1. {{Correction: DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism}}. {PLoS Genet};2014 (Apr);10(4):e1004373.
[This corrects the article DOI: 10.1371/journal.pgen.1004241.].
Lien vers le texte intégral (Open Access ou abonnement)
2. {{Correction: comparison of genomic and epigenomic expression in monozygotic twins discordant for rett syndrome}}. {PLoS One};2014;9(4):e94737.
[This corrects the article DOI: 10.1371/journal.pone.0066729.].
Lien vers le texte intégral (Open Access ou abonnement)
3. Asano M, Ishitobi M, Kosaka H, Hiratani M, Wada Y. {{Ramelteon Monotherapy for Insomnia and Impulsive Behavior in High-Functioning Autistic Disorder}}. {J Clin Psychopharmacol};2014 (Apr 8)
Lien vers le texte intégral (Open Access ou abonnement)
4. Careaga M, Rose D, Tassone F, Berman RF, Hagerman R, Ashwood P. {{Immune Dysregulation as a Cause of Autoinflammation in Fragile X Premutation Carriers: Link between FMRI CGG Repeat Number and Decreased Cytokine Responses}}. {PLoS One};2014;9(4):e94475.
BACKGROUND: Increased rates of autoinflammatory and autoimmune disorders have been observed in female premutation carriers of CGG repeat expansion alleles of between 55-200 repeats in the fragile X mental retardation 1 (FMR1) gene. To determine whether an abnormal immune profile was present at a cellular level that may predispose female carriers to autoinflammatory conditions, we investigated dynamic cytokine production following stimulation of blood cells. In addition, splenocyte responses were examined in an FMR1 CGG knock-in mouse model of the fragile X premutation. METHODS: Human monocyte and peripheral blood leukocytes (PBLs) were isolated from the blood of 36 female FMR1 premutation carriers and 15 age-matched controls. Cells were cultured with media alone, LPS or PHA. In the animal model, splenocytes were isolated from 32 CGG knock-in mice and 32 wild type littermates. Splenocytes were cultured with media alone or LPS or PMA/Ionomycin. Concentrations of cytokines (GM-CSF, IL-1beta, IL-6, IL-10, IL-13, IL-17, IFNgamma, TNFalpha, and MCP-1) were determined from the supernatants of cellular cultures via Luminex multiplex assay. Additionally, phenotypic cellular markers were assessed on cells isolated from human subjects via flow cytometry. RESULTS: We found decreases in cytokine production in human premutation carriers as well as in the FMR1 knock-in mice when compared with controls. Levels of cytokines were found to be associated with CGG repeat length in both human and mouse. Furthermore, T cells from human premutation carriers showed decreases in cell surface markers of activation when compared with controls. CONCLUSIONS: In this study, FMR1 CGG repeat expansions are associated with decreased immune responses and immune dysregulation in both humans and mice. Deficits in immune responses in female premutation carriers may lead to increased susceptibility to autoimmunity and further research is warranted to determine the link between FMR1 CGG repeat lengths and onset of autoinflammatory conditions.
Lien vers le texte intégral (Open Access ou abonnement)
5. Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M, Iakoucheva LM. {{Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism}}. {Nat Commun};2014;5:3650.
Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.
Lien vers le texte intégral (Open Access ou abonnement)
6. Downs J, Torode I, Ellaway C, Jacoby P, Bunting C, Wong K, Christodoulou J, Leonard H. {{Family satisfaction following spinal fusion in Rett syndrome}}. {Dev Neurorehabil};2014 (Apr 11)
Abstract Purpose: We evaluated family satisfaction following spinal fusion in girls with Rett syndrome. Methods: Families participating in the population-based and longitudinal Australian Rett Syndrome Database whose daughter had undergone spinal fusion provided data on satisfaction overall, care processes and expected changes in health and function. Content analysis of responses to open-ended questions was conducted. Results: Families reported high levels of overall satisfaction and consistently high ratings in relation to surgical and ICU care. Outstanding clinical care and the development of strong partnerships with clinical staff were much appreciated by families, whereas poor information exchange and inconsistent care caused concerns. Conclusions: Family satisfaction is an important outcome within a patient-centred quality of care framework. Our findings suggest strategies to inform the delivery of care in relation to spinal fusion for Rett syndrome and could also inform the hospital care of other children with disability and a high risk of hospitalization.
