1. {{Erratum: Assessments of Amino Acids, Ammonia and Oxidative Stress Among Cohort of Egyptian Autistic Children: Correlations with Electroencephalogram and Disease Severity [Corrigendum]}}. {Neuropsychiatr Dis Treat};2020;16:325.
[This corrects the article DOI: 10.2147/NDT.S233105.].
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2. Aldosary M, Al-Bakheet A, Al-Dhalaan H, Almass R, Alsagob M, Al-Younes B, AlQuait L, Mustafa OM, Bulbul M, Rahbeeni Z, Alfadhel M, Chedrawi A, Al-Hassnan Z, AlDosari M, Al-Zaidan H, Al-Muhaizea MA, AlSayed MD, Salih MA, AlShammari M, Faizal-Ul-Haque M, Chishti MA, Al-Harazi O, Al-Odaib A, Kaya N, Colak D. {{Rett Syndrome, a Neurodevelopmental Disorder, Whole-Transcriptome, and Mitochondrial Genome Multiomics Analyses Identify Novel Variations and Disease Pathways}}. {Omics};2020 (Feb 27)
Rett syndrome (RTT) is a severe neurodevelopmental disorder reported worldwide in diverse populations. RTT is diagnosed primarily in females, with clinical findings manifesting early in life. Despite the variable rates across populations, RTT has an estimated prevalence of approximately 1 in 10,000 live female births. Among 215 Saudi Arabian patients with neurodevelopmental and autism spectrum disorders, we identified 33 patients with RTT who were subsequently examined by genome-wide transcriptome and mitochondrial genome variations. To the best of our knowledge, this is the first in-depth molecular and multiomics analyses of a large cohort of Saudi RTT cases with a view to informing the underlying mechanisms of this disease that impact many patients and families worldwide. The patients were unrelated, except for 2 affected sisters, and comprised of 25 classic and eight atypical RTT cases. The cases were screened for methyl-CpG binding protein 2 (MECP2), CDKL5, FOXG1, NTNG1, and mitochondrial DNA (mtDNA) variants, as well as copy number variations (CNVs) using a genome-wide experimental strategy. We found that 15 patients (13 classic and two atypical RTT) have MECP2 mutations, 2 of which were novel variants. Two patients had novel FOXG1 and CDKL5 variants (both atypical RTT). Whole mtDNA sequencing of the patients who were MECP2 negative revealed two novel mtDNA variants in two classic RTT patients. Importantly, the whole-transcriptome analysis of our RTT patients’ blood and further comparison with previous expression profiling of brain tissue from patients with RTT revealed 77 significantly dysregulated genes. The gene ontology and interaction network analysis indicated potentially critical roles of MAPK9, NDUFA5, ATR, SMARCA5, RPL23, SRSF3, and mitochondrial dysfunction, oxidative stress response and MAPK signaling pathways in the pathogenesis of RTT genes. This study expands our knowledge on RTT disease networks and pathways as well as presents novel mutations and mtDNA alterations in RTT in a population sample that was not previously studied.
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3. Alsaedi RH, Carrington S, Watters JJ. {{Behavioral and Neuropsychological Evaluation of Executive Functions in Children with Autism Spectrum Disorder in the Gulf Region}}. {Brain Sci};2020 (Feb 22);10(2)
This study examined the executive functioning abilities and development profiles of children with autism spectrum disorder (ASD). The participants were 119 children with ASD and 30 typically developing children (age range: 6-12 years) who were recruited from three Gulf states. The findings revealed executive functioning deficits in the ASD population when compared to the normative data or to those children without ASD. However, not all the forms of executive functioning were found to be impaired. Age-related differences in the patterns of performance on the utilized measures of executive functioning were also identified. The overall findings provide valuable information regarding the different components of the executive functions, which may prove useful in relation to the development of assessment protocols for ASD.
