1. Accardo AL, Finnegan EG. {{Teaching reading comprehension to learners with autism spectrum disorder: Discrepancies between teacher and research-recommended practices}}. {Autism}. 2017: 1362361317730744.
Students with autism spectrum disorder have been found to experience difficulty with reading comprehension despite intact decoding and word recognition. This identified need for targeted reading comprehension remediation results in a need for teachers to utilize research-based practices and to individualize instruction for students with autism spectrum disorder; however, teachers report a lack of access to such practices. This study utilized survey methodology to gather perceptions and experiences of teachers and to compare teacher preparedness to use effective instructional practices emerging from the extant research to teacher-reported effective practices in the classroom. Study findings, based on 112 participants, reveal a discrepancy between teacher-reported effective practices, and the practices identified as effective through research, indicating a research to practice gap. Implications for practice include professional development recommendations, and the need for increased communication between researchers and teachers.
Lien vers le texte intégral (Open Access ou abonnement)
2. Baixauli-Fortea I, Miranda Casas A, Berenguer-Forner C, Colomer-Diago C, Rosello-Miranda B. {{Pragmatic competence of children with autism spectrum disorder. Impact of theory of mind, verbal working memory, ADHD symptoms, and structural language}}. {Appl Neuropsychol Child}. 2017: 1-12.
The primary aim of this study is to increase the existing knowledge about the pragmatic skills of children with autism spectrum disorders (ASD). Specifically, the study has two objectives. The first is to provide a profile of characteristics based on The Children’s Communication Checklist (CCC-2) pragmatics scales (inappropriate initiation, stereotyped language, use of context, nonverbal communication, and general pragmatics) and narrative task indicators. To this end, children with ASD will be compared to children with typical development (TD), controlling the effects of sex and structural language (speech, syntax, semantics, coherence). The second objective is to analyze whether theory of mind (ToM), verbal working memory, ADHD symptoms, and structural language can predict pragmatic competence in children with ASD without intellectual disability (ID). The results showed worse performance in the group with ASD on the majority of the pragmatic aspects evaluated. In addition, the application of ToM skills and structural language were significant predictors of the pragmatic skills of the children with ASD. These findings reinforce the importance of focusing intervention programs on mentalist abilities through experiences in real social scenarios, along with strengthening structural language components.
Lien vers le texte intégral (Open Access ou abonnement)
3. Burke SL, Bresnahan T, Li T, Epnere K, Rizzo A, Partin M, Ahlness RM, Trimmer M. {{Using Virtual Interactive Training Agents (ViTA) with Adults with Autism and Other Developmental Disabilities}}. {J Autism Dev Disord}. 2017.
Conversational virtual human (VH) agents are increasingly used to support role-play experiential learning. This project examined whether a Virtual Interactive Training Agent (ViTA) system would improve job interviewing skills in individuals with autism and developmental disabilities (N = 32). A linear mixed model was employed to evaluate adjusted least square mean differences of means scores on the Marino Interview Assessment Scale (MIAS) across different time points. The mean score of MIAS over all questions increased between the first ViTA session and the final face-to-face interview. Participants developed the ability to identify strengths, self-promote, self-advocate, answer situational questions, and respond to behavioral/social questions as measured by multiple evaluations using the MIAS.
Lien vers le texte intégral (Open Access ou abonnement)
4. Creaby-Attwood A, Allely CS. {{A psycho-legal perspective on sexual offending in individuals with autism Spectrum disorder}}. {Int J Law Psychiatry}. 2017; 55: 72-80.
It is important to consider whether there are innate vulnerabilities that increase the risk of an individual with an autistic spectrum disorder (ASD), predominantly those defendants with a diagnosis of Asperger’s Syndrome, being charged and convicted of a sexual offence. The significance of such can be readily seen in recent English case law, with judgments on appeal finding convictions unsafe where there have been a number of failings in the Judge’s summing up. In this article, we will consider the gravity of Judges omitting to highlight a defendant’s diagnosis of autism spectrum disorder and the necessity of detailed explanations to jury members regarding the condition and its effect upon thoughts and behaviour. Consideration will be specifically given to the necessity to prove sexual motivation in such offences and the judicial direction required in relation to whether the appellant’s actions had been sexually motivated. Recognition of the social impairments inherent in ASDs are vital to this work and we shall consider whether the difficulty with the capacity to develop appropriate, consenting sexual relationships as a result of impaired social cognition may be one of the factors which increases the risk of sexual offending in individuals with ASD (Higgs & Carter, 2015).
Lien vers le texte intégral (Open Access ou abonnement)
5. Esnafoglu E, Cirrik S. {{Increased serum Midkine levels in Autism Spectrum Disorder patients}}. {Int J Neurosci}. 2017: 1-14.
