"After adjustment for several confounders, longer duration of breastfeeding was independently associated with better cognitive development and with fewer autistic traits."So said the paper by Olivier Boucher and colleagues  communicating findings based on the examination of data from "the INMA Project, a Spanish multicenter birth-cohort study" (an initiative that has cropped up on this blog before).Including over 1300 children who were subject to a battery of psychometric and behavioural assessments, researchers set about examining how various scores might be 'associated' with breastfeeding patterns: "Duration of any, predominant, and exclusive breastfeeding." The results as I've mentioned, seemed to show something of a connection between breastfeeding and particularly when it came to 'autistic traits' as assessed by the Childhood Autism Spectrum Test (CAST). I'll leave readers to draw their own conclusions about the relevance of this finding. Insofar as the more general conclusion on breastfeeding potentially aiding offspring cognitive development, well, let's just say that this has previously been mentioned before in the research literature (see here).Having talked about breastfeeding in the context of autism before on this blog (see here) I don't really want to head too far into the collected literature in this area alongside the other aspects/discussions that it draws in. All I will say is that the relationship between breastfeeding patterns and offspring autism/autistic traits is not likely to be straight-forward  (few things with regards to autism research ever are) and there could even be occasions when breast milk might not be the preferred option* (see here) (*I should reiterate that I am not providing medical or clinical advice on this blog). There are, for example, a multitude of potentially confounding variables that could impact on any association between the two; not least that early manifestations of offspring autism might already be present and impacting on the ease of breastfeeding practices during the very earliest days and weeks of infancy. I'm not gonna say too much more on this topic at this time but will perhaps return to the subject in future posts.---------- Boucher O. et al. Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatr Res. 2016 Nov 15. Penn AH. et al. Breast Milk Protects Against Gastrointestinal Symptoms in Infants at High Risk for Autism During Early Development. J Pediatr Gastroenterol Nutr. 2016 Feb;62(2):317-27.----------Boucher O, Julvez J, Guxens M, Arranz E, Ibarluzea J, Sánchez de Miguel M, Fernández-Somoano A, Tardon A, Rebagliato M, Garcia-Esteban R, O'Connor G, Ballester F, & Sunyer J (2016). Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatric research PMID: 27846197... Read more »
Boucher O, Julvez J, Guxens M, Arranz E, Ibarluzea J, Sánchez de Miguel M, Fernández-Somoano A, Tardon A, Rebagliato M, Garcia-Esteban R.... (2016) Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatric research. PMID: 27846197
Shoulder taping is associated with early activation of scapular muscles; however, this only resulted in a minimal effect on shoulder kinematics. ... Read more »
Leong, H., Ng, G., & Fu, S. (2016) Effects of scapular taping on the activity onset of scapular muscles and the scapular kinematics in volleyball players with rotator cuff tendinopathy. Journal of Science and Medicine in Sport. DOI: 10.1016/j.jsams.2016.10.013
"This study does not support the hypothesis that MPH [methylphenidate] increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment."The results published by Man and colleagues  (open-access) sit right with me. I say that on the basis that previous research suggesting that attention-deficit hyperactivity disorder (ADHD) may 'prime' someone for an elevated risk of developing psychosis (see here) has potentially received some welcome substantiation. That MPH might not be the bogeyman that some people might think (see here too) is also an important part of the Man findings (minus any charges of me providing medical or clinical advice on this blog... I'm not).The Man paper is open-access but a few choice details are worthwhile mentioning:Based on data from the "Clinical Data Analysis and Reporting System (CDARS)" an initiative based in Hong Kong, researchers set about identifying those "aged 6–19 years who received at least one prescription of MPH with at least one psychotic disorder and/or hallucination diagnostic code (psychotic events) during the study period (January 2001 to December 2014)." Given that only MPH and atomoxetine are seemingly licensed in the Hong Kong for "the treatment of ADHD", the authors were able to focus specifically on MPH quite easily.Although over 20,000 patients were in receipt of MPH prescriptions, only data for 103 participants were used in the study as a result of that diagnosis of a psychotic/hallucinatory condition. Most were male and 76 out of the 103 participants had "a clinical ADHD diagnosis."Researchers looked at MPH treatment and those psychotic/hallucinatory events taking into the account timing and including "a 90-day pre-exposure period" representing a period before MPH use (see here).Results: "The primary analysis indicated no statistically significant association between MPH treatment and occurrence of incident psychotic events." But, when compared with baseline data, there did seem to be something to see during that pre-exposure period (before MPH) and incident psychotic event(s). Ergo, something other than MPH use seemed to be linked to the experience of psychosis and we therefore head back to the idea that ADHD as one reason for MPH use might have some quite profound implications for future mental health.There is still quite a bit more to do in this area as per more longitudinal research with greater participant numbers. I might also draw your attention to Table 2 of the Man paper (see here) examining other 'psychiatric comorbidities' when it came to those participants experiencing a psychotic episode. The list of potential correlates is interesting in light of other work (see here).Whilst MPH comes out of such research with more than a whiff of roses, it is perhaps important to understand that medicines, all medicines come with potential side-effects and that includes MPH. Nevertheless, the idea that the benefits of controlled use of MPH might trump the risk of serious psychiatric side-effects such as psychosis is something that needs to be said and with it, a realisation that treating/managing the signs and symptoms of ADHD early, might have more profound repercussions for those diagnosed...---------- Man KKC. et al. Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Translational Psychiatry. 2016; 6: e956.----------Man, K., Coghill, D., Chan, E., Lau, W., Hollis, C., Liddle, E., Banaschewski, T., McCarthy, S., Neubert, A., Sayal, K., Ip, P., & Wong, I. (2016). Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system Translational Psychiatry, 6 (11) DOI: 10.1038/tp.2016.216... Read more »
