1. Broome K, McCabe P, Docking K, Doble M. {{A Systematic Review of Speech Assessments for Children With Autism Spectrum Disorder: Recommendations for Best Practice}}. {Am J Speech Lang Pathol};2017 (Aug 03):1-19.
Purpose: The purpose of this systematic review was to provide a summary and evaluation of speech assessments used with children with autism spectrum disorders (ASD). A subsequent narrative review was completed to ascertain the core components of an evidence-based pediatric speech assessment, which, together with the results of the systematic review, provide clinical and research guidelines for best practice. Method: A systematic search of eight databases was used to find peer-reviewed research articles published between 1990 and 2014 assessing the speech of children with ASD. Eligible articles were categorized according to the assessment methods used and the speech characteristics described. Results: The review identified 21 articles that met the inclusion criteria, search criteria, and confidence in ASD diagnosis. The speech of prelinguistic participants was assessed in seven articles. Speech assessments with verbal participants were completed in 15 articles with segmental and suprasegmental aspects of speech analyzed. Assessment methods included connected speech samples, single-word naming tasks, speech imitation tasks, and analysis of the production of words and sentences. Conclusions: Clinical and research guidelines for speech assessment of children with ASD are outlined. Future comparisons will be facilitated by the use of consistent reporting methods in research focusing on children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
2. Dimmock DP. {{Should we implement population screening for fragile X?}}. {Genet Med};2017 (Aug 03)
Lien vers le texte intégral (Open Access ou abonnement)
3. Fitzgerald M. {{The clinical utility of the ADI-R and ADOS in diagnosing autism}}. {Br J Psychiatry};2017 (Aug);211(2):117.
Lien vers le texte intégral (Open Access ou abonnement)
4. Frye RE, Slattery JC, Quadros EV. {{Folate metabolism abnormalities in autism: potential biomarkers}}. {Biomark Med};2017 (Aug 03)
Autism spectrum disorder (ASD) has been linked to abnormalities in folate metabolism. Polymorphisms in folate genes may act in complex polygenic ways to increase the risk of developing ASD. Autoantibodies that block folate transport into the brain have been associated with ASD and children with ASD and these autoantibodies respond to high doses of a reduced form of folate known as folinic acid (leucovorin calcium). Some of the same abnormalities are also found in mothers of children with ASD and supplementing folate during preconception and gestational periods reduces the risk to the offspring from developing ASD. These data suggest that folate pathway abnormalities may be a major metabolic disturbance underlying ASD that can be leveraged as biomarkers to improve symptoms and prevent ASD.
Lien vers le texte intégral (Open Access ou abonnement)
5. Gray WA, Billock VA. {{Developmental neurotoxicity and autism: A potential link between indoor neuroactive pollutants and the curious birth order risk factor}}. {Int J Dev Neurosci};2017 (Jul 29);62:32-36.
Epidemiological and demographic studies find an increased risk of autism among first-borns. Toxicological studies show that some semi-volatile substances found in infant products produce adverse effects in neural and endocrine systems of animals, including behavioral and developmental effects. Several factors elevate the exposure of human infants to these chemicals. The highest exposures found in infants are comparable to the exposures that induce neural toxicity in animals. A review of these literatures suggests a linking hypothesis that could bridge the epidemiological and toxicological lines of evidence: an infant’s exposure to neuroactive compounds emitted by infant products is increased by product newness and abundance; exposure is likely maximized for first-born children in families that can afford new products. Exposure is reduced for subsequently-born children who reuse these now neuroactive-depleted products. The presence of neuroactive chemical emissions from infant products has implications for birth-order effects and for other curious risk factors in autism, including gender, socioeconomic status, and season-of-birth risk factors.
Lien vers le texte intégral (Open Access ou abonnement)
6. Griesi-Oliveira K, Sertie AL. {{Autism spectrum disorders: an updated guide for genetic counseling}}. {Einstein (Sao Paulo)};2017 (Apr-Jun);15(2):233-238.