BACKGROUND: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of midkine, this study researched whether MK is involved in Autism spectrum disorders (ASD) pathogenesis. METHODS: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group. MK levels were measured with ELISA, while ASD severity was assessed with Childhood Autism Rating Scale. RESULTS: Our data showed that the serum MK concentration in ASD patients (mean+/-SD, 11.51 +/- 8.53 pg/ml) is significantly higher than healthy controls (mean+/-SD, 6.19 +/- 3.94 pg/ml) (p = 0.007). CONCLUSIONS: According to these results, midkine may play a role in ASD pathogenesis.
Lien vers le texte intégral (Open Access ou abonnement)
6. Fordyce TA, Leonhard MJ, Chang ET. {{A critical review of developmental exposure to particulate matter, autism spectrum disorder, and attention deficit hyperactivity disorder}}. {J Environ Sci Health A Tox Hazard Subst Environ Eng}. 2017: 1-31.
Autism spectrum disorder (ASD) and attention deficit (hyperactivity) disorder (ADD/ADHD) are key focuses of current health research due to their increasing prevalence. The objective of this systematic literature search and critical review was to evaluate whether the human epidemiologic data indicate a pattern of association between ASD or ADD/ADHD and developmental exposure to particulate matter (PM), with a focus on exposures encountered before the age of three. A MEDLINE and EMBASE search was conducted; following preliminary and full-text screening, 14 relevant articles were identified for review. Three of the 14 studies were prospective cohort studies evaluating exposure to PM10; 11 studies had a case-control design. There was no consistent association between developmental PM exposure and ASD across the three of the cohort studies. Seven of the case-control studies examined the relationship between PM2.5 and/or PM10 and ASD; four examined the relationship between developmental diesel PM exposure and ASD. Overall, there was low external consistency in results among studies of PM2.5/PM10 and ASD, with some reporting high internal consistency without significant associations, others showing associations with high internal consistency for specific exposure windows only (e.g., third trimester), and still others showing high consistency for moderate to strong associations between PM and ASD. The majority of studies reporting significant results had low effect sizes in conjunction with small sample sizes. The four studies of diesel PM and ASD also had low external consistency of results. Only one study evaluated associations with ADD/ADHD, and it found no significant associations with PM10. The inconsistent findings across studies of developmental exposure to PM and ASD may be attributed to differences in the study populations, exposure assessments, outcome assessments, or chance. Further research is needed to understand the underlying biological mechanisms that lead to ASD and ADD/ADHD and how PM might be involved in those mechanisms, if at all. High-quality epidemiologic studies are also needed to conclusively determine whether developmental PM exposure is a causal factor for ASD or ADD/ADHD, with focus on a well-developed exposure assessment.
Lien vers le texte intégral (Open Access ou abonnement)
7. George R, Stokes MA. {{Sexual Orientation in Autism Spectrum Disorder}}. {Autism Res}. 2017.
Clinical impressions suggest a different sexual profile between individuals with and without Autism Spectrum Disorder (ASD). Little is presently known about the demographics of sexual orientation in ASD. Sexual Orientation was surveyed using the Sell Scale of Sexual Orientation in an international online sample of individuals with ASD (N = 309, M = 90, F= 219), aged (M = 32.30 years, SD = 11.93) and this was compared to sexual orientation of typically-developing individuals (N = 310, M = 84, F= 226), aged (M = 29.82 years, SD = 11.85). Findings suggested that sexual orientation was contingent on diagnosis (N = 570, chi(2)(9) =104.05, P < 0.001, phi = 0.43). In the group with ASD, 69.7% of the sample reported being non-heterosexual, while in the TD group, 30.3% reported being non-heterosexual. The group with ASD reported higher rates of homosexuality, bisexuality and asexuality, but lower rates of heterosexuality. The results support the impression that non-heterosexuality is more prevalent in the autistic population. Increased non-heterosexuality in ASD has important clinical implications to target unique concerns of this population, and suggests a need for specialized sex education programs for autistic populations for increased support and awareness. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Research suggests that individuals with Autism Spectrum Disorder (ASD) report increased homosexuality, bisexuality, and asexuality, but decreased heterosexuality. It is important to increase awareness about increased non-heterosexuality in ASD among autistic populations, medical professionals and care-takers, so as to provide specialized care, if needed and increase support and inclusion for non-heterosexual autistic individuals. Lien vers le texte intégral (Open Access ou abonnement)
8. Gillespie-Smith K, Ballantyne C, Branigan HP, Turk DJ, Cunningham SJ. {{The I in autism: Severity and social functioning in autism are related to self-processing}}. {Br J Dev Psychol}. 2017.