Man, K., Coghill, D., Chan, E., Lau, W., Hollis, C., Liddle, E., Banaschewski, T., McCarthy, S., Neubert, A., Sayal, K.... (2016) Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Translational Psychiatry, 6(11). DOI: 10.1038/tp.2016.216
I'm gonna be fairly brief today and draw your attention to yet another systematic review and meta-analysis this time looking at how "probiotic supplementation can have a positive effect on mood and psychological symptoms such as depression and anxiety."  Probiotics by the way, include a variety of bacteria and related lifeforms that are thought to confer some health advantage.The review/re-analysis by Jennifer McKean and colleagues found 7 studies on this topic in the peer-reviewed research literature, that overall "showed that supplementation with probiotics resulted in a statistically significant improvement in psychological symptoms... compared with placebo." Personally, I wasn't surprised at these findings having covered a few bits of science on probiotics and psychology before on this blog (see here for example). Some recent discussions on how probiotics might be a possible 'stress-reliever' (see here) also add to this area.I know some people are still a little sceptical of the whole 'gut-brain' thing (i.e. what goes on in the gut might have the ability to influence what goes on the grey/pink matter floating in the skull) and all the associated 'hype' that has accompanied the new science around the gut microbiota including the use of probiotics. There is lots more to do in this area; also overlapping with how other interventions may more detrimentally affect the trillions of bacteria that call us home and onwards may have 'psychological consequences' too (see here).But it is getting rather more difficult not to think that there may be some important processes at work in these times of psychobiotics ...---------- McKean J. et al. Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis. J Altern Complement Med. 2016 Nov 14. Dinan TG. et al. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013 Nov 15;74(10):720-6.----------McKean J, Naug H, Nikbakht E, Amiet B, & Colson N (2016). Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis. Journal of alternative and complementary medicine (New York, N.Y.) PMID: 27841940... Read more »
McKean J, Naug H, Nikbakht E, Amiet B, & Colson N. (2016) Probiotics and Subclinical Psychological Symptoms in Healthy Participants: A Systematic Review and Meta-Analysis. Journal of alternative and complementary medicine (New York, N.Y.). PMID: 27841940
Parkinson's disease (PD) is a progressive neurodegerative disorder estimated to affect 7 to 10 million individual worldwide.The primary mechanism for Parkinson's disease is a reduction in the neurotransmitter dopamine in the midbrain region of the substantia nigra highlighted in red in the figure.PD impairs motor and cognitive functions and leads to significant decline in psychosocial functioning.Drugs for PD can be effective in reversing and slowing the progression of the illness. However, response is often limited with relapse over time.Physical exercise appears to be an adjunctive option in the multidisciplinary treatment of PD. Martine Lauze along with colleagues in France and the U.S. recently conducted a literature review of this topic.Their review covered 106 published papers between 1981 and 2015. A total of 868 outcome measures were examined. The key findings from their review included:Physical activity is most effective in improving physical capabilitiesPhysical activity is also effective in improving physical and cognitive function capacityPhysical activity appears to improve flexibilityLesser response to physical activity was found in the domains of PD clinical symptoms, depression, psychosocial function They noted clinical PD symptoms of bradykinesia, freezing of gait and tremor were very resistant to physical acitivity interverventions. On a more hopeful note, gait and postural alterations in PD are more responsive to physical activity.Physical therapy protocols that appear to have the best chance of producing improving PD include:Gait training, walking for increased speed and enduranceStrength training for improvement muscle mass in legs and armsFlexibility exercises for upper, lower extremities and trunkInterventions to reduce risk of falls (balance)The evidence supports routine referral for physical therapy and physical rehabilitation in those suffering from Parkinson's disease.You can access the free full text manuscript in this post by clicking on the citation link below.The figure in this post is a Creative Commons file from Wikipedia authored:By Madhero88 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=7157181Follow me on Twitter.Lauzé M, Daneault JF, & Duval C (2016). The Effects of Physical Activity in Parkinson's Disease: A Review. Journal of Parkinson's disease, 6 (4), 685-698 PMID: 27567884... Read more »
Lauzé M, Daneault JF, & Duval C. (2016) The Effects of Physical Activity in Parkinson's Disease: A Review. Journal of Parkinson's disease, 6(4), 685-698. PMID: 27567884