Autism spectrum disorder is a complex and genetically heterogeneous disorder, which has hampered the identification of the etiological factors in each patient and, consequently, the genetic counseling for families at risk. However, in the last decades, the remarkable advances in the knowledge of genetic aspects of autism based on genetic and molecular research, as well as the development of new molecular diagnostic tools, have substantially changed this scenario. Nowadays, it is estimated that using the currently available molecular tests, a potential underlying genetic cause can be identified in nearly 25% of cases. Combined with clinical assessment, prenatal history evaluation and investigation of other physiological aspects, an etiological explanation for the disease can be found for approximately 30 to 40% of patients. Therefore, in view of the current knowledge about the genetic architecture of autism spectrum disorder, which has contributed for a more precise genetic counseling, and of the potential benefits that an etiological investigation can bring to patients and families, molecular genetic investigation has become increasingly important. Here, we discuss the current view of the genetic architecture of autism spectrum disorder, and list the main associated genetic alterations, the available molecular tests and the key aspects for the genetic counseling of these families. RESUMO O transtorno do espectro autista e um disturbio complexo e geneticamente heterogeneo, o que sempre dificultou a identificacao de sua etiologia em cada paciente em particular e, por consequencia, o aconselhamento genetico das familias. Porem, nas ultimas decadas, o acumulo crescente de conhecimento oriundo das pesquisas sobre os aspectos geneticos e moleculares desta doenca, assim como o desenvolvimento de novas ferramentas de diagnostico molecular, tem mudado este cenario de forma substancial. Atualmente, estima-se que, por meio de testes moleculares, e possivel detectar uma alteracao genetica potencialmente causal em cerca de 25% dos casos. Considerando-se tambem a avaliacao clinica, a historia pre-natal e a investigacao de outros aspectos fisiologicos, pode-se atribuir uma etiologia para aproximadamente 30 a 40% dos pacientes. Assim, em vista do conhecimento atual sobre a arquitetura genetica do transtorno do espectro autista, que tem tornado o aconselhamento genetico cada vez mais preciso, e dos potenciais beneficios que a investigacao etiologica pode trazer aos pacientes e familiares, tornam-se cada vez mais importantes os testes geneticos moleculares. Apresentamos aqui uma breve discussao sobre a visao atual da arquitetura genetica dos transtornos do espectro autista, listando as principais alteracoes geneticas associadas, os testes moleculares disponiveis e os principais aspectos a se considerar para o aconselhamento genetico destas familias.
Lien vers le texte intégral (Open Access ou abonnement)
7. Habib SS, Al-Regaiey K, Bashir S, Iqbal M. {{Role of Endocannabinoids on Neuroinflammation in Autism Spectrum Disorder Prevention}}. {J Clin Diagn Res};2017 (Jun);11(6):Ce01-ce03.
Autism Spectrum Disorder (ASD) disease has become a mounting socio-economical alarm around the world. Neuroinflammtion had been shown in postmortem brain specimens from ASD patients. The Endocannabinoids System (ES) consists of a family of locally produced, short-lived, endogenous, phospholipid-derived agonists (endocannabinoids) that control energy balance and body composition. The growing number of medical benefits of ES, such as their ability to regulate processes like neuroinflammation, neurogenesis and memory, raise the question of their potential role as a preventive treatment of ASD. To test this hypothesis, basic and clinical studies allow us a thorough investigation of the role of ES in the pathogenesis of ASD. This hypothesis will help to understand the mechanism of ES and its role in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. Harada K, Yamamoto M, Konishi Y, Koyano K, Takahashi S, Namba M, Kusaka T. {{Hypoplastic hippocampus in atypical Rett syndrome with a novel FOXG1 mutation}}. {Brain Dev};2017 (Aug 03)
The forkhead box G1 (FOXG1) gene encodes a brain-specific transcription factor and is associated with a congenital variant of atypical Rett syndrome (RTT); several FOXG1 mutations have been identified. The congenital variant of RTT shows a hypoplastic corpus callosum, delayed myelination, and frontal and temporal atrophy. Although no report has described a hippocampal abnormality in humans, the current study suggests that FOXG1 also regulates neurogenesis in the postnatal hippocampus. In the present case, severe developmental delay was observed in a patient with a congenital variant of RTT from about 4months, in conjunction with acquired microcephaly, hypotonia, limited motor function, absent purposeful hand use, and repetitive jerky movements of the upper limbs. A novel missense mutation was identified in FOXG1 on gene analysis (c. 569T>A, p. Ile190Asn). The patient showed not only the typical cerebral abnormalities of a congenital variant of RTT, but also a hypoplastic hippocampus. This novel mutation and cerebral findings may provide new insights into the pathophysiology of the congenital variant of RTT.