It is well established that children with autism spectrum disorder (ASD) show impaired understanding of others and deficits within social functioning. However, it is still unknown whether self-processing is related to these impairments and to what extent self impacts social functioning and communication. Using an ownership paradigm, we show that children with ASD and chronological- and verbal-age-matched typically developing (TD) children do show the self-referential effect in memory. In addition, the self-bias was dependent on symptom severity and socio-communicative ability. Children with milder ASD symptoms were more likely to have a high self-bias, consistent with a low attention to others relative to self. In contrast, severe ASD symptoms were associated with reduced self-bias, consistent with an ‘absent-self’ hypothesis. These findings indicate that deficits in self-processing may be related to impairments in social cognition for those on the lower end of the autism spectrum. Statement of contribution What is already known on this subject? Impaired self-processing in autism is linked to social and cognitive deficits. There are discrepancies across the literature, with reports of both intact and impaired self-processing in autism. Ownership tasks are developmentally appropriate and have shown to induce self-memory bias in young children. What does this study add? Using an ownership task, children with autism showed a significant self-memory bias, greater than typical peers. Severity was negatively correlated with level of self-bias, potentially explaining the previous discrepancies. Severe autism symptoms are associated with an ‘absent self’, and mild autism symptoms reduce attention to others.
Lien vers le texte intégral (Open Access ou abonnement)
9. Kadam A, Pandit A, Patole S. {{Fragile X Syndrome with Congenital Diaphragmatic Hernia}}. {J Trop Pediatr}. 2017.
The authors present a case of Fragile X syndrome (FXS) in siblings from an Indian family with no developmental delay in previous generations. The boy presented with developmental delay, autistic features and defiant behaviours that raised clinical suspicion. He also had congenital diaphragmatic hernia (CDH). Social anxiety and difficulty in making friends were the subtle features in his sister with dull normal intelligence. FXS was confirmed by clinical features and DNA testing. Intervention was initiated for both the siblings. Screening siblings in FXS is important. CDH can be associated with FXS.
Lien vers le texte intégral (Open Access ou abonnement)
10. Kuvalanka KA, Mahan DJ, McGuire JK, Hoffman TK. {{Perspectives of Mothers of Transgender and Gender-Nonconforming Children with Autism Spectrum Disorder}}. {J Homosex}. 2017.
This study represents findings from interviews at two time points with three mothers of transgender and gender-nonconforming (TGNC) children (ages eight to 12 years at T1) with autism spectrum disorder (ASD). Of interest was the mothers’ experiences of raising a TGNC child with ASD, and whether/how the children’s autism played a role in their understandings of their children’s gender identities and expressions. The mothers’ fear of a transphobic/cisnormative society and wondering about whether their children’s ASD influenced or caused their children’s gender variance were barriers to fully embracing their children’s gender nonconformity. Unclear causes of children’s social/emotional difficulties and lack of adequate resources and support were identified challenges. Positive interventions and resources were also discussed. Recommendations for clinicians and other professionals who serve TGNC youth with autism and their families are presented.
Lien vers le texte intégral (Open Access ou abonnement)
11. Lacivita E, Perrone R, Margari L, Leopoldo M. {{Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions}}. {J Med Chem}. 2017; 60(22): 9114-41.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities. Various factors are involved in the etiopathogenesis of ASD, including genetic factors, environmental toxins and stressors, impaired immune responses, mitochondrial dysfunction, and neuroinflammation. The heterogeneity in the phenotype among ASD patients and the complex etiology of the condition have long impeded the advancement of the development of pharmacological therapies. In the recent years, the integration of findings from mouse models to human genetics resulted in considerable progress toward the understanding of ASD pathophysiology. Currently, strategies to treat core symptoms of ASD are directed to correct synaptic dysfunctions, abnormalities in central oxytocin, vasopressin, and serotonin neurotransmission, and neuroinflammation. Here, we present a survey of the studies that have suggested molecular targets for drug development for ASD and the state-of-the-art of medicinal chemistry efforts in related areas.