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4. Chen K, Fu Y, Wang Y, Liao L, Xu H, Zhang A, Zhang J, Fan L, Ren J, Fang B. {{Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder}}. {Microb Ecol};2020 (Feb 26)
Autism spectrum disorder (ASD) is a brain-based neurodevelopmental disorder characterized by behavioral abnormalities. Accumulating studies show that the gut microbiota plays a vital role in the pathogenesis of ASD, and gut microbiota transplantation (GMT) is a promising technique for the treatment of ASD. In clinical applications of GMT, it is challenging to obtain effective transplants because of the high costs of donor selection and heterogeneity of donors’ gut microbiota, which can cause different clinical responses. In vitro batch culture is a fast, easy-to-operate, and repeatable method to culture gut microbiota. Thus, the present study investigates the feasibility of treating ASD with in vitro cultured gut microbiota as transplants. We cultured gut microbiota via the in vitro batch culture method and performed GMT in the maternal immune activation (MIA)-induced ASD mouse model with original donor microbiota and in vitro cultured microbiota. Open field, three-chamber social, marble burying, and self-grooming tests were used for behavioral improvement assessment. Serum levels of chemokines were detected. Microbial total DNA was extracted from mouse fecal samples, and 16S rDNA was sequenced using Illumina. Our results showed that GMT treatment with original and cultured donor gut microbiota significantly ameliorated anxiety-like and repetitive behaviors and improved serum levels of chemokines including GRO-alpha (CXCL1), MIP-1alpha (CCL3), MCP-3 (CCL7), RANTES (CCL5), and Eotaxin (CCL11) in ASD mice. Meanwhile, the gut microbial communities of the two groups that received GMT treatment were changed compared with the ASD mice groups. In the group treated with in vitro cultured donor gut microbiota, there was a significant decrease in the relative abundance of key differential taxa, including S24-7, Clostridiaceae, Prevotella_other, and Candidatus Arthromitus. The relative abundance of these taxa reached close to the level of healthy mice. Prevotella_other also decreased in the group treated with original donor gut microbiota, with a significant increase in Ruminococcaceae and Oscillospira. The present study demonstrated that GMT with in vitro cultured microbiota also improved behavioral abnormalities and chemokine disorders in an ASD mouse model compared with GMT with original donor gut microbiota. In addition, it significantly modified several key differential taxa in gut microbial composition.
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5. Gatarek P, Rosiak A, Borowczyk K, Glowacki R, Kaluzna-Czaplinska J. {{Higher Levels of Low Molecular Weight Sulfur Compounds and Homocysteine Thiolactone in the Urine of Autistic Children}}. {Molecules};2020 (Feb 21);25(4)
In this study, the levels of concentration of homocysteine thiolactone (HTL), cysteine (Cys), and cysteinylglycine (CysGly) in the urine of autistic and non-autistic children were investigated and compared. HTL has never been analyzed in autistic children. The levels of low molecular weight sulfur compounds in the urine of both groups were determined by validated methods based on high-performance liquid chromatography with spectrofluorometric and diode-array detectors. The statistical data show a significant difference between the examined groups. Children with autism were characterized by a significantly higher level of HTL (p = 5.86 x 10(-8)), Cys (p = 1.49 x 10(-10)) and CysGly (p = 1.06 x 10(-8)) in urine compared with the control group. A difference in the p-value of <0.05 is statistically significant. Higher levels of HTL, Cys, and CysGly in the urine of 41 children with autism, aged 3 to 17, were observed. The obtained results may indicate disturbances in the metabolism of methionine, Cys, and glutathione in some autistic patients. These preliminary results suggest that further research with more rigorous designs and a large number of subjects is needed. Lien vers le texte intégral (Open Access ou abonnement)
6. Howe SJ, Hewitt K, Baraskewich J, Cassidy S, McMorris CA. {{Suicidality Among Children and Youth With and Without Autism Spectrum Disorder: A Systematic Review of Existing Risk Assessment Tools}}. {J Autism Dev Disord};2020 (Feb 25)
Individuals with autism are at heightened risk for experiencing suicidality compared to those without autism. Despite this, it is unknown what tools are used to assess suicide risk in research and clinical practice among children and youth with autism. This systematic review examined tools commonly used to measure suicidality in children and youth with and without autism spectrum disorder. Four databases were searched. We identified five tools (C-SSRS, PSS, SITBI, SIQ-JR, BSS) commonly used with youth in the general population; however, we did not identify any tools that were commonly used autistic children and youth. Results highlight the lack of available tools utilized to measure suicidality in autistic children and youth. We propose a framework to facilitate research to fill this gap.
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7. Jin BX, Li N, Zhao Y, Qian XG, Liu ZH, Yang Y, Lin ZT, Zeng ZY. {{[Effect of acupoint catgut embedding therapy on joint attention and social communication in children with autism spectrum disorder: a randomized controlled trial]}}. {Zhongguo Zhen Jiu};2020 (Feb 12);40(2):162-166.
