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  • May 20, 2016
  • 10:50 AM

Predicting Depression Treatment Response: Machine Learning

by William Yates, M.D. in Brain Posts

Treatment of depression remains primarily an uninformed clinical process. Several effective drug and psychotherapy interventions are available. However, there is no reliable way to determine which treatment is likely to be the most effective for an individual patient.A recent study that used machine learning techniques to address this problem has been published.A research team from Yale University used clinical data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial in the U.S. I served as an investigator in the STAR*D and am happy to see this database still in use.In the current study, the research team used machine learning with a group of 164 pre-treatment variables. From this group of variables, 25 were identified as providing predictive value of response/non-response to treatment with a standard antidepressant drug citalopram.Clinical predictors of non-response included:High baseline depression severity scoresPresence of psychomotor agitation at baselineReduced energy ratings at baseline (fatigue) Predictors of depression remission included:Current employmentHigher level of educationLower scores on depression insight The research team was able to build a machine learning model that showed a 63% sensitivity and 66% specificity in prediction response to citalopram. This was statistically greater than random (chance) prediction.Addition support for their model was gained by replication in a second study of citalopram in depression.This is an important and exciting finding that suggests low-cost symptom biomarkers may aid in the treatment selection for depression.Follow the author on Twitter WRY999 HERE.Photo of sunset on Captiva Island, Florida is from my personal files. Chekroud AM, Zotti RJ, Shehzad Z, Gueorguieva R, Johnson MK, Trivedi MH, Cannon TD, Krystal JH, & Corlett PR (2016). Cross-trial prediction of treatment outcome in depression: a machine learning approach. The lancet. Psychiatry, 3 (3), 243-50 PMID: 26803397... Read more »

Chekroud AM, Zotti RJ, Shehzad Z, Gueorguieva R, Johnson MK, Trivedi MH, Cannon TD, Krystal JH, & Corlett PR. (2016) Cross-trial prediction of treatment outcome in depression: a machine learning approach. The lancet. Psychiatry, 3(3), 243-50. PMID: 26803397  

  • May 20, 2016
  • 04:30 AM

Athletes With High Baseline Concussion Symptom Scores May Need Special Considerations

by Joshua Baracks in Sports Medicine Research (SMR): In the Lab & In the Field

Athletes who report numerous concussion symptoms during baseline testing may experience greater neurocognitive impairment after a concussion than athletes who do not report baseline symptoms.... Read more »

Custer A, Sufrinko A, Elbin RJ, Covassin T, Collins M, & Kontos A. (2016) High Baseline Postconcussion Symptom Scores and Concussion Outcomes in Athletes. Journal of athletic training, 51(2), 136-41. PMID: 26885702  

  • May 20, 2016
  • 02:53 AM

On the question of valproate use and pregnancy

by Paul Whiteley in Questioning Answers

I very much want to stress the point that 'no medical or clinical advice is given or intended' on this blog before proceeding further with discussions based on the commentary paper by Richard Balon & Michelle Riba titled: 'Should Women of Childbearing Potential Be Prescribed Valproate?' [1].Valproate, as in preparations like sodium valproate, has been a particular talking point in recent years as a consequence of something of an emerging body of peer-reviewed science suggesting that its use during pregnancy may place offspring at some elevated risk for various neurodevelopmental outcomes (see here). The Medicines and Healthcare Products Regulatory Agency (MHRA) here in Blighty issued some revised guidance last year (2015) 'strengthening' warnings about the use of valproate under certain circumstances. This follows some research history on how for example, a valproic acid mouse model of autism has been used as "environmentally induced ASD [autism spectrum disorder] models in rodents" [2] for quite a few years.Balon & Riba cover various points in the debate about valproate use during pregnancy specifically focused on the known "teratogenic outcome[s]" that have been reported down the years bearing in mind that valproate serves an important (sometimes life-saving) use. I was particularly struck by the 'interference' with folic acid metabolism discussed in their commentary on the basis of some science in this area [3]. With that pinch of salt at the ready, some readers might already know that folate metabolism has some research history in autism circles (albeit not necessarily settled science) and indeed, continues to make scientific waves. Accepting that valproate might have more than one action when potential offspring outcomes are concerned (see here), I do wonder if further research focus could be directed on the folate aspect of the drug when it comes to risk of various neurodevelopmental diagnoses for example?The question of valproate use outside of the management of epilepsy is a focus of the Balon/Riba article; specifically "used in acute mania or in prophylaxis of bipolar disorder." Bearing in mind that various other medicines are available to manage these conditions and that "unplanned pregnancies are common in this population" [4] I don't think it's out of place for the authors to "recommend that the FDA and valproate manufacturers declare valproate contraindicated in women of childbearing age and issue guidelines for counseling women of childbearing potential with bipolar disorder." Indeed, NICE here in England, seem to have taken a lead on this...If in doubt, please consult with your medical physician.----------[1] Balon R. & Riba M. Should Women of Childbearing Potential Be Prescribed Valproate? J Clin Psychiatry. 2016; 77: 525–526.[2] Ergaz Z. et al. Genetic and non-genetic animal models for Autism Spectrum Disorders (ASD). Reprod Toxicol. 2016 Apr 30. pii: S0890-6238(16)30077-6.[3] Fathe K. et al. Brief report novel mechanism for valproate-induced teratogenicity. Birth Defects Res A Clin Mol Teratol. 2014 Aug;100(8):592-7.[4] Marengo E. et al. Unplanned pregnancies and reproductive health among women with bipolar disorder. J Affect Disord. 2015 Jun 1;178:201-5.----------Balon R, & Riba M (2016). Should women of childbearing potential be prescribed valproate? a call to action. The Journal of clinical psychiatry, 77 (4), 525-6 PMID: 27137420... Read more »

