Pubmed du 13/08/19

mardi 13 août 2019

1. Bilder DA, Esplin MS, Coon H, Burghardt P, Clark EAS, Fraser A, Smith KR, Worsham W, Chappelle K, Rayner T, Bakian AV. Early Second Trimester Maternal Serum Steroid-Related Biomarkers Associated with Autism Spectrum Disorder. J Autism Dev Disord ;2019 (Aug 13)

Epidemiologic studies link increased autism spectrum disorder (ASD) risk to obstetrical conditions associated with inflammation and steroid dysregulation, referred to as prenatal metabolic syndrome (PNMS). This pilot study measured steroid-related biomarkers in early second trimester maternal serum collected during the first and second trimester evaluation of risk study. ASD case and PNMS exposure status of index offspring were determined through linkage with autism registries and birth certificate records. ASD case (N = 53) and control (N = 19) groups were enriched for PNMS exposure. Higher estradiol and lower sex hormone binding globulin (SHBG) were significantly associated with increased ASD risk. Study findings provide preliminary evidence to link greater placental estradiol activity with ASD and support future investigations of the prenatal steroid environment in ASD.

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2. Hamrick LR, Seidl A, Tonnsen BL. Acoustic properties of early vocalizations in infants with fragile X syndrome. Autism Res ;2019 (Aug 13)

Fragile X syndrome (FXS) is a neurogenetic syndrome characterized by cognitive impairments and high rates of autism spectrum disorder (ASD). FXS is often highlighted as a model for exploring pathways of symptom expression in ASD due to the high prevalence of ASD symptoms in this population and the known single-gene cause of FXS. Early vocalization features-including volubility, complexity, duration, and pitch-have shown promise in detecting ASD in idiopathic ASD populations but have yet to be extensively studied in a population with a known genetic cause for ASD such as FXS. Investigating early trajectories of these features in FXS may inform our limited knowledge of potential mechanisms that predict later social communication outcomes. The present study addresses this need by presenting preliminary findings which (a) characterize early vocalization features in FXS relative to low-risk controls (LRC) and (b) test the specificity of associations between these features and language and ASD outcomes. We coded vocalization features during a standardized child-examiner interaction for 39 nine-month-olds (22 FXS, 17 LRC) whose clinical outcomes were assessed at 24 months. Our results provide preliminary evidence that within FXS, associations between vocalization features and 24-month language outcomes may diverge from those observed in LRC, and that vocalization features may be associated with later ASD symptoms. These findings provide a starting point for more research exploring these features as potential early markers of ASD in FXS, which in turn may lead to improved early identification methods, treatment approaches, and overall well-being of individuals with ASD. Autism Res2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY : Although vocal features of 9-month-olds with FXS did not differ from those of low-risk controls, several features were associated with later language and ASD outcomes at 24 months in FXS. These preliminary results suggest acoustic data may be related to clinical outcomes in FXS and potentially other high-risk populations. Further characterizing these associations may facilitate understanding of biological mechanisms and risk factors associated with social communication development and ASD.

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3. Knights E, Sunderland B, Parsons R, Ziatas K, Caccetta R. An evaluation of community pharmacists’ understanding of autism spectrum disorder : a cross-sectional study in Western Australia. Int J Pharm Pract ;2019 (Aug 13)

OBJECTIVES : To assess the knowledge and understanding of autism spectrum disorder (ASD) by community pharmacists, across Western Australia (WA) and evaluate the extent to which they incorporate ASD friendly practices in their pharmacy. METHODS : A cross-sectional study involved a postal questionnaire sent to a stratified random sample of 250 community pharmacies across WA. A score of >/=10/13 (>/=76.9%) appropriate responses to selected questions was considered an indication of ’good knowledge’ of ASD. Univariate associations between ’good knowledge’ and variables in the questionnaire were analysed using chi-square statistics, and multivariate analysis was performed using a logistic regression model. Demographic data relating to the pharmacy were used to determine the likelihood it was ASD friendly. KEY FINDINGS : Overall, 97/250 (38.8%) questionnaires were returned. There were 34/96 (35.4%) respondents classified as having ’good knowledge’. Stigma surrounding ASD was the single best indicator of ’good knowledge’ (P < 0.0001). None of the respondents indicated they catered specifically for ASD, and 38/97 (39.2%) reported that no changes were needed to their pharmacy to improve accessibility. There were a number of demographic features that increased the likelihood that pharmacies had the potential to be ASD friendly. CONCLUSIONS : Pharmacists overall had a basic understanding of ASD. Pharmacists who identified that stigma surrounding ASD existed in the community were more likely to achieve ’good knowledge’. There was a reluctance to improve pharmacy accessibility to patients with ASD. Pharmacists did not appear to incorporate ASD beneficial practices into their pharmacy and pharmacy environment.