"CRP [C-reactive protein] concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia, suggesting an increased inflammatory burden in mania."So said the systematic review and meta-analysis published by Brisa Fernandes and colleagues  who surveyed the peer-reviewed literature on the topic of "measured serum and plasma CRP concentrations in adult patients with bipolar disorder (as defined by DSM-IV-TR) and healthy controls" and arrived at their conclusions based on an analysis of some 2000 people diagnosed with bipolar disorder (BD). CRP by the way, a member of the pentraxin family, is the molecule of choice when it comes to looking at response to inflammation. BD, previously known as manic depression, is a condition characterised by periods of depression and mania.Continuing an important theme in psychiatry - that the immune system or expression of the immune system whether in terms of genetics or biology, seems to show some important associations with behaviour (see here for example) - the Fernandes paper represents important work. Of course it's not the first time that CRP levels and bipolar disorder have been mentioned on this blog (see here) but the 'collecting' of results based on the use of systematic review and meta-analysis this time around strengthens the association between these variables.Where next I hear you ask? Well, the idea that CRP levels might be linked to cases of BD needs further research not least to ensure that certain over-represented medical comorbidity linked to BD are not an interfering variable when it comes to CRP levels (see here). The findings should also perhaps be seen in a larger context where CRP levels have been reported in other psychiatric / behavioural labels (see here). The non-specificity of CRP (i.e. not tied to just one label) also has implications for the idea that many different psychiatric / behavioural labels might show overlapping features (see here) for example.With no medical or clinical advice given or intended, there is also the intriguing idea that interventions targeting specific immune function findings may also have behavioural implications (see here for example). This alongside the idea that some medicines intended for the treatment or management of aspects of BD may already have some 'immune-modulating' actions (see here) potentially tied into their potential efficacy (or not). Again, further research is very much implied.---------- Fernandes BS. et al. C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2016 Nov 9. pii: S2215-0366(16)30370-4.----------Fernandes BS, Steiner J, Molendijk ML, Dodd S, Nardin P, Gonçalves CA, Jacka F, Köhler CA, Karmakar C, Carvalho AF, & Berk M (2016). C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. The lancet. Psychiatry PMID: 27838212... Read more »
Fernandes BS, Steiner J, Molendijk ML, Dodd S, Nardin P, Gonçalves CA, Jacka F, Köhler CA, Karmakar C, Carvalho AF.... (2016) C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. The lancet. Psychiatry. PMID: 27838212
The results published by Robert Joseph and colleagues  provide some blogging fodder today, observing that as part of the ELGAN (Extremely Low Gestational Age Newborns) Research Study, gestational age might matter when it comes to offspring risk of autism spectrum disorder (ASD).Gestational age is a measure of how far along a pregnancy is but in the context of the Joseph study refers to premature birth or those "born at least 3 months early." Researchers included data for nearly 1000 children born extremely premature using a prospective (rather than retrospective) methodology who, at age 10, were "evaluated for ASD and ID [intellectual disability]." They also took into account various other 'pregnancy information' derived from both medical records and interviews with mums. This included instances of cervical-vaginal ‘infection’ among other things.The results: over 90% of their cohort were assessed for autism/ASD and ID. Rates of ASD alone (without ID) were 3.2%. Some 3.8% of participants screened positive for autism and ID and 8.5% of participants presented with ID but not autism. Whilst these autism (with or without ID) rates might seem high, I'm not actually convinced that they are 'significantly higher' than that suggested in modern times (see here). The authors also noted that: "The lowest gestational age category (23-24 weeks) was associated with increased risk of ASD+/ID+... and ASD+/ID-."Also: "Maternal report of presumed cervical-vaginal ‘infection’ during pregnancy was associated with increased risk of ASD+/ID+." The sorts of things included under the heading of cervical-vaginal infection were "bacterial infection (n = 4), bacterial vaginosis (n = 30), yeast infection (n = 62), mixed infection (n = 4) or other/unspecified infection (n=43; e.g., chlamydia, trichomonas or herpes, etc.)."I agree with the authors that "low gestational age is associated with increased risk for ASD" and this research does seem to tally with other studies on this topic (see here for example). The one caveat I do want to make however is that the absolute numbers of children diagnosed with autism (with or without ID) were quite low (27 and 32 children respectively out of a total of 840) and somewhat dwarfed in comparison to those presenting with ID without autism (71 children out of 840). Still, preferential screening for autism and ID might be implied from these results; assuming that is, that the screening instrument in question is up to the job .As to potential mechanisms of effect... well, it's rather difficult to pin any 'excess autism risk' to any one mechanism in light of the various factors that can accompany prematurity. Aside from the immaturity of various biological system associated with premature birth (including the brain), the obvious effect of a reduced birth weight is something to consider (see here). I am also interested in the idea that infection (using the term quite broadly) during pregnancy might also impact on offspring autism risk in light of other data (see here). Specific pathogens during pregnancy affecting offspring developmental risks have already made a mark on the peer-reviewed research literature (see here for example) and could provide a template for the processes pertinent to infection plus prematurity too.---------- Joseph RM. et al. Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation. American Journal of Obstetrics and Gynecology. 2016. Aug 13. Kim SH. et al. Predictive Validity of the Modified Checklist for Autism in Toddlers (M-CHAT) Born Very Preterm. J Pediatr. 2016 Nov;178:101-107.e2.----------Joseph, R., Korzeniewski, S., Allred, E., O’Shea, T., Heeren, T., Frazier, J., Ware, J., Hirtz, D., Leviton, A., & Kuban, K. (2016). Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation American Journal of Obstetrics and Gynecology DOI: 10.1016/j.ajog.2016.11.1009... Read more »
Joseph, R., Korzeniewski, S., Allred, E., O’Shea, T., Heeren, T., Frazier, J., Ware, J., Hirtz, D., Leviton, A., & Kuban, K. (2016) Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation. American Journal of Obstetrics and Gynecology. DOI: 10.1016/j.ajog.2016.11.1009
I don’t mean to brag, but I’ve got irritable bowel syndrome, says a character of a sitcom.
Irritable bowel syndrome used to be a rare condition, but became a problem of epidemic proportions, until the disease "came out of the closet". Then Internet searches and doctor visits started to dwindle down and less than halved compared to earlier decades.