  • May 19, 2016
  • 11:53 AM

To Beat Sleep Apnea, Try the Didgeridoo

by Elizabeth Preston in Inkfish

People with sleep apnea are at war with their windpipes. But they might be able to get some help from a different kind of wind pipe—namely, the Australian Aboriginal instrument called the didgeridoo.

In sleep apnea, obstructed airways stop a person's breathing over and over at night. It's normal for the throat muscles to relax during sleep, but for sleep apnea sufferers this relaxation combines with other factors to make breathing impossible. Apnea leads to broken sleep, snoring, and exha... Read more »

  • May 19, 2016
  • 11:33 AM

Language Disorder in Preschoolers

by William Yates, M.D. in Brain Posts

Well-designed large population-based studies of the prevalence and correlates of learning disabilities in preschool children are rare.A research group working out of University College London has address that issues with a large study of language disorder in a group of over 7000 4 and 5 year olds in England.A stratified group of 529 children received a comprehensive assessment of language along with assessment of IQ, social, emotional and behavior function.The study found the following important points.The prevalence of language disorders in the sample was 9.9%This group consisted of 7.6% with language disorder of unknown origin and 2.3% with language disorder associated with intellectual disability or known medical conditionLanguage disorder diagnosis was linked to a wide array of other problems including failure to make academic progressA significant number of children with normal non-verbal IQ demonstrated language disorderThe authors of the study not their findings suggest that out of every classroom with 30 students, two will have significant language problems. This supports comprehensive screening early to identify these children at high-risk for academic failure.You can read more about this study in MedicalXpress HERE.The free full-text manuscript can be accessed HERE.Follow me on Twitter WRY999.Photo of children at play during sunset is from my personal collection. Norbury, C., Gooch, D., Wray, C., Baird, G., Charman, T., Simonoff, E., Vamvakas, G., & Pickles, A. (2016). The impact of nonverbal ability on prevalence and clinical presentation of language disorder: evidence from a population study Journal of Child Psychology and Psychiatry DOI: 10.1111/jcpp.12573... Read more »

