1. Bailey DB, Jr., Berry-Kravis E, Wheeler A, Raspa M, Merrien F, Ricart J, Koumaras B, Rosenkranz G, Tomlinson M, von Raison F, Apostol G. {{Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study}}. {J Neurodev Disord};2016;8:1.
BACKGROUND: A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. METHODS: In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran-Mantel-Haenszel test. RESULTS: A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI-I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). CONCLUSIONS: A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. TRIAL REGISTRATION: The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354.
Lien vers le texte intégral (Open Access ou abonnement)
2. Beltrao-Braga PC, Muotri AR. {{Modeling autism spectrum disorders with human neurons}}. {Brain Res};2016 (Feb 4)
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders characterized by impaired social communication and interactions and by restricted and repetitive behaviors. Although ASD is suspected to have a heritable or sporadic genetic basis, its underlying etiology and pathogenesis are not well understood. Therefore, viable human neurons and glial cells produced using induced pluripotent stem cells (iPSC) to reprogram cells from individuals affected with ASD provide an unprecedented opportunity to elucidate the pathophysiology of these disorders, providing novel insights regarding ASD and a potential platform to develop and test therapeutic compounds. Herein, we discuss the state of art with regards to ASD modeling, including limitations of this technology, as well as potential future directions.
Lien vers le texte intégral (Open Access ou abonnement)
3. Blazewicz A, Makarewicz A, Korona-Glowniak I, Dolliver W, Kocjan R. {{Iodine in autism spectrum disorders}}. {J Trace Elem Med Biol};2016 (Mar);34:32-37.
OBJECTIVE: The aim of our study was to assess the iodine status of Polish boys with severe autism compared to their healthy peers and evaluate the relationship between urinary iodine, thyroid hormones, body mass index and Autism Spectrum Disorder (ASD) symptomatology. SUBJECTS AND METHODS: Tests were performed in 40 boys with ASD and 40 healthy boys, aged 2-17 from the same geographic region in Poland. Urinary iodine (UI), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), BMI, and individual symptoms measured by the Childhood Autism Rating Scale (CARS) were correlated. Validated ion chromatography method with pulsed amperometric detection was applied for the determination of urinary iodine after optimized alkaline digestion in a closed system assisted with microwaves. RESULTS: 19 out of 40 children with ASD had mild to moderate iodine deficiency. Statistically significant lower levels of UI, fT3 and fT4 and higher levels of TSH were found in the autistic group when compared with the control group. Concentration of iodine in urine was negatively associated with clinician’s general impression for children between 11 and 17 years. Emotional response, adaptation to environmental change, near receptor responsiveness, verbal communication, activity level, and intellectual functioning are more associated with UI than other symptoms listed in CARS. CONCLUSION: The severity of certain symptoms in autism is associated with iodine status in maturing boys. Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required.
Lien vers le texte intégral (Open Access ou abonnement)
4. Brasa S, Mueller A, Jacquemont S, Hahne F, Rozenberg I, Peters T, He Y, McCormack C, Gasparini F, Chibout SD, Grenet O, Moggs J, Gomez-Mancilla B, Terranova R. {{Reciprocal changes in DNA methylation and hydroxymethylation and a broad repressive epigenetic switch characterize FMR1 transcriptional silencing in fragile X syndrome}}. {Clin Epigenetics};2016;8:15.
BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from the loss of function of the fragile X mental retardation 1 (FMR1) gene. The molecular pathways associated with FMR1 epigenetic silencing are still elusive, and their characterization may enhance the discovery of novel therapeutic targets as well as the development of novel clinical biomarkers for disease status. RESULTS: We have deployed customized epigenomic profiling assays to comprehensively map the FMR1 locus chromatin landscape in peripheral mononuclear blood cells (PBMCs) from eight FXS patients and in fibroblast cell lines derived from three FXS patient. Deoxyribonucleic acid (DNA) methylation (5-methylcytosine (5mC)) and hydroxymethylation (5-hydroxymethylcytosine (5hmC)) profiling using methylated DNA immunoprecipitation (MeDIP) combined with a custom FMR1 microarray identifies novel regions of DNA (hydroxy)methylation changes within the FMR1 gene body as well as in proximal flanking regions. At the region surrounding the FMR1 transcriptional start sites, increased levels of 5mC were associated to reciprocal changes in 5hmC, representing a novel molecular feature of FXS disease. Locus-specific validation of FMR1 5mC and 5hmC changes highlighted inter-individual differences that may account for the expected DNA methylation mosaicism observed at the FMR1 locus in FXS patients. Chromatin immunoprecipitation (ChIP) profiling of FMR1 histone modifications, together with 5mC/5hmC and gene expression analyses, support a functional relationship between 5hmC levels and FMR1 transcriptional activation and reveal cell-type specific differences in FMR1 epigenetic regulation. Furthermore, whilst 5mC FMR1 levels positively correlated with FXS disease severity (clinical scores of aberrant behavior), our data reveal for the first time an inverse correlation between 5hmC FMR1 levels and FXS disease severity. CONCLUSIONS: We identify novel, cell-type specific, regions of FMR1 epigenetic changes in FXS patient cells, providing new insights into the molecular mechanisms of FXS. We propose that the combined measurement of 5mC and 5hmC at selected regions of the FMR1 locus may significantly enhance FXS clinical diagnostics and patient stratification.
Lien vers le texte intégral (Open Access ou abonnement)
5. Campione GC, Piazza C, Villa L, Molteni M. {{Three-Dimensional Kinematic Analysis of Prehension Movements in Young Children with Autism Spectrum Disorder: New Insights on Motor Impairment}}. {J Autism Dev Disord};2016 (Feb 9)
The study was aimed at better clarifying whether action execution impairment in autism depends mainly on disruptions either in feedforward mechanisms or in feedback-based control processes supporting motor execution. To this purpose, we analyzed prehension movement kinematics in 4- and 5-year-old children with autism and in peers with typical development. Statistical analysis showed that the kinematics of the grasp component was spared in autism, whereas early kinematics of the reach component was atypical. We discussed this evidence as suggesting impairment in the feedforward processes involved in action execution, whereas impairment in feedback-based control processes remained unclear. We proposed that certain motor abilities are available in autism, and children may use them differently as a function of motor context complexity.
Lien vers le texte intégral (Open Access ou abonnement)
6. Casartelli L, Molteni M, Ronconi L. {{SO CLOSE YET SO FAR: MOTOR ANOMALIES IMPACTING ON SOCIAL FUNCTIONING IN AUTISM SPECTRUM DISORDER}}. {Neurosci Biobehav Rev};2016 (Feb 5)
Difficulties in the social domain and motor anomalies have been widely investigated in Autism Spectrum Disorder (ASD). However, they have been generally considered as independent, and therefore tackled separately. Recent advances in neuroscience have hypothesized that the cortical motor system can play a role not only as a controller of elementary physical features of movement, but also in a complex domain as social cognition. Here, going beyond previous studies on ASD that described difficulties in the motor and in the social domain separately, we focus on the impact of motor mechanisms anomalies on social functioning. We consider behavioral, electrophysiological and neuroimaging findings supporting the idea that motor cognition is a critical « intermediate phenotype » for ASD. Motor cognition anomalies in ASD affect the processes of extraction, codification and subsequent translation of « external » social information into the motor system. Intriguingly, this alternative « motor » approach to the social domain difficulties in ASD may be promising to bridge the gap between recent experimental findings and clinical practice, potentially leading to refined preventive approaches and successful treatments.
Lien vers le texte intégral (Open Access ou abonnement)
7. Castro K, Baronio D, Perry IS, Riesgo RD, Gottfried C. {{The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid}}. {Nutr Neurosci};2016 (Feb 9)
OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. METHODS: Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). RESULTS: When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. DISCUSSION: VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
8. Christiansz JA, Gray KM, Taffe J, Tonge BJ. {{Autism Spectrum Disorder in the DSM-5: Diagnostic Sensitivity and Specificity in Early Childhood}}. {J Autism Dev Disord};2016 (Feb 9)
Changes to the DSM-5 Autism Spectrum Disorder (ASD) criteria raised concerns among parents and practitioners that the criteria may exclude some children with Pervasive Developmental Disorder (PDD). Few studies have examined DSM-5 sensitivity and specificity in children less than 5 years of age. This study evaluated 185 children aged 20-55 months with DSM-IV PDD or developmental delay. Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) data was assigned to DSM-5 subdomains. Children displaying the required symptomatology were classified with DSM-5 ASD. DSM-IV clinical diagnoses were compared to DSM-5 classifications. Using combined ADI-R/ADOS information, sensitivity was .84 and specificity was .54. Comorbid behaviour and emotional problems were significantly lower in children with PDD that did not meet DSM-5 criteria.