Lien vers le texte intégral (Open Access ou abonnement)
7. Goh S, Dong Z, Zhang Y, Dimauro S, Peterson BS. {{Mitochondrial Dysfunction as a Neurobiological Subtype of Autism Spectrum Disorder: Evidence From Brain Imaging}}. {JAMA Psychiatry};2014 (Apr 9)
IMPORTANCE Impaired mitochondrial function impacts many biological processes that depend heavily on energy and metabolism and can lead to a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). Although evidence that mitochondrial dysfunction is a biological subtype of ASD has grown in recent years, no study, to our knowledge, has demonstrated evidence of mitochondrial dysfunction in brain tissue in vivo in a large, well-defined sample of individuals with ASD. OBJECTIVES To assess brain lactate in individuals with ASD and typically developing controls using high-resolution, multiplanar spectroscopic imaging; to map the distribution of lactate in the brains of individuals with ASD; and to assess correlations of elevated brain lactate with age, autism subtype, and intellectual ability. DESIGN, SETTING, AND PARTICIPANTS Case-control study at Columbia University Medical Center and New York State Psychiatric Institute involving 75 children and adults with ASD and 96 age- and sex-matched, typically developing controls. MAIN OUTCOMES AND MEASURES Lactate doublets (present or absent) on brain magnetic resonance spectroscopic imaging. RESULTS Lactate doublets were present at a significantly higher rate in participants with ASD (13%) than controls (1%) (P = .001). In the ASD group, the presence of lactate doublets correlated significantly with age (P = .004) and was detected more often in adults (20%) than in children (6%), though it did not correlate with sex, ASD subtype, intellectual ability, or the Autism Diagnostic Observation Schedule total score or subscores. In those with ASD, lactate was detected most frequently within the cingulate gyrus but it was also present in the subcortical gray matter nuclei, corpus callosum, superior temporal gyrus, and pre- and postcentral gyri. CONCLUSIONS AND RELEVANCE In vivo brain findings provide evidence for a possible neurobiological subtype of mitochondrial dysfunction in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. McLay LL, France K. {{Empirical research evaluating non-traditional approaches to managing sleep problems in children with autism}}. {Dev Neurorehabil};2014 (Apr 11)
Abstract Objective: This paper examines the efficacy of non-behavioural and non-pharmacological approaches to the treatment of sleep disturbance in individuals with autism spectrum disorder. Methods: A systematic search of electronic databases and reference lists identified eight studies that met inclusion criteria. Studies were evaluated according to (a) treatment used, (b) participants, (c) experimental design, (d) baseline measures, (e) dependent variables, (f) follow-up measures, (g) reliability and treatment integrity, (h) results and certainty of evidence and (i) implications for treatment. Results: Positive outcomes were reported for the use of massage therapy and vitamin supplements. Aromatherapy was reported to have no effect on sleep. No studies were found that examined other non-traditional treatment approaches, nor did any of the studies provide conclusive evidence. Conclusions: The limited corpus of evidence and the methodological limitations suggests that the efficacy of non-traditional approaches to treatment of sleep problems in individuals with autism is yet to be demonstrated.
Lien vers le texte intégral (Open Access ou abonnement)
9. Meyer BJ, Gardiner JM, Bowler DM. {{Directed Forgetting in High-Functioning Adults with Autism Spectrum Disorders}}. {J Autism Dev Disord};2014 (Apr 11)
Rehearsal strategies of adults with autism spectrum disorders (ASDs) and demographically matched typically developed (TD) adults were strategically manipulated by cueing participants to either learn, or forget each list word prior to a recognition task. Participants were also asked to distinguish between autonoetic and noetic states of awareness using the Remember/Know paradigm. The ASD group recognised a similar number of to-be-forgotten words as the TD group, but significantly fewer to-be-learned words. This deficit was only evident in Remember responses that reflect autonoetic awareness, or episodic memory, and not Know responses. These findings support the elaborative encoding deficit hypothesis and provide a link between the previously established mild episodic memory impairments in adults with high functioning autism and the encoding strategies employed.
Lien vers le texte intégral (Open Access ou abonnement)
10. Ollington N. {{Comparison of a direct and an indirect approach for the functional assessment of insistence on sameness in a child with autism spectrum disorder and a typically developing child}}. {Dev Neurorehabil};2014 (Apr 11)
Abstract Objective: To compare indirect and direct functional assessment of insistence on sameness associated with autism spectrum disorder (ASD) and typical development. Methods: Parents rated the function of insistence on sameness for a 6-year-old boy with ASD (Peter) and a typically developing 4-year-old boy (Nathan) using the Motivation Assessment Scale (MAS). Ratings were compared to the results of a direct assessment. Results: The results of the assessment procedures were mainly consistent for Peter and suggested that his tendency to insist on sameness was maintained by sensory consequences. The finding of an attention function for Nathan in the play-based assessment was consistent with previous functional assessment studies surrounding typically developing children, but in contrast to the MAS. Conclusion: While the play-based assessment may be more suitable for assessing the high rate insistence on sameness observed in individuals with ASD, the MAS may be more suitable for low rate insistence on sameness.
Lien vers le texte intégral (Open Access ou abonnement)
11. Pohl A, Cassidy S, Auyeung B, Baron-Cohen S. {{Uncovering steroidopathy in women with autism: a latent class analysis}}. {Mol Autism};2014 (Apr 9);5(1):27.
