The paper by Jennifer Jaskiewicz and colleagues  recently offered a further important insight into the relationship between autism and seizure or seizure disorder (i.e. epilepsy).Based on the examination of records of nearly 50,000 children and young adults diagnosed with an autism spectrum disorder (ASD) compared with approximately quarter of a million 'not-autism' participants, authors reported some interesting trends. Concluding that some 19% of participants with autism experienced "some kind of seizure or seizure disorder", the study in particular reaffirms something of an important relationship between [some] autism and [some] epilepsy or seizure disorder.Drawing on data derived from the US Military Health System database between 2000-2013, the records of children and young adults aged 0-18 years were the focus of analysis, where those with autism were age and sex-matched with asymptomatic (not autism) controls. Alongside the heightened risk of a general description of 'seizure or seizure disorder' in the autism group, authors also reported that specific issues such as status epilepticus and absence seizures were over-represented in the autism group. Febrile seizures - seizures that accompany fever - were also over-represented in the autism group although to a slightly lower extent than other seizure types. The authors conclude that: "Rates of epilepsy in children with autism are vastly increased in a wide variety of seizure types, known to have different etiologies, genetic and otherwise." Compare also the estimate of epilepsy or seizure disorder shown here with other population figures  and you get a flavour for how advanced the risk might be...---------- Jaskiewicz J. et al. Quantification of Risks of Seizure in Autism. Neurology. 2016; 86: suppl. S32.003. Russ SA. et al. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012 Feb;129(2):256-64----------Jennifer Jaskiewicz, Apryl Susi, Elizabeth Hisle-Gorman, David Dennison, Gregory Gorman, Cade Nylund, & Christine Erdie-Lalena (2016). Quantification of Risks of Seizure in Autism Neurology... Read more »
Jennifer Jaskiewicz, Apryl Susi, Elizabeth Hisle-Gorman, David Dennison, Gregory Gorman, Cade Nylund, & Christine Erdie-Lalena. (2016) Quantification of Risks of Seizure in Autism. Neurology. info:/
In my last post I reported on the use of machine learning to aid in predicting response to depression treatment.Another interesting depression prediction tool is being investigated in a trial in England funded by the Oxford Health NHS Foundation Trust.This trial uses a visual facial recognition tool. The hypothesis is that early antidepressant action can be identified by changes in facial emotional recognition.This trial stems from work by Catherine Harmer Ph.D. from the University of Oxford. Her work in this area is highlighted in the free full-text manuscript citation at the end of this post.In this full-text manuscript the authors review research suggesting antidepressants drug action may be due to the direct effect on emotional processing. Clinicians know that clinical recognition of an antidepressant response may take six weeks for a single antidepressant drug. It may be even longer if dosage escalation is needed to test a specific drug.Facial emotional recognition is a potential earlier marker of antidepressant response. In the review cited below, facial recognition changes as early as two weeks have predicted a positive drug response.Antidepressant drugs appear to alter emotional processing in healthy non-depressed adults. This may allow for wider screening of new investigational antidepressant drugs.You can read more about the NHS trial at MedicalXpress HERE.Click on the PMID link in the citation below for a link to the free full-text review.Image of limbic system known to be involved in emotional processing is my screen shot from the iPad app 3D Brain.Follow me on Twitter HERE. Pringle A, & Harmer CJ (2015). The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment. Dialogues in clinical neuroscience, 17 (4), 477-87 PMID: 26869848... Read more »
Pringle A, & Harmer CJ. (2015) The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment. Dialogues in clinical neuroscience, 17(4), 477-87. PMID: 26869848
I have quite a bit of time for the various members of the Stanley Division of Developmental Neurovirology at Johns Hopkins on this blog. Not least because of the interesting work of one researcher in particular - Emily Severance - as a name behind some potentially very important research on how food, infection and immune function might come together in complicated conditions such as [some] schizophrenia and [some] bipolar disorder (see here and see here).Continuing their 'gut-brain' theme (oh, yes) new research from Prof/Dr Severance and colleagues  has been published observing that "sex-specific C. albicans immune responses were evident in psychiatric disorder subsets." C. albicans refers to Candida albicans, a fungus that I'm sure most people will have heard of at one time or another if not only as a function of those TV adverts for preparations to combat C. albicans when tied into yeast infection.On this most recent occasion, researchers were testing the idea of "C. albicans as a new candidate infectious disease target for studies of schizophrenia and bipolar disorder" as a extension of other research talking about 'bacterial dysbioses' potentially contributing "to C. albicans overgrowth by failing to provide the competition needed to keep the fungus in check." If you're furrowing your brow about the thought that the trillions of wee beasties that call us home (the gut microbiome) might exert an effect on behavioural or psychiatric presentation, relax yourself slightly: interest is growing in this area  following on from other investigations in other areas (see here).So, researchers: "measured and compared IgG antibodies directed against this fungus in two psychiatric cohorts: one composed of 261 people with schizophrenia, 270 with bipolar disorder and 277 individuals without a history of psychiatric disorder; the other cohort was composed of 139 people with first-episode schizophrenia, 78 of whom were antipsychotic naive." They also examined cognitive symptoms and took into account various factors that might act as confounders onwards to the idea that IgG antibodies to C. albicans *might* be considered a risk factor for either schizophrenia or bipolar disorder.Results: well it wasn't as straight-forward as blanket saying that the presence of IgG antibodies (seropositivity) or quantitative levels of these antibodies to C. albicans equals schizophrenia or bipolar disorder (or not-schizophrenia