Pubmed du 12/08/20

mercredi 12 août 2020

1. Amini A, Namvarpour Z, Namvarpour M, Raoofi A. Risperidone accelerates bone loss in rats with autistic-like deficits induced by maternal lipopolysaccharides exposure. Life Sci ;2020 (Aug 8):118197.

AIMS : Patients with neurodevelopmental disorders, usually suffer from bone diseases. Many studies have revealed a higher risk of fracture after atypical antipsychotic drug Risperidone (RIS) treatment, which is usually used to treat such disorders. It remains debatable whether neurodevelopmental disorders by itself are the cause of bone diseases or pharmacotherapy may be the reason. MATERIALS AND METHODS : This study attempts to evaluate the biomechanical, histological, stereological, and molecular properties of bones in the offspring of Lipopolysaccharide (LPS) and saline-treated mothers that received saline, drug vehicle or the atypical antipsychotic drug risperidone (RIS) at different days of postnatal development. After postnatal drug treatment, animals were assessed for autistic-like behaviors. Then their bones were taken for evaluations. RESULTS : Maternal LPS exposure resulted in deficits in all behavioral tests and RIS ameliorated these behaviors (p < 0.01& p < 0.05). The administration of LPS and RIS individually led to a significant decrease in the biomechanical parameters such as bone stiffness, strength and the energy used to fracture of bone. The numerical density of osteocalcin-positive cells were significantly decreased in these groups. These rats also had decreased RUNX2 and osteocalcin gene expression. When LPS rats were treated with RIS, these conditions were accelerated (p < 0.001). DISCUSSIONS : The results of our preclinical study, consistent with previous studies in animals, explore that autistic-like deficits induced by prenatal exposure to LPS, can reduce bone stability and bone mass similar to those observed in neurodevelopmental disorders, and, for the first time, reveal that this condition worsened when these animals were treated with RIS.

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2. Aubé B, Follenfant A, Goudeau S, Derguy C. Public Stigma of Autism Spectrum Disorder at School : Implicit Attitudes Matter. J Autism Dev Disord ;2020 (Aug 11)

This study examines the public stigma of children with autism spectrum disorder (ASD) by their school-aged peers, focusing on both explicit and implicit attitudes. The twofold aims were to provide a broader picture of public stigma and to explore age-related changes in attitudes. Students completed an explicit measure of the public stigma and an implicit measure of attitudes after watching a video displaying children with ASD vs. typically developing (TD) children. Both measures showed more negative perceptions towards children with ASD compared to TD children. However, while explicit attitudes improved with age, implicit attitudes remained constantly negative. This finding suggests that both explicit and implicit attitudes should be considered when promoting an inclusive climate at school.

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3. Chao OY, Pathak SS, Zhang H, Dunaway N, Li JS, Mattern C, Nikolaus S, Huston JP, Yang YM. Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism. Mol Brain ;2020 (Aug 10) ;13(1):111.

The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T(+)Itpr3(tf)/J (BTBR) mice and Fragile X Mental Retardation 1 knockout (Fmr1-KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6 J wild-type ones. In contrast, Fmr1-KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher "complexity" and lower "texture". Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1-KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.

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4. Chung LMY, Law QPS, Fong SSM. Using Physical Food Transformation to Enhance the Sensory Approval of Children with Autism Spectrum Disorders for Consuming Fruits and Vegetables. J Altern Complement Med ;2020 (Aug 11)

Introduction : Children with autistic spectrum disorders (ASD) commonly exhibit aberrant tactile, taste, and smell sensitivity to foods. Food transformation that alters the appearance, texture, and temperature of foods is promising for solving this sensitivity problem. Objectives : This study evaluated the effect of physical transformation of fruits and vegetables (FV) to snacks to enhance ASD children’s sensory approval for eating them. Design : This was a quasiexperimental design study. It lasted for 4 weeks with three episodes of FV exposure to the ASD children per week. The original condition was conducted in the first and fourth week, while intervention was performed in the second and third week. Settings : Food exposure took place in schools in a quiet room. Subjects : This study recruited 56 ASD children. Intervention : Food transformation constituted changing bananas into ice-cream, zucchinis and sweet potatoes into chips, apples and kiwis into popsicles, and carrots into juice. Outcome Measures : FV acceptance and habitual consumption were measured at baseline and postintervention. Results : ASD children increased their consumption of all FV, but only banana consumption was statistically significant from 55.3 to 78.0 g (p < 0.05). For habitual consumption, parents reported increases in all FV consumption for all three measured fruits and 2 of 3 measures of vegetables (pre vs. post mean for bananas : 2.4 vs. 2.9, apples 2.6 vs. 3.2, kiwis 2.4 vs. 2.9, zucchinis 1.9 vs. 2.5, and sweet potatoes 1.8 vs. 2.4 ; p < 0.05). Conclusion : Physical changes of foods may improve impaired sensory processing of ASD children to promote their FV acceptance. Project Code : RG 55/2019-2020R.