Is IBS no longer a problem? [...]... Read more »
Camilleri M, Oduyebo I, & Halawi H. (2016) Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions. American journal of physiology. Gastrointestinal and liver physiology, 311(5). PMID: 27609770
Lacy BE, Patel H, Guérin A, Dea K, Scopel JL, Alaghband R, Wu EQ, & Mody R. (2016) Variation in Care for Patients with Irritable Bowel Syndrome in the United States. PloS one, 11(4). PMID: 27116612
Dorn, S., & Meek, P. (2013) Su1024 Ambulatory Care for Irritable Bowel Syndrome in the United States, 1993-2010. Gastroenterology, 144(5). DOI: 10.1016/S0016-5085(13)61392-X
Lackner, J., Brasel, A., Quigley, B., Keefer, L., Krasner, S., Powell, C., Katz, L., & Sitrin, M. (2010) The ties that bind: perceived social support, stress, and IBS in severely affected patients. Neurogastroenterology , 22(8), 893-900. DOI: 10.1111/j.1365-2982.2010.01516.x
Follicular lymphoma is a B-cell lymphoma that remains incurable with conventional therapies. Ying et al. (2016) present a new study exploring the biological and genetic features of follicular lymphoma and identifying potential new therapeutic targets. The authors identified recurrent mutations in the mTOR regulator RRAGC, a small G-protein, in approximately 10% of follicular lymphoma cases. Mutations in RRAGC localized to one protein surface area surrounding the GTP/GDP–binding sites. In stable retrovirally transfected HEK293T cells, multiple RRAGC mutations showed higher mTOR activation. A similar phenotype was observed in lymphoma cell lines and in yeast. Mutated RRAGC proteins showed increased binding to RPTOR, a binding protein for RRAG heterodimers, and decreased interactions with FLCN , a known tumour suppressor that plays a role in mTOR signalling and the causative gene of BHD syndrome.... Read more »
Ying ZX, Jin M, Peterson LF, Bernard D, Saiya-Cork K, Yildiz M, Wang S, Kaminski MS, Chang AE, Klionsky DJ.... (2016) Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research, 22(21), 5383-5393. PMID: 27267853
Consider this short blog post an extension of some previous discussions (see here and see here) on a rather peculiar 'association' between urinary tract infections (UTIs) and psychosis. UTIs basically refer to an infection in any part of the urinary system (kidneys, bladder, etc) typically treated with antibiotics. Psychosis is a state that causes a person to perceive or interpret things around them in an atypical way, usually accompanied by delusions or hallucinations. For a while now research has been connecting these two conditions.The paper by Chelsea Carson and colleagues  further adds to the peer-reviewed literature in this area with the observation of: "an association between UTIs and children and adolescents with acute non-affective psychosis." Based on a "retrospective chart review of 227 subjects ages 10–18 who were hospitalized between 2005 and 2014 for an acute episode of DSM-IV non-affective psychosis" compared with those presenting with depression with and without psychotic features, researchers noted that a UTI was not an uncommon diagnosis (20%). Bearing in mind the lack of any asymptomatic control group, authors concluded that screening for [comorbid] UTI in those presenting with acute psychosis might be warranted.I can't disagree with these findings and conclusions. Combined with other work  looking at "an association between an increased prevalence of UTI and acute psychotic relapse" in those diagnosed with schizophrenia, the idea that infection or immunological response to infection might have behavioural as well as physiological outcomes gathers strength from such findings. We still don't know all the hows-and-whys of such an association outside of the idea that inflammatory mechanisms may be at work (see here) but further investigations are most definitely implied.---------- Carson CM. et al. Urinary tract infections in children and adolescents with acute psychosis. Schizophrenia Research. 2016. Nov 10. Miller BJ. et al. A prevalence study of urinary tract infections in acute relapse of schizophrenia. J Clin Psychiatry. 2013 Mar;74(3):271-7.----------Carson, C., Phillip, N., & Miller, B. (2016). Urinary tract infections in children and adolescents with acute psychosis Schizophrenia Research DOI: 10.1016/j.schres.2016.11.004... Read more »
Carson, C., Phillip, N., & Miller, B. (2016) Urinary tract infections in children and adolescents with acute psychosis. Schizophrenia Research. DOI: 10.1016/j.schres.2016.11.004
Rates of myocardial infarction and stroke have been declining over the last decade in the U.S. and Europe. However, a recent manuscript suggests there are still significant missed opportunities to prevent stroke.This manuscript presents results of review of electronic primary care records in the United Kingdom.The authors examines a group of over 29,000 subjects with a diagnosis of stroke or transient ischemic attack over a 10 year period.Records were reviewed to assess for compliance with guideline drug treatments that are proven to reduce the incidence of stroke including:Lipid-lowering drugsAnticoagulant drug use in those with atrial fibrillationAntihypertension drug use in hypertensionThe record review found that around 50% of subjects experiencing stroke or TIA had indications but were not receiving lipid-lowering or anticoagulant drugs prior to their cerebrovascular event. For hypertension, compliance with antihypertension drug use was 75% with 25% not receiving drug.One of the attractive features of this type of primary prevention is the potential for electronic records. Centralized records could be scanned with identification of high-risk patients that might benefit from targeted drug therapy. Patients and physicians could be alerted and a medical visit triggered to address the issue.The authors conclude that improving prevention efforts in these areas could potentially reduce the number of first strokes in the U.K. by 12,000 every year.Here is a table from the Creative Commons free full-text manuscript that outlines the indications and methods in the study for use of stroke prevention drugs.I am not aware of a similar type of study of stroke prevention in the United States.We do know that despite some promising trends in stroke reduction, significant geographic challenges remain.This map from the U.S. CDC shows the clustering of high stroke rates in the Southeastern portion of the U.S.Stroke prevention intervention efforts could be directed to areas of high risk for stroke as these areas are likely to yield the greatest results.Readers with more interest in this research can access the free full-text manuscript by clicking on the link in the citation below.U.S. Stroke map is from the U.S. CDC with data source the National Vital Statistics System, National Center for Health Statistics.Follow me on Twitter WRY999Turner GM, Calvert M, Feltham MG, Ryan R, Fitzmaurice D, Cheng KK, & Marshall T (2016). Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis. PLoS medicine, 13 (11) PMID: 27846215... Read more »