BACKGROUND: Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms (‘steroidopathy’) in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC. METHODS: We tested two groups of women, screened using the Autism Spectrum Quotient – Group 1: n = 415 women with ASC (mean age 36.39 +/- 11.98 years); and Group 2: n = 415 controls (mean age 39.96 +/- 11.92 years). All participants completed the Testosterone-related Medical Questionnaire online. A multiple-group LCA was used to identify differences in latent class structure between women with ASC and controls. RESULTS: There were significant differences in frequency of steroid-related conditions and symptoms between women with ASC and controls. A two-class semi-constrained model best fit the data. Based on response patterns, we identified the classes as ‘Typical’ and ‘Steroidopathic’. The prevalence of the ‘Steroidopathic’ class was significantly increased within the ASC group (DeltaG2 = 15, df =1, P = 0.0001). In particular, we confirmed higher frequencies of epilepsy, amenorrhea, dysmenorrhea, severe acne, gender dysphoria, and transsexualism, and differences in sexual preference in women with ASC. CONCLUSIONS: Women with ASC are at increased risk for symptoms and conditions linked to steroids. LCA revealed this steroidopathy despite the apparent underdiagnosis of PCOS.
Lien vers le texte intégral (Open Access ou abonnement)
12. Prontera P, Serino D, Caldini B, Scarponi L, Merla G, Testa G, Muti M, Napolioni V, Mazzotta G, Piccirilli M, Donti E. {{Brief Report: Functional MRI of a Patient with 7q11.23 Duplication Syndrome and Autism Spectrum Disorder}}. {J Autism Dev Disord};2014 (Apr 11)
The duplication of the Williams-Beuren syndrome (WBS) region (7q11.23) is a copy number variant associated with autism spectrum disorder (ASD). One of the most intriguing aspects is that the reciprocal microdeletion causes WBS, characterized by hypersociability, marked empathy, and a relative capacity in verbal short-term memory and language. Herein, we studied, by using functional morphological and volumetric magnetic resonance, a 17-year-old male patient who displays a de novo 7q11.23 duplication and ASD. The limbic system of the patient appeared hypo-functional, while the total brain volume was increased, thus contrasting, in an opposite and intriguing manner, with the global brain volume reduction reported in WBS. Even if these findings come from the analysis of a single patient and, therefore, have to be considered preliminary results, they encourage carrying on further functional and volumetric studies in patients with 7q11.23 duplication, to fully elucidate the role of this gene-dosage alteration on brain development and limbic system function.
Lien vers le texte intégral (Open Access ou abonnement)
13. Schaaf RC, Leiby B, Benevides T, Hunt J, van Hooydonk E, Faller P, Mailloux Z. {{Response from Authors to Comments on « An Intervention for Sensory Difficulties in Children with Autism: A Randomized Trial »}}. {J Autism Dev Disord};2014 (Apr 11)
Lien vers le texte intégral (Open Access ou abonnement)
14. Srivastava S, Landy-Schmitt C, Clark B, Kline AD, Specht M, Grados MA. {{Autism traits in children and adolescents with Cornelia de Lange syndrome}}. {Am J Med Genet A};2014 (Apr 9)
Cornelia de Lange syndrome (CdLS) is a cohesinopathy causing delayed growth and limb deficits. Individuals with CdLS have mild to profound intellectual disability and autistic features. This study characterizes the behavioral phenotype of children with CdLS, focusing on autistic features, maladaptive behaviors, and impact of age. Children with CdLS (5-18 years) were administered normed instruments to characterize autism features (Childhood Autism Rating Scale, CARS), maladaptive behaviors (Aberrant Behavior Checklist), and adaptive skills (Vineland Adaptive Behaviors Scales). CdLS features and severity were rated with Diagnostic Criteria for CdLS. Forty-one children with CdLS (23 females, 18 males) were classified as having « no autism » (n = 7; 17.1%), « mild autism » (n = 17; 41.4%), and « severe autism » (n = 17; 41.4%), using CARS scores. Characteristic items were abnormal emotional response, stereotypies, odd object use, rigidity, lack of verbal communication, and low intellectual functioning. Verbal communication deficits and repetitive behaviors were higher compared to sensory, social cognition, and behavior abnormalities (P </= 0.0001). Maladaptive behaviors associated with autism traits were stereotypies (P = 0.003), hyperactivity (P = 0.01), and lethargy (P = 0.03). Activities of daily living were significantly affected; socialization adaptive skills were a relative strength. However, with advancing age, both socialization (P < 0.0001) and communication (P = 0.001) domains declined significantly. CdLS is characterized by autistic features, notably excessive repetitive behaviors and expressive language deficits. While other adaptive skills are impacted, socialization adaptive skills are less affected. Advancing age can worsen communication and socialization deficits relative to neurotypical peers. (c) 2014 Wiley Periodicals, Inc.