Lien vers le texte intégral (Open Access ou abonnement)
9. Ligsay A, Van Dijck A, Nguyen DV, Lozano R, Chen Y, Bickel ES, Hessl D, Schneider A, Angkustsiri K, Tassone F, Ceulemans B, Kooy RF, Hagerman RJ. {{A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome}}. {J Neurodev Disord};2017 (Aug 02);9(1):26.
BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo. CONCLUSIONS: While ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01725152.
Lien vers le texte intégral (Open Access ou abonnement)
10. Mezzedimi C, Livi W, De Felice C, Cocca S. {{Dysphagia in Rett Syndrome: A Descriptive Study}}. {Ann Otol Rhinol Laryngol};2017 (Aug 01):3489417723033.
OBJECTIVES: Rett syndrome (RS) is a neurodevelopmental disorder and the second major cause of mental retardation in females. The aim of this study was to evaluate swallowing problems of RS patients by endoscopic assessment and compile a list of suggestions for managing feeding and preventing complications. METHODS: The sample consisted of 61 female patients (mean age = 13.6 years, range, 2-33 years) admitted to the Department of Neuropsychiatry, where they had previously been diagnosed with RS. Speech evaluation associated with observation during mealtimes was useful to formulate suggestions for caregivers. RESULTS: Progressive deterioration of feeding was commonly noted by caregivers. Fifty-four patients had a history of recurrent episodes of bronchitis. Oral apraxia, dyskinetic tongue movements, prolonged oral stage, and poor bolus formation were the most common findings in all patients. CONCLUSIONS: Dysphagia was primarily limited to oral preparatory phases, while the pharyngeal phase was normal in most patients. The high percentage of dysphagia suggests the need to accurately monitor the feeding capability of RS children. It is critical to correctly inform caregivers about safe swallowing procedures to reduce the incidence of fatal complications.
Lien vers le texte intégral (Open Access ou abonnement)
11. Rodas NV, Eisenhower A, Blacher J. {{Structural and Pragmatic Language in Children with ASD: Longitudinal Impact on Anxiety and Externalizing Behaviors}}. {J Autism Dev Disord};2017 (Aug 03)
Children with autism spectrum disorder (ASD) are at heightened risk for developing comorbid psychological disorders, including anxiety disorders, which may be further exacerbated by the presence of externalizing behaviors. Here, we examined how structural language and pragmatic language predicted anxiety and externalizing behaviors. Participants were 159 young children (4-7 years old) with ASD and their mothers. Utilizing structural equation modeling we examined associations among structural language, pragmatic language, anxiety symptoms, and externalizing behaviors. Pragmatic language, was inversely related to child anxiety and co-occurring externalizing behaviors. Structural language skills positively predicted child anxiety. These findings suggest that children with ASD may be at heightened risk for anxiety and externalizing disorders due to their pragmatic language deficits.
Lien vers le texte intégral (Open Access ou abonnement)
12. Wen Z, Cheng TL, Li GZ, Sun SB, Yu SY, Zhang Y, Du YS, Qiu Z. {{Identification of autism-related MECP2 mutations by whole-exome sequencing and functional validation}}. {Mol Autism};2017;8:43.