Lien vers le texte intégral (Open Access ou abonnement)
9. Crane L, Maras KL, Hawken T, Mulcahy S, Memon A. {{Experiences of Autism Spectrum Disorder and Policing in England and Wales: Surveying Police and the Autism Community}}. {J Autism Dev Disord};2016 (Feb 9)
An online survey gathered the experiences and views of 394 police officers (from England and Wales) regarding autism spectrum disorder (ASD). Just 42 % of officers were satisfied with how they had worked with individuals with ASD and reasons for this varied. Although officers acknowledged the need for adjustments, organisational/time constraints were cited as barriers. Whilst 37 % of officers had received training on ASD, a need for training tailored to policing roles (e.g., frontline officers, detectives) was identified. Police responses are discussed with respect to the experiences of the ASD community (31 adults with ASD, 49 parents), who were largely dissatisfied with their experience of the police and echoed the need for police training on ASD.
Lien vers le texte intégral (Open Access ou abonnement)
10. Duda M, Ma R, Haber N, Wall DP. {{Use of machine learning for behavioral distinction of autism and ADHD}}. {Transl Psychiatry};2016;6:e732.
Although autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) continue to rise in prevalence, together affecting >10% of today’s pediatric population, the methods of diagnosis remain subjective, cumbersome and time intensive. With gaps upward of a year between initial suspicion and diagnosis, valuable time where treatments and behavioral interventions could be applied is lost as these disorders remain undetected. Methods to quickly and accurately assess risk for these, and other, developmental disorders are necessary to streamline the process of diagnosis and provide families access to much-needed therapies sooner. Using forward feature selection, as well as undersampling and 10-fold cross-validation, we trained and tested six machine learning models on complete 65-item Social Responsiveness Scale score sheets from 2925 individuals with either ASD (n=2775) or ADHD (n=150). We found that five of the 65 behaviors measured by this screening tool were sufficient to distinguish ASD from ADHD with high accuracy (area under the curve=0.965). These results support the hypotheses that (1) machine learning can be used to discern between autism and ADHD with high accuracy and (2) this distinction can be made using a small number of commonly measured behaviors. Our findings show promise for use as an electronically administered, caregiver-directed resource for preliminary risk evaluation and/or pre-clinical screening and triage that could help to speed the diagnosis of these disorders.
Lien vers le texte intégral (Open Access ou abonnement)
11. Goncalves TF, Dos Santos JM, Goncalves AP, Tassone F, Mendoza-Morales G, Ribeiro MG, Kahn E, Boy R, Goncalves Pimentel MM, Santos-Reboucas CB. {{Finding FMR1 mosaicism in Fragile X syndrome}}. {Expert Rev Mol Diagn};2016 (Feb 9):1-7.
OBJECTIVE: Almost all patients with Fragile X Syndrome (FXS) exhibit a CGG repeat expansion (full mutation) in the Fragile Mental Retardation 1 gene (FMR1). Here, the authors report five unrelated males with FXS harboring a somatic full mutation/deletion mosaicism. METHODS: Mutational profiles were only elucidated by using a combination of molecular approaches (CGG-based PCR, Sanger sequencing, MS-MLPA, Southern blot and mPCR). RESULTS: Four patients exhibited small deletions encompassing the CGG repeats tract and flanking regions, whereas the remaining had a larger deletion comprising at least exon 1 and part of intron 1 of FMR1 gene. The presence of a 2-3 base pairs microhomology in proximal and distal non-recurrent breakpoints without scars supports the involvement of microhomology mediated induced repair (MMBIR) mechanism in three small deletions. CONCLUSION: The authors data highlights the importance of using different research methods to elucidate atypical FXS mutational profiles, which are clinically undistinguishable and may have been underestimated.