Turner GM, Calvert M, Feltham MG, Ryan R, Fitzmaurice D, Cheng KK, & Marshall T. (2016) Under-prescribing of Prevention Drugs and Primary Prevention of Stroke and Transient Ischaemic Attack in UK General Practice: A Retrospective Analysis. PLoS medicine, 13(11). PMID: 27846215
Papers such as the one published by Nikko Da Paz & Jan Wallander  I think represent one of the most important areas of autism research and practice when it comes to the practical translation of science to real-life. Tackling a very important topic - caring for the carers - the authors provide a "narrative review" of the peer-reviewed science literature looking at how "treatments that directly target parents' psychological well-being" in the context of autism are doing so far.Personally, I don't like the use of the word 'treatment' in this context because it implies that caring for the carers is akin to tackling some sort of disease. It's not. It also 'medicalises' the experience of caring for/raising children on the autism spectrum which I don't think anyone really wants to do. I might suggest that 'intervention' could be a better word to use.Da Paz and Wallander reported on "a total of 13 studies, seven randomized controlled trials (RCTs) and six pre-post test designs" that looked at various interventions pertinent to improving parent stress and reducing instances of depression and anxiety. They report: "Interventions that appeared promising included: Stress Management and Relaxation Techniques, Expressive Writing, Mindfulness-Based Stress Reduction, and Acceptance and Commitment Therapy" with some important caveats. Not least that if English is not your language of choice and/or you are not aged between 39-42 years old, the evidence base is rather sparse when it comes to what might be useful or not for managing your psychological health. In light of other research  there is quite a bit more to do in this area.Accepting that the publishing journal - Clinical Psychology Review - gives a rather large hint as to why the listed 'psychological' interventions were focused upon, I might also add a few comments about how other science and practice might also aid parents raising children on the autism spectrum. I've for example, covered the topic of respite care and parent stress before on this blog (see here) and how depending on your definition of respite, there is perhaps some value in either the utilisation of short break facilities or the use of domiciliary care/support where available. As per my previous discussion of this area, there is a rather large stumbling block to any talk about respite care insofar as in these austere times in which we live, some of the first social services that seem to suffer when budgets need to be reduced are respite services.I'm also minded to bring in the idea that outside of psychological techniques potentially impacting on parenting stress and any adverse outcomes, one might also look at more physical interventions too. So, for example, exercise is something that could be a rather useful intervention to look at given the pretty strong research links being forged between body and mind. The thing about exercise is that (a) depending on what regime you choose costs can range from free to expensive, and (b) there are a whole host of other factors potentially tied into a chosen sport, based on the choice of solitary sports vs. group sports for example and other factors. That various health agencies are already shifting when it comes to notions of potentially 'prescribing exercise' for something like depression and anxiety (see here for example) reflects how valuable moving a little more might be to lots of groups.I would champion the idea that quite a few more resources need to be put into caring for the carers when it specifically comes to parenting and autism. This is not about further 'blaming autism' for parenting stress or adverse outcomes but rather acknowledging that parenting whether in the context of autism or not, is a sometimes difficult task. And nobody benefits if parents/carers are just left to fend for themselves without the appropriate help and support...---------- Da Paz NS. & Wallander JL. Interventions that target improvements in mental health for parents of children with autism spectrum disorders: A narrative review. Clin Psychol Rev. 2016 Oct 27;51:1-14. Zuckerman KE. et al. Pediatrician identification of Latino children at risk for autism spectrum disorder. Pediatrics. 2013 Sep;132(3):445-53.----------Da Paz NS, & Wallander JL (2016). Interventions that target improvements in mental health for parents of children with autism spectrum disorders: A narrative review. Clinical psychology review, 51, 1-14 PMID: 27816800... Read more »
Da Paz NS, & Wallander JL. (2016) Interventions that target improvements in mental health for parents of children with autism spectrum disorders: A narrative review. Clinical psychology review, 1-14. PMID: 27816800
Video feedback was a more effective tool to correct landing patterns in males to compared to females, which may be helpful in reducing anterior cruciate ligament (ACL) injury risk. ... Read more »
Dallinga J, Benjaminse A, Gokeler A, Cortes N, Otten E, & Lemmink K. (2016) Innovative Video Feedback on Jump Landing Improves Landing Technique in Males. International Journal of Sports Medicine. PMID: 27428644
With all rights reserved for Keith Geraghty and his publication in the Journal of Health Psychology  (open-access) I want to reproduce his abstract relevant to the PACE trial commenting on the ups-and-downs of this study looking at the use of CBT (cognitive behaviour therapy) and GET (graded exercise therapy) for chronic fatigue syndrome (CFS) (also known as myalgic encephalomyelitis, ME):"Science is not always plain sailing and sometimes the voyage is across an angry sea. A recent clinical trial of treatments for chronic fatigue syndrome (the PACE trial) has whipped up a storm of controversy. Patients claim the lead authors overstated the effectiveness of cognitive behavioural therapy and graded exercise therapy by lowering the thresholds they used to determine improvement. In this extraordinary case, patients discovered that the treatments tested had much lower efficacy after an information tribunal ordered the release of data from the PACE trial to a patient who had requested access using a freedom of information request."For those familiar with PACE  and the 'angry sea' saga following its publication (see here for some of that saga), this paper represents one of the the first 'peer-reviewed' discussions that makes reference to the reanalysis of 'trial improvers' vs. that included in the original PACE trial publication (see here). Indeed, combined with other (as yet unpublished in the peer-reviewed domain) re-analyses (see here), there seem to be some pretty stark differences noted between the different 'versions' in terms of the effectiveness of different arms of the intervention tested during the PACE trial. Even before these latest re-analyses, some agencies were already adjusting the strength of their recommendations when it came to CBT and/or GET for CFS/ME (see