1. Adams JB, Audhya T, Geis E, Gehn E, Fimbres V, Pollard EL, Mitchell J, Ingram J, Hellmers R, Laake D, Matthews JS, Li K, Naviaux JC, Naviaux RK, Adams RL, Coleman DM, Quig DW. {{Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder-A Randomized, Controlled 12-Month Trial}}. {Nutrients}. 2018; 10(3).
This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3-58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 +/- 11 IQ points vs. -0.6 +/- 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.
Lien vers le texte intégral (Open Access ou abonnement)
2. Alessio N, Riccitiello F, Squillaro T, Capasso S, Del Gaudio S, Di Bernardo G, Cipollaro M, Melone MAB, Peluso G, Galderisi U. {{Neural stem cells from a mouse model of Rett syndrome are prone to senescence, show reduced capacity to cope with genotoxic stress, and are impaired in the differentiation process}}. {Experimental & molecular medicine}. 2018; 50(3): 1.
Several aspects of stem cell life are governed by epigenetic variations, such as DNA methylation, histone modifications, and chromatin remodeling. Epigenetic events are also connected with the impairment of stem cell functions. For example, during senescence, there are significant changes in chromatin organization that alter transcription. The MECP2 protein can bind methylated cytosines and contribute to regulating gene expression at one of the highest hierarchical levels. Researchers are particularly interested in this protein, as up to 90% of Rett syndrome patients have an MECP2 gene mutation. Nevertheless, the role of MECP2 in this disease remains poorly understood. We used a mouse model of Rett syndrome to evaluate whether residual MECP2 activity in neural stem cells (NSCs) induced the senescence phenomena that could affect stem cell function. Our study clearly demonstrated that the reduced expression of MECP2 is connected with an increase in senescence, an impairment in proliferation capacity, and an accumulation of unrepaired DNA foci. Mecp2 (+/-) NSCs did not cope with genotoxic stress in the same way as the control cells did. Indeed, after treatment with different DNA-damaging agents, the NSCs from mice with mutated Mecp2 accumulated more DNA damage foci (gamma-H2AX+) and were more prone to cell death than the controls. Senescence in Mecp2 (+/-) NSCs decreased the number of stem cells and progenitors and gave rise to a high percentage of cells that expressed neither stem/progenitor nor differentiation markers. These cells could be senescent and dysfunctional.
Lien vers le texte intégral (Open Access ou abonnement)
3. Alhazmi A, Petersen R, Donald KA. {{Quality of life among parents of South African children with autism spectrum disorder}}. {Acta neuropsychiatrica}. 2018: 1-6.
OBJECTIVE: To describe the quality of life (QOL) of South African parents caring for children with autism spectrum disorder (ASD) as compared with parents of typically developing (TD) children from the same community. METHODS: A cross-sectional study was done evaluating the QOL of parents of 52 children (26 parents of children with ASD versus 26 parents of TD children) using a structured measure, (World Health Organization Quality of Life Assessment-BREF). RESULTS: The mean age of the children with ASD was 64.9 months (SD 14.5) versus 60.1 months (SD 13.5) for TD group. There was a male predominance among group of children with ASD (48 boys, four girls). The mean parental age of the ASD group was 32.9 years (SD 7.8) compared with 33.8 years (SD 6.8) for the TD group. As compared with parents of the TD children, parents of children with ASD had lower mean QOL scores in the four QOL domains: physical, psychological, social and environmental health (p<0.0001). the domain where the discrepancy between groups was greatest was the physical domain Where the mean score was 52.1 (SD 18.7) in the ASD group and 92 (SD 10.4) in the TD group. Lower income, severity level of ASD and lack of access to school placement of children with ASD were found significantly associated with parents' QOL domains. CONCLUSION: QOL of parents of children with ASD is significant lower than that of the parents of their TD peers across all domains and is an important component in management of the family which needs to be explored and addressed. Lien vers le texte intégral (Open Access ou abonnement)
4. Bag O, Alsen Guney S, Cevher Binici N, Tuncel T, Sahin A, Berksoy E, Ecevit C. {{Is it Infant colic or early symptom of autistic spectrum disorder?}}. {Pediatrics international : official journal of the Japan Pediatric Society}. 2018.
