Pubmed du 06/08/19

Pubmed du jour

2019-08-06 12:03:50

1. Baum RA. {{Learning To Play and Playing To Learn: Enhancing Interactions in Young Children With ASD}}. {Pediatrics};2019 (Aug 6)

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2. Benachenhou S, Etcheverry A, Galarneau L, Dube J, Caku A. {{Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case-control study}}. {Autism Res};2019 (Aug 6)

Autism spectrum disorder (ASD) has been associated with low cholesterol levels in a limited number of studies. However, the prevalence of hypocholesterolemia as well as the degree of association with ASD remains to be elucidated. We therefore sought to investigate the lipid profiles of a group of French-Canadian ASD individuals. The medical records of 79 ASD individuals and 79 age and gender-matched healthy controls were retrospectively reviewed. The fasting lipid profiles including total cholesterol (TC), high-density lipoprotein, triglycerides, and low-density lipoprotein were extracted for individuals of both groups along with the following clinical data: anthropometric measurements, medication use and associated disorders. Lipid parameters were compared to age and gender-based normative population and categorized in centile groups. The prevalence of hypocholesterolemia was revealed to be more than threefold higher in ASD individuals as compared to the general population (23%; P = 0.005). The 25th centile was determined as a potential TC threshold that could best predict the ASD (odds ratio [OR] = 3.04; 95% confidence interval [CI]: 1.58-6.65; P < 0.001). This study identified specific ASD comorbidities associated with hypocholesterolemia: TC levels below the 10th centile were associated with a higher rate of ASD-associated intellectual disability (OR = 3.33; 95% CI: 1.26-8.00) and anxiety/depression (OR = 4.74; 95% CI: 1.40-15.73). Overall, these results support a potential association between hypocholesterolemia and ASD occurrence. Application of this study to larger populations is urging to provide more extensive data that may further elucidate the association between hypocholesterolemia and ASD. Autism Res 2019, 00: 1-10. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Association of autism spectrum disorder (ASD) with abnormally low levels of cholesterol (hypocholesterolemia) has been documented before. These studies were incomplete, and the conclusion remains speculative. Here, we reviewed the medical records of 79 French-Canadian ASD individuals and compared their total cholesterol (TC) levels to healthy individuals matched for age and gender. We observed four times more hypocholesterolemia in ASD than in the general population. Furthermore, low TC in ASD was associated with higher rates of ASD-associated intellectual disability and anxiety/depression. Our results support an association between hypocholesterolemia and ASD and open novel opportunities for the diagnosis and treatment of specific forms of ASD. Lien vers le texte intégral (Open Access ou abonnement)

3. Cordero C, Schieve LA, Croen LA, Engel SM, Maria Siega-Riz A, Herring AH, Vladutiu CJ, Seashore CJ, Daniels JL. {{Neonatal jaundice in association with autism spectrum disorder and developmental disorder}}. {J Perinatol};2019 (Aug 6)

OBJECTIVE: To examine the association between neonatal jaundice and autism spectrum disorder (ASD) and non-ASD developmental disorder (DD). STUDY DESIGN: We analyzed data from the Study to Explore Early Development, a US multisite, case-control study conducted from 2007 to 2011. Developmental assessment classified children aged 2-5 years into: ASD (n = 636), DD (n = 777), or controls (POP; n = 926). Neonatal jaundice (n = 1054) was identified from medical records and maternal interviews. We examined associations between neonatal jaundice and ASD and DD using regression models to obtain adjusted odds ratios (aOR). RESULTS: Our results showed interaction between gestational age and neonatal jaundice. Neonatal jaundice was associated with ASD at 35-37 weeks (aOR = 1.83, 95%CI 1.05, 3.19), but not >/=38 weeks gestation (aOR = 0.97, 95%CI 0.76, 1.24). Similar results were observed with DD. CONCLUSIONS: Further exploration of timing and severity of neonatal jaundice and ASD/DD is warranted.

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4. Dimitropoulos A, Zyga O, Russ SW. {{Early Social Cognitive Ability in Preschoolers with Prader-Willi Syndrome and Autism Spectrum Disorder}}. {J Autism Dev Disord};2019 (Aug 6)

Children with Prader-Willi syndrome (PWS) and autism spectrum disorder (ASD) present with challenges in social cognitive ability, Research comparing PWS to ASD is important given the implication of 15q11-q13 region in the biology of autism. However, recent findings question the accuracy of relying solely on parent report in behavioral characterization. Thus, this study examined social cognition in an observable pretend play task and by parent report in 50 preschool children (ages 3-5) with PWS, by subtype, compared to ASD. Behaviorally, the paternal deletion subtype expressed overall higher functioning, whereas the maternal uniparental disomy subtype performed more similarly to the ASD group. Results are the first to show deficits in social cognitive ability early in development. The severity and differences in deficits between PWS subtypes are important in informing early intervention efforts.