  • May 19, 2016
  • 08:31 AM

Antimicrobial antenna bacteria of bee-hunting wasps

by Rosin Cerate in Rosin Cerate

For many people, including myself, a mention of the word wasp brings to mind a particular yellow and black annoyance found hovering around garbage cans in the summertime. However, as is usually the case with the natural world, wasps are far more interesting than our common experiences with them let on. To start, there are thousands upon thousands of species, not just the yellow jackets we try to avoid being stung by as we eat at a picnic table out in the park. Wasps are close cousins of bees and ants. Some live in groups, but most are loners (solitary wasps). Many wasps, as adults, feed upon sugary liquids (be they nectar, rotting fallen apples, or unfinished cans of soda). It's a whole other ballgame when it comes to their young though. Solitary wasps have a tendency to lay their eggs inside other living things, including oak trees and various insects. The larvae then feed upon their living surroundings. As many of the insects consumed by wasp larvae themselves consume plants we like to eat, look at, or make things from, wasps are a big help to us.Beewolves refer to several genera of bee-hunting solitary wasps. In addition to having an awesome name, they are involved in a neat mutually-beneficial symbiosis. Females dig underground nests in which to lay their eggs. They then go out and capture bees by injecting them with a paralytic venom, bringing them back to the nest as fresh food for their offspring. After devouring the immobilized bees, the wasp larvae encase themselves in cocoons and undergo metamorphosis. Adults emerge the following summer.Beewolf emerging from its underground nest (Source)Now, the soil surrounding a beewolf nest is typically filled with a diverse collection of bacteria and fungi, some of which are capable of infecting and killing the larvae as they hang out in their cocoons. This is particularly likely since it's fairly warm and humid inside the nest, ideal growth conditions for many microbes. To minimize the chances of infection, beewolf mothers douse their nests with a white liquid they release from glands within their antennae. These glands happen to house an antibiotic-producing bacterium belonging to the genus Streptomyces. The bacterium is taken up by the larvae as they construct their cocoons, providing protection against bacteria and fungi seeking to get inside and chow down on the immature wasps. Imaging of the outside of the cocoons has revealed they are thoroughly coated with protective antibiotics. The beewolf Streptomyces produces at least nine different antibiotics, making it difficult for disease-causing microbes to develop resistance to their collective lethal effects.That a species of Streptomyces should be producing antibiotics is of no surprise. This genus is responsible for many of the antibacterial and antifungal drugs we use to treat our infections. We isolated them from the soil in which they lived and uncovered the killer compounds they were pumping out. While we've only gained access to their antimicrobial weapons in the last hundred years, beewolves have been using Streptomyces to ward off infections for tens or millions of years now!ReferencesKaltenpoth M et al. 2014. Partner choice and fidelity stabilize coevolution in a Cretaceous-age defensive symbiosis. PNAS 111(17):6359-6364. [Full text]Seipke RF, Kaltenpoth M, Hutchings MI. 2012. Streptomyces as symbionts: An emerging and widespread theme? FEMS Microbiology Reviews 36(4):862-876. [Full text]... Read more »

Seipke RF, Kaltenpoth M, & Hutchings MI. (2012) Streptomyces as symbionts: An emerging and widespread theme?. FEMS Microbiology Reviews, 36(4), 862-876. PMID: 22091965  

  • May 19, 2016
  • 03:09 AM

Brain GABA levels and autism meta-analysed

by Paul Whiteley in Questioning Answers

The paper by Remmelt Schür and colleagues [1] provides some (brief) blogging fodder today and the observation that following a "systematic literature review and meta-analysis of 1 H-MRS studies" brain GABA levels were found to be significantly lower in cases of autism spectrum disorder (ASD) than compared to control (not autism) populations.GABA - gamma-Aminobutyric acid - has been something of interest for quite a few years in autism research circles (see here). It's particular role as an inhibitory neurotransmitter has perhaps been where the lion's share of research has been targeted, bearing in mind it's actions might extend quite a bit further [2]. Indeed, whilst the over-representation of epilepsy in cases of autism (see here) hints at a possible dual role for GABA in relation to autism, I'd be minded to suggest that far more complicated processes might also be at work for some people (see here).Schür and colleagues surveyed the peer-reviewed research literature for several developmental and psychiatric labels with measured brain levels of GABA in mind. They concluded that outside of autism, there was also some evidence for lower levels of brain GABA in those diagnosed with major depressive disorder (MDD) too (albeit those still presenting with symptoms). Further: "No significant differences in GABA levels were found in bipolar disorder, panic disorder, PTSD [post-traumatic stress disorder], and ADHD [attention-deficit hyperactivity disorder] compared with controls."Minus any sweeping generalisations about how GABA levels could be a 'uniting' feature of autism and MDD (even though there may be overlap including at a clinical level) I do find the possibility of shared physiology to be an important one. Not least because of discussions about how interventions "aimed at either autism symptoms or symptoms of depression may improve the other" [2] could very much include GABA as one of several potential clinical parameters.----------[1] Schür RR. et al. Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of 1 H-MRS studies. Hum Brain Mapp. 2016 May 4.[2] Andersen PN. et al. Associations Among Symptoms of Autism, Symptoms of Depression and Executive Functions in Children with High-Functioning Autism: A 2 Year Follow-Up Study. J Autism Dev Disord. 2015 Aug;45(8):2497-507.----------Schür RR, Draisma LW, Wijnen JP, Boks MP, Koevoets MG, Joëls M, Klomp DW, Kahn RS, & Vinkers CH (2016). Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of 1 H-MRS studies. Human brain mapping PMID: 27145016... Read more »

  • May 18, 2016
  • 09:15 AM

Ironing Out The Black Death

by Mark Lasbury in As Many Exceptions As Rules

The black plague has taken the lives of millions over the centuries. Recent evidence shows that a small number of genetic changes were required to allow Y. pestis to use fleas as a vector. This increased Y. pestis virulence in humans, and might have wiped us out if it weren't for a genetic disease called hereditary hemochromatosis.... Read more »