Lien vers le texte intégral (Open Access ou abonnement)
12. McCauley JB, Zajic MC, Oswald TM, Swain-Lerro LE, McIntyre NC, Harris MA, Trzesniewski K, Mundy PC, Solomon M. {{Brief Report: Investigating Relations Between Self-Concept and Performance in Reading and Math for School-Aged Children and Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
A typically developing student’s perceptions of his or her own capabilities (academic self-concept), is predictive of later academic achievement. However, little is known about academic self-concept in youth with autism spectrum disorder (ASD). To understand whether students math self-concept and reading self-concept predicted their performance, 44 school-aged children and adolescents with ASD and 36 age-matched individuals with typical development (TYP) rated their perceived math and reading abilities and were administered standardized achievement measures. Results showed self-concept was predictive of performance in math and reading in the TYP group. For youth with ASD, there was agreement between self-concept and performance only in math. These findings suggest that educators should be cautious when interpreting the self-assessments of reading ability in students with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
13. Mitelman SA, Buchsbaum MS, Young DS, Haznedar MM, Hollander E, Shihabuddin L, Hazlett EA, Bralet MC. {{Increased white matter metabolic rates in autism spectrum disorder and schizophrenia}}. {Brain Imaging Behav}. 2017.
Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used (18)fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.
Lien vers le texte intégral (Open Access ou abonnement)
14. Nomura T, Musial TF, Marshall JJ, Zhu Y, Remmers CL, Xu J, Nicholson DA, Contractor A. {{Delayed Maturation of Fast-Spiking Interneurons Is Rectified by Activation of the TrkB Receptor in the Mouse Model of Fragile X Syndrome}}. {J Neurosci}. 2017; 37(47): 11298-310.
Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABA-mediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS.SIGNIFICANCE STATEMENT Fragile X (FXS) individuals have a range of sensory related phenotypes, and there is growing evidence of alterations in neuronal circuits in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABAergic interneurons are central to the correct formation of circuits during cortical critical periods. Here we demonstrate a delay in the maturation of the properties and synaptic connectivity of interneurons in Fmr1 KO mice during a critical period of cortical development. The delays both in cellular and synaptic maturation were rectified by administration of a TrkB receptor agonist, suggesting reduced BDNF-TrkB signaling as a contributing factor. These results provide evidence that the function of fast-spiking interneurons is disrupted due to a deficiency in neurotrophin signaling during early development in FXS.
Lien vers le texte intégral (Open Access ou abonnement)
15. Odom SL, Cox A, Sideris J, Hume KA, Hedges S, Kucharczyk S, Shaw E, Boyd BA, Reszka S, Neitzel J. {{Assessing Quality of Program Environments for Children and Youth with Autism: Autism Program Environment Rating Scale (APERS)}}. {J Autism Dev Disord}. 2017.
The purpose of this study was to examine the psychometric properties of the Autism Program Environment Rating Scale (APERS), an instrument designed to assess quality of program environments for students with autism spectrum disorder. Data sets from two samples of public school programs that provided services to children and youth with autism spectrum disorder were utilized. Cronbach alpha analyses indicated high coefficients of internal consistency for the total APERS and moderate levels for item domains for the first data set, which was replicated with the second data set. A factor analysis of the first data set indicated that all domain scores loaded on one main factor, in alignment with the conceptual model, with this finding being replicated in the second data set. Also, the APERS was sensitive to changes resulting from a professional development program designed to promote program quality.
Lien vers le texte intégral (Open Access ou abonnement)
16. Parrend P, Mazzucotelli T, Colin F, Collet P, Mandel JL. {{Cerberus, an Access Control Scheme for Enforcing Least Privilege in Patient Cohort Study Platforms : A Comprehensive Access Control Scheme Applied to the GENIDA Project – Study of Genetic Forms of Intellectual Disabilities and Autism Spectrum Disorders}}. {J Med Syst}. 2017; 42(1): 1.
Cohort Study Platforms (CSP) are emerging as a key tool for collecting patient information, providing new research data, and supporting family and patient associations. However they pose new ethics and regulatory challenges since they cross the gap between patients and medical practitioners. One of the critical issues for CSP is to enforce a strict control on access privileges whilst allowing the users to take advantage of the breadth of the available data. We propose Cerberus, a new access control scheme spanning the whole life-cycle of access right management: design, implementation, deployment and maintenance, operations. Cerberus enables switching from a dual world, where CSP data can be accessed either from the users who entered it or fully de-identified, to an access-when-required world, where patients, practitioners and researchers can access focused medical data through explicit authorisation by the data owner. Efficient access control requires application-specific access rights, as well as the ability to restrict these rights when they are not used. Cerberus is implemented and evaluated in the context of the GENIDA project, an international CSP for Genetically determined Intellectual Disabilities and Autism Spectrum Disorders. As a result of this study, the software is made available for the community, and validated specifications for CSPs are given.
Lien vers le texte intégral (Open Access ou abonnement)
17. Pokorny JJ, Hatt NV, Rogers SJ, Rivera SM. {{What Are You Doing With That Object? Comparing the Neural Responses of Action Understanding in Adolescents With and Without Autism}}. {J Autism Dev Disord}. 2017.