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5. Ezzeddine EW, DeBar RM, Reeve SA, Townsend DB. {{Using video modeling to teach play comments to dyads with ASD}}. {J Appl Behav Anal};2019 (Aug 4)

Individuals with autism spectrum disorder (ASD) often display deficits in social and conversational skills. One method used to improve social deficits includes video modeling. When targeting conversational skills, few studies have included individuals with ASD as conversational partners. We evaluated the effects of video modeling on commenting (i.e., scripted statements) during leisure activities with dyads of children with ASD using a multiple-probe-across-activities design. Video modeling alone was found to be effective in increasing scripted statements for 3 of 6 participants. Video modeling, tangible reinforcement, and additional prompts were necessary for the remaining participants. Results maintained 1 and 3 weeks after mastery. Procedures, goals and outcomes were reported as socially valid. Limitations and areas of future research are discussed.

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6. Faundez V, Wynne M, Crocker A, Tarquinio D. {{Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype}}. {Front Integr Neurosci};2019;13:30.

Neurodevelopmental disorders represent a challenging biological and medical problem due to their genetic and phenotypic complexity. In many cases, we lack the comprehensive understanding of disease mechanisms necessary for targeted therapeutic development. One key component that could improve both mechanistic understanding and clinical trial design is reliable molecular biomarkers. Presently, no objective biological markers exist to evaluate most neurodevelopmental disorders. Here, we discuss how systems biology and « omic » approaches can address the mechanistic and biomarker limitations in these afflictions. We present heuristic principles for testing the potential of systems biology to identify mechanisms and biomarkers of disease in the example of Rett syndrome, a neurodevelopmental disorder caused by a well-defined monogenic defect in methyl-CpG-binding protein 2 (MECP2). We propose that such an approach can not only aid in monitoring clinical disease severity but also provide a measure of target engagement in clinical trials. By deepening our understanding of the « big picture » of systems biology, this approach could even help generate hypotheses for drug development programs, hopefully resulting in new treatments for these devastating conditions.

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7. Gengoux GW, Abrams DA, Schuck R, Millan ME, Libove R, Ardel CM, Phillips JM, Fox M, Frazier TW, Hardan AY. {{A Pivotal Response Treatment Package for Children With Autism Spectrum Disorder: An RCT}}. {Pediatrics};2019 (Aug 6)

OBJECTIVES: Our aim was to conduct a randomized controlled trial to evaluate a pivotal response treatment package (PRT-P) consisting of parent training and clinician-delivered in-home intervention on the communication skills of children with autism spectrum disorder. METHODS: Forty-eight children with autism spectrum disorder and significant language delay between 2 and 5 years old were randomly assigned to PRT-P (n = 24) or the delayed treatment group (n = 24) for 24 weeks. The effect of treatment on child communication skills was assessed via behavioral coding of parent-child interactions, standardized parent-report measures, and blinded clinician ratings. RESULTS: Analysis of child utterances during the structured laboratory observation revealed that, compared with the delayed treatment group, children in PRT-P demonstrated greater improvement in frequency of functional utterances (F1,41 = 6.07; P = .026; d = 0.61). The majority of parents in the PRT-P group (91%) were able to implement pivotal response treatment (PRT) with fidelity within 24 weeks. Children receiving PRT-P also demonstrated greater improvement on the Brief Observation of Social Communication Change, on the Clinical Global Impressions Improvement subscale, and in number of words used on a parent-report questionnaire. CONCLUSIONS: This is the first 24-week randomized controlled trial in which community treatment is compared with the combination of parent training and clinician-delivered PRT. PRT-P was effective for improving child social communication skills and for teaching parents to implement PRT. Additional research will be needed to understand the optimal combination of treatment settings, intensity, and duration, and to identify child and parent characteristics associated with treatment response.

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8. Gottlieb MM. {{A Mathematical Model Relating Pitocin Use during Labor with Offspring Autism Development in terms of Oxytocin Receptor Desensitization in the Fetal Brain}}. {Comput Math Methods Med};2019;2019:8276715.

