1. Althaus M, Groen Y, A AW, Noltes H, Tucha O, Sweep FC, Calcagnoli F, Hoekstra PJ. {{Do blood plasma levels of oxytocin moderate the effect of nasally administered oxytocin on social orienting in high-functioning male adults with autism spectrum disorder?}}. {Psychopharmacology (Berl)};2016 (Jun 2)
OBJECTIVE: The study investigated whether baseline plasma oxytocin (OXT) concentrations might moderate the effects of nasally administered OXT on social orienting. METHODS: Thirty-one males with Autism spectrum disorder (ASD) and thirty healthy males participated in a double-blind placebo-controlled crossover trial. After administration of the compound, participants were viewing pictures from the International Affective Picture System that represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. The outcome measures were a cardiac evoked response (ECR) and a cortical evoked long latency parietal positivity (LPP). RESULTS: Males with ASD had significantly higher plasma baseline levels than the controls. In the absence of general treatment effects, higher baseline concentrations were found to be associated with larger treatment effects, particularly in the group of males with ASD. Higher post-treatment plasma OXT concentrations were found to be associated with smaller treatment effects and larger orienting responses in the placebo situation in the group of controls. CONCLUSIONS: We interpret our findings as suggesting that it is the central availability of OXT determining how much of the nasally administered OXT will become centrally absorbed and how much of it will become released into the bloodstream.
Lien vers le texte intégral (Open Access ou abonnement)
2. Ashworth S. {{Autism is underdiagnosed in prisoners}}. {BMJ};2016;353:i3028.
Lien vers le texte intégral (Open Access ou abonnement)
3. Berg KL, Shiu CS, Acharya K, Stolbach BC, Msall ME. {{Disparities in adversity among children with autism spectrum disorder: a population-based study}}. {Dev Med Child Neurol};2016 (Jun 2)
AIM: People with autism spectrum disorders (ASDs) experience disparities in health. An important but overlooked risk factor for health disparities in the ASD population is adverse childhood experiences (ACEs). The purpose of this study was to identify the prevalence of ACEs among families of children with and without ASD, using a population-based sample. METHOD: Data from the 2011 to 2012 National Survey of Child Health were analyzed to estimate prevalence of ACEs among families of children with and without ASD, age 3 to 17 years (ASD=1611; estimated population=1 165 34). The child’s ASD status was obtained from parent report; ACEs were assessed with the modified Adverse Childhood Experiences Scale. Bivariate and multinomial logistic regression analyses were utilized to investigate the relationship between ACEs and childhood ASD status. RESULTS: ASD status among children was significantly and independently associated with higher probability of reporting one to three ACEs (adjusted relative risk ratio [aRRR] 1.53; 95% CI: 1.16-2.0; p<0.010) and four or more ACEs (aRRR 1.99; 95% CI: 1.35-2.91; p<0.010). INTERPRETATION: Children with ASD may experience a greater number of family and neighborhood adversities, potentially compromising their chances for optimal physical and behavioral health outcomes. Assessment and reduction of ACEs among families of young people with ASD could potentially contribute to the reduction of population health disparities. Lien vers le texte intégral (Open Access ou abonnement)
4. Christianto A, Katayama S, Kameshita I, Inazu T. {{A Novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome}}. {Clin Chim Acta};2016 (Jun 2)
Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function. DNA sequence analysis showed a novel heterozygous mutation in CDKL5 identified as c.530A>G which resulted in an amino acid substitution at position 177, from tyrosine to cysteine. Genotyping analysis indicated that the mutation was not merely a single nucleotide polymorphism (SNP). We also revealed that patient’s blood lymphocytes had random X-chromosome inactivation (XCI) pattern. Further examination by bioinformatics analysis demonstrated the mutation caused damage or deleterious in its protein. In addition, we demonstrated in vitro kinase assay of mutant protein showed impairment of its activity. Taken together, the results suggested the mutant CDKL5 was responsible for the disease.
Lien vers le texte intégral (Open Access ou abonnement)
5. Cortelazzo A, De Felice C, Guerranti R, Signorini C, Leoncini S, Zollo G, Leoncini R, Timperio AM, Zolla L, Ciccoli L, Hayek J. {{Expression and oxidative modifications of plasma proteins in autism spectrum disorders: Interplay between inflammatory response and lipid peroxidation}}. {Proteomics Clin Appl};2016 (Jun 1)
PURPOSE: A role for inflammation and oxidative stress is reported in autism spectrum disorders (ASDs). Here, we tested possible changes in expression and/or oxidative status for plasma proteins in subjects with ASDs. EXPERIMENTAL DESIGN: To evaluate protein expression and protein adducts of lipid peroxidation-derived aldehyde, analysis of plasma proteins was performed in 30 subjects with ASDs and compared with 30 healthy controls with typical development, using a proteomic approach. RESULTS: Significant changes were evidenced for a total of 12 proteins. Of these, 10 were identified as proteins involved in the acute inflammatory response including alpha-2-macroglobulin, alpha-1-antitrypsin, haptoglobin, fibrinogen, serum transferrin, prealbumin, apolipoprotein A-I apolipoprotein A-IV, apolipoprotein J and serum albumin. In addition, significant changes occurred for 2 immunoglobulins alpha and gamma chains. CONCLUSIONS AND CLINICAL RELEVANCE: Our present data indicate that an inflammatory response, coupled with increased lipid peroxidation, is present in subjects with ASDs. This information can provide new insight into the identification of potential plasma protein biomarkers in autism. This article is protected by copyright. All rights reserved.