Understanding another’s actions, including what they are doing and why they are doing it, can be difficult for individuals with autism spectrum disorder (ASD). This understanding is supported by the action observation (AON) and mentalizing (MZN) networks, as well as the superior temporal sulcus. We examined these areas in children with ASD and typically developing controls by having participants view eating and placing actions performed in conventional and unconventional ways while functional magnetic resonance images were collected. We found an effect of action-type, but not conventionality, in both groups, and a between groups difference only when viewing conventional eating actions. Findings suggest there are not global AON/MZN deficits in ASD, and observing unconventional actions may not spontaneously activate the MZN.
Lien vers le texte intégral (Open Access ou abonnement)
18. Poquerusse J, Azhari A, Setoh P, Cainelli S, Ripoli C, Venuti P, Esposito G. {{Salivary alpha-amylase as a marker of stress reduction in individuals with intellectual disability and autism in response to occupational and music therapy}}. {J Intellect Disabil Res}. 2017.
BACKGROUND: Although the benefits of a range of disability-centric therapies have been well studied, little remains known about how they work, let alone how to monitor these benefits in a precise and reliable way. METHODS: Here, in two independent studies, we examine how sessions consisting of occupational or music therapy, both widely recognised for their effectiveness, modulate levels of salivary alpha-amylase (sAA), a now time- and cost-efficient marker of stress, in individuals with intellectual disability and autism spectrum disorder. Pre-session and post-session levels of sAA were compared in both groups in response to therapy and control sessions. RESULTS: In comparison to control sessions, occupational therapy significantly dampened rises in sAA levels while music therapy significantly decreased baseline sAA levels, highlighting the ability of both types of therapy to reduce stress and by proxy contribute to enhancing overall well-being. CONCLUSIONS: Not only do these results confirm the stress-reducing nature of two types of multisensory therapy, but they support the use of sAA as a potential tool for evaluating stress levels in individuals with intellectual disability and autism spectrum disorder, providing an important physiological lens that may guide strategies in clinical and non-clinical care for individuals with disabilities.
Lien vers le texte intégral (Open Access ou abonnement)
19. Rahbar MH, Swingle HM, Christian MA, Hessabi M, Lee M, Pitcher MR, Campbell S, Mitchell A, Krone R, Loveland KA, Patterson DG, Jr. {{Environmental Exposure to Dioxins, Dibenzofurans, Bisphenol A, and Phthalates in Children with and without Autism Spectrum Disorder Living near the Gulf of Mexico}}. {Int J Environ Res Public Health}. 2017; 14(11).
Environmental exposure to organic endocrine disrupting chemicals, including dioxins, dibenzofurans, bisphenol A (BPA), and phthalates has been associated with neurodevelopmental disorders, including autism spectrum disorder (ASD). We conducted a pilot monitoring study of 30 ASD cases and 10 typically developing (TD) controls ages 2-8 years from communities along the Gulf of Mexico near Alabama, which houses 14 Superfund sites, to assess the concentrations of dioxins and dibenzofurans in serum, and BPA and phthalate ester metabolites in urine. Based on General Linear Models, the lipid- or creatinine-adjusted geometric mean concentrations of the aforementioned chemicals did not differ between the ASD case and TD control groups (all p >/= 0.27). We compared our findings to the adjusted means as reported by the National Health and Nutrition Examination Survey, survey years 2011-2012, and found that TD controls in our study had lower BPA (59%) and MEHHP (26%) concentrations, higher MBP (50%) concentration, and comparable (<20% difference) MEP, MBZP, MEOHP, and MCPP concentrations. We also conducted a preliminary investigation of dietary exposures and found that the consumption of certain types of fish may be associated with higher OCDD concentrations, and the consumption of soft drinks and juices may be associated with lower BPA and MEOHP concentrations, respectively. Lien vers le texte intégral (Open Access ou abonnement)
20. Rai-Bhogal R, Ahmad E, Li H, Crawford DA. {{Microarray analysis of gene expression in the cyclooxygenase (COX) knockout mice – a connection to Autism Spectrum Disorder}}. {Eur J Neurosci}. 2017.
The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid signalling molecules such as prostaglandin E2 (PGE2 ) play an important role in healthy brain development. Abnormalities along the COX/PGE2 signalling pathway due to genetic or environmental causes have been linked to Autism Spectrum Disorders (ASDs). This study aims to evaluate the effect of altered COX/PGE2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and -2 (COX-1(-/-) and COX-2(-/-) ) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes and affected biological pathways containing various ASD associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD-risk genes identified in both COX-1(-/-) and COX-2(-/-) models belong to protein-interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified 8 genes that belong to the Wnt signalling pathways exclusively in the COX-2(-/-) mice at E16. The level of PKA-phosphorylated beta-catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting cross-talk between the COX-2/PGE2 and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX/PGE2 pathways to ASD and demonstrate that COX-1(-/-) and COX-2(-/-) animals might be suitable new model systems for studying the disorders. This article is protected by copyright. All rights reserved.
