Pubmed du 14/06/20

dimanche 14 juin 2020

1. Abdellatif B, McVeigh C, Bendriss G, Chaari A. The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders. Int J Mol Sci ;2020 (Jun 10) ;21(11)

Gastrointestinal symptoms (GIS) have been reported repeatedly in people with autism spectrum disorder (ASD) and studies have reported interesting correlations between severity of behavioral and gastrointestinal symptoms. Growing evidence indicates that the gut microbiota in ASD is altered with various shifts described at different taxonomic levels, pointing to the importance of considering the gut-brain axis in treatment of these disorders. Probiotics are live beneficial bacteria that are ingested as food or customized pills. These beneficial bacteria, when added in sufficient amounts, can correct the dysbiosis. Because probiotics have shown success in treating irritable bowel syndrome (IBS), it is plausible to investigate whether they can induce alleviation of behavioral symptoms as well. Probiotics show, in some clinical studies, their potential benefits (1) in improving gastrointestinal dysfunction, (2) in correcting dysbiosis, (3) in consequently reducing the severity of ASD symptoms. This review compiles data from selected studies that investigate these benefits and the mechanisms that mediate these effects, which include the production of metabolites, hormones, and neurotransmitters and the regulation of pro-inflammatory and regulatory cytokines. Future research based on more randomized, controlled studies with a larger population size and standardized use of strains, concentration of probiotics, duration of treatments, and methods of DNA extraction is still needed in this area, which may lead to more robust results.

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2. Albizua I, Chopra P, Allen EG, He W, Amin AS, Sherman SL. Study of telomere length in men who carry a fragile X premutation or full mutation allele. Hum Genet ;2020 (Jun 12)

The fragile X premutation is defined by the expansion of the CGG trinucleotide repeat at the 5’ UTR of the FMR1 gene to between 55 and 200 repeats, while repeat tracks longer than 200 are defined as full mutations. Men carrying a premutation are at increased risk for fragile X-associated tremor/ataxia syndrome (FXTAS) ; those with > 200 repeats have fragile X syndrome, a common genetic form of intellectual disabilities. In our study, we tested the hypothesis that men carrying a fragile X premutation or full mutation are "biologically older", as suggested by the associated age-related disorder in the presence of the fragile X premutation or the altered cellular pathology that affects both the fragile X premutation and full mutation carriers. Thus, we predicted that both groups would have shorter telomeres than men carrying the normal size repeat allele. Using linear regression models, we found that, on average, premutation carriers had shorter telomeres compared with non-carriers (n = 69 vs n = 36 ; p = 0.02) and that there was no difference in telomere length between full mutation carriers and non-carriers (n = 37 vs n = 29 ; p > 0.10). Among premutation carriers only, we also asked whether telomere length was shorter among men with vs without symptoms of FXTAS (n = 28 vs n = 38 and n = 27 vs n = 41, depending on criteria) and found no evidence for a difference (p > 0.10). Previous studies have shown that the premutation is transcribed whereas the full mutation is not, and the expanded repeat track in FMR1 transcript is thought to lead to the risk for premutation-associated disorders. Thus, our data suggest that the observed premutation-only telomere shortening may be a consequence of the toxic effect of the premutation transcript and suggest that premutation carriers are "biologically older" than men carrying the normal size allele in the same age group.

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3. Brazendale K, Brazendale AB, Garcia JM, Monroe CM, Weaver RG, Beets MW. Brief Report : Obesogenic Behaviors of Children with Developmental Disabilities During Summer. J Autism Dev Disord ;2020 (Jun 12)

The ’Structured Days Hypothesis’ suggests that children’s obesogenic behaviors (e.g., activity, diet, sleep, and screen time) are less favorable during times when there is less-structure to a child’s day (e.g., summer). To compare obesogenic behaviors of children with developmental disabilities (DD) during summer on days with differing amounts of ’structure’. Seventeen children with DD (mean age 9.8 years) attending a day camp wore a Fitbit(©) activity monitor on the non-dominant wrist during summer, and parents completed a survey packet, to capture obesogenic behaviors. Participants displayed improved physical activity levels, diets, and sleep timing on camp days versus other days. Providing children with DD ’structure’ over summer is a potential intervention approach requiring further investigation.