This paper develops a mathematical model describing the potential buildup of high oxytocin concentrations in the maternal circulation during labor in terms of continuous Pitocin infusion rate, half-life, and maternal weight. Oxytocin override of the degradation of oxytocin by placental oxytocinase is introduced to model the potential transfer of oxytocin from the maternal circulation across the placenta into the fetal circulation and from there into the brain of the fetus. The desensitization unit D equal to 1.8E6 (pg.min)/ml is employed to establish a desensitization threshold and by extension, a downregulation threshold as a function of oxytocin override concentration and continuous Pitocin infusion time, that could be a factor in the subsequent development of autism among offspring. Epidemiological studies by Duke University [1], Yale University [2], and Harvard University [3] are discussed regarding Pitocin use and offspring autism development for an explanation of the weak correlations they identified. The findings of the Harvard epidemiological study are reinterpreted regarding Pitocin use and its conclusion questioned. Further evaluations of the findings of these three epidemiological studies are called for to incorporate medical information on quantity of Pitocin used, continuous Pitocin infusion rate, length of labor, and maternal weight to determine if a correlation can be established with offspring autism development above an empirically determined desensitization threshold for Pitocin use. Suggestions for research are discussed, including an alternative to continuous Pitocin infusion, pulsatile infusion of Pitocin during labor induction, which may mitigate possible offspring autism development.

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9. Guo D, Peng Y, Wang L, Sun X, Wang X, Liang C, Yang X, Li S, Xu J, Ye WC, Jiang B, Shi L. {{Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function}}. {Mol Psychiatry};2019 (Aug 6)

Genetic studies of autism spectrum disorder (ASD) have revealed multigene variations that converge on synaptic dysfunction. DOCK4, a gene at 7q31.1 that encodes the Rac1 guanine nucleotide exchange factor Dock4, has been identified as a risk gene for ASD and other neuropsychiatric disorders. However, whether and how Dock4 disruption leads to ASD features through a synaptic mechanism remain unexplored. We generated and characterized a line of Dock4 knockout (KO) mice, which intriguingly displayed a series of ASD-like behaviors, including impaired social novelty preference, abnormal isolation-induced pup vocalizations, elevated anxiety, and perturbed object and spatial learning. Mice with conditional deletion of Dock4 in hippocampal CA1 recapitulated social preference deficit in KO mice. Examination in CA1 pyramidal neurons revealed that excitatory synaptic transmission was drastically attenuated in KO mice, accompanied by decreased spine density and synaptic content of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)- and NMDA (N-methyl-D-aspartate)-type glutamate receptors. Moreover, Dock4 deficiency markedly reduced Rac1 activity in the hippocampus, which resulted in downregulation of global protein synthesis and diminished expression of AMPA and NMDA receptor subunits. Notably, Rac1 replenishment in the hippocampal CA1 of Dock4 KO mice restored excitatory synaptic transmission and corrected impaired social deficits in these mice, and pharmacological activation of NMDA receptors also restored social novelty preference in Dock4 KO mice. Together, our findings uncover a previously unrecognized Dock4-Rac1-dependent mechanism involved in regulating hippocampal excitatory synaptic transmission and social behavior.

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10. Hesp C, Steenbeek HW, van Geert PLC. {{Socio-Emotional Concern Dynamics in a Model of Real-Time Dyadic Interaction: Parent-Child Play in Autism}}. {Front Psychol};2019;10:1635.

We used a validated agent-based model-Socio-Emotional CONcern DynamicS (SECONDS)-to model real-time playful interaction between a child diagnosed with Autism Spectrum Disorders (ASD) and its parent. SECONDS provides a real-time (second-by-second) virtual environment that could be used for clinical trials and testing process-oriented explanations of ASD symptomatology. We conducted numerical experiments with SECONDS (1) for internal model validation comparing two parental behavioral strategies for stimulating social development in ASD (play-centered vs. initiative-centered) and (2) for empirical case-based model validation. We compared 2,000 simulated play sessions of two particular dyads with (second-by-second) time-series observations within 29 play sessions of a real parent-child dyad with ASD on six variables related to maintaining and initiating play. Overall, both simulated dyads provided a better fit to the observed dyad than reference null distributions. Given the idiosyncratic behaviors expected in ASD, the observed correspondence is non-trivial. Our results demonstrate the applicability of SECONDS to parent-child dyads in ASD. In the future, SECONDS could help design interventions for parental care in ASD.

