal (see here). I might also advance the idea that a person's social environment can also influence risk of suicide; such that this should likewise be assessed and acted upon accordingly. Social attitudes and policy have to change.Epilepsy has a long history of association with autism (see here). Again, it's all about appropriate (and perhaps preferential) screening and monitoring as and when autism is diagnosed to keep an eye on symptoms pertinent to the development of epilepsy or seizure disorder. Medication can be life-saving when it comes to epilepsy but this should perhaps also come with some good medicines management including screening other parameters (see here). That quite a few 'types' of autism might actually come with epilepsy as part of the diagnostic package (see here) is worth noting in terms of receipt of a diagnosis of autism being a springboard to further screening and assessment. The idea that some of the more complementary interventions indicated for autism might also have an important impact on comorbid seizure issues outside of the label (see here) should be pointed out (with no medical or clinical advice given or intended).As uncomfortable as it might be, the idea that a diagnosis of autism elevates the risk of premature mortality provokes the questions: should science be doing more to help lessen the risk(s) of someone developing autism in the first place and/or should we be focusing greater attention on ways to 'alleviate' the more disabling - life-threatening - symptoms of the label? I've already aired some of my views on this in previous posts on the equally emotive topic of euthanasia / assisted suicide in respect to behavioural / psychiatric labels where autism has been mentioned (see here). Alongside various research suggesting that childhood behavioural issues elevate the risk of adult psychopathology and onwards poorer life outcomes (see here), childhood neurodevelopmental issues such as autism have similarly been tied to later outcomes adversely affecting quality of life (see here). In short, what happens in childhood affects what happens in adulthood. Armed with that knowledge, should we not be doing all we can in childhood as well as adulthood?Moves to increase awareness of autism - including the idea of heterogeneity - and importantly, creating a more welcoming society for people on the autism spectrum should of course remain a priority. I dare say that if more meaningful and 'sustainable' opportunities were afforded to those with autism, the risk of suicide might, for example, be lessened for quite a few who consider turning to such an extreme option. But alongside all the talk about 'celebrating autism' (to coin a term - see here) the report from Autistica highlights some very real and very raw implications attached to the diagnosis. How potentially moving autism from the (generalised) description of a 'life-long condition' to that of a potentially 'life-limiting condition' should be a call to action to ensure that a reduction of between 16 and 30 YEARS of life is no longer tolerated as and when autism is diagnosed. I'd say that represents a crisis indeed.----------&... Read more »
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