Lien vers le texte intégral (Open Access ou abonnement)
21. Rendall AR, Ford AL, Perrino PA, Holly Fitch R. {{Auditory processing enhancements in the TS2-neo mouse model of Timothy Syndrome, a rare genetic disorder associated with autism spectrum disorders}}. {Adv Neurodev Disord}. 2017; 1(3): 176-89.
Lien vers le texte intégral (Open Access ou abonnement)
22. Schertz HH, Odom SL, Baggett KM, Sideris JH. {{Mediating Parent Learning to Promote Social Communication for Toddlers with Autism: Effects from a Randomized Controlled Trial}}. {J Autism Dev Disord}. 2017.
A randomized controlled trial was conducted to evaluate effects of the Joint Attention Mediated Learning (JAML) intervention. Toddlers with autism spectrum disorders (ASD) aged 16-30 months (n = 144) were randomized to intervention and community control conditions. Parents, who participated in 32 weekly home-based sessions, followed a mediated learning process to target preverbal social communication outcomes (social visual synchrony, reciprocity, and responding and initiating forms of joint attention) throughout daily interactions. The analysis found post-intervention effects for all outcomes, with all except initiating joint attention sustaining 6 months post-intervention. Findings support the value of very early intervention targeting explicitly social functions of preverbal communication and of promoting active engagement in the learning process for both toddlers and parents.
Lien vers le texte intégral (Open Access ou abonnement)
23. Schieve LA, Tian LH, Drews-Botsch C, Windham GC, Newschaffer C, Daniels JL, Lee LC, Croen LA, Danielle Fallin M. {{Autism spectrum disorder and birth spacing: Findings from the study to explore early development (SEED)}}. {Autism Res}. 2017.
Previous studies of autism spectrum disorder (ASD) and birth spacing had limitations; few examined phenotypic case subtypes or explored underlying mechanisms for associations and none assessed whether other (non-ASD) developmental disabilities (DDs) were associated with birth spacing. We assessed associations between inter-pregnancy interval (IPI) and both ASD and other DDs using data from the Study to Explore Early Development, a multi-site case-control study with rigorous case-finding and case-classification methods and detailed data collection on maternal reproductive history. Our sample included 356 ASD cases, 627 DD cases, and 524 population (POP) controls born in second or later births. ASD and DD cases were further sub-divided according to whether the child had intellectual disability (ID). ASD cases were also sub-divided by ASD symptom severity, and DD cases were subdivided by presence of some ASD symptoms (indicated on an autism screener). Odds ratios, adjusted for maternal-child sociodemographic factors, (aORs) and 95% confidence intervals were derived from logistic regression models. Among term births, ASD was associated with both IPI <18 months (aOR 1.5 [1.1-2.2]) and >/=60 months (1.5 [0.99-2.4]). Both short and long IPI associations were stronger among ASD cases with high severity scores (aORs 2.0 [1.3-3.3] and 1.8 [0.99-3.2], respectively). Associations were unchanged after adding several factors potentially related to the causal pathway to regression models. DD was not associated with either short or long IPI-overall, among term births, or in any subgroup examined. These findings extend those from previous studies and further inform recommendations on optimal pregnancy spacing. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We investigated whether the amount of time between pregnancies was associated autism spectrum disorder (ASD) or other developmental disabilities (DD) in children. ASD was increased in second and later-born children who were conceived less than 18 months or 60 or more months after the mother’s previous birth. Other DDs were not associated with birth spacing.
Lien vers le texte intégral (Open Access ou abonnement)
24. Skylark WJ, Baron-Cohen S. {{Initial evidence that non-clinical autistic traits are associated with lower income}}. {Mol Autism}. 2017; 8: 61.
Among non-clinical samples, autistic traits correlate with a range of educational and social outcomes. However, previous work has not investigated the relationship between autistic traits and income, a key determinant of socio-economic status and well-being. In five studies (total N = 2491), we recruited participants without a diagnosis of autism from the general US population via an online platform and administered the short-form Autism Spectrum Quotient (AQ) as well as asked a range of demographic questions. We found a negative association between AQ and household income, which remained robust after controlling for age, gender, education, employment status, ethnicity, and socially desirable responding. The effect was primarily driven by the participant’s own income and was mainly due to the social subscale of the AQ. These results provide initial evidence that income is negatively related to autistic traits among the general population, with potential implications for a range of social, psychological, and health outcomes.