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4. Goldman SE, Gilmour AF. Educating Students with Autism Spectrum Disorders : Is Teacher Certification Area Associated with Academic Outcomes ?. J Autism Dev Disord ;2020 (Jun 12)

Although typically taught by special educators, few studies have examined if certification area is associated with academic outcomes for students with autism spectrum disorders (ASDs). The purpose of this study was to determine whether students with ASD scored better on language arts and mathematics state assessments depending on teacher certification, and whether these associations varied by assessment type. We analyzed 3 years of state administrative data from students with ASD in grades 4-8 receiving special education services. Results showed students taking the regular or alternate assessment had similar academic outcomes regardless of teacher certification. Students who were taught by special education certified teachers and took the modified assessment had lower academic outcomes. Implications for practice, policy, and research are discussed.

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5. Jasoliya M, Bowling H, Petrasic IC, Durbin-Johnson B, Klann E, Bhattacharya A, Hagerman R, Tassone F. Blood-Based Biomarkers Predictive of Metformin Target Engagement in Fragile X Syndrome. Brain Sci ;2020 (Jun 10) ;10(6)

Recent advances in neurobiology have provided several molecular entrees for targeted treatments for Fragile X syndrome (FXS). However, the efficacy of these treatments has been demonstrated mainly in animal models and has not been consistently predictive of targeted drugs’ response in the preponderance of human clinical trials. Because of the heterogeneity of FXS at various levels, including the molecular level, phenotypic manifestation, and drug response, it is critically important to identify biomarkers that can help in patient stratification and prediction of therapeutic efficacy. The primary objective of this study was to assess the ability of molecular biomarkers to predict phenotypic subgroups, symptom severity, and treatment response to metformin in clinically treated patients with FXS. We specifically tested a triplex protein array comprising of hexokinase 1 (HK1), RAS (all isoforms), and Matrix Metalloproteinase 9 (MMP9) that we previously demonstrated were dysregulated in the FXS mouse model and in blood samples from patient with FXS. Seventeen participants with FXS, 12 males and 5 females, treated clinically with metformin were included in this study. The disruption in expression abundance of these proteins was normalized and associated with significant self-reported improvement in clinical phenotypes (CGI-I in addition to BMI) in a subset of participants with FXS. Our preliminary findings suggest that these proteins are of strong molecular relevance to the FXS pathology that could make them useful molecular biomarkers for this syndrome.

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6. Juybari KB, Sepehri G, Meymandi MS, Shahrbabaki SSV, Moslemizadeh A, Saeedi N, Aminzadeh A, Nozari M, Khaksari M, Haghpanah T, Bashiri H. Sex dependent alterations of resveratrol on social behaviors and nociceptive reactivity in VPA-induced autistic-like model in rats. Neurotoxicol Teratol ;2020 (Jun 10):106905.

INTRODUCTION : The present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. METHODS : Pregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. RESULTS : The results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. CONCLUSION : It can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.

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7. Kern JK, Geier DA, Mehta JA, Homme KG, Geier MR. Mercury as a hapten : A review of the role of toxicant-induced brain autoantibodies in autism and possible treatment considerations. J Trace Elem Med Biol ;2020 (May 19) ;62:126504.