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5. Golden CEM, Yee Y, Wang VX, Harony-Nicolas H, Hof PR, Lerch JP, Buxbaum JD. Reduced axonal caliber and structural changes in a rat model of Fragile X syndrome with a deletion of a K-Homology domain of Fmr1. Transl Psychiatry ;2020 (Aug 12) ;10(1):280.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene. Neuroanatomical alterations have been reported in both male and female individuals with FXS, yet the morphological underpinnings of these alterations have not been elucidated. In the current study, we found structural changes in both male and female rats that model FXS, some of which are similarly impaired in both sexes, including the superior colliculus and periaqueductal gray, and others that show sex-specific changes. The splenium of the corpus callosum, for example, was only impaired in males. We also found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Furthermore, we found that overall, male rats have higher brain-wide diffusion than female rats. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and reveal an impairment at the level of the axon that could cause structural changes in white matter regions.

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6. Kylliäinen A, Häkkinen S, Eränen S, Rantanen K, Ebeling H, Bölte S, Helminen TM. Social competence group intervention (SOCO) for children with autism spectrum disorder : A pilot study. Scand J Psychol ;2020 (Aug 11)

This study aimed to describe concept of social competence as a theoretical background for social skills group intervention for children with autism spectrum disorder (ASD). A model of social competence comprised of three components : social skills, social performance, and social adjustment. We also examined the feasibility and preliminary efficacy of the manualized Social Competence group intervention for children with autism spectrum disorder (SOCO) using a variety of outcome measures. The nine-month intervention included children groups, parental support groups and co-operation with teachers. A pilot study involved 23 children aged 7 to 12 years (n = 16 intervention, n = 7 control) and intervention outcomes were measured with questionnaires for parents and teachers, neuropsychological tests, and observations. The parents of the intervention group reported improvements in social skills and social adjustment, whereas the teachers reported increases in social performance. Findings also indicated that affect recognition skills, social overtures, and reactions to peers were improved in the intervention group. Although the evidence of the pilot study should be considered as preliminary, it gives some indication of the feasibility of the SOCO group intervention and supports the usability of the theoretical background and approach for multiple outcome measures.

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7. Luo Y, Eran A, Palmer N, Avillach P, Levy-Moonshine A, Szolovits P, Kohane IS. A multidimensional precision medicine approach identifies an autism subtype characterized by dyslipidemia. Nat Med ;2020 (Aug 10)

The promise of precision medicine lies in data diversity. More than the sheer size of biomedical data, it is the layering of multiple data modalities, offering complementary perspectives, that is thought to enable the identification of patient subgroups with shared pathophysiology. In the present study, we use autism to test this notion. By combining healthcare claims, electronic health records, familial whole-exome sequences and neurodevelopmental gene expression patterns, we identified a subgroup of patients with dyslipidemia-associated autism.

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8. Magen-Molho H, Harari-Kremer R, Pinto O, Kloog I, Dorman M, Levine H, Weisskopf MG, Raz R. Spatiotemporal distribution of autism spectrum disorder prevalence among birth cohorts during 2000-2011 in Israel. Ann Epidemiol ;2020 (Aug) ;48:1-8.