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11. Krahn G, Havercamp S. {{Shining the Light on Mental Health in a Population at Risk: Cerebral Palsy and Other Developmental Disabilities}}. {Ann Intern Med};2019 (Aug 6)

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12. Krishnaraj R, Haase F, Coorey B, Luca EJ, Wong I, Boyling A, Ellaway C, Christodoulou J, Gold WA. {{Genome-wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signalling pathways and cellular functions as potential therapeutic targets}}. {Hum Mutat};2019 (Aug 5)

The discovery that Rett syndrome is caused by mutations in the MECP2 gene has provided a major breakthrough in our understanding of the disorder. However, despite this, there is still limited understanding of the underlying pathophysiology of the disorder hampering the development of curative treatments. Over the years, a number of animal models have been developed contributing to our knowledge on the role of MECP2 in development and improving our understanding of how subtle expression levels affect brain morphology and function. Transcriptomic and proteomic studies of animal models are useful in identifying perturbations in functional pathways and providing avenues for novel areas of research into disease. This review focuses on published transcriptomic and proteomic studies of mouse models of Rett syndrome with the aim of providing a summary of all the studies, the reported dysregulated genes and functional pathways that are found to be perturbed. The 36 articles identified highlighted a number of dysfunctional pathways as well as perturbed biological networks and cellular functions including synaptic dysfunction and neuronal transmission, inflammation and mitochondrial dysfunction. These data reveal biological insights that contribute to the disease process which may be targeted to investigate curative treatments. This article is protected by copyright. All rights reserved.

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13. Liang S, Li Z, Wang Y, Li X, Yang X, Zhan X, Huang Y, Gao Z, Zhang M, Sun C, Zhang Y, Wu L. {{Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder}}. {Front Neurosci};2019;13:712.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Aberrant DNA methylation has been observed in ASD but the mechanisms remain largely unknown. Here, we employed discordant monozygotic twins to investigate the contribution of DNA methylation to ASD etiology. Genome-wide DNA methylation analysis was performed using samples obtained from five pairs of ASD-discordant monozygotic twins, which revealed a total of 2,397 differentially methylated genes. Further, such gene list was annotated with Kyoto Encyclopedia of Genes and Genomes and demonstrated predominant activation of neurotrophin signaling pathway in ASD-discordant monozygotic twins. The methylation of SH2B1 gene was further confirmed in the ASD-discordant, ASD-concordant monozygotic twins, and a set of 30 pairs of sporadic case-control by bisulfite-pyrosequencing. The results showed that there was a greater DNA methylation difference in ASD-discordant monozygotic twins than ASD-concordant monozygotic twins. Further, verification of the Chr.16:28856743 of SH2B1 showed significant differences in DNA methylation between case and control. These results suggest abnormal methylation of SH2B1 is associated with ASD etiology. Our data suggest that it might be worthwhile to further explore the functions of SH2B1 and related genes of neurotrophin signaling pathway in ASD.

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14. Lugo-Marin J, Diez-Villoria E, Magan-Maganto M, Perez-Mendez L, Alviani M, de la Fuente-Portero JA, Canal-Bedia R. {{Spanish Validation of the Autism Quotient Short Form Questionnaire for Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2019 (Aug 5)

The objective of this study was to adapt and validate the abbreviated version of the « Autism-Spectrum Quotient » (AQ-Short) in a sample of Spanish native adults. A total of 46 individuals with ASD, 41 ASD-relatives, 17 patients with schizophrenia spectrum disorders and 190 non-clinical adults were administered the Spanish version of the AQ-Short. The results of the confirmatory factorial analysis found two high-order factors (Social Behaviour and Numbers/Patterns) and four subscales (Social Skills, Routines, Switching and Imagination). The reliability analysis showed very good internal structure and test-retest reliability. The AQ-Short also showed moderate convergent validity with ADOS-2. Differences by group were found in the ASD group when compared to other groups. Gender differences were only found in the non-clinical group.

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15. Lukmanji S, Manji SA, Kadhim S, Sauro KM, Wirrell EC, Kwon CS, Jette N. {{The co-occurrence of epilepsy and autism: A systematic review}}. {Epilepsy Behav};2019 (Aug 6);98(Pt A):238-248.