OBJECTIVE: Gastrointestinal disorders (GI) are common in autistic spectrum disorder (ASD). Infant colic (IC), the functional GI disorder of infancy, has not been evaluated in this patient group. The aim of this study is to determine the rate of IC in ASD and investigate a possible association between ASD and IC. METHODS: The study group included patient group (ASD) and healthy controls. The parents were questioned with Diagnostic Criteria for Infant Colic for clinical research purposes defined in Rome IV to diagnose IC, retrospectively. The sample size was estimated by considering a maximum type I error probability of 5% (alpha) and a type II error of 20%. RESULTS: The study consisted of 100 ASD patients (mean age: 6.6+/-3.5 years) and 100 healthy controls (mean age: 5.3+/-2.8 years). The rate of IC was 16% and 17% in ASD group and control group, respectively (p>0.05). A group of infants with excessive crying was observed with late-onset, long duration and was described as persistent crying infants. The rate of persistent crying infants was significantly higher in ASD group than controls (32% vs 9%, p<0.001). The relative risk of persistent crying was 4.40 in ASD. The rate of being misdiagnosed as IC in this group was 78%. CONCLUSION: The rate of IC is not increased in patients with ASDs. But infants with excessive crying should be well evaluated before being diagnosed with IC. Especially late onset and long duration of an infant crying may be a risk factor for developing ASD. This article is protected by copyright. All rights reserved. Lien vers le texte intégral (Open Access ou abonnement)
5. Bitsika V, Arnold WM, Sharpley CF. {{Cluster analysis of autism spectrum disorder symptomatology: Qualitatively distinct subtypes or quantitative degrees of severity of a single disorder?}}. {Res Dev Disabil}. 2018; 76: 65-75.
The decision to collapse several related disorders into a single diagnosis of Autism Spectrum Disorder (ASD) generated significant controversy and debate. There has been mixed evidence as to whether various ASD subtypes are qualitatively distinct or if they exist on a spectrum of symptom severity. The present study conducted a two-step cluster analysis of major ASD symptoms in a sample of 147 young males with ASD aged between 6yr and 18yr with IQ>70. Results indicated that a two-cluster solution (high and low severity of ASD symptomatology) was reliable and valid. Further, the construct of challenging behaviour was not a necessary component of the two-cluster solution, verifying the new conceptualisation of ASD. Further replication of these findings with other subsets of individuals with ASD is needed.
Lien vers le texte intégral (Open Access ou abonnement)
6. Borst HE, Townend GS, van Eck M, Smeets E, van den Berg M, Laan A, Curfs LMG. {{Abnormal Foot Position and Standing and Walking Ability in Rett Syndrome: an Exploratory Study}}. {Journal of developmental and physical disabilities}. 2018; 30(2): 281-95.
This study aimed to determine whether there is a relationship between abnormal foot position and standing and walking ability in individuals with Rett syndrome (RTT), a rare neurological condition primarily affecting females, often accompanied by impaired gross motor function and musculoskeletal deformities. Through means of an online survey, physiotherapists were asked to share information about their work and experience with individuals with RTT. They were asked about their clients’ scores on the Rett Syndrome Gross Motor Scale and measures of their foot deformity, passive range of motion of dorsiflexion of the foot, use of supportive footwear, pressure load on the foot, and symmetry in weight bearing. 45 physiotherapists gave answers relating to 67 individuals with RTT who ranged in age from 2 to over 50 years. Almost 80% had an abnormal foot position which required support of special shoes or orthoses. Approximately 55% experienced abnormal pressure load on the foot and 65% demonstrated asymmetrical weight-bearing; 22% could sit independently and 17% were able to stand and walk independently. Of all the variables investigated, only abnormal distribution of pressure on the foot and asymmetry in weight bearing through the legs were found to be (negatively) correlated with standing and walking ability. Physiotherapists can use this information to give advice on othopedic support for the feet of individuals with RTT.
Lien vers le texte intégral (Open Access ou abonnement)
7. Casanova EL, Sharp JL, Edelson SM, Kelly DP, Casanova MF. {{A Cohort Study Comparing Women with Autism Spectrum Disorder with and without Generalized Joint Hypermobility}}. {Behav Sci (Basel)}. 2018; 8(3).