Lien vers le texte intégral (Open Access ou abonnement)
6. Foote M, Arque G, Berman RF, Santos M. {{Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice}}. {Cerebellum};2016 (Jun 2)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.
Lien vers le texte intégral (Open Access ou abonnement)
7. Jacobs S, Cheng C, Doering LC. {{Hippocampal neuronal subtypes develop abnormal dendritic arbors in the presence of Fragile X astrocytes}}. {Neuroscience};2016 (Jun 2);324:202-217.
Astrocytes are now recognized as key players in the neurobiology of neurodevelopmental disorders such as Fragile X syndrome. However, the nature of Fragile X astrocyte-mediated control of dendrite development in subtypes of hippocampal neurons is not yet known. We used a co-culture procedure in which wildtype primary hippocampal neurons were cultured with astrocytes from either a wildtype or Fragile X mouse, for either 7, 14 or 21days. The neurons were processed for immunocytochemistry with the dendritic marker MAP2, classified by morphological criteria into one of five neuronal subtypes, and subjected to Sholl analyses. Both linear and semi-log methods of Sholl analyses were applied to the neurons in order to provide an in depth analysis of the dendritic arborizations. We found that Fragile X astrocytes affect the development of dendritic arborization of all subtypes of wildtype hippocampal neurons. Furthermore, we show that hippocampal neurons with spiny stellate neuron morphology exhibit the most pervasive developmental delays, with significant dendritic arbor alterations persisting at 21days in culture. The results further dictate the critical role astrocytes play in governing neuronal morphology including altered dendrite development in Fragile X.
Lien vers le texte intégral (Open Access ou abonnement)
8. Li Q, Zhou JM. {{The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder}}. {Neuroscience};2016 (Jun 2);324:131-139.
Autism spectrum disorder (ASD) is a series of neurodevelopmental disorders that are characterized by deficits in both social and cognitive functions. Although the exact etiology and pathology of ASD remain unclear, a disorder of the microbiota-gut-brain axis is emerging as a prominent factor in the generation of autistic behaviors. Clinical studies have shown that gastrointestinal symptoms and compositional changes in the gut microbiota frequently accompany cerebral disorders in patients with ASD. A disturbance in the gut microbiota, which is usually induced by a bacterial infection or chronic antibiotic exposure, has been implicated as a potential contributor to ASD. The bidirectional microbiota-gut-brain axis acts mainly through neuroendocrine, neuroimmune, and autonomic nervous mechanisms. Application of modulators of the microbiota-gut-brain axis, such as probiotics, helminthes and certain special diets, may be a promising strategy for the treatment of ASD. This review mainly discusses the salient observations of the disruptions of the microbiota-gut-brain axis in the pathogenesis of ASD and reveals its potential therapeutic role in autistic deficits.
Lien vers le texte intégral (Open Access ou abonnement)
9. Mikic B, Jotic A, Miric D, Nikolic M, Jankovic N, Arsovic N. {{Receptive speech in early implanted children later diagnosed with autism}}. {Eur Ann Otorhinolaryngol Head Neck Dis};2016 (May 27)
INTRODUCTION: Incidence of children with autism spectrum disorder (ASD) is rising through the years with estimated 1 in 68 in the US in 2014. This incidence is also rising in the population of congenitally deaf children. Favorable outcome after early cochlear implantation is expected due to plasticity and reorganization capacity of brain in infants and toddlers, but outcomes could be significantly modified in children with diagnosed ASD. Current methods of screening for autism have difficulties in establishing diagnosis in children who have both autism and other developmental delays, especially at such an early age. The aim of the study was to assess the development of auditory perception and speech intelligibility in implanted children with profound congenital hearing loss who were diagnosed with ASD comparing to those who were typically developing. MATERIAL AND METHODS: Fourteen children underwent cochlear implantation; four were later diagnosed with ASD and ten were typically developing. All children underwent intensive postoperative speech and hearing therapy. The development of auditory perception and speech intelligibility was assessed using the Categories of Auditory Performance (CAP) and the Speech Intelligibility Rating (SIR) during the 5-years follow-up. RESULTS: In children later diagnosed with ASD, auditory processing developed slowly. Depending on the individual capabilities, by the age of six they could identify environmental sounds or discriminate speech sounds. Speech Intelligibility in children with ASD was at best rated as category 2, with very little or no progress up to the age of six, despite extensive speech and language therapy. Communication skills were strongly affected by a degree of autistic features expression. CONCLUSION: Preoperative psychological assessment in congenitally deaf infants should be expanded by the use of validated instruments for early detection of autism. The possibility of developing ASD should be kept in mind by all professionals involved in programs for cochlear implantation.