PURPOSE : Studies indicate an apparent sharp increasing trend in autism spectrum disorder (ASD) incidence and prevalence worldwide. This nationwide study aims at depicting ASD prevalence distribution in Israel in both space and time. METHODS : Based on data from Israel National Insurance Institute, the study population included all children born in Israel 2000-2011 (n = 1,786,194), of whom 11,699 (0.655%) were subsequently diagnosed with ASD (until December 31, 2016). Prevalence was calculated and mapped by dividing the number of ASD cases within each year of birth by the number of births during that year, for each spatial unit, and similarly for several spatiotemporal levels of aggregation. RESULTS : ASD prevalence varies substantially across different geographic areas in Israel, with considerably higher prevalence concentrated in central Israel. Strong associations were found between locality-level socioeconomic index, ethnicity, and peripherality and ASD prevalence, and even after adjustment for them, excess prevalence for ASD still persisted in certain localities. No spatial dependence of prevalence, with and without adjustment for the locality-level variables, was found (Moran’s I = -0.000546, -0.00335, respectively). CONCLUSIONS : Our findings provide important insights regarding health disparities affecting ASD diagnosis, directing further health policy intervention and further research.

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9. Nagano M, Zane E, Grossman RB. Structural and Contextual Cues in Third-Person Pronoun Interpretation by Children with Autism Spectrum Disorder and Their Neurotypical Peers. J Autism Dev Disord ;2020 (Aug 12)

This study investigates the use of structural and discourse contextual cues in the interpretation of third-person pronouns by children and adolescents with autism and their neurotypical peers. Results show that referent-biasing contextual information influences pronominal interpretation and modulates looking patterns in both groups compared to a context-neutral condition. These results go against the predictions of Weak Central Coherence and the notion that pragmatics in general is impaired in ASD, since the ASD group was able to use details in discourse context to influence the pronominal interpretation process. However, although discourse context influenced looking patterns in both groups, the groups nevertheless diverged in the nature of these patterns, suggesting that behavioral differences may emerge in more complicated discourse tasks.

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10. Okazaki K, Ota T, Makinodan M, Kishimoto N, Yamamuro K, Ishida R, Takahashi M, Yasuda Y, Hashimoto R, Iida J, Kishimoto T. Associations of childhood experiences with event-related potentials in adults with autism spectrum disorder. Sci Rep ;2020 (Aug 10) ;10(1):13447.

Childhood maltreatment is defined as experiencing of physical, emotional and sexual abuse and neglect in childhood. Maltreatment in childhood leads to substantial psychosocial problems later in life in the general population. Individuals with autism spectrum disorder (ASD) have a higher risk of experiencing stressful and traumatic events, such as maltreatment, during childhood. Although childhood maltreatment reportedly leads to psychosocial problems in adults with ASD, the biological associations between childhood experiences and brain function in this population remain understudied. Here, we evaluated the relationships between childhood experiences and event-related potential (ERP) components during the auditory odd-ball task in adults with ASD (N = 21) and typically developed (TD) individuals (N = 22). We found that the higher the severity of sexual abuse, the larger the amplitude of P300 at Fz, Cz, C3, and C4 in individuals with ASD. Conversely, the severity of child maltreatment was associated with P300 latency at Cz and C3 in TD individuals. Moreover, full IQ was significantly associated with the MMN amplitude at Fz, Cz, C3, and C4 in TD individuals. These findings provide the first evidence that ERPs could be used to study the impacts childhood experiences on the brain of individuals with ASD and that childhood sexual abuse has salient impacts on brain function in this population.

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11. Smythe T, Zuurmond M, Tann CJ, Gladstone M, Kuper H. Early intervention for children with developmental disabilities in low and middle-income countries - the case for action. Int Health ;2020 (Aug 11)

In the last two decades, the global community has made significant progress in saving the lives of children <5 y of age. However, these advances are failing to help all children to thrive, especially children with disabilities. Most early child development research has focussed on the impact of biological and psychosocial factors on the developing brain and the effect of early intervention on child development. Yet studies typically exclude children with disabilities, so relatively little is known about which interventions are effective for this high-risk group. In this article we provide an overview of child development and developmental disabilities. We describe family-centred care interventions that aim to provide optimal stimulation for development in a safe, stable and nurturing environment. We make the case for improving opportunities for children with developmental disabilities to achieve their full potential and thrive, including through inclusive early childhood development intervention. Finally, we call for the global research community to adopt a systematic approach for better evidence for and implementation of early interventions for children with developmental disabilities in low-resource settings.

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12. Zhang H. Synaptic dysregulation in autism spectrum disorders. J Neurosci Res ;2020 (Aug 11)

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