  • May 18, 2016
  • 07:28 AM

Why antibiotics in ointments differ from those in pills

by Rosin Cerate in Rosin Cerate

There are many ways to get a drug into a person. Two common approaches are to swallow a small soluble solid or inject a liquid into a vein, causing it to be transported throughout the body to wherever it is needed.Topical medications are those applied to a body surface, be it skin, eyeballs, or the insides of your lungs. This is usually done to deliver the drug to the particular place requiring repair (e.g. eye drops for an eye infection) while minimizing the amount of drug ending up in other parts of the body where it can cause unwanted (side) effects. Alternatively, a drug may be administered topically but in such a way to ensure it ends up all over (e.g. fentanyl transdermal patches applied to the skin to alleviate severe pain by slowing releasing the drug into the body).In the case of antibacterial ointments, the gooey greases applied to cuts and scrapes to prevent infection, the drugs they contain differ from those typically given as pills or injections. Ointments such Neosporin or the classic Triple Antibiotic Ointment tend to contain three drugs: neomycin, polymyxin B, and bacitracin. All three were originally isolated from bacteria (bacitracin has a particularly interesting origin story) and act in different ways to harm particular groups of bacteria. Together they form a potent team of bacteria killers.Triple Antibiotic Ointment still life (Source)However, none of three drugs are commonly used to fight internal infections. There are two major reasons for this. First of all, they aren't particularly adept at making their way into your bloodstream if you ingest them. In other words, they are poorly absorbed from the gastrointestinal tract. Neomycin has instead been fed to people in order to selectively target and kill off a bunch of the bacteria growing inside their guts, essentially an external internal body surface (and so still a sort of topical application).The second reason for the restricted use of these drugs is their toxicity. All three are toxic to the kidneys if they end up in the bloodstream. Neomycin also tends to cause ear damage and allergic reactions in form of contact dermatitis. Bacitracin also likes to cause allergic reactions (it's up there with penicillin as far as common drug allergies go). Funnily enough, neomycin is pretty good at killing the Gram-negative bacteria usually responsible for kidney-damaging urinary tract infections. It just happens to be a bit overzealous and can hurt the organ it should be helping to protect.Polymyxin B doesn't like the kidneys or nervous system. However, it looks as though its toxicity might not actually be too severe, so the drug has found some use as a non-topical antibacterial agent in cases where people-infecting bacteria have developed resistance to other drugs.ReferencesLeyden JJ, Bartelt NM. 1987. Comparison of topical antibiotic ointments, a wound protectant, and antiseptics for the treatment of human blister wounds contaminated with Staphylococcus aureus. Journal of Family Practice 24(6):601-604.Powell LW, Hooker JW. 1956. Neomycin nephropathy. Journal of the American Medical Association 160(7):557-560. [First page]Weinberg ED. 1967. Bacitracin. In: Antibiotics (Eds. Gottlieb D, Shaw PD). Pages 90-101. Springer. [First two pages]Zavascki AP, Goldani LZ, Li J, Nation RL. 2007. Polymyxin B for the treatment of multidrug-resistant pathogens: A critical review. Journal of Antimicrobial Chemotherapy 60(6):1206-1215. [Full text]... Read more »

  • May 18, 2016
  • 02:57 AM

Siblings of probands with autism: preferential screening suggested?