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4. LaGasse AB, Manning RCB, Crasta JE, Gavin WJ, Davies PL. Assessing the Impact of Music Therapy on Sensory Gating and Attention in Children With Autism : A Pilot and Feasibility Study. J Music Ther ;2019 (Aug 13) ;56(3):287-314.

Children with autism spectrum disorder (ASD) frequently demonstrate atypical processing of sensory information and deficits in attentional abilities. These deficits may impact social and academic functioning. Although music therapy has been used to address sensory and attentional needs, there are no studies including physiologic indicators of sensory processing to determine the impact of music therapy. The objective of this study was to determine the feasibility of conducting study protocols, determine the adequacy of electroencephalography (EEG) and behavioral measures in identifying attentional differences in children with ASD compared with typically developing (TD) children, and to gather preliminary evidence of intervention effects on brain responses and attention outcomes. Seven children with high functioning ASD ages 5 -12 and seven age- and gender-matched TD completed procedures measuring brain responses (EEG) and behaviors (the Test of Everyday Attention for Children). Children with ASD then completed a 35-min individual music therapy attention protocol delivered by a board-certified music therapist ten times over 5 weeks. Children with ASD completed measures of brain responses and behavior post-intervention to determine pre- to post-test differences. Consent and completion rates were 100% for children who met the study criteria. Feasibility measures indicated that measures of brain responsivity could be used to determine attentional differences between children with ASD and typical children. Initial outcome data for brain responses and behavior indicated positive trends for the impact of music therapy on selective attention skills.

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5. Mouga S, Correia BR, Cafe C, Duque F, Oliveira G. Language Predictors in Autism Spectrum Disorder : Insights from Neurodevelopmental Profile in a Longitudinal Perspective. J Abnorm Child Psychol ;2019 (Aug 13)

Language outcome in individuals with autism spectrum disorder (ASD) is predicted by early developmental milestones and cognitive abilities. The development and acquisition of expressive language (particularly the onset of first phrases) is a relevant clinical milestone by school age, since its early presentation is associated to better long-term life outcomes and to lower core clinical severity of ASD. Focusing on predictors of language in ASD children, a number of outstanding questions remain to be answered, namely, whether there are differences in the early key neurodevelopmental abilities and whether those differences in a specific period of time might predict verbal development and acquisition of expressive language. We aim to understand how the neurodevelopmental profile of ASD children evolves from the preschool to the school age and if and which subarea can better predict acquisition of expressive language. Children with ASD (N = 205) were evaluated with a structured assessment of neurodevelopment in two different age periods : 1) preschool period (mean age four years) and 2) reassessment in the school period (mean age seven years). Our findings demonstrate that in nonverbal preschool children with ASD normal or near normal Performance Developmental Quotient (superior to 73.5) evaluated at preschool age is a good predictor of later language development in ASD, which has important implications for intervention programs targeting this population and family information.