or not-bipolar disorder). There was nothing statistically significant between the various groupings in the cohorts included for study. But... when the groups were categorised according to sex (gender), researchers reported "significant elevations of C. albicans IgG in males with schizophrenia and bipolar disorder compared with male controls."Further analyses suggested that there may be some 'associations' with other variables examined across the sexes when it came to those IgG antibodies ("females with schizophrenia who were C. albicans IgG-seropositive performed more poorly on these [cognitive] tests than did females with schizophrenia who were C. albicans IgG-seronegative or than female controls") and it appeared that antipsychotic medication use did little to impact on the findings. The bottom line: "antibodies directed against the opportunistic fungal pathogen, C. albicans, were elevated in distinct subsets of individuals with psychiatric disorders" and minus any sweeping generalisations, a research agenda incorporating brain, immune function, gut and also contents of the gut could be indicated in future study. This of course set among the idea that schizophrenia might be better represented by the more plural 'schizophrenias'.Some of the media around this study and its findings are perhaps a little 'sensational' as per the headline asking: Is a sexually transmitted yeast infection making people mentally ill? I perhaps wouldn't go as far as that at the moment given that C. albicans is present in everyone(?) and overgrowth of such a yeast is not necessarily due to sex or related activities. Yes, certain sexual diseases can manifest as psychological symptoms but an important basis of the Severance study is that intrinsic factors such as gut dysbiosis might start a chain reaction whereby C. albicans is able to flourish and becomes rather more systemic and pathogenic linked to the presentation of behavioural symptoms. Or at least that is part of the hypothesis requiring further testing...---------- Severance EG. et al. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophrenia 2016; 2: 16018. Dinan TG. et al. Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry. 2014 Dec;19(12):1252-7.----------Severance, E., Gressitt, K., Stallings, C., Katsafanas, E., Schweinfurth, L., Savage, C., Adamos, M., Sweeney, K., Origoni, A., Khushalani, S., Leweke, F., Dickerson, F., & Yolken, R. (2016). Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder npj Schizophrenia, 2 DOI: 10.1038/npjschz.2016.18... Read more »
Severance, E., Gressitt, K., Stallings, C., Katsafanas, E., Schweinfurth, L., Savage, C., Adamos, M., Sweeney, K., Origoni, A., Khushalani, S.... (2016) Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophrenia, 16018. DOI: 10.1038/npjschz.2016.18
Treating depression is kind of a guessing game. Trying to find a medication that works without causing side effects can take months, or more likely, years. However, new research demonstrates the effectiveness of ketamine to treat depression in a mouse model of the disease and brings together two hypotheses for the cause of depression.
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Ren, Z., Pribiag, H., Jefferson, S., Shorey, M., Fuchs, T., Stellwagen, D., & Luscher, B. (2016) Bidirectional Homeostatic Regulation of a Depression-Related Brain State by Gamma-Aminobutyric Acidergic Deficits and Ketamine Treatment. Biological Psychiatry. DOI: 10.1016/j.biopsych.2016.02.009
A free full-text commentary in the Lancet summarizes recent evidence of the benefit of aspirin in stroke prevention.This commentary focused on what is called secondary prevention. Secondary prevention is defined as prevention following events related to the disease in question.So secondary prevention in stroke would be reduction in stroke risk in those who have had a stroke or pre-stroke syndromes such as transient ischemic attacks (TIA).The key take-home message from the commentary by Graeme Hankey includes:Aspirin following mild stroke reduced risk of recurrent ischemic stroke by 49%In a summary of 12 trials in those with TIA or ischemic stroke, aspirin reduced risk of any further stroke by 51%, reduced risk of fatal or disabiling stroke by 66% and reduced risk of myocardial infarction by 70%Adding another agent (dipyridamole) to aspirin did not reduce stroke risk any further in 12 weeks of follow-up but did appear to add some benefit long-termActive trials of new drugs for stroke prevention are ongoing and will become available in the next several years. These interventions may provide additional secondary prevention options for clinicians and patients. Readers with more interest in this topic can access the free-full text manuscript by clicking on the citation link below.Follow me on Twitter @WRY999 HERE.Image is an iPad screenshot from the app 3D Brain.Hankey, G. (2016). The benefits of aspirin in early secondary stroke prevention The Lancet DOI: 10.1016/S0140-6736(16)30511-6... Read more »
Hankey, G. (2016) The benefits of aspirin in early secondary stroke prevention. The Lancet. DOI: 10.1016/S0140-6736(16)30511-6
It came as no surprise to me that the systematic review and meta-analysis article by Jerome Sarris and colleagues  found what it did in relation to the use of [certain] adjunctive (add-on) nutraceuticals alongside antidepressants to reduce depressive symptoms: some of them might actually be clinically useful.With no medical or clinical advice given or intended, the authors report that "adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants" might be something to consider "for improving inadequate response to antidepressants." Dr Sarris was one among many authors who contributed to the 'personal view' paper titled: 'Nutritional medicine as mainstream in psychiatry'  which was also covered a while back on this blog (see here). This latest addition to that and other opinions  which covered the peer-reviewed literature on a variety of nutrients also found something of a mixed bag of results for various other compounds including the aromatic amino acid tryptophan, zinc, folic acid and vitamin C.Quite a bit more science needs to be done in this area, not least around the hows and whys that the various preparations might exert some effect. Vitamin D has of course been covered quite a bit on this blog in relation to something like depression (see here for example) so that particular nutraceutical might already have a research head start compared to others. I'm also minded to suggest that the involvement of something like SAMe (S-adenosylmethionine) as an add-on treatment might also imply a role for epigenetic variables in relation to at least some depression . And then there is the question of who might be best responders to such nutraceutical use which implies heterogeneity and possible plural depressions...---------- Sarris J. et al. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. American Journal of Psychiatry. 2016. April 26. Sarris J. et al. Nutritional medicine as mainstream in psychiatry. Lancet Psychiatry. 2015 Mar;2(3):271-4. Sarris J. et al. International Society for Nutritional Psychiatry Research consensus position statement: nutritional medicine in modern psychiatry. World Psychiatry. 2015 Oct;14(3):370-1. McGowan PO. & Kato T. Epigenetics in mood disorders. Environ Health Prev Med. 2008 Jan;13(1):16-24.----------Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, & Ng CH (2016). Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. The American journal of psychiatry PMID: 27113121... Read more »
Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, & Ng CH. (2016) Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. The American journal of psychiatry. PMID: 27113121
Scientists have identified the trigger for immune cells' inflammatory response -- a discovery that may pave the way for new treatments for many human diseases. Immune cells play essential roles in the maintenance and repair of our bodies. When we injure ourselves, immune cells mount a rapid inflammatory response to protect us against infection and help heal the damaged tissue.
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Helen Weavers, Iwan R. Evans, Paul Martin, & Will Wood. (2016) Corpse engulfment generates a molecular memory that primes the macrophage inflammatory response. Cell. DOI: http://dx.org/10.1016/j.cell.2016.04.049
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
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?' .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"  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 . 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"  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.---------- Balon R. & Riba M. Should Women of Childbearing Potential Be Prescribed Valproate? J Clin Psychiatry. 2016; 77: 525–526. 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. 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. 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 »
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
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 »
Puhan MA, Suarez A, Lo Cascio C, Zahn A, Heitz M, & Braendli O. (2006) Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial. BMJ (Clinical research ed.), 332(7536), 266-70. PMID: 16377643
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 »
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
The paper by Remmelt Schür and colleagues  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 . 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"  could very much include GABA as one of several potential clinical parameters.---------- 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. 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 »
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
This week’s Video Tip of the Week is actually a whole bunch of videos. Although I’ll highlight one here as our tip, there are many great talks from the recent JGI Genomics of Energy & Environment meeting. Although typically we focus on specific software tools for our tips, I think this is a nice case […]... Read more »
Afshinnekoo, E., Meydan, C., Chowdhury, S., Jaroudi, D., Boyer, C., Bernstein, N., Maritz, J., Reeves, D., Gandara, J., Chhangawala, S.... (2015) Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics. Cell Systems, 1(1), 72-87. DOI: 10.1016/j.cels.2015.01.001
"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  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  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...----------- Jokiranta-Olkoniemi E. et al. Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders. JAMA Psychiatry. 2016. May 4. 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
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 »
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
"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  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 . 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 ; indeed, with recent political situations in mind, one wonders whether future surveillance may be very much indicated.---------- Lehti V. et al. Association between immigrant background and ADHD: a nationwide population-based case-control study. J Child Psychol Psychiatry. 2016 May 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. 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
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.
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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
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 »
Pritt BS, Mead PS, Johnson DK, Neitzel DF, Respicio-Kingry LB, Davis JP, Schiffman E, Sloan LM, Schriefer ME, Replogle AJ.... (2016) Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. The Lancet. Infectious diseases. PMID: 26856777
The paper by Xiyue Xiong and colleagues  (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 . 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 . 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'  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 .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  bearing in mind how diet might affect results...---------- 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. 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. Rogers GB. et al. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Molecular Psychiatry. 2016. April 19. Shen EP. & Surawicz CM. Current Treatment Options for Severe Clostridium difficile–associated Disease. Gastroenterology & Hepatology. 2008;4(2):134-139. Sandler RH. et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000 Jul;15(7):429-35. Kristensen NB. et al. Alterations in fecal microbiota composition by probiotic supplementation i... Read more »
Xiong X, Liu D, Wang Y, Zeng T, & Peng Y. (2016) Urinary 3-(3-Hydroxyphenyl)-3-hydroxypropionic Acid, 3-Hydroxyphenylacetic Acid, and 3-Hydroxyhippuric Acid Are Elevated in Children with Autism Spectrum Disorders. BioMed research international, 9485412. PMID: 27123458
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.
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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
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