by Paul Whiteley in Questioning Answers

"Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD [autism spectrum disorder]."That was the research bottom line presented in the paper by Elina Jokiranta-Olkoniemi and colleagues [1] who extracted data from the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A). FIPS-A has been mentioned previously on this blog (see here) but this time around the aim was to look not at the various risk factors potentially associated with receipt of an autism diagnosis, but rather how siblings of those with autism might require some preferential screening for a variety of potential psychiatric and/or neurodevelopmental labels. I know that might not make great reading but burying ones head in the sand is not likely to do anyone any good.With a starting participant sample in the thousands - "31, 2005, who received a diagnosis of ASD" - researchers matched cases with asymptomatic (not autism) controls to a ratio of 4:1. "This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers." Various psychiatric and behavioural diagnoses were searched for among siblings of those with autism and compared with rates among control participant siblings. An adjusted risk ratio was generated; authors also taking into account the various ASD sub-diagnoses (many of which have been subsumed under the latest DSM-5 definition of autism).Results: as per the opening sentence, siblings of those diagnosed with autism were at a significantly increased risk of various psychiatric and neurodevelopmental outcomes. Around 10% of siblings of those with autism were diagnosed with an ASD tallying with what has been previously reported in the peer-reviewed literature on familial recurrence (see here). This compared with the similarly standard 1% of siblings of asymptomatic controls who were diagnosed with an ASD. Actually, 1% might not be the standard any longer...Other associations were also noted; so learning and coordination disorders were reported in around 15% of siblings of those with autism compared with 6% in control siblings. Similar patterns were noted with regards to attention-deficit hyperactivity disorder (ADHD) and interestingly, tic disorders too (a particular interest to this blog). The bottom line again being that siblings of those with autism might have something of an increased risk of receiving various developmental or behavioural diagnoses.The authors conclude that when it comes to discussions about aetiology, there may be some common risk factors that predispose to the various labels included for study. Of course this is not necessarily new news as per other research looking at 'overlapping' structural genetics for example (see here) and the realisation that a diagnosis of autism is by no means protective against other conditions occurring (see here). Indeed, other research published in the same journal hints at some important genetic overlap when it comes to autism and other diagnoses [2] which may be particularly relevant (see here). If there is anything that I would add to any future research agenda it would be some way of incorporating the concept of the broader autism phenotype (BAP) into proceedings (see here) and also the inclusion of more somatic diagnoses (see here) as well as neurodevelopmental and psychiatric as a means to search for overlapping variables. As for clinical practice, well to reiterate again, the implication is to potentially offer preferential screening for a variety of neurodevelopmental and/or psychiatric labels when autism appears in the family...-----------[1] Jokiranta-Olkoniemi E. et al. Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders. JAMA Psychiatry. 2016. May 4.[2] Goes FS. et al. Exome Sequencing of Familial Bipolar Disorder. JAMA Psychiatry. 2016. April 27.----------Jokiranta-Olkoniemi, E., Cheslack-Postava, K., Sucksdorff, D., Suominen, A., Gyllenberg, D., Chudal, R., Leivonen, S., Gissler, M., Brown, A., & Sourander, A. (2016). Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2016.0495... Read more »

Jokiranta-Olkoniemi, E., Cheslack-Postava, K., Sucksdorff, D., Suominen, A., Gyllenberg, D., Chudal, R., Leivonen, S., Gissler, M., Brown, A., & Sourander, A. (2016) Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2016.0495  

  • May 17, 2016
  • 02:35 PM

Nurses Frequently Attending Church Live Longer

by William Yates, M.D. in Brain Posts

The Harvard-based Nurses' Health Study has been a remarkably productive longitudinal health study.My wife has been a subject in this study and frequently completes interval questionnaires regarding her health status.A recent publication looked at the relationship between religious service attendance and mortality in the Nurses's Health Study cohort.This manuscript tried to provide a more valid look at the relationship between religiosity/spirituality and health. Previous studies have found a link between church attendance and longer life but these studies were vulnerable to reverse causation confounding.Mortality rates over a 20 year period were reduced in a scaled manner compared to those control subjects who id not attend church by the following amounts:Attends church less than once per week: 13% lower mortalityAttends church once per week: 26% lower mortalityAttends church more than once per week: 33% lower mortalityPotentially confounding factors that were controlled included diet, physical activity, smoking status and body mass index.The research team suggests church attendance rates may be a proxy for social support, a factor known to influence mortality risk.Read more about this study at the ScienceDaily website HERE.Follow me on Twitter HERE.Photo of willet birds on seashore is from the my files.Li, S., Stampfer, M., Williams, D., & VanderWeele, T. (2016). Association of Religious Service Attendance With Mortality Among Women JAMA Internal Medicine DOI: 10.1001/jamainternmed.2016.1615... Read more »