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6. Seymour RA, Rippon G, Gooding-Williams G, Schoffelen JM, Kessler K. Dysregulated oscillatory connectivity in the visual system in autism spectrum disorder. Brain ;2019 (Aug 13)

Autism spectrum disorder is increasingly associated with atypical perceptual and sensory symptoms. Here we explore the hypothesis that aberrant sensory processing in autism spectrum disorder could be linked to atypical intra- (local) and interregional (global) brain connectivity. To elucidate oscillatory dynamics and connectivity in the visual domain we used magnetoencephalography and a simple visual grating paradigm with a group of 18 adolescent autistic participants and 18 typically developing control subjects. Both groups showed similar increases in gamma (40-80 Hz) and decreases in alpha (8-13 Hz) frequency power in occipital cortex. However, systematic group differences emerged when analysing intra- and interregional connectivity in detail. First, directed connectivity was estimated using non-parametric Granger causality between visual areas V1 and V4. Feedforward V1-to-V4 connectivity, mediated by gamma oscillations, was equivalent between autism spectrum disorder and control groups, but importantly, feedback V4-to-V1 connectivity, mediated by alpha (8-13 Hz) oscillations, was significantly reduced in the autism spectrum disorder group. This reduction was positively correlated with autistic quotient scores, consistent with an atypical visual hierarchy in autism, characterized by reduced top-down modulation of visual input via alpha-band oscillations. Second, at the local level in V1, coupling of alpha-phase to gamma amplitude (alpha-gamma phase amplitude coupling) was reduced in the autism spectrum disorder group. This implies dysregulated local visual processing, with gamma oscillations decoupled from patterns of wider alpha-band phase synchrony (i.e. reduced phase amplitude coupling), possibly due to an excitation-inhibition imbalance. More generally, these results are in agreement with predictive coding accounts of neurotypical perception and indicate that visual processes in autism are less modulated by contextual feedback information.

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7. So R, Makino K, Hirota T, Fujiwara M, Ocho K, Ikeda S, Tsubouchi S, Inagakip M. The 2-Year Course of Internet Addiction Among a Japanese Adolescent Psychiatric Clinic Sample with Autism Spectrum Disorder and/or Attention-Deficit Hyperactivity Disorder. J Autism Dev Disord ;2019 (Aug 13)

Internet addiction (IA) has been reported as prevalent in adolescents with autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD). However, the course of IA in this population has not been elucidated. The authors performed a 2-year follow-up study including 89 out of 132 adolescents with ASD and/or ADHD in a psychiatric clinical setting who participated in the original cross-sectional study assessing IA prevalence. Within this sample of participants from both the original and the follow-up study, results showed a 2-year IA remission and incidence rate of 60% and 5%, respectively. Our findings imply that the course of IA in psychiatric populations with ASD and/or ADHD might be similar to reports from previous studies with general adolescent populations.

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8. Zhuang Y, Xu HC, Shinde PV, Warfsmann J, Vasilevska J, Sundaram B, Behnke K, Huang J, Hoell JI, Borkhardt A, Pfeffer K, Taha MS, Herebian D, Mayatepek E, Brenner D, Ahmadian MR, Keitel V, Wieczorek D, Haussinger D, Pandyra AA, Lang KS, Lang PA. Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury. Gut ;2019 (Aug 13)

OBJECTIVE : The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease. DESIGN : Mice lacking Fmr1 gene expression were used to study the role of FMRP during tumour necrosis factor (TNF)-induced liver damage in disease model systems. Liver damage and mechanistic studies were performed using real-time PCR, Western Blot, staining of tissue sections and clinical chemistry. RESULTS : Fmr1(null) mice exhibited increased liver damage during virus-mediated hepatitis following infection with the lymphocytic choriomeningitis virus. Exposure to TNF resulted in severe liver damage due to increased hepatocyte cell death. Consistently, we found increased caspase-8 and caspase-3 activation following TNF stimulation. Furthermore, we demonstrate FMRP to be critically important for regulating key molecules in TNF receptor 1 (TNFR1)-dependent apoptosis and necroptosis including CYLD, c-FLIPS and JNK, which contribute to prolonged RIPK1 expression. Accordingly, the RIPK1 inhibitor Necrostatin-1s could reduce liver cell death and alleviate liver damage in Fmr1(null) mice following TNF exposure. Consistently, FMRP-deficient mice developed increased pathology during acute cholestasis following bile duct ligation, which coincided with increased hepatic expression of RIPK1, RIPK3 and phosphorylation of MLKL. CONCLUSIONS : We show that FMRP plays a central role in the inhibition of TNF-mediated cell death during infection and liver disease.

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