here). Does this mean other organisations might follow suit?The other issue central to the Geraghty discussions is that of 'enforced data release' and data transparency. This has been a focal point when it comes to PACE (including that with reference to other papers on the trial) and perhaps something that has significantly added to the sometimes bitter discussions about the trial. As Geraghty notes: "The PACE-Trial stands out as a showcase example of why data transparency is needed in contemporary science. Patients suffering from health conditions like CFS, and independent scientists, should have the right to see the evidence behind the claims of any scientific study, especially if this evidence is used to direct health policy or promote certain treatments – as was the case for the PACE-Trial." In light of how PACE has been contributory to public policy, and indeed was part funded by agencies such as "the UK Department for Work and Pensions", I don't think many people would argue against suitable data transparency in this case.I say nothing more at this point in time but will no doubt be returning to this topic as the peer-reviewed literature allows (which should be quite soon). If there are however, some lessons that can already be learned from PACE-gate (e.g. stick to your "original protocol thresholds", make your data 'open-access' and think about how to do this in the planning/recruitment stages of your trial, be mindful that short-term gains don't necessarily translate into long-term ones, work with the ME/CFS community rather than labelling elements of them 'vexatious' or worse) one would hope that they would be applied to future research projects related to CFS/ME (see here) as well as their anticipated long-term follow-up ...Music: The King and what wise men (might) say (easily recognisable to any Black Cats fan).---------- Geraghty KJ. 'PACE-Gate': When clinical trial evidence meets open data access. J Health Psychol. 2016 Nov 1. pii: 1359105316675213. White PD. et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. Nijhof SL. et al. Internet-based therapy for adolescents with chronic fatigue syndrome: long-term follow-up. Pediatrics. 2013 Jun;131(6):e1788-95.----------Geraghty KJ (2016). 'PACE-Gate': When clinical trial evidence meets open data access. Journal of health psychology PMID: 27807258... Read more »
Geraghty KJ. (2016) 'PACE-Gate': When clinical trial evidence meets open data access. Journal of health psychology. PMID: 27807258
I ran into an interesting article at ScienceDaily providing data on a small sample size study of the anti-inflammatory drug celecoxib (Celebrex) in depression.Access the ScienceDaily report on this study by clicking HERE.This study focused on subjects with bipolar depression. All subjects were in a depressed phase and received the antidepressant drug escitalopram (Lexapro).Although only 55 subjects participated in this study, the results were significant and large. Adding Celebrex to escitalopram increased depression remission rates from 10% to 63%. I have summarized the data from the article in this attached graph.Additionally, the study team found a more rapid response to antidepressant drug therapy when Celebrex was added.I have been involved in use of anti-inflammatory agents in the treatment of bipolar depression. Dr. Jonathan Savitz and our colleagues at the Laureate Institute of Brain Research and the University of Kansas examined aspirin and minocycline in a clinical trial that has not yet been published.I have included the methods manuscript for our study that can be accessed by clicking the the link provided below.Neuroinflammation may be a contributing factor in a variety of brain disorders including depression. Better understanding of the role and treatment of inflammation may improve depression outcomes.Follow me on Twitter WRY999Figure in this post is an original figure from data abstracted from the research report.Savitz, J., Preskorn, S., Teague, T., Drevets, D., Yates, W., & Drevets, W. (2012). Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial BMJ Open, 2 (1) DOI: 10.1136/bmjopen-2011-000643... Read more »
Savitz, J., Preskorn, S., Teague, T., Drevets, D., Yates, W., & Drevets, W. (2012) Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomised, double-blind, placebo-controlled, 2×2 clinical trial. BMJ Open, 2(1). DOI: 10.1136/bmjopen-2011-000643
I talked about ESSENCE - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - only yesterday (see here) and here I am covering the topic again on this blog. There is good reason however that this concept appears once more, as I draw your attention to the paper by Anne-Katrin Kantzer and colleagues  and the specific observation that: "Co-existence with other conditions was the rule" when it comes to the diagnosis of autism.OK, it's nothing new to say that the label of autism rarely appears in some sort of diagnostic vacuum (see here). Indeed, if there is anything that has been learned about autism over the years it is that aside from the incredible heterogeneity present across the spectrum in terms of clinical presentation, many grand theories 'about autism' have been scuppered as a consequence of their assumptions on autism being some sort of stand-alone label. A case in point: theory of mind (ToM); that even some of the major proponents of this theory have come to realise  has seen a "a widening of interest to other clinical groups." Indeed it has (see here for example), indeed it has. And other grand theories appear also to be following suit ...The Kantzer paper - including some notable names on the authorship list - set out to examine the diagnostic outcomes of some 96 children "initially assessed for suspected ASD [autism spectrum disorder] at an average age of 2.9 years" who were followed up some two years later. There is an important word included in the Kantzer study: prospectively; as opposed to retrospectively, meaning that participants were assessed and followed in real-time (rather than solely relying on the examination of previous historical records). Various behavioural and psychometric measures were employed by the authors as part of a "broad neurodevelopmental examination... by a multi-professional team" and some rather interesting details emerged.So: "In a cohort of young children who screened positive for autism spectrum symptoms, 93% of all with an Autism spectrum disorder (ASD) at time1 (T1) had ASD two years later." What this tell us is that in the most part, the diagnosis of autism/ASD over 2 years in young children is fairly stable. Other data has highlighted similar things. But then the question: what about the ~7% where an ASD diagnosis perhaps wasn't as stable? I've covered this topic a few times on this blog (see here and see here), where for whatever reason, the diagnosis of autism is not necessarily a lifelong label for everyone. The still controversial idea that around 9% of those originally diagnosed with autism might 'lose' their diagnosis (see here) and indeed any/many 'broader autism features' (see here) could be pertinent here accepting that in the Kantzer data we are told: "The children who did not meet criteria for ASD at T2 had symptoms of or met criteria for other neurodevelopmental/neuropsychiatric disorders in combination with marked autistic traits." I might also draw your attention to other work from members of the Kantzer group that indicated that even into adulthood, diagnoses along the autism spectrum might similarly not always be 'lifelong' for whatever reason(s) (see here).Next: "The vast majority of children with ASD also had other neurodevelopmental symptoms or diagnoses." This kinda reiterates the notion of ESSENCE, as details such as: "Hyperactivity was observed in 42% of children with ASD at T2, and Intellectual Developmental Disorder in 30%" provide some diagnostic flesh on the bones of what ESSENCE might look like in clinical terms. Indeed, although the topic of continued debate  insofar as how one screens for something like attention-deficit hyperactivity disorder (ADHD) in autism, the overlap between the conditions is likely to be significant (see here).Finally: "The risk of “over-diagnosis” of ESSENCE/ASD problems by screening for ASD at 2.5 years appears to be minimal." Accepting that important changes to the way that autism is diagnosed by at least one schedule is likely to produce some important differences in who fulfils criteria (see here), the authors seem to be fairly confident that early diagnosis might actually be (a) possible and (b) pretty accurate. The stress is most definitely on 'early diagnosis' save any charges of further health inequalities facing those on the autism spectrum.I titled this post 'Autism, ESSENCE and the question of reassessment' because I do also want to pass some brief comment about the value of reassessment picked up by the authors: "Reassessments covering the whole range of these conditions are necessary for an optimized intervention—adapted to the individual child’s needs." This is going to take quite a huge shift in thinking and practice insofar as ensuring that a diagnostic assessment for autism does not just include an ADOS or something related but rather includes a wider spread of behavioural and psychometric instruments pertinent to various other labels/features. I can see there being objections to this line of thought; not least that in these austere times we live in when waiting times for an initial assessment can already be quite long (see here) and money and resources are stretched thin on the ground for autism, screening for a range of potential additional issues is likely to further burden limited resources. The idea also that not hitting diagnostic thresholds for autism at one point does not rule out a child hitting them at a later time point is also something likely to impact on screening and assessment services. I suppose it all depends on whether policy-makers and purse-string holders value detail or value cost-saving?Either way, the Kantzer paper once again highlights that a diagnosis of autism rarely exists in a diagnostic vacuum.Music to close (it's been a while) and an 80's blast from the past: Billy Ocean - Get Outta My Dreams, Get Into My Car (although please, do not get into a car with someone you don't know, no matter how well they serenade you).---------- Kantzer A-K. et al. Young children who screen positive for autism: Stability, change and “comorbidity” over two years. Research in Developmental Disabilities. 2016. Nov 3. Happé F. & Conway JR. Recent progress in understanding skills and impairments in social cognition. Curr Opin Pediatr. 2016 Dec;28(6):736-742. Dajani DR. et al. Heterogeneity of executive functions among comorbid neurodevelopmental disorders. Sci Rep. 2016 Nov 9;6:36566. Yerys BE. et al. Evaluation of the... Read more »
Kantzer, A., Fernell, E., Westerlund, J., Hagberg, B., Gillberg, C., & Miniscalco, C. (2016) Young children who screen positive for autism: Stability, change and “comorbidity” over two years. Research in Developmental Disabilities. DOI: 10.1016/j.ridd.2016.10.004
ESSENCE referred to in the title of this post concerns 'Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations', a concept championed by the ever-intrepid Prof. Christopher Gillberg and colleagues. Combined with some rather important discussions about the research validity of the concept of a singular 'autism' (see here) [part of the ESSENCE issues described] I'm drawn to quite a few of the proposals put forward by this research group it has to be said.It is with ESSENCE in mind, that I'm rather interested in the paper by Carolina Baeza-Velasco and colleagues  and the observation that following a review of the pertinent research literature, there is some support for a possible connection between ESSENCE issues and another favourite topic on this blog: Joint Hypermobility Syndrome (JHS) and the spectrum of connective tissue disorders (see here for example). JHS and connective tissue disorders refer to a group of conditions where various connective tissues are 'weaker' than they should typically be, with various knock-on effects and symptoms."The clinical picture of EDS-HT/JHS [EDS = Ehlers-Danlos syndrome] is poorly known by the medical community, as is the presence of "ESSENCE" (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) problems in affected children" was the starting point for this review paper of the various research literature on this topic. Authors searched, surveyed and concluded that: "Children with EDS-HT/JHS present ESSENCE problems that often coexist and tend to be recognized before the HDCT [hereditary disorder of the connective tissue]." Further: "Awareness of these interconnected clinical problems might help improve early referral, diagnosis and treatment of EDS-HT/JHS."In a previous blog post on the issue of 'joint hypermobility, gait and autism' (see here), discussions turned to how there may be some important 'intersection' going on with regards to the presentation of motor and gait issues in autism and connective tissues disorders present in some people. I don't want to make sweeping generalisations nor move too far away from the current thinking linking specific brain functions and motor issues  but there is some sound logic in how neurodevelopmental issues might go hand-in-hand with connective tissue disorders. If for example, we turn to some of the other manifestations of something like JHS - functional bowel issues such as constipation and/or irritable bowel syndrome (IBS) - there are other potential overlapping features that might also prove to be just as important (see here).There is a need for quite a bit more research in this area before any grand, sweeping generalisations are made. That and the idea that yet another level of screening might be implied for those with ESSENCE issues or conversely, those diagnosed with connective tissue disorders...Music to close: The JCB song. For the next time you're stuck behind one....---------- Baeza-Velasco C. et al. A connective tissue disorder may underlie ESSENCE problems in childhood. Res Dev Disabil. 2016 Oct 29. pii: S0891-4222(16)30240-2. Gillberg C. et al. Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. The Scientific World Journal. 2013;2013:710570.----------Baeza-Velasco C, Grahame R, & Bravo JF (2016). A connective tissue disorder may underlie ESSENCE problems in childhood. Research in developmental disabilities PMID: 27802895... Read more »