Lien vers le texte intégral (Open Access ou abonnement)
25. Sturman N, Deckx L, van Driel ML. {{Methylphenidate for children and adolescents with autism spectrum disorder}}. {Cochrane Database Syst Rev}. 2017; 11: CD011144.
BACKGROUND: Children with autistic spectrum disorder (ASD) frequently present with inattention, impulsivity and hyperactivity, which are the cardinal symptoms of attention deficit hyperactivity disorder (ADHD). The effectiveness of methylphenidate, a commonly used ADHD treatment, is therefore of interest in these children. OBJECTIVES: To assess the effects of methylphenidate for symptoms of ADHD (inattention, impulsivity and hyperactivity) and ASD (impairments in social interaction and communication, and repetitive, restricted or stereotypical behaviours) in children and adolescents aged 6 to 18 years with ASD. SEARCH METHODS: In November 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 11 other databases and two trials registers. We also checked reference lists and contacted study authors and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) that investigated the effect of methylphenidate versus placebo on the core symptoms of ASD or ADHD-like symptoms, or both, in children aged 6 to 18 years who were diagnosed with ASD or pervasive developmental disorder. The primary outcome was clinical efficacy, defined as an improvement in ADHD-like symptoms (inattention, impulsivity and hyperactivity) and in the core symptoms of ASD (impaired social interaction, impaired communication, and stereotypical behaviours), and overall ASD. Secondary outcomes examined were: rate of adverse events; caregiver well-being; need for institutionalisation, special schooling or therapy to achieve learning outcomes; and overall quality of life. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We combined outcome measures that used different psychometric scales, where clinically appropriate. We used a coefficient of 0.6 to calculate standard deviations and adjust for the studies’ cross-over design. We considered a standardised mean difference (SMD) of 0.52 as the minimum clinically relevant inter-treatment difference. We applied the GRADE rating for strength of evidence for each outcome. MAIN RESULTS: The studies: we included four cross-over studies, with a total of 113 children aged 5 to 13 years, most of whom (83%) were boys. We included two studies with five-year-old children since we were unable to obtain the disaggregated data for those aged six years and above, and all other participants were in our target age range. All participants resided in the USA. The duration of treatment in the cross-over phase was one week for each dose of methylphenidate. Studies used a range of outcome scales, rated by parents, teachers or both; clinicians; or programme staff. We report parent-rated outcomes separately. Risk of bias: we considered three trials to be at high risk of bias due to selective reporting and all trials to be at unclear risk of bias for blinding of participants and assessors, due to the potential for recognising the side effects of methylphenidate. We judged all trials to be at low or unclear risk of bias for other items. Primary outcomes: the meta-analysis suggested that high-dose methylphenidate (0.43 mg/kg/dose to 0.60 mg/kg/dose) had a significant and clinically relevant benefit on hyperactivity, as rated by teachers (SMD -0.78, 95% confidence interval (CI) -1.13 to -0.43; 4 studies, 73 participants; P < 0.001; low-quality evidence) and parents (mean difference (MD) -6.61 points, 95% CI -12.19 to -1.03, rated on the hyperactivity subscale of the Aberrant Behviour Checklist, range 0 to 48; 2 studies, 71 participants; P = 0.02; low-quality evidence). Meta-analysis also showed a significant but not clinically relevant benefit on teacher-rated inattention (MD -2.72 points, 95% CI -5.37 to -0.06, rated on the inattention subscale of the Swanson, Nolan and Pelham, Fourth Version questionnaire, range 0 to 27; 2 studies, 51 participants; P = 0.04; low-quality evidence). There were inadequate data to conduct a meta-analysis on the symptom of impulsivity. There was no evidence that methylphenidate worsens the core symptoms of ASD or benefits social interaction (SMD -0.51, 95% CI -1.07 to 0.05; 3 studies, 63 participants; P = 0.07; very low-quality evidence), stereotypical behaviours (SMD -0.34, 95% CI -0.84 to 0.17; 3 studies, 69 participants; P = 0.19; low-quality evidence), or overall ASD (SMD -0.53, 95% CI -1.26 to 0.19; 2 studies, 36 participants; P = 0.15; low-quality evidence), as rated by teachers. There were inadequate data to conduct a meta-analysis on the symptom of impaired communication. SECONDARY OUTCOMES: no data were available for the secondary outcomes of caregiver well-being; need for institutionalisation, special schooling options or therapy to achieve learning outcomes; or overall quality of life. No trials reported serious adverse events. The only adverse effect that was significantly more likely with treatment was reduced appetite as rated by parents (risk ratio 8.28, 95% CI 2.57 to 26.73; 2 studies, 74 participants; P < 0.001; very low-quality evidence). Subgroup analysis by dose did not identify any significant differences in effect on our primary outcomes between low-, medium- or high-dose ranges. AUTHORS' CONCLUSIONS: We found that short-term use of methylphenidate might improve symptoms of hyperactivity and possibly inattention in children with ASD who are tolerant of the medication, although the low quality of evidence means that we cannot be certain of the true magnitude of any effect. There was no evidence that methylphenidate has a negative impact on the core symptoms of ASD, or that it improves social interaction, stereotypical behaviours, or overall ASD. The evidence for adverse events is of very low quality because trials were short and excluded children intolerant of methylphenidate in the test-dose phase. Future RCTs should consider extending the duration of treatment and follow-up. The minimum clinically important difference also needs to be confirmed in children with ASD using outcome scales validated for this population. Lien vers le texte intégral (Open Access ou abonnement)
26. Williams DM, Nicholson T, Grainger C. {{The Self-Reference Effect on Perception: Undiminished in Adults with Autism and No Relation to Autism Traits}}. {Autism Res}. 2017.
