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
A novel clinical risk score developed for the acutely concussed pediatric population has a modest ability to discriminate between those at low, medium, or high risk for persistent postconcussion symptoms at 28 days.... Read more »
Zemek R, Barrowman N, Freedman SB, Gravel J, Gagnon I, McGahern C, Aglipay M, Sangha G, Boutis K, Beer D.... (2016) Clinical Risk Score for Persistent Postconcussion Symptoms Among Children With Acute Concussion in the ED. JAMA, 315(10), 1014-25. PMID: 26954410
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.
... Read more »
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
No matter how much I like modeling for the sake of modeling, or science for the sake of science, working in a hospital adds some constraints. At some point people look over at you measuring games in the Petri dish and ask “why are you doing this?” They expect an answer that involves something that […]... Read more »
Gatenby, R.A., & Gawlinski, E.T. (2003) The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models. Cancer Research, 63(14), 3847-54. PMID: 12873971
'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
Had Teresa Dzieweczynski chosen to publish her recent findings as an updated children's classic, rather than as a research paper, she could have titled it If You Give a Fish an Antidepressant. The book would probably be less charming than If You Give a Mouse a Cookie. But it would also be, unfortunately, more realistic. Our pharmaceuticals are steadily trickling into the homes of fish and other animals. And—as the hero of the original book could have told us, his house in disarray after fulf... Read more »
Dzieweczynski, T., Campbell, B., & Kane, J. (2016) Dose-dependent fluoxetine effects on boldness in male Siamese fighting fish. Journal of Experimental Biology, 219(6), 797-804. DOI: 10.1242/jeb.132761
Following a first-time lateral ankle sprain, a patient who was unable to complete the single-leg drop landing and drop vertical jump at 2 weeks post injury was more likely to be classified as having chronic ankle instability. Patient-reported outcomes at 6 months was also associated with onset of chronic ankle instability.... Read more »
Doherty C, Bleakley C, Hertel J, Caulfield B, Ryan J, & Delahunt E. (2016) Recovery From a First-Time Lateral Ankle Sprain and the Predictors of Chronic Ankle Instability: A Prospective Cohort Analysis. The American Journal of Sports Medicine. PMID: 26912285
"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
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
The Eatles have been busy munching away for the first time on a non-mammal vertebrate! Specifically, they are devouring the soft tissue remains of a White's Tree Frog (Litoria caerulea) from Grant's Farm in St. Louis, MO, named Nona.White's Tree Frog. Photo from Animal Diversity Web.Also known as the Smiling Frog, and the Dumpy Frog, this animal is fascinating. It belongs to the Hylidae family of frogs, which is an interesting group because it is united by a single morhpological character shared by all of its members (well, almost all...): claw-shaped terminal phalanges (bones of the fingers and toes). White's tree frogs are native to Australia, Indonesia, and New Guinea, and they live mostly in rainforests and coastal areas. They are usually bright green in color (before The Eatles get ahold of 'em), although the color of their skin can range from brown to light blue and even gray. These frogs are arboreal, as their name implies, and therefore their diet consists largely of insects like moths, locusts, and roaches. But that's not all! They also are known to eat other animals like spiders, worms, and even small mammals (rodents). Because their diet is varied, it is not surprising that they have multiple modes of prey capture. To capture small prey like insects, these frogs extend their sticky tongues and reel in the catch; but to capture larger prey like mice, they will pounce on their victim and force it into their mouth with their hands - much like college students devouring a pizza after a long night at the bar or Buddy the Elf...... Read more »
Boland MP, & Separovic F. (2006) Membrane interactions of antimicrobial peptides from Australian tree frogs. Biochimica et biophysica acta, 1758(9), 1178-83. PMID: 16580625
Campbell CR, Voyles J, Cook DI, & Dinudom A. (2012) Frog skin epithelium: electrolyte transport and chytridiomycosis. The international journal of biochemistry , 44(3), 431-4. PMID: 22182598
Manzano AS, Abdala V, & Herrel A. (2008) Morphology and function of the forelimb in arboreal frogs: specializations for grasping ability?. Journal of anatomy, 213(3), 296-307. PMID: 18565111
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
Different humeral elevation exercises result in different levels of scapulothoracic muscle activity. Knowledge of muscle activity levels for different exercises could help clinicians optimize rehabilitation protocols.... Read more »
Castelein B, Cagnie B, Parlevliet T, & Cools A. (2016) Superficial and Deep Scapulothoracic Muscle Electromyographic Activity During Elevation Exercises in the Scapular Plane. The Journal of Orthopaedic and Sports Physical Therapy, 46(3), 184-93. PMID: 26868896
"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 »
A new study is the first to report that the relationship between nightmares and suicidal behaviors is partially mediated by a multi-step pathway via defeat, entrapment, and hopelessness. Results show that suicidal thoughts, plans or attempts were present in 62 percent of participants who experienced nightmares and only 20 percent of those without nightmares.
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Littlewood, D., Gooding, P., Panagioti, M., & Kyle, S. (2016) Nightmares and Suicide in Posttraumatic Stress Disorder: The Mediating Role of Defeat, Entrapment, and Hopelessness. Journal of Clinical Sleep Medicine, 12(03), 393-399. DOI: 10.5664/jcsm.5592
Traumatic brain injury (TBI), also known as intracranial injury, is a substantial head injury that results in damage to the brain. This damage can cause a wide spectrum of possible health outcomes. Factors that are likely to influence neuropsychiatric outcome in TBI can be classified as pre-injury, injury and post-injury factors. Injury-related factors include a) the type of physical injury
The post Neuropsychiatric Outcomes Of Traumatic Brain Injury appeared first on UBRF: UberBrain Research Frontier.
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Arciniegas DB, Anderson CA, Topkoff J, & McAllister TW. (2005) Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatric disease and treatment, 1(4), 311-27. PMID: 18568112
Bigler ED. (2001) Distinguished Neuropsychologist Award Lecture 1999. The lesion(s) in traumatic brain injury: implications for clinical neuropsychology. Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists, 16(2), 95-131. PMID: 14590180
Bigler ED. (2007) Anterior and middle cranial fossa in traumatic brain injury: relevant neuroanatomy and neuropathology in the study of neuropsychological outcome. Neuropsychology, 21(5), 515-31. PMID: 17784800
They say that once you’ve learned to ride a bicycle, you never forget how to do it. Unfortunately for students who hope this applies to studying, they might not like new research suggesting that while learning, the brain is actively trying to forget. While this may at first blush seem like a bad thing, it actually may be useful for those suffering from PTSD.
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Madroñal, N., Delgado-García, J., Fernández-Guizán, A., Chatterjee, J., Köhn, M., Mattucci, C., Jain, A., Tsetsenis, T., Illarionova, A., Grinevich, V.... (2016) Rapid erasure of hippocampal memory following inhibition of dentate gyrus granule cells. Nature Communications, 10923. DOI: 10.1038/ncomms10923
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