OBJECTIVE: We aimed to review the literature to determine the incidence and prevalence of autism in epilepsy and epilepsy in autism, conditions that are often comorbid. METHODS: We adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards, and the protocol was registered with PROSPERO. MEDLINE, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews were searched from inception until July 4, 2016. Studies were included if they reported an incidence or prevalence of autism in epilepsy or epilepsy in autism. These estimates were described using mean, standard deviation, median, and interquartile range. RESULTS: Seventy-four studies reporting on 283,549 patients were included. The median overall period prevalence of epilepsy in people with autism was 12.1% while the median overall period prevalence of autism in people with epilepsy was 9.0% when including all population types. When excluding studies that investigated patients with syndromic epilepsy or developmental delay, the median overall period prevalence of epilepsy in people with autism was 11.2% while the median overall period prevalence of autism in people with epilepsy was 8.1%. We observed trends for sex as the prevalence of autism in epilepsy was higher in males while the prevalence of epilepsy in autism was higher in females. It is important to interpret these estimates with caution, as there was significant heterogeneity between studies. Meta-regression found no association between study quality and prevalence or incidence estimates (all p-values>0.05). CONCLUSIONS: The period prevalence of epilepsy in people with autism, and vice versa, was consistently higher than previously reported estimates of the occurrence of these disorders in the general population. These findings highlight the importance of screening for autism in people who have epilepsy and epilepsy in people who have autism and may help shed light on shared pathogenesis between these conditions.

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16. Mazon-Cabrera R, Vandormael P, Somers V. {{Antigenic Targets of Patient and Maternal Autoantibodies in Autism Spectrum Disorder}}. {Front Immunol};2019;10:1474.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose behavioral symptoms become apparent in early childhood. The underlying pathophysiological mechanisms are only partially understood and the clinical manifestations are heterogeneous in nature, which poses a major challenge for diagnosis, prognosis and intervention. In the last years, an important role of a dysregulated immune system in ASD has emerged, but the mechanisms connecting this to a disruption of brain development are still largely unknown. Although ASD is not considered as a typical autoimmune disease, self-reactive antibodies or autoantibodies against a wide variety of targets have been found in a subset of ASD patients. In addition, autoantibodies reactive to fetal brain proteins have also been described in the prenatal stage of neurodevelopment, where they can be transferred from the mother to the fetus by transplacental transport. In this review, we give an extensive overview of the antibodies described in ASD according to their target antigens, their different origins, and timing of exposure during neurodevelopment.

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17. Modi B, Pimpinella D, Pazienti A, Zacchi P, Cherubini E, Griguoli M. {{Possible Implication of the CA2 Hippocampal Circuit in Social Cognition Deficits Observed in the Neuroligin 3 Knock-Out Mouse, a Non-Syndromic Animal Model of Autism}}. {Front Psychiatry};2019;10:513.

Autism spectrum disorders (ASDs) comprise a heterogeneous group of neuro-developmental abnormalities with a strong genetic component, characterized by deficits in verbal and non-verbal communication, impaired social interactions, and stereotyped behaviors. In a small percentage of cases, ASDs are associated with alterations of genes involved in synaptic function. Among these, relatively frequent are mutations/deletions of genes encoding for neuroligins (NLGs). NLGs are postsynaptic adhesion molecules that, interacting with their presynaptic partners neurexins, ensure the cross talk between pre- and postsynaptic specializations and synaptic stabilization, a condition needed for maintaining a proper excitatory/inhibitory balance within local neuronal circuits. We have focused on mice lacking NLG3 (NLG3 knock-out mice), animal models of a non-syndromic form of autism, which exhibit deficits in social behavior reminiscent of those found in ASDs. Among different brain areas involved in social cognition, the CA2 region of the hippocampus has recently emerged as a central structure for social memory processing. Here, in vivo recordings from anesthetized animals and ex vivo recordings from hippocampal slices have been used to assess the dynamics of neuronal signaling in the CA2 hippocampal area. In vivo experiments from NLG3-deficient mice revealed a selective impairment of spike-related slow wave activity in the CA2 area and a significant reduction in oscillatory activity in the theta and gamma frequencies range in both CA2 and CA3 regions of the hippocampus. These network effects were associated with an increased neuronal excitability in the CA2 hippocampal area. Ex vivo recordings from CA2 principal cells in slices obtained from NLG3 knock-out animals unveiled a strong excitatory/inhibitory imbalance in this region accompanied by a strong reduction of perisomatic inhibition mediated by CCK-containing GABAergic interneurons. These data clearly suggest that the selective alterations in network dynamics and GABAergic signaling observed in the CA2 hippocampal region of NLG3 knock-out mice may account for deficits in social memory reminiscent of those observed in autistic patients.

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18. Narin N, Baspinar O, Pamukcu O, Sunkak S, Tuncay A, Tasci O, Baykan A. {{Percutaneous ASD closure of children weighing less than 10 kg}}. {Acta Cardiol};2019 (Aug 3):1-6.