OBJECTIVE: To compare the clinical effect on the joint attention and social communication in children with autism spectrum disorder (ASD) between the combined treatment of acupoint catgut embedding therapy with rehabilitation training and the simple application of rehabilitation training. METHODS: A total of 60 children with ASD were randomized into an observation group and a control group, 30 cases in each one. In the control group, the routine ASD rehabilitation training was adopted, including conductive education, speech training and music therapy, once a day. In the observation group, on the base of the treatment as the control group, the catgut embedding therapy was applied to Shenting (GV 24), Baihui (GV 20), Shenmen (HT 7) and the optic area (the point of scalp acupuncture), once a week. In the two groups, the treatment for 4 weeks was as one course, at the interval of 1 week between the courses. A total of 3 courses of treatment were required. The social domain of the autism treatment evaluation checklist (ATEC) and the autism behavior checklist (ABC) were adopted to assess the therapeutic effect of the two groups. RESULTS: After treatment, the scores of each item of the social domain in ATEC and the scores of ABC (feeling, communication, physical movement, language and healthy behavior) were all lower than those before treatment in the two groups (P<0.01). The scores of each item in the observation group were lower than those in the control group after treatment (P<0.05). CONCLUSION: The combined treatment of acupoint catgut embedding therapy with the rehabilitation training effectively improves in the joint attention and social communication. The therapeutic effect of this combined treatment is better than the simple application of rehabilitation training. Lien vers le texte intégral (Open Access ou abonnement)
8. Kozlowski KF, Lopata C, Donnelly JP, Thomeer ML, Rodgers JD, Seymour C. {{Feasibility and Associated Physical Performance Outcomes of a High-Intensity Exercise Program for Children With Autism}}. {Res Q Exerc Sport};2020 (Feb 26):1-12.
Purpose: Children with autism spectrum disorder (ASD) without intellectual disability (ID) exhibit social and motor impairments and circumscribed interests/behaviors that contribute to lower physical activity (PA) levels. Despite the need for exercise interventions for these children, there is a dearth of evidence-based treatments. This study tested the feasibility of a high-intensity exercise program for children with ASD without ID, and associated changes in physical performance. Method: Fifty-eight children, ages 7-12 with ASD without ID participated. The intervention (5 weeks, 19 sessions, 60 mins ea.) was conducted during the summer. Each session was manualized (operationalized instructional procedure and curriculum) and targeted components of fitness and motor performance using skill development exercises, workouts, and game-related activities. Feasibility was assessed via fidelity (implementation accuracy), satisfaction surveys, attrition, and injuries. Physical performance was tested at baseline and posttest using measures of work production (completed rounds of an exercise circuit) and within-session activity levels (time in moderate-to-vigorous PA), and six exercise tests (sit and reach, push-ups, sit-ups, air squats, long jump, and PACER). Results: Results indicated high levels of fidelity (93.7%) and child and staff satisfaction, and no attrition or injuries, supporting the feasibility, tolerability, and safety of the protocol. Significant increases were found in work production and activity levels (ds 0.83 and 1.05, respectively) and on three exercise tests (sit ups, air squats, and long jump; ds 0.29-0.37). Conclusion: The exercise program was feasible and safe, and completion was associated with significant improvements in multiple areas of performance; a randomized controlled trial appears warranted.
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9. Nadeem MS, Al-Abbasi FA, Kazmi I, Murtaza BN, Zamzami MA, Kamal MA, Arif A, Afzal M, Anwar F. {{Multiple risk factors: A challenge in the management of Autism}}. {Curr Pharm Des};2020 (Feb 25)
Autism Spectrum Disorder (ASD) is an emerging health problem involving 1 out of every 68 children. The incidence rate of autism has increased 3 folds during last 3 decades. Due to the illusive picture of aetiology a considerable number of autistic children fail to receive proper behavioural and medicational treatment. The present study provides a cumulative account of autism risk factors. Several factors including the gene expression and gene mutations, environmental pollution, metal ion accumulation, exposure to pesticides, immune deficiencies, viral infections, mother’s age, health, mental status, mother’s interactions with the foetus, vaccination of mother and children, and modulations in gut microbiota have been debated. These risk factors may contribute to the development of autism either independently or synergistically leading to a broad spectrum of characteristics observed in the autistic patients. The variable quantitative influence of a wide spectrum of risk factors may result in a unique set of features in each autistic individual. However, the exact mechanism behind the combined impact of various aetiological factors is poorly understood hindering the adaptation of specified and effective therapies.