  • May 17, 2016
  • 02:43 AM

Immigrant background and risk of offspring ADHD

by Paul Whiteley in Questioning Answers

"The likelihood of being diagnosed with ADHD [attention-deficit hyperactivity disorder] was significantly increased among children of two immigrant parents... and children of an immigrant father."So said the findings published by Venla Lehti and colleagues [1] continuing a research theme from this authorship group (see here) on how immigration might, for various reasons, bring about an increased or decreased risk of certain behavioural and/or psychiatric outcomes. This time around ADHD was in the research spotlight and how analysis "based on a national birth cohort" numbering in the tens of thousands suggested there may be more to see when it comes to a diagnosis in light of parental immigration status.The records of over 10,000 children/young adults born between 1991 and 2005 and diagnosed with ADHD by 2011 were compared with matched - not ADHD - controls (n=39,124) taking into account "parents' country of birth and native language." Various other variables were added into the subsequent statistical mix including "time since maternal migration." As per that opening sentence, there did appear to be more to see when it came to immigration status and offspring outcome; where a child was born to two immigrant parents, the adjusted odds ratios were not to be sniffed at (4.7, 95% CI 3.4-6.6) insofar as an increased risk of offspring ADHD diagnosis.I was also taken by another finding reported by Lehti et al: "Children, whose parents were born in countries with low Human Development Index (HDI), were more often diagnosed with ADHD." The HDI is a sort of summary measure taking into account variables such as education, life expectancy and income ranking countries in terms of their human development. Quite a few of the countries in places like sub-Saharan Africa, North Africa and Latin America rank 'low' on the HDI and also seemed to tally with the specific data on country of origin when it came to the Lehti findings.As interesting as the current findings are, the universal idea that ADHD risk might be elevated in children of immigrant families is by no means a settled issue [2]. As per my sentiments on quite a few issues covered on this blog, sweeping generalisations are not required. I would however like to see a lot more research done on this issue focused not just on 'risk' of diagnosis but also around the possible factors that might contribute to immigrant offspring being more readily diagnosed with something like ADHD. Lehti et al suggest that their results might indicate "increased exposure to environmental risk factors, differences in the use of health services, or challenges in diagnosing immigrants' children" as being relevant. Certainly one could draw on work in other clinical areas as being potentially relevant (see here for example) to the current findings including potential biological correlates too (see here and see here).One further point that might also be particularly important to the Lehti findings: that linked to socio-economic status (SES) and how that seems to affect risk of a diagnosis of ADHD more generally (see here). Without generalising about any relationship between immigration status and SES, it is not outside the realms of possibility that at least for some migrants, entry to places like Finland where the current research was carried out, might not be accompanied by significant wealth for example. SES deprivation and ADHD diagnosis is an area of continuing interest [3]; indeed, with recent political situations in mind, one wonders whether future surveillance may be very much indicated.----------[1] Lehti V. et al. Association between immigrant background and ADHD: a nationwide population-based case-control study. J Child Psychol Psychiatry. 2016 May 2.[2] Tan TX. Emotional and Behavioral Disorders in 1.5th Generation, 2nd Generation Immigrant Children, and Foreign Adoptees. J Immigr Minor Health. 2016 Mar 14.[3] Russell AE. et al. The Association Between Socioeconomic Disadvantage and Attention Deficit/Hyperactivity Disorder (ADHD): A Systematic Review. Child Psychiatry Hum Dev. 2016 Jun;47(3):440-58.----------Lehti V, Chudal R, Suominen A, Gissler M, & Sourander A (2016). Association between immigrant background and ADHD: a nationwide population-based case-control study. Journal of child psychology and psychiatry, and allied disciplines PMID: 27133554... Read more »

Lehti V, Chudal R, Suominen A, Gissler M, & Sourander A. (2016) Association between immigrant background and ADHD: a nationwide population-based case-control study. Journal of child psychology and psychiatry, and allied disciplines. PMID: 27133554  

  • May 16, 2016
  • 11:45 PM

Acidity and vascularization as linear goods in cancer

by Artem Kaznatcheev in Evolutionary Games Group

Last month, Robert Vander Velde discussed a striking similarity between the linear version of our model of two anti-correlated goods and the Haert et al. (2002) optional public good game. Robert didn’t get a chance to go into the detailed math behind the scenes, so I wanted to do that today. The derivations here will […]... Read more »

Hauert, C., De Monte, S., Hofbauer, J., & Sigmund, K. (2002) Replicator dynamics for optional public good games. Journal of Theoretical Biology, 218(2), 187-94. PMID: 12381291  

  • May 16, 2016
  • 03:50 PM

Converting cells to burn fat, not store it

by Dr. Jekyll in Lunatic Laboratories

Researchers have uncovered a new molecular pathway for stimulating the body to burn fat -- a discovery that could help fight obesity and cardiovascular disease.By focusing on a protein known as folliculin, and knocking out the gene that produces it in fat cells, the researchers triggered a series of biomolecular signals that switched the cells from storing fat to burning it.

... Read more »

Yan, M., Audet-Walsh., Manteghi, S., Rosa Dufour, C., Walker, B., Baba, M., St-Pierre, J., Giguère, V., & Pause, A. (2016) Chronic AMPK activation via loss of FLCN induces functional beige adipose tissue through PGC-1α/ERRα. Genes , 30(9), 1034-1046. DOI: 10.1101/gad.281410.116  

  • May 16, 2016
  • 03:34 PM

Novel Borrelia Species Causes Lyme Disease with High Spirochetemia

by Pranab Chatterjee in Zoonoticus

In a recent paper in the Lancet Infectious Diseases, Pritt et al  have identified a new genospecies of Borrelia which is attributed to have caused several cases of Lyme disease, marked by a high degree of spirochetemia. In their research article abstract, they state: Methods At the Mayo clinic, from 2003 to 2014, we tested […]... Read more »

  • May 16, 2016
  • 04:30 AM

Is the Struggle Mechanical or Neurological?

by Adam Kelly in Sports Medicine Research (SMR): In the Lab & In the Field

A group of individuals with chronic ankle instability have sensorimotor system deficits compared with a group of healthy controls and copers; however, the authors found no mechanical differences between any of the groups.... Read more »