Background: Traditionally the procedure of percutaneous ASD closure is carried out in children weighing more than 15 kg. The aim of this study was to discuss the success, efficacy and safety of the percutaneous closure of symptomatic ASD in children weighing less than 10 kg. Material and methods: This study was performed in two centres. A total of 44 patients were included. Demographic and angiographic data of these patients were gathered retrospectively from patients’ records. Main indications for ASD closure were: failure to thrive, recurrent respiratory infections, bronchopulmonary dysplasia and genetic syndromes. Results: Median weight of patients was 9.0(8.12-9.50) kg. Bodyweight of 22 patients was less than 3 percentiles. In the follow-up, this number was lowered to 9 patients at 12 months. Median age of patients was 18.0(12.0-285) months. Minimum age and weight of patients was 3 months and 4.5 kg, respectively. Median mean pulmonary pressure was 24.0(20.0-29.5). The values of median defect size were measured in Cath lab as 13.0(10.75-15.3) mm. Median device size was 13(9-15) mm. Defect size was evaluated according to body weight and body surface area. The ratio of weight per defect size was 0.65(0.54-0.84) also the ratio of body surface area per defect size was 0.032(0.028-0.04). The ratio of total septum per device diameter was 2.5(2.1-3.1). Types of devices used were Amplatzer Septal Occluder, Cera Flex Septal Occluder, Figulla Flex II Atrial Septal Occluder, Memopart Septal Occluder. All cases were closed successfully, but the device had to be retrieved in one patient after successful positioning because it was detected that device compressed the aorta. No major complications were seen. Conclusion: In the experienced centres, percutaneous ASD closure can be done effectively and safely in symptomatic children weighing less than 10 kg.

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19. Oyku Memis C, Sevincok D, Dogan B, Baygin C, Ozbek M, Kutlu A, Cakaloz B, Sevincok L. {{The subthreshold autistic traits in patients with adult-onset obsessive-compulsive disorder: a comparative study with adolescent patients}}. {Riv Psichiatr};2019 (Jul-Aug);54(4):168-174.

OBJECTIVE: The primary objective of this study was to compare the adult-onset and adolescent obsessive-compulsive disorder (OCD) patients in terms of the subthreshold autistic traits. METHODS: 29 adolescent, and 45 adult-onset OCD patients were assessed by Autism-spectrum Quotient (AQ). RESULTS: The ratio of males to females, the frequency of ritualistic compulsions, and the mean number of lifetime compulsions were significantly higher in adolescents with OCD compared to adult-onset patients. Adult-onset OCD patients had significantly higher scores on total, social skills, attention shifting, and imagination subscales of AQ than adolescent OCD patients. The mean number of compulsions, attention shifting scores of AQ, and female gender significantly predicted the distinction between adolescent and adult-onset OCD patients. In adult-onset patients, there were significant correlations between the mean number of lifetime obsessions and total, social skills, attention switching, communication, and imagination subscale scores of AQ. CONCLUSIONS: We suggest that subthreshold autistic traits may play a significant role in the occurence of obsessive-complusive symptoms (OCS) in adult-onset OCD. Autistic traits seemed to be higher and had an closer relationship with the frequency of lifetime obsessions in AO-OCD patients than in adolescent patients.

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20. Protopopova A, Matter AL, Harris BN, Wiskow KM, Donaldson JM. {{Comparison of contingent and noncontingent access to therapy dogs during academic tasks in children with autism spectrum disorder}}. {J Appl Behav Anal};2019 (Aug 4)

This study compared contingent and noncontingent access to therapy dogs during educational tasks for children with autism spectrum disorder using a multielement design. The experimenters assessed whether initial preference for the dog predicted reinforcer efficacy and how preference changed across time. A higher response rate during contingent dog sessions than baseline sessions occurred for 4 out of 5 participants, suggesting that the dog functioned as a reinforcer. One participant engaged in a high rate of responding in both contingent and noncontingent dog conditions. Preference assessments revealed idiosyncrasies, suggesting that further research is needed into the predictive nature of initial preference assessments with animals as part of the stimulus array. The experimenters also analyzed salivary cortisol before and after sessions to determine if learning about the upcoming interaction with a dog reduced salivary cortisol in children. Cortisol was variable across participants, with only some deriving a potential physiological benefit from expecting to interact with the dog.

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21. Rezae M, McMeekin D, Tan T, Krishna A, Lee H, Falkmer T. {{Public transport planning tool for users on the autism spectrum: from concept to prototype}}. {Disabil Rehabil Assist Technol};2019 (Aug 5):1-11.