BACKGROUND: Methyl-CpG-binding protein-2 (MeCP2) is a critical regulator for neural development. Either loss- or gain-of-function leads to severe neurodevelopmental disorders, such as Rett syndrome (RTT) and autism spectrum disorder (ASD). We set out to screen for MECP2 mutations in patients of ASD and determine whether these autism-related mutations may compromise the proper function of MeCP2. METHODS: Whole-exome sequencing was performed to screen MECP2 and other ASD candidate genes for 120 patients diagnosed with ASD. The parents of patients who were identified with MECP2 mutation were selected for further Sanger sequencing. Each patient accomplished the case report form including general information and clinical scales applied to assess their clinical features. Mouse cortical neurons and HEK-293 cells were cultured and transfected with MeCP2 wild-type (WT) or mutant to examine the function of autism-associated MeCP2 mutants. HEK-293 cells were used to examine the expression of MeCP2 mutant constructs with Western blot. Mouse cortical neurons were used to analyze neurites and axon outgrowth by immunofluorescence experiments. RESULTS: We identified three missense mutations of MECP2 from three autism patients by whole-exome sequencing: p.P152L (c.455C>T), p.P376S (c.1162C>T), and p.R294X (c.880C>T). Among these mutations, p.P152L and p.R294X were de novo mutations, whereas p.P376S was inherited maternally. The diagnosis of RTT was excluded in all three autism patients. Abnormalities of dendritic and axonal growth were found after autism-related MeCP2 mutants were expressed in mouse cortical neurons; suggesting that autism-related MECP2 mutations impair the proper development of neurons. CONCLUSIONS: Our study identified genetic mutations of the MECP2 gene in autism patients, which were previously considered to be associated primarily with RTT. This finding suggests that loss-of-function mutations of MECP2 may also lead to autism spectrum disorders.
Lien vers le texte intégral (Open Access ou abonnement)
13. Xie J, Huang L, Li X, Li H, Zhou Y, Zhu H, Pan T, Kendrick KM, Xu W. {{Immunological cytokine profiling identifies TNF-alpha as a key molecule dysregulated in autistic children}}. {Oncotarget};2017 (Jul 18)
Recent studies have suggested that the etiology of Autism Spectrum Disorder (ASD) may be caused by immunological factors, particularly abnormalities in the innate immune system. However, it is still unclear which specific cytokines may be of most importance. The current study therefore investigated which cytokines showed altered concentrations in blood in ASD compared with healthy control children and which were also correlated with symptom severity. Our study sample included 32 children diagnosed with ASD and 28 age and sex-matched typically developing children. Autism symptoms were measured using the Autistic Behavior Checklist (ABC) and blood samples were taken from all subjects. We used Milliplex cytokine kits to determine serum concentrations of 11 Th1, Th2 and Th17 related cytokines. Additionally, expression of THRIL (TNFalpha and hnRNPL related immunoregulatory LincRNA), a long non-coding RNA involved in the regulation of tumor necrosis factor- alpha (TNF-alpha), was determined using real-time PCR. Of the 11 cytokines measured only concentrations of TNF-alpha (p=0.002), IL-1beta (p=0.02) and IL-17a (p=0.049) were significantly increased in ASD children compared to typically developing controls, but only TNF-alpha concentrations were positively correlated with severity of ASD symptoms on all 5 different ABC sub-scales and were predictive of an ASD phenotype (area under the curve = 0.74). Furthermore, THRIL RNA expression was significantly decreased in ASD children. Our results provide further support for altered innate immunity being an important autism pathogenic factor, with autistic children showing increased blood TNF-alpha concentrations associated with symptom severity, and decreased expression of the THRIL gene involved in regulating TNF-alpha.
Lien vers le texte intégral (Open Access ou abonnement)
14. Yamasue H, Domes G. {{Oxytocin and Autism Spectrum Disorders}}. {Curr Top Behav Neurosci};2017 (Aug 02)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose core symptoms include deficits in social interaction and communication besides restricted and repetitive behaviors. Although ASD is highly prevalent, affecting 1/100 in the general population, no medication for the core symptoms has been established. Therefore, the disorder is considered a huge unmet medical need and a heavy burden on individuals with ASD, their families, and entire society. Oxytocin is expected to be a potential therapeutic resource for the social core symptoms of ASD, since this neuropeptide can modulate human social behavior and cognition. This review article provides an overview of both experimental and clinical studies on effects of oxytocin administration on behavior, neural underpinnings, and symptomatology of ASD. Although the number of studies is increasing, several issues remain for further development of clinical application of the neuropeptide. The issues include optimization of administration route, doses, treatment duration, interval of administrations, and timing of starting treatment. Additional issues involve investigating neurobiological mechanisms of treatment and developing a reliable tool to accurately and objectively assess longitudinal changes in the core symptoms of ASD. Some of these issues are discussed in this review.