  • May 16, 2016
  • 02:40 AM

More [metabolomic] evidence for dysbiosis and some autism?

by Paul Whiteley in Questioning Answers

The paper by Xiyue Xiong and colleagues [1] (open-access available here) took my attention recently and some further evidence contributory to the idea that the trillions of wee beasties that call our gastrointestinal (GI) tract home - collectively known as the gut microbiome - might have some important links to at least 'some' autism.Describing the results of "a GC/MS based metabolomic approach"  - GC-MS being gas chromatography-mass spectrometry and metabolomic(s) being the analysis of 'small molecule metabolites found in biological fluids such as blood, saliva and urine' - the authors report results based on analysis of urine specimens for some 62 children diagnosed with an autism spectrum disorder (ASD) compared to 62 'not-autism' controls. Bearing in mind that quite a few of the compounds normally found in urine are linked to the goings-on in the gut microbiome, the authors ensured that "Children included in the study had no antianaerobic drug use history" (i.e. certain types of antibiotics were not used).Results: "Three compounds identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), 3-hydroxyphenylacetic acid (3HPA), and 3-hydroxyhippuric acid (3HHA) were found in higher concentrations in autistic children than in the controls." I was rather interested in the HPHPA finding in particular given that it has previously appeared on this blog in relation to autism and the gut microbiome (see here) following other peer-reviewed findings [2]. The watchword on that previous post was 'dysbiosis' and how alterations in the relative levels of certain gut bacterial species might have some rather intriguing outcomes [3]. The idea therefore being that the action of certain types of bacteria on the proposed starting material for HPHPA (the aromatic amino acids phenylalanine and tyrosine) might influence metabolism and lead to elevations in this metabolite. At this point I'll also refer you to some other musing on research on another aromatic amino acid (tryptophan) that might also be 'autism-relevant' (see here).Indeed to further test the idea of a gut microbial link to the elevations noted in HPHPA and related metabolites, Xiong et al provide further details: "Fifty HPHPA-positive autistic children (9/50 patients 3HPA-positive and 17/50 patients 3HHA-positive) were selected for oral vancomycin treatment at standard age-appropriate dosages (50 mg/kg/d, 30 days as one therapeutic course) followed by supplement therapy with Bifidobacterium agent (Bifidobacterium BB-12, 2 pills a day)." Use of vancomycin - a quite powerful antibiotic indicated for the treatment of 'Clostridium difficile–associated Disease' [4] among other things - is not unheard of in autism research and practice circles (see here) and this time around there were significant decreases in the levels of HPHPA and related metabolites "which indicated that these compounds may also be from gut Clostridium species." Further, when vancomycin was stopped: "3–6 months later, the concentration of HPHPA almost recovered to its initial level in 3 patients and recovered to 0.08–0.45 times their initial values in 12 patients." Authors also noted that some behavioural scores might have been affected by the use of vancomycin that could be construed along the same lines as when Sandler et al reported on the use of vancomycin with 'regressive-onset autism' in mind [5].The authors also add in some details about how "measurements of the three metabolites are strong predictors of ASDs and support the potential clinical utility for identifying a subgroup of ASDs subjects in whom disordered phenylalanine metabolism may be a salient characteristic." On this point I'm not convinced that on the basis of 60 or so children and with 3 metabolites in mind (out of the thousands that we excrete everyday influenced by all manner of 'internal' and 'external' forces) there is biomarker potential for 'all autism' just yet. I am in agreement that 'disordered phenylalanine metabolism' for a subgroup on the autism spectrum is a possibility based on the use of 'phenylalanine mopping up' compounds in other peer-reviewed work (see here) for example. But much more research is indicated...These are interesting results that, yet again, require independent replication. Because I am a bit of stickler when it comes to all-things metabolomics (especially where mass spectrometry is involved) I might be inclined to mention about how adjustment using creatinine might have issues when it comes to autism (see here) which could affect the final quantification of metabolites. I might also suggest that the GC-MS system used and the urine sample pre-treatment applied before analysis could be 'up-graded' taking into account more accurate detection methods (e.g. q-ToF mass spectrometry with liquid chromatography separation) with a greater focus on features like accurate mass.But don't let me put you off from the idea that marrying metabolomics and microbiomics could be a good autism research idea. Although on the topic of whether we might be able to 'alter' our microbiomes/metabolome in ways other than the use of potent antibiotics, the jury is still out [6] bearing in mind how diet might affect results...----------[1] Xiong X. et al. Urinary 3-(3-Hydroxyphenyl)-3-hydroxypropionic Acid, 3-Hydroxyphenylacetic Acid, and 3-Hydroxyhippuric Acid Are Elevated in Children with Autism Spectrum Disorders. Biomed Res Int. 2016;2016:9485412.[2] Shaw W. Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia. Nutr Neurosci. 2010 Jun;13(3):135-43.[3] Rogers GB. et al. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Molecular Psychiatry. 2016. April 19.[4] Shen EP. & Surawicz CM. Current Treatment Options for Severe Clostridium difficile–associated Disease. Gastroenterology & Hepatology. 2008;4(2):134-139.[5] Sandler RH. et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429-35.[6] Kristensen NB. et al. Alterations in fecal microbiota composition by probiotic supplementation i... Read more »