Purpose: This research explored the challenges of public transport use for individuals on the autism spectrum. It, subsequently, proposed a mobile application solution, coproduced by individuals on the autism spectrum, to facilitate public transport use. Methods: We, first, conducted a review of the literature to highlight the challenges people on the autism spectrum face when utilizing public transport. We, then, designed a list of mobile application functionalities that address the identified problems. To validate these functionalities, 27 young autistic adults and 19 families of autistic individuals were employed. Finally, based on the findings, we designed a mobile application that helps facilitate public transport use for those on the autism spectrum. Results: We found that the most prevalent concerns, in public transport use, amongst autistic individuals and their families are safety and spatial awareness. Specific problems include finding one’s way to the bus stop, boarding the correct service and disembarking at the correct stop. Interestingly, anxiety about unexpected events was also a barrier. Sensory sensitivity, similarly, was found to be an obstacle. Conclusions: This study defined the challenges of public transport use for autistic individuals and proposed a technological solution. The findings can also inform innovators, public transport providers and policymakers to improve public transport accessibility. Implications for rehabilitation People on the autism spectrum heavily rely on other individuals, namely family and friends, for their transportation needs. This dependence results in immobility for the autistic individuals and significant time and economical sacrifice for the person responsible for the transportation. Public transport, a cheap and widely available form of transportation, has not yet been clearly studied with individuals on the autism spectrum. We clearly define the challenges of using public transport and put forward a trip planner mobile application, coproduced by autistic individuals, that facilitate it. In the long term, this enhanced travel independence can lead to greater education and employment opportunities and an overall improved quality of life.

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22. Sedgewick F, Kerr-Gaffney J, Leppanen J, Tchanturia K. {{Anorexia Nervosa, Autism, and the ADOS: How Appropriate Is the New Algorithm in Identifying Cases?}}. {Front Psychiatry};2019;10:507.

Thirty years of scholarship has suggested that anorexia nervosa (AN) may be a « female presentation » of autism, supported by work which has found elevated rates of autism traits and diagnoses among women with clinical levels of AN. These traits are often assessed using the Autism Diagnostic Observation Schedule 2nd Edition (ADOS-2), considered the « gold-standard » tool. Recently, the authors of the ADOS-2 revised the diagnostic algorithm for the adult version of the assessment-the one most often used with AN patients. We therefore examined differences in the scores, rates of diagnosis, and correlations with other mental health issues between the two diagnostic algorithms among women with and without AN. One hundred seventy-five women with current AN, who had recovered from AN, and with no history of AN, between the ages of 12 and 53, took part in an ADOS-2 assessment. Their scores were then calculated according to both the original and the new algorithms. The new ADOS-2 algorithm identifies more women as potentially being on the autism spectrum than the old algorithm. Under both algorithms, more currently ill AN patients were identified as potentially being autistic than those with no history of AN. Recovered individuals represented a midpoint between the scores of those with and without AN on both algorithms. There were no correlations with mental health scores in any group, meaning that the new ADOS-2 algorithm is not falsely identifying anxious behaviors or depressive presentations as signs of autism in this group. Overall, we found that more AN patients and recovered individuals scored above cut-off on the new ADOS-2 algorithm, suggesting that women who experience AN may have more autistic traits, which in part persist following weight restoration and recovery. However, the ADOS-2 should not be used alone but in combination with broader clinical assessments to determine whether an autism diagnosis is appropriate for these women.

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23. Tsang LPM, How CH, Yeleswarapu SP, Wong CM. {{Autism spectrum disorder: early identification and management in primary care}}. {Singapore Med J};2019 (Jul);60(7):324-328.

Autism spectrum disorder (ASD) is characterised by persistent deficits in social communication and interaction as well as restricted, repetitive patterns of behaviour and interests. Early detection and early intervention programmes improve functional outcomes. Family physicians should screen for ASD opportunistically when children attend clinics for acute issues and during scheduled well-child assessments. Early warning signs of ASD include the lack of social gestures at 12 months, using no meaningful single words at 18 months, and having no interest in other children or no spontaneous two-word phrases at 24 months. Children with suspected ASD should be referred to appropriate specialist centres as early as possible for multidisciplinary assessment and diagnosis.