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10. Rahman R, Kodesh A, Levine SZ, Sandin S, Reichenberg A, Schlessinger A. {{Identification of newborns at risk for autism using electronic medical records and machine learning}}. {Eur Psychiatry};2020 (Feb 26);63(1):e22.
BACKGROUND.: Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome. The aim of the current study was to test the ability of machine learning (ML) models applied to electronic medical records (EMRs) to predict ASD early in life, in a general population sample. METHODS.: We used EMR data from a single Israeli Health Maintenance Organization, including EMR information for parents of 1,397 ASD children (ICD-9/10) and 94,741 non-ASD children born between January 1st, 1997 and December 31st, 2008. Routinely available parental sociodemographic information, parental medical histories, and prescribed medications data were used to generate features to train various ML algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross-validation by computing the area under the receiver operating characteristic curve (AUC; C-statistic), sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value [PPV]). RESULTS.: All ML models tested had similar performance. The average performance across all models had C-statistic of 0.709, sensitivity of 29.93%, specificity of 98.18%, accuracy of 95.62%, false positive rate of 1.81%, and PPV of 43.35% for predicting ASD in this dataset. CONCLUSIONS.: We conclude that ML algorithms combined with EMR capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.
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11. Schnider P, Bissantz C, Bruns A, Dolente C, Goetschi E, Jakob-Roetne R, Kunnecke B, Mueggler T, Muster W, Parrott N, Pinard E, Ratni H, Risterucci C, Rogers-Evans M, von Kienlin M, Grundschober C. {{Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder}}. {J Med Chem};2020 (Feb 27);63(4):1511-1525.
We recently reported the discovery of a potent, selective, and brain-penetrant V1a receptor antagonist, which was not suitable for full development. Nevertheless, this compound was found to improve surrogates of social behavior in adults with autism spectrum disorder in an exploratory proof-of-mechanism study. Here we describe scaffold hopping that gave rise to triazolobenzodiazepines with improved pharmacokinetic properties. The key to balancing potency and selectivity while minimizing P-gp mediated efflux was fine-tuning of hydrogen bond acceptor basicity. Ascertaining a V1a antagonist specific brain activity pattern by pharmacological magnetic resonance imaging in the rat played a seminal role in guiding optimization efforts, culminating in the discovery of balovaptan (RG7314, RO5285119) 1. In a 12-week clinical phase 2 study in adults with autism spectrum disorder balovaptan demonstrated improvements in Vineland-II Adaptive Behavior Scales, a secondary end point comprising communication, socialization, and daily living skills. Balovaptan entered phase 3 clinical development in August 2018.
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12. Stanley IH, Day TN, Gallyer AJ, Shelef L, Kalla C, Gutierrez PM, Joiner TE. {{Autism-related traits and suicide risk among active duty U.S. military service members}}. {Psychol Serv};2020 (Feb 27)
Suicide rates within the U.S. military are elevated. The interpersonal theory of suicide, supported within military samples, suggests that social disconnectedness confers risk for suicide. Autism spectrum disorder (ASD) is characterized by symptoms-difficulties in social communication/interaction (SCI) and restricted and repetitive behaviors (RRBs)-that contribute to social disconnectedness. To our knowledge, no study has examined ASD-related traits and suicide risk among active duty U.S. military service members. Participants included 292 active duty U.S. military service members (M [SD] age = 28.67 [7.40] years, 68.5% male, 78.1% White). The Autism Spectrum Quotient, Repetitive Behaviours Questionnaire-2 for Adults, Self-Injurious Thoughts and Behaviors Interview-Short Form, and Interpersonal Needs Questionnaire assessed for SCI difficulties, RRBs, suicidal symptoms, and interpersonal theory of suicide constructs (i.e., perceived burdensomeness, thwarted belongingness), respectively. Elevated levels of SCI difficulties and RRBs were associated with increased odds of reporting suicidal thoughts and behaviors occurring since joining the military, controlling for the number of years of service and suicidal symptoms occurring prior to joining the military. Perceived burdensomeness and thwarted belongingness statistically accounted for the relationship between ASD-related traits and suicidal ideation occurring since joining the military; a rival mediator, emotion dysregulation, was not a significant mediator. Among active duty U.S. military service members, greater ASD-related traits were associated with an increased likelihood of reporting suicidal thoughts and behaviors occurring since joining the military. Clinical efforts targeting perceived burdensomeness and thwarted belongingness might reduce suicide risk among military service members with elevated ASD-related traits. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