  • May 15, 2016
  • 03:22 PM

Brain cells that aid appetite control identified

by Dr. Jekyll in Lunatic Laboratories

It's rare for scientists to get what they describe as "clean" results without spending a lot of time repeating the same experiment over and over again. But when researchers saw the mice they were working with doubling their weight within a month or two, they knew they were on to something.

... Read more »

Djogo, T., Robins, S., Schneider, S., Kryzskaya, D., Liu, X., Mingay, A., Gillon, C., Kim, J., Storch, K., Boehm, U.... (2016) Adult NG2-Glia Are Required for Median Eminence-Mediated Leptin Sensing and Body Weight Control. Cell Metabolism, 23(5), 797-810. DOI: 10.1016/j.cmet.2016.04.013  

  • May 15, 2016
  • 08:07 AM

Hyperthermia as an Antidepressant?

by Neuroskeptic in Neuroskeptic_Discover

Getting warm has a dramatic antidepressant effect, according to a new report published in the prestigious journal JAMA Psychiatry. But is it hot science or a hot mess?

The researchers, led by Clemens Janssen of the University of Wisconsin-Madison, studied 29 people with depression who were not receiving any other treatments. Half were randomized to receive whole-body hyperthermia (WBH), using a setup which raised their core body temperature to 38.5 degrees (37 degrees is normal).

The o... Read more »

Janssen CW, Lowry CA, Mehl MR, Allen JJ, Kelly KL, Gartner DE, Medrano A, Begay TK, Rentscher K, White JJ.... (2016) Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry. PMID: 27172277  

  • May 14, 2016
  • 03:29 AM

On autism symptoms in ADHD (again)

by Paul Whiteley in Questioning Answers

Continuing a research theme (see here), the paper by Jessica Green and colleagues [1] again focuses the spotlight on how the various childhood developmental diagnoses often enjoy mingling together when it comes to their real-life presentation; real ESSENCE in action. Such overlaps can and do present challenges to diagnosticians to unpick often complicated presentations (no, your 'Am I autistic?' screen is not really a good idea) and onwards the best way forward to manage symptoms further to hopefully improving current and future outcomes.Looking at over 350 children (6-10 years old), some diagnosed with attention-deficit hyperactivity disorder (ADHD) (n=164) and some not diagnosed (n=198), researchers set about examining "the association between autism spectrum disorder (ASD) symptoms and (a) social functioning, (b) mental health, (c) quality of life and (d) sleep in children with and without attention-deficit hyperactivity disorder (ADHD)." Various measures were included for study including the Social Communication Questionnaire (SCQ) to assessing autistic symptoms.The authors concluded that: "ASD symptoms are associated with poorer functioning in children with ADHD" and that further moves should be made to both disentangle autistic features from a core diagnosis of ADHD and "potentially manage ASD symptoms in children with ADHD given that they exacerbate functional impairments in this already vulnerable group."As per the reference to other work from this group [2] these authors are kinda approaching the whole ADHD-autism link from an opposing end to that normally included on this blog (see here). You could say that it doesn't really matter whether science says that autism is over-represented in ADHD or ADHD is over-represented in autism because for those [growing numbers] where both diagnoses are received, the result is similar in terms of functioning and challenges compared to receipt of just an individual diagnosis. And without scaremongering, science is already starting to come to grips with just what that might mean (see here and see here)...----------[1] Green JL. et al. Association between autism symptoms and functioning in children with ADHD. Arch Dis Child. 2016 Apr 26. pii: archdischild-2015-310257.[2] Green JL. et al. Autism spectrum disorder symptoms in children with ADHD: A community-based study. Res Dev Disabil. 2015 Dec;47:175-84.----------Green JL, Sciberras E, Anderson V, Efron D, & Rinehart N (2016). Association between autism symptoms and functioning in children with ADHD. Archives of disease in childhood PMID: 27117836... Read more »

Green JL, Sciberras E, Anderson V, Efron D, & Rinehart N. (2016) Association between autism symptoms and functioning in children with ADHD. Archives of disease in childhood. PMID: 27117836  

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