Reports suggest comorbidity between autism spectrum disorder (ASD) and the connective tissue disorder, Ehlers-Danlos syndrome (EDS). People with EDS and the broader spectrum of Generalized Joint Hypermobility (GJH) often present with immune- and endocrine-mediated conditions. Meanwhile, immune/endocrine dysregulation is a popular theme in autism research. We surveyed a group of ASD women with/without GJH to determine differences in immune/endocrine exophenotypes. ASD women 25 years or older were invited to participate in an online survey. Respondents completed a questionnaire concerning diagnoses, immune/endocrine symptom history, experiences with pain, and seizure history. ASD women with GJH (ASD/GJH) reported more immune- and endocrine-mediated conditions than their non-GJH counterparts (p = 0.001). Autoimmune conditions were especially prominent in the ASD/GJH group (p = 0.027). Presence of immune-mediated symptoms often co-occurred with one another (p < 0.001-0.020), as did endocrine-mediated symptoms (p < 0.001-0.045), irrespective of the group. Finally, the numbers of immune- and endocrine-mediated symptoms shared a strong inter-relationship (p < 0.001), suggesting potential system crosstalk. While our results cannot estimate comorbidity, they reinforce concepts of an etiological relationship between ASD and GJH. Meanwhile, women with ASD/GJH have complex immune/endocrine exophenotypes compared to their non-GJH counterparts. Further, we discuss how connective tissue regulates the immune system and how the immune/endocrine systems in turn may modulate collagen synthesis, potentially leading to higher rates of GJH in this subpopulation. Lien vers le texte intégral (Open Access ou abonnement)
8. Cristiano C, Lama A, Lembo F, Mollica MP, Calignano A, Mattace Raso G. {{Interplay Between Peripheral and Central Inflammation in Autism Spectrum Disorders: Possible Nutritional and Therapeutic Strategies}}. {Frontiers in physiology}. 2018; 9: 184.
Pre- and post-natal factors can affect brain development and function, impacting health outcomes with particular relevance to neurodevelopmental diseases, such as autism spectrum disorders (ASDs). Maternal obesity and its associated complications have been related to the increased risk of ASDs in offspring. Indeed, animals exposed to maternal obesity or high fat diets are prone to social communication impairment and repetitive behavior, the hallmarks of autism. During development, fatty acids and sugars, as well as satiety hormones, like insulin and leptin, and inflammatory factors related to obesity-induced low grade inflammation, could play a role in the impairment of neuroendocrine system and brain neuronal circuits regulating behavior in offspring. On the other side, post-natal factors, such as mode of delivery, stress, diet, or antibiotic treatment are associated to a modification of gut microbiota composition, perturbing microbiota-gut-brain axis. Indeed, the interplay between the gastrointestinal tract and the central nervous system not only occurs through neural, hormonal, and immune pathways, but also through microbe-derived metabolic products. The modification of unhealthy perinatal and postnatal environment, manipulation of gut microbiota, nutritional, and dietary interventions could represent possible strategies in preventing or limiting ASDs, through targeting inflammatory process and gut microbiota.
Lien vers le texte intégral (Open Access ou abonnement)
9. Davis PE, Simon H, Meins E, Robins DL. {{Imaginary Companions in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
One of the deficits observed in autism spectrum disorder (ASD) is impaired imaginative play. One form of imaginative play common in many typically developing (TD) children is having an imaginary companion (IC). The occurrence of ICs has not been investigated extensively in children with ASD. We examined differences in parent report of IC between TD and ASD populations in 215 (111 with ASD) gender-matched children aged between 2 and 8 years. Findings indicate that significantly fewer children with ASD created ICs, although there were many between-group similarities in IC forms and functions. Results are discussed in terms of qualitative differences in play, social attributions, and how children with ASD conceptualize their ICs’ minds.
Lien vers le texte intégral (Open Access ou abonnement)
10. Hamilton A, Pelphrey K. {{Sensory and social features of autism – can they be integrated?}}. {Developmental cognitive neuroscience}. 2018; 29: 1-3.
Lien vers le texte intégral (Open Access ou abonnement)
11. Hertz-Picciotto I, Schmidt RJ, Krakowiak P. {{Understanding environmental contributions to autism: Causal concepts and the state of science}}. {Autism Res}. 2018.