BACKGROUND : Mercury has many direct and well-recognized neurotoxic effects. However, its immune effects causing secondary neurotoxicity are less well-recognized. Mercury exposure can induce immunologic changes in the brain indicative of autoimmune dysfunction, including the production of highly specific brain autoantibodies. Mercury, and in particular, Thimerosal, can combine with a larger carrier, such as an endogenous protein, thereby acting as a hapten, and this new molecule can then elicit the production of antibodies. METHODS : A comprehensive search using PubMed and Google Scholar for original studies and reviews related to autism, mercury, autoantibodies, autoimmune dysfunction, and haptens was undertaken. All articles providing relevant information from 1985 to date were examined. Twenty-three studies were identified showing autoantibodies in the brains of individuals diagnosed with autism and all were included and discussed in this review. RESULTS : Research shows mercury exposure can result in an autoimmune reaction that may be causal or contributory to autism, especially in children with a family history of autoimmunity. The autoimmune pathogenesis in autism is demonstrated by the presence of brain autoantibodies (neuroantibodies), which include autoantibodies to : (1) human neuronal progenitor cells ; (2) myelin basic protein (MBP) ; (3) neuron-axon filament protein (NAFP) ; (4) brain endothelial cells ; (5) serotonin receptors ; (6) glial fibrillary acidic protein (GFAP) ; (7) brain derived neurotrophic factor (BDNF) ; (8) myelin associated glycoprotein (MAG) ; and (9) various brain proteins in the cerebellum, hypothalamus, prefrontal cortex, cingulate gyrus, caudate putamen, cerebral cortex and caudate nucleus. CONCLUSION : Recent evidence suggests a relationship between mercury exposure and brain autoantibodies in individuals diagnosed with autism. Moreover, brain autoantibody levels in autism are found to correlate with both autism severity and blood mercury levels. Treatments to reduce mercury levels and/or brain autoantibody formation should be considered in autism.

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8. Linnsand P, Gillberg C, Nilses Å, Hagberg B, Nygren G. A High Prevalence of Autism Spectrum Disorder in Preschool Children in an Immigrant, Multiethnic Population in Sweden : Challenges for Health Care. J Autism Dev Disord ;2020 (Jun 12)

This study examines the prevalence of autism spectrum disorder (ASD) in preschool children in an immigrant population. Possible risk factors for ASD and individual needs for the children and their families are described, as well as implications for health care. The estimated minimum prevalence for ASD in the area was 3.66% for children aged 2-5 years. Multiple risk factors and extensive individual needs for the children and their families were observed. The high prevalence of ASD and the plethora of needs in immigrant communities pose challenges for health care. A coordinated health care system is necessary to meet the many and individual needs.

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9. Petersson Bloom L. Professional Development for Enhancing Autism Spectrum Disorder Awareness in Preschool Professionals. J Autism Dev Disord ;2020 (Jun 12)

The current study describes the design, implementation, and analysis of a professional development programme using a Lesson Study model to enhance awareness in preschool professionals regarding inclusive education for children with autism spectrum disorder. The mixed method approach included pre- and post-intervention questionnaires, audio-recordings of group seminars, and an interview. The results indicated an increase in autism awareness among the professionals, suggesting that professionals changed their practice as a result of the programme. This was particularly clear regarding making adjustments to the learning environment and taking measures to prevent challenging situations. In addition to describing the implementation of a professional development programme in a preschool, this paper emphasises the importance of appropriate conditions for such initiatives.

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10. Skuse D. Autism - 25 years on : A lot has changed !. Clin Child Psychol Psychiatry ;2020 (Jun 14):1359104520929729.

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11. Stokholm L, Juhl M, Talge NM, Gissler M, Obel C, Strandberg-Larsen K. Obstetric oxytocin exposure and ADHD and ASD among Danish and Finnish children. Int J Epidemiol ;2020 (Jun 14)

BACKGROUND : Some studies have indicated an increased risk of attention deficit hyperactivity disorder (ADHD) and a small, sex-specific association with autism spectrum disorder (ASD) among children prenatally exposed to obstetric oxytocin. Since oxytocin is widely used in the obstetric ward, these potentially deleterious effects are of concern. Thus, we aimed to examine whether obstetric oxytocin treatment for labour induction or augmentation is associated with ADHD and ASD in offspring born in a two-country design based on data from Denmark and Finland. METHODS : This population-based study used data from national registers in Denmark and Finland. Singletons born in Denmark 2000-10 (n = 577 380) and Finland 1991-2010 (n = 945 543), who survived infancy, were followed until 31 December 2015. ADHD and ASD were defined using diagnostic codes. For ADHD, we also included information on prescribed and redeemed ADHD medication in the definition. Hazards ratios (HRs) with 95% confidence intervals (CI), modelled with age as the underlying time scale, were calculated to estimate the associations. RESULTS : Oxytocin was used in 31% and 46% of the included deliveries in Denmark and Finland, respectively. In crude analyses, prenatal oxytocin was associated with an approximately 20% increased risk of ADHD and ASD, but confounder adjustment attenuated the association. The adjusted HR was 1.03, 95% CI 1.01-1.05, for ADHD and 1.05, 95% CI 1.02-1.08, for ASD. The results were similar in across country and gender. CONCLUSIONS : We found an association between synthetic oxytocin and ADHD or ASD which is unlikely to reflect a causal association and thus should not support the concern of clinical use. Our results help to allay concerns of obstetric use of oxytocin causing ADHD or ASD.