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24. Wong CH, Gau SS, Chou TL. {{Neural correlates of association strength and categorical relatedness in youths with autism spectrum disorder}}. {Autism Res};2019 (Aug 6)

Impaired language and communication are commonly observed in youths with autism spectrum disorders (ASDs). However, the organization of semantic knowledge in youths with ASD remains unclear compared to typically developing (TD) youths. The present study addresses this issue by using functional magnetic resonance imaging (fMRI) to examine the distinction between association strength and categorical relatedness of semantic knowledge. A sample of 31 male youths with ASD (mean age = 12.1 years, SD = 1.2) and 38 TD youths (mean age = 11.9 years, SD = 1.0) was recruited with matched age, gender, and handedness. Participants decided if two visually presented Chinese characters were semantically related during fMRI scanning. For weaker association strength, the ASD group showed greater left cuneus activation, which was positively correlated with the picture completion for visual perception, whereas the TD group showed greater middle temporal gyrus and inferior frontal gyrus activation. For higher categorical relatedness, the TD group showed greater activation than the ASD group in the occipitotemporal cortex and left precuneus, which was positively correlated with the similarities for concept formulation. Findings imply that the ASD group may use lower-level visual information for both association strength and categorical relatedness. The TD group showed higher-level controlled processes of more elaborate semantic representations for association strength and more elaborate features of categorical knowledge for semantic selection and integration. Autism Res 2019, 00: 1-11. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) often present language/communication impairments. Exploring the difference of semantic processing between youths with ASD and typically developing (TD) youths is crucial for understanding the organization of semantic knowledge. We found different neural substrates of semantic knowledge between these two groups. ASD youths may rely more on lower-level visual information during semantic judgments, whereas TD youths showed higher-level controlled processes of more elaborate semantic representations for selection and integration of words, phrases, and sentences.

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25. Wu HF, Lu TY, Chu MC, Chen PS, Lee CW, Lin HC. {{Targeting the inhibition of fatty acid amide hydrolase ameliorate the endocannabinoid-mediated synaptic dysfunction in a valproic acid-induced rat model of Autism}}. {Neuropharmacology};2019 (Aug 6):107736.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social interaction impairment, stereotypical/repetitive behaviors and emotional deregulation. The endocannabinoid (eCB) system plays a crucial role in modulating the behavioral traits that are typically core symptoms of ASD. The major molecular mechanisms underlying eCB-dependent long-term depression (eCB-LTD) are mediated by group 1 metabotropic glutamate receptor (mGluR)-induced removal of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Recently, modulation of anandamide (AEA), one of the main endocannabinoids in the brain, has been reported to alter social behaviors in genetic models of ASD. On this basis, we investigated the effects of treatment and the synaptic mechanism underlying AEA-mediated signaling in prenatal exposure to valproic acid (VPA) in rats. We found that the social deficits, repetitive behaviors and abnormal emotion-related behaviors in VPA-exposed offspring were improved after treatment with an inhibitor of AEA degrading enzyme, URB597. Using an integrative approach combing electrophysiological and cellular mechanisms, the results showed that the impaired eCB-LTD, abnormal mGluR-mediated LTD (mGluR-LTD) and decreased removal of AMPAR subunits GluA1 and GluA2 were reversed by URB597 in the prefrontal cortex (PFC) of VPA-exposed offspring. Taken together, these results provide the first evidence that rescue of the ASD-like phenotype by URB597 is mediated by enhancing the mechanism of removal of AMPAR subunits GluA1/2 underlying AEA signaling in the PFC in a VPA-induced model of ASD.

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26. Yingling ME, Bell BA, Hock RM. {{Comparing Neighborhoods of Children With Autism Spectrum Disorder in a Medicaid Waiver Program and a State Population, 2007-2015}}. {Psychiatr Serv};2019 (Aug 5):appips201800479.

OBJECTIVE: This study investigated equity in enrollment in a Medicaid waiver program for early intensive behavioral intervention for children with autism spectrum disorder (ASD). METHODS: State administrative, Medicaid, and U.S. Census data for children enrolled in the waiver program between 2007 and 2015 (N=2,111) were integrated. Multivariate and bivariate analyses were used to compare enrollees’ neighborhood demographic characteristics with those of the state’s general population, with controls for enrollees’ age, sex, and race-ethnicity. RESULTS: Findings indicate that in general, enrollment was equitable. During the years in which there were inequities, children who lived in neighborhoods of privilege were favored. These neighborhoods had higher median incomes, lower poverty levels, and fewer female-headed households and were located in urban areas. CONCLUSIONS: As states work to provide equitable treatment to children with ASD and their families, it is important to track potential inequities between children who do and do not enroll in services and to use this information to inform outreach efforts. States may turn to South Carolina for insight on how to ensure equity.

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