Lien vers le texte intégral (Open Access ou abonnement)
10. Sener EF, Canatan H, Ozkul Y. {{Recent Advances in Autism Spectrum Disorders: Applications of Whole Exome Sequencing Technology}}. {Psychiatry Investig};2016 (May);13(3):255-264.
Autism spectrum disorders (ASD) is characterized by three core symptoms with impaired reciprocal social interaction and communication, a pattern of repetitive behavior and/or restricted interests in early childhood. The prevalence is higher in male children than in female children. As a complex neurodevelopmental disorder, the phenotype and severity of autism are extremely heterogeneous with differences from one patient to another. Genetics has a key role in the etiology of autism. Environmental factors are also interacting with the genetic profile and cause abnormal changes in neuronal development, brain growth, and functional connectivity. The term of exome represents less than 1% of the human genome, but contains 85% of known disease-causing variants. Whole-exome sequencing (WES) is an application of the next generation sequencing technology to determine the variations of all coding regions, or exons of known genes. For this reason, WES has been extensively used for clinical studies in the recent years. WES has achieved great success in the past years for identifying Mendelian disease genes. This review evaluates the potential of current findings in ASD for application in next generation sequencing technology, particularly WES. WES and whole-genome sequencing (WGS) approaches may lead to the discovery of underlying genetic factors for ASD and may thereby identify novel therapeutic targets for this disorder.
Lien vers le texte intégral (Open Access ou abonnement)
11. Simonstein F, Mashiach-Eizenberg M. {{Attitudes Toward Autism Spectrum Disorders Among Students of Allied Health Professions}}. {J Genet Couns};2016 (Jun 2)
The prevalence of autism has increased dramatically. The objectives of this study were to explore attitudes toward prenatal diagnosis to detect autism prenatally and avoid having an affected child and to understand social acceptability of these disorders among students of allied health professions. In this study, college students of nursing and health systems management answered a structured self-report questionnaire (n = 305). The first part addressed the respondent’s personal data. The second part targeted the respondent’s attitudes toward prenatal diagnosis of non-life-threatening disorders, including autism spectrum disorders. We found that almost two thirds of the students responded that they would not proceed with a pregnancy if the child were diagnosed with autism, and more than half thought that they would not continue with a pregnancy if the fetus were diagnosed with Asperger’s. Age, level of religiosity, and years of education were influential. This study is limited in scope; however, the positive attitude of the students toward prenatal diagnosis to avoid having an affected child might also reflect a negative view of autism spectrum disorders in future health care professionals. Further research of attitudes and the social acceptability of autism spectrum disorders, particularly among health care professionals, is required.
Lien vers le texte intégral (Open Access ou abonnement)
12. Trimmer E, McDonald S, Rushby JA. {{Not knowing what I feel: Emotional empathy in autism spectrum disorders}}. {Autism};2016 (May 30)
While there is a general consensus in the literature that individuals with autism spectrum disorder have difficulty with cognitive empathy, much less is known about emotional empathy processing in these individuals. Most research has employed subjective self-report measures, which can often be misinterpreted or under-reported/over-reported. More objective measures such as psychophysiological recordings of arousal offer a more objective response. Furthermore, combining physiological responses with self-report ratings allows us to explore the relationship between these two responses to emotionally charged stimuli. A total of 25 individuals with autism spectrum disorder were compared with 25 matched controls on their physiological (arousal) and psychological (self-report) responses to emotionally distressing video scenes. These responses were also then compared with self-report cognitive and emotional trait empathy. Results indicate that while individuals with autism spectrum disorder appear to respond similarly to controls physiologically, their interpretation of this response is dampened emotionally. Furthermore, this dampening of self-report emotional response is associated with a general reduction in trait empathy.
Lien vers le texte intégral (Open Access ou abonnement)
13. Wilkinson M, Wang R, van der Kouwe A, Takahashi E. {{White and gray matter fiber pathways in autism spectrum disorder revealed by ex vivo diffusion MR tractography}}. {Brain Behav};2016 (May 5):e00483.
INTRODUCTION: The goal of this project was to study the white and gray matter brain pathways of young children with autism spectrum disorder (ASD) and investigate how ASD brains differ from those of typically developing children of the same age. METHODS: High angular resolution resolution diffusion imaging tractography and diffusion tensor imaging tractography were used to analyze the brains of two 3-year-old children with ASD and two age-matched controls. RESULTS: In the ASD brains, the callosal and corticopontine pathways were thinner overall and terminal areas in the cortical gray matter were significantly smaller. The ASD brains had more short-range u-fibers in the frontal lobe compared to the control brains. Gray matter pathways were found disorganized with less coherency in the ASD brain, specifically the lateral aspects of the middle part of the brain including motor areas, and both medial and lateral surfaces of the anterior frontal brain regions. CONCLUSION: These findings show our tractography technique is useful for identifying differences in brain pathways between the ASD and control groups. Given that scanning the brain of 3-year-old children with or even without ASD is challenging, postmortem scanning may offer valuable insights into the connectivity in the brain of young children with ASD.