The complexity of neurodevelopment, the rapidity of early neurogenesis, and over 100 years of research identifying environmental influences on neurodevelopment serve as backdrop to understanding factors that influence risk and severity of autism spectrum disorder (ASD). This Keynote Lecture, delivered at the May 2016 annual meeting of the International Society for Autism Research, describes concepts of causation, outlines the trajectory of research on nongenetic factors beginning in the 1960s, and briefly reviews the current state of this science. Causal concepts are introduced, including root causes; pitfalls in interpreting time trends as clues to etiologic factors; susceptible time windows for exposure; and implications of a multi-factorial model of ASD. An historical background presents early research into the origins of ASD. The epidemiologic literature from the last fifteen years is briefly but critically reviewed for potential roles of, for example, air pollution, pesticides, plastics, prenatal vitamins, lifestyle and family factors, and maternal obstetric and metabolic conditions during her pregnancy. Three examples from the case-control CHildhood Autism Risks from Genes and the Environment Study are probed to illustrate methodological approaches to central challenges in observational studies: capturing environmental exposure; causal inference when a randomized controlled clinical trial is either unethical or infeasible; and the integration of genetic, epigenetic, and environmental influences on development. We conclude with reflections on future directions, including exposomics, new technologies, the microbiome, gene-by-environment interaction in the era of -omics, and epigenetics as the interface of those two. As the environment is malleable, this research advances the goal of a productive and fulfilling life for all children, teen-agers and adults. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This Keynote Lecture, delivered at the 2016 meeting of the International Society for Autism Research, discusses evidence from human epidemiologic studies of prenatal factors contributing to autism, such as pesticides, maternal nutrition and her health. There is no single cause for autism. Examples highlight the features of a high-quality epidemiology study, and what comprises a compelling case for causation. Emergent research directions hold promise for identifying potential interventions to reduce disabilities, enhance giftedness, and improve lives of those with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
12. Karhson DS, Krasinska KM, Dallaire JA, Libove RA, Phillips JM, Chien AS, Garner JP, Hardan AY, Parker KJ. {{Plasma anandamide concentrations are lower in children with autism spectrum disorder}}. {Mol Autism}. 2018; 9: 18.
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112). Findings: Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034). Conclusions: These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
13. Lovrecic L, Rajar P, Volk M, Bertok S, Gnidovec Strazisar B, Osredkar D, Jekovec Vrhovsek M, Peterlin B. {{Diagnostic efficacy and new variants in isolated and complex autism spectrum disorder using molecular karyotyping}}. {Journal of applied genetics}. 2018.
Autism spectrum disorder (ASD) is a group of the neurodevelopment disorders presenting as an isolated ASD or more complex forms, where a broader clinical phenotype comprised of developmental delay and intellectual disability is present. Both the isolated and complex forms have a significant causal genetic component and submicroscopic genomic copy number variations (CNV) are the most common identifiable genetic factor in these patients. The data on microarray testing in ASD cohorts are still accumulating and novel loci are often identified; therefore, we aimed to evaluate the diagnostic efficacy of the method and the relevance of implementing it into routine genetic testing in ASD patients. A genome-wide CNV analysis using the Agilent microarrays was performed in a group of 150 individuals with an isolated or complex ASD. Altogether, 11 (7.3%) pathogenic CNVs and 15 (10.0%) variants of unknown significance (VOUS) were identified, with the highest proportion of pathogenic CNVs in the subgroup of the complex ASD patients (14.3%). An interesting case of previously unreported partial UPF3B gene deletion was identified among the pathogenic CNVs. Among the CNVs with unknown significance, four VOUS involved genes with possible correlation to ASD, namely genes SNTG2, PARK2, CADPS2 and NLGN4X. The diagnostic efficacy of aCGH in our cohort was comparable with those of the previously reported and identified an important proportion of genetic ASD cases. Despite the continuum of published studies on the CNV testing in ASD cohorts, a considerable number of VOUS CNVs is still being identified, namely 10.0% in our study.
Lien vers le texte intégral (Open Access ou abonnement)
14. Muscatelli F, Desarmenien MG, Matarazzo V, Grinevich V. {{Erratum to: Oxytocin Signaling in the Early Life of Mammals: Link to Neurodevelopmental Disorders Associated with ASD}}. {Current topics in behavioral neurosciences}. 2018.
Lien vers le texte intégral (Open Access ou abonnement)
15. Naguy A. {{A Roadmap to Clinical Assessment and Evaluation of Autism Spectrum Disorder}}. {Journal of family medicine and primary care}. 2017; 6(4): 883-4.
Lien vers le texte intégral (Open Access ou abonnement)
16. Pulikkan J, Maji A, Dhakan DB, Saxena R, Mohan B, Anto MM, Agarwal N, Grace T, Sharma VK. {{Gut Microbial Dysbiosis in Indian Children with Autism Spectrum Disorders}}. {Microbial ecology}. 2018.
Autism spectrum disorder (ASD) is a term associated with a group of neurodevelopmental disorders. The etiology of ASD is not yet completely understood; however, a disorder in the gut-brain axis is emerging as a prominent factor leading to autism. To identify the taxonomic composition and markers associated with ASD, we compared the fecal microbiota of 30 ASD children diagnosed using Childhood Autism Rating Scale (CARS) score, DSM-5 approved AIIMS-modified INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD), and Indian Scale for Assessment of Autism (ISAA) tool, with family-matched 24 healthy children from Indian population using next-generation sequencing (NGS) of 16S rRNA gene amplicon. Our study showed prominent dysbiosis in the gut microbiome of ASD children, with higher relative abundances of families Lactobacillaceae, Bifidobacteraceae, and Veillonellaceae, whereas the gut microbiome of healthy children was dominated by the family Prevotellaceae. Comparative meta-analysis with a publicly available dataset from the US population consisting of 20 ASD and 20 healthy control samples from children of similar age, revealed a significantly high abundance of genus Lactobacillus in ASD children from both the populations. The results reveal the microbial dysbiosis and an association of selected Lactobacillus species with the gut microbiome of ASD children.
Lien vers le texte intégral (Open Access ou abonnement)
17. Sapmaz D, Baykal S, Akbas S. {{The Clinical Features of Comorbid Pediatric Bipolar Disorder in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
The aim of this study was to describe clinical features of PBD comorbidity in children with ASD. Forty children with ASD and PBD aged 6-18 years, and 40 age- and sex-matched ASD subjects with no affective episodes were included in the study. Autism Behavior CheckList, Abberant Behavior CheckList, and Young Mania Rating Scale-Parent Version were completed. This study shows that PBD comorbidity in children with ASD involves a highly episodic course, with manic episodes, subsyndromal symptoms and interepisodic periods commonly being described in the manic symptom profile of these children. These findings need to be repeated with large samples, together with controlled studies concerning therapeutic interventions directed toward PBD comorbidity in children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
18. Zhao H, Jiang YH, Zhang YQ. {{Modeling autism in non-human primates: Opportunities and challenges}}. {Autism Res}. 2018.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted, repetitive patterns of behavior. For more than a decade, genetically-modified, risk factor-induced, as well as naturally occurring rodent models for ASD have been used as the most predominant tools to dissect the molecular and circuitry mechanisms underlying ASD. However, the apparent evolutionary differences in terms of social behavior and brain anatomy between rodents and humans have become an issue of debate regarding the translational value of rodent models for studying ASD. More recently, genome manipulation of non human primates using lentivirus-based gene expression, TALEN and CRISPR/Cas9 mediated gene editing techniques, has been reported. Genetically modified non-human primate models for ASD have been produced and characterized. While the feasibility, value, and exciting opportunities provided by the non-human primate models have been clearly demonstrated, many challenges still remain. Here, we review current progress, discuss the remaining challenges, and highlight the key issues in the development of non-human primate models for ASD research and drug development. Autism Res 2018,. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Over the last two decades, genetically modified rat and mouse models have been used as the most predominant tools to study mechanisms underlying autism spectrum disorder (ASD). However, the apparent evolutionary differences between rodents and humans limit the translational value of rodent models for studying ASD. Recently, several non-human primate models for ASD have been established and characterized. Here, we review current progress, discuss the challenges, and highlight the key issues in the development of non-human primate models for ASD research and drug development.