Memory for (and perception of) information about the self is superior to memory for (and perception of) other kinds of information. This self-reference effect (SRE) in memory appears diminished in ASD and related to the number of ASD traits manifested by neurotypical individuals (fewer traits = larger SRE). Here, we report the first experiments exploring the relation between ASD and the SRE in perception. Using a « Shapes » Task (Sui et al., Journal of Experimental Psychology: Human Perception and Performance, 38, 1105, 2012), participants learned to associate three different shapes (triangle, circle, square) with three different labels representing self, a familiar other, or an unfamiliar other (e.g., « you », « mother », « stranger »). Participants then completed trials during which they were presented with one shape and one label for 100 ms, and made judgments about whether the shape and label was a match. In Experiment 1, neurotypical participants (n = 124) showed the expected SRE, detecting self-related matches more reliably and quickly than matches involving familiar or unfamiliar other. Most important, number of ASD traits was unrelated to the size of the SRE for either accuracy or RT. Bayesian association analyses strongly supported the null hypothesis. In Experiment 2, there were no differences between 22 adults with ASD and 21 matched comparison adults in performance on the Shapes Task. Despite showing large and significant theory of mind impairments, participants with ASD showed the typical SRE and there were no associations with ASD traits in either group. In every case, Bayesian analyses favored the null hypothesis. These findings challenge theories about self-representation in ASD, as discussed in the article. Autism Res 2017. (c) 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: Neurotypical people tend to find it easier to perceive and remember information that relates to themselves than information that relates to others. Research suggests that people with ASD show a diminished (or absent) self-bias in memory and that severity of ASD predicts the extent of this diminution (more severe ASD = smaller self-bias in memory). However, the current research suggests strongly that people with ASD do show a self-bias in their perception. This research informs our understanding of psychological functioning in ASD and challenges theories regarding self-awareness in this disorder.
Lien vers le texte intégral (Open Access ou abonnement)
27. Zhou JH, Wang XT, Zhou L, Xu FX, Su LD, Wang H, Jia F, Xu FQ, Chen GQ, De Zeeuw CI, Shen Y. {{Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors}}. {J Neurosci}. 2017; 37(47): 11335-52.
Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice. We show that conditional knock-out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1 expression at synapses. This regulation by TFR1 acts in concert with that by Rab8 and Rab11, which modulate the internalization and recycling of mGlu1, respectively. TFR1 can bind to Rab proteins and facilitate their expression at synapses. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-LTP and PC intrinsic excitability are not affected. Finally, we demonstrate that PC ablation of TFR1 impairs motor coordination, but does not affect social behaviors in mice. Together, these findings underscore the importance of TFR1 in regulating mGlu1 trafficking and suggest that mGlu1- and mGlu1-dependent parallel fiber-LTD are associated with regulation of motor coordination, but not autistic behaviors.SIGNIFICANCE STATEMENT Group 1 metabotropic glutamate receptor (mGlu1/5) signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases. Recent work suggests that altered mGlu1 signaling in Purkinje cells (PCs) may be involved in not only motor learning, but also autistic-like behaviors. We find that conditional knock-out of transferrin receptor 1 (TFR1) in PCs reduces synaptic mGlu1 by tethering Rab8 and Rab11 in the cytosol. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-PC LTP and PC intrinsic excitability are intact. Motor coordination is impaired, but social behaviors are normal in TFR1(flox/flox);pCP2-cre mice. Our data reveal a new regulator for trafficking and synaptic expression of mGlu1 and suggest that mGlu1-dependent LTD is associated with motor coordination, but not autistic-like behaviors.