Baeza-Velasco C, Grahame R, & Bravo JF. (2016) A connective tissue disorder may underlie ESSENCE problems in childhood. Research in developmental disabilities. PMID: 27802895
More of the same...... Read more »
Fuller, J., Buckley, J., Tsiros, M., Brown, N., & Thewlis, D. (2016) Redistribution of Mechanical Work at the Knee and Ankle Joints During Fast Running in Minimalist Shoes. Journal of Athletic Training. DOI: 10.4085/1062-6050-51.12.05
It's been quite a week hasn't it? Indeed for quite a few people it's been a stressful few days so perhaps timely that I'm talking about the 'attenuation of stress' in today's post.Despite the relatively small sample size included in the paper by by AP Allen and colleagues  there is something rather tantalising about their results suggesting that in healthy volunteers "consumption of B. longum [Bifidobacterium longum 1714] 1714 is associated with reduced stress and improved memory."Tantalising because as well as further directing research attention towards the important relationship that is the gut-brain axis (see here for another example) the findings provide initial support for the concept of "psychobiotics—live microorganisms with a potential mental health benefit" set within a human (not mouse) context.The Allen paper (who incidentally is on Twitter) is open-access and has previously provided signs that it was to be published (see here). Here are a few choice details:Take 22 (male) volunteers aged between 18 and 40 years of age who fitted various inclusion/exclusion criteria including no "self-report habitually taking any probiotic products" and ask them to take B. longum 1714 for 4 weeks after giving them a placebo preparation containing just maltodextrin and magnesium stearate and no probiotic for 4 weeks. Deliver various physical, psychometric and self-report questionnaires/tests at various intervals covering things like the "Socially evaluated cold pressor procedure" (SECPT) and other measures and see how things pan out according to placebo/psychobiotic use and after "a 2-week post-probiotic follow-up."Results: well, as per the opening paragraph of this post, there did seem to be some effects to be had potentially associated with B. longum administration. So, when it came to that 'put your hand in cold water' test (SECPT), participants as a group lasted slightly longer in the cold water than on previous testing occasions. When researchers looked at salivary cortisol levels (a measure of psychological stress) following this acute stress test, they observed some potentially important differences between the initial (baseline) test, the period covering placebo use and the period covering the psychobiotic use. This accompanied some differences in reported state anxiety. Such acute stress findings were also complemented by some subtle but potentially important differences in self-reported daily stress levels (lower) following the period of psychobiotic use (something that "returned to a higher level during the 2-week follow-up period"). The authors also report on some findings associated with testing cognition across the various phases of the study but I'm gonna stay focused on the stress part of things for now before anyone moves towards describing B. longum 1714 as some sort of nootropic of choice just yet.Of course there is still much to do in this area before anyone gets too carried away with things (how about a few more blinded RCTs pitting placebo against psychobiotic?) but the results are interesting. You could argue that there may have been some influence of practice effects associated with some of the results given the short timescales but I'm gonna take the findings at face-value. More so when when set in the context of other microbial preparations also potentially dealing with certain types of stress under experimental conditions (see here for example).Mode of action? Well, the authors mention the 'vagus nerve' as potentially being important given the suggestion of a connection between the trillions of wee beasties that populate our gut (the gut microbiota) and brain function(s). The specifics however are yet to be decided upon; and it is also worth noting that as part of the probiotic formulation called VSL#3, B. longum 1714 might have some important 'bowel' effects as per other findings (see here) onwards to behaviour(s) and labels (see here). I'm also intrigued by the finding that post-probiotic there was a suggestion of a waning of some of the previously reported effects implying that far from probiotics being accepted and 'assimilated' into our collected gut microbiota, there may be mechanisms at work tied to going back to the status quo."Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects." Wise words before anyone makes a run on B. longum 1714 or any related preparations but this is an interesting piece of research. Given also the so-far relatively good safety profile of various probiotics, there is an important argument for experimentally testing such stress relief and/or cognition-aiding properties under a wide range of contexts.To close, we lost another one in 2016. There must be a helluva party going on upstairs...---------- Allen AP. et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational Psychiatry. 2016; 6: e939.----------Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G, Murphy E, Cryan JF, Dinan TG, & Clarke G (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational psychiatry, 6 (11) PMID: 27801892... Read more »
Allen AP, Hutch W, Borre YE, Kennedy PJ, Temko A, Boylan G, Murphy E, Cryan JF, Dinan TG, & Clarke G. (2016) Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational psychiatry, 6(11). PMID: 27801892
Renal cell carcinoma (RCC) is by far the most common type of kidney cancer and it can be caused by genetic conditions such as BHD (Randall et al., 2014). BHD patients can develop multiple kidney tumours. In most cases these tumours can be surgically removed. However, surgery and traditional chemotherapies can leave patients with reduced renal function and at risk of relapse. In addition, advanced or metastatic RCC is difficult to treat with surgery. Therefore, the development and improvement of molecular targeted drug treatments is becoming a very active field. The standard first-line treatment for RCC is an anti-angiogenic and anti-proliferative tyrosine kinase inhibitor (TKI) such as sunitinib or sorafenib. This blog summarises recent results from a clinical trial assessing a new RCC drug treatment and the initiation of a new study.... Read more »
Randall, J., Millard, F., & Kurzrock, R. (2014) Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art. Cancer and Metastasis Reviews, 33(4), 1109-1124. DOI: 10.1007/s10555-014-9533-1
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