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12. Sweigert JR, St John T, Begay KK, Davis GE, Munson J, Shankland E, Estes A, Dager SR, Kleinhans NM. Characterizing Olfactory Function in Children with Autism Spectrum Disorder and Children with Sensory Processing Dysfunction. Brain Sci ;2020 (Jun 10) ;10(6)

Abnormalities in olfactory function have been identified in a number of neurological and psychiatric disorders, including Parkinson’s disease and schizophrenia. However, little is known about olfactory function in autism spectrum disorder (ASD). The present study aims to assess the olfactory profiles of children with ASD, compared to an age- and sex-matched comparison group of typically developing children and a second clinical control group consisting of non-ASD children with sensory processing dysfunction (SPD). Participants completed a battery of sensory and behavioral assessments including olfactory tasks (Sniffin’ Sticks Threshold Test and self-reported valence ratings for two target odorants (phenylethyl alcohol and vanillin) and the University of Pennsylvania Smell Identification Test), and an autism evaluation (Autism Diagnostic Observation Schedule-2). Children with ASD showed intact odor detection with reduced odor identification ability. Poor odor identification was significantly correlated with autism symptom severity. Children with SPD demonstrated reduced odor detection and identification ability. These findings provide evidence for differential patterns of smell processing among ASD and non-ASD neurodevelopmental disorders. Future studies are needed to determine whether the association of impaired olfaction and increased autism symptoms is due to shared etiology.

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13. Wright B, Teige C, Watson J, Hodkinson R, Marshall D, Varley D, Allgar V, Mandefield L, Parrott S, Kingsley E, Hargate R, Mitchell N, Ali S, McMillan D, Wang H, Hewitt C. Autism Spectrum Social Stories In Schools Trial 2 (ASSSIST2) : study protocol for a randomised controlled trial analysing clinical and cost-effectiveness of Social Stories™ in primary schools. BMC Psychol ;2020 (Jun 12) ;8(1):60.

BACKGROUND : Interventions designed to support children with a diagnosis of Autism Spectrum Conditions (ASC) can be time consuming, needing involvement of outside experts. Social Stories™ are a highly personalised intervention aiming to give children with ASC social information or describing an otherwise difficult situation or skill. This can be delivered daily by staff in education settings. Studies examining Social Story™ use have yielded mostly positive results but have largely been single case studies with a lack of randomised controlled trials (RCTs). Despite this numerous schools are utilising Social Stories™, and a fully powered RCT is timely. METHODS : A multi-site pragmatic cluster RCT comparing care as usual with Social Stories™ and care as usual. This study will recruit 278 participants (aged 4-11) with a clinical diagnosis of ASC, currently attending primary school in the North of England. Approximately 278 school based staff will be recruited to provide school based information about participating children with approximately 140 recruited to deliver the intervention. The study will be cluster randomised by school. Potential participants will be screened for eligibility prior to giving informed consent. Follow up data will be collected at 6 weeks and 6 months post randomisation and will assess changes in participants’ social responsiveness, goal based outcomes, social and emotional health. The primary outcome measure is the Social Responsiveness Scale Second Edition (SRS-2) completed by school based staff at 6 months. Approvals have been obtained from the University of York’s Research Governance Committee, Research Ethics Committee and the Health Research Authority. Study results will be submitted for publication in peer-reviewed journals and disseminated to participating families, educational staff, local authority representatives, community groups and Patient and Participant Involvement representatives. Suggestions will be made to NICE about treatment evidence dependent on findings. DISCUSSION : This study addresses a much used but currently under researched intervention and results will inform school based support for primary school children with a diagnosis of ASC. TRIAL REGISTRATION : The trial is registered on the ISRCTN registry (registration number : ISRCTN11634810). The trial was retrospectively registered on 23rd April 2019.

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