Lien vers le texte intégral (Open Access ou abonnement)
12. Gungor O, Kirik S, Cevizli D, Karaokur F, Ozer L, Uysal S, Dilber C. {{A RETT SYNDROME CASE WITH NOVEL NON-IDENTICAL MUTATION IN MECP2 GENE}}. {Genet Couns};2015;26(4):387-392.
The Rett syndrome (RTT; OMIM #312750) is a rare genetic disease observed predominantly among girls that affects neurological development. The incidence of this disorder is approximately 1 in 10,000 female births. Diagnosis of the RTT is based on specific clinical criteria and the identification of a mutation in the methyl-CpG-binding protein (MECP), which mainly occurs on exons 3 and 4 of the gene. Mutations in the X-linked methyl-CpG binding protein 2 gene (MECP2) are observed in nearly 95% of RTT cases. RTT is associated with considerable genotypic and phenotypic heterogeneity. Recently, it has been observed that mutations in the genes Netrin G1 and cyclin-dependent kinase like 5 (CDKL5) also lead to clinical pictures resembling RTT. In this case report, we describe a 4-years-old female patient who met all the relevant criteria for the diagnosis of RTT. Sequence analyses performed on the patient identified a de novo, heterozygous c.489G>A mutation at exon 4 of the MECP2 gene.
Lien vers le texte intégral (Open Access ou abonnement)
13. Lever AG, Geurts HM. {{Psychiatric Co-occurring Symptoms and Disorders in Young, Middle-Aged, and Older Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Feb 9)
Although psychiatric problems are less prevalent in old age within the general population, it is largely unknown whether this extends to individuals with autism spectrum disorders (ASD). We examined psychiatric symptoms and disorders in young, middle-aged, and older adults with and without ASD (Nmax = 344, age 19-79 years, IQ > 80). Albeit comparable to other psychiatric patients, levels of symptoms and psychological distress were high over the adult lifespan; 79 % met criteria for a psychiatric disorder at least once in their lives. Depression and anxiety were most common. However, older adults less often met criteria for any psychiatric diagnosis and, specifically, social phobia than younger adults. Hence, despite marked psychological distress, psychiatric problems are also less prevalent in older aged individuals with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
14. Pickard KE, Wainer AL, Bailey KM, Ingersoll BR. {{A mixed-method evaluation of the feasibility and acceptability of a telehealth-based parent-mediated intervention for children with autism spectrum disorder}}. {Autism};2016 (Feb 9)
Research within the autism spectrum disorder field has called for the use of service delivery models that are able to more efficiently disseminate evidence-based practices into community settings. This study employed telehealth methods in order to deliver an Internet-based, parent training intervention for autism spectrum disorder, ImPACT Online. This study used mixed-methods analysis to create a more thorough understanding of parent experiences likely to influence the adoption and implementation of the program in community settings. Specific research questions included (1) What are parents’ perceptions of the online program? (2) How does ImPACT Online compare to other services that parents are accessing for their children? And (3) Do parents’ experience in, and perceptions of, the program differ based on whether they received a therapist-assisted version of the program? Results from 28 parents of a child with autism spectrum disorder indicate that parents saw improvements in their child’s social communication skills and their own competence during the course of the program, regardless of whether they received therapist assistance. However, qualitative interviews indicate that parents who received therapist assistance were more likely endorse the acceptability and observability of the program. These findings support the potential for Internet-based service delivery to more efficiently disseminate evidence-based parent training interventions for autism spectrum disorder.
Lien vers le texte intégral (Open Access ou abonnement)
15. Pietropaolo S, Crusio WE, D’Amato F R. {{Treatment Approaches in Rodent Models for Autism Spectrum Disorder}}. {Curr Top Behav Neurosci};2016 (Feb 9)
Recent years have seen an impressive amount of research devoted to the developing of therapies to treat autism spectrum disorder (ASD). This work has been largely based on rodent models, employing a multitude of genetic and environmental manipulations. Unfortunately, the task of identifying suitable treatments for ASD is extremely challenging, due to a variety of problems specific to the research in this field. Here, we first discuss these problems, including (I) the presence of a large variety of rodent models (often without universal consensus on their validity), (II) the difficulties in choosing the most appropriate behavioural markers to assess the efficacy of possible treatments, (III) the limited knowledge we still have of the neurobiological bases of ASD pathology and of its aetiology, and (IV) the complexity of ASD itself, including a highly heterogeneous group of disorders sometimes with markedly different symptoms (therefore unlikely to be treated with the same approaches). Second, we give a critical overview of the most relevant advances in designing treatments for ASD, focusing on the most commonly used animal model, the laboratory mouse. We include pharmacological and non-pharmacological approaches, underlining their specific advantages, but also their current limitations especially in relation to the problems discussed before. Finally, we highlight the theoretical (e.g. the combination of multiple rather than single treatments) and methodological (e.g. use of single-gene mouse models) approaches that seem more promising to us, suggesting various strategies that can be adopted to simplify the complex field of research on treatments for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
16. Powell G, Wass SV, Erichsen JT, Leekam SR. {{First evidence of the feasibility of gaze-contingent attention training for school children with autism}}. {Autism};2016 (Feb 9)
A number of authors have suggested that attention control may be a suitable target for cognitive training in children with autism spectrum disorder. This study provided the first evidence of the feasibility of such training using a battery of tasks intended to target visual attentional control in children with autism spectrum disorder within school-based settings. Twenty-seven children were recruited and randomly assigned to either training or an active control group. Of these, 19 completed the initial assessment, and 17 (9 trained and 8 control) completed all subsequent training sessions. Training of 120 min was administered per participant, spread over six sessions (on average). Compliance with the training tasks was generally high, and evidence of within-task training improvements was found. A number of untrained tasks to assess transfer of training effects were administered pre- and post-training. Changes in the trained group were assessed relative to an active control group. Following training, significant and selective changes in visual sustained attention were observed. Trend training effects were also noted on disengaging visual attention, but no convincing evidence of transfer was found to non-trained assessments of saccadic reaction time and anticipatory looking. Directions for future development and refinement of these new training techniques are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
17. Quick VB, Davis JM, Olincy A, Sikela JM. {{DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases}}. {Transl Psychiatry};2016;6:e735.
Lien vers le texte intégral (Open Access ou abonnement)
18. Robinson A, Elliott R. {{Brief Report: An Observational Measure of Empathy for Autism Spectrum: A Preliminary Study of the Development and Reliability of the Client Emotional Processing Scale}}. {J Autism Dev Disord};2016 (Feb 9)
People with autism spectrum disorder (ASD), can have difficulties in emotion processing, including recognising their own and others’ emotions, leading to problems in emotion regulation and interpersonal relating. This study reports the development and piloting of the Client Emotional Processing Scale-Autism Spectrum (CEPS-AS), a new observer measure of four interrelated aspects of emotional processing: emotion recognition, self-reflection, cognitive empathy, and affective empathy. Results showed good interrater reliability (alpha: .69-.91), while inter-dimension associations were high (r = .66-.82). The measure was able to detect significant differences on the four dimensions across a short-term humanistic-experiential group therapy. The CEPS-AS shows promise as a potential addition to current self-report instruments measuring empathy or emotion processes in individuals with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
19. Stevenson RA, Sun SZ, Hazlett N, Cant JS, Barense MD, Ferber S. {{Seeing the Forest and the Trees: Default Local Processing in Individuals with High Autistic Traits Does Not Come at the Expense of Global Attention}}. {J Autism Dev Disord};2016 (Feb 9)
Atypical sensory perception is one of the most ubiquitous symptoms of autism, including a tendency towards a local-processing bias. We investigated whether local-processing biases were associated with global-processing impairments on a global/local attentional-scope paradigm in conjunction with a composite-face task. Behavioural results were related to individuals’ levels of autistic traits, specifically the Attention to Detail subscale of the Autism Quotient, and the Sensory Profile Questionnaire. Individuals showing high rates of Attention to Detail were more susceptible to global attentional-scope manipulations, suggesting that local-processing biases associated with Attention to Detail do not come at the cost of a global-processing deficit, but reflect a difference in default global versus local bias. This relationship operated at the attentional/perceptual level, but not response criterion.
Lien vers le texte intégral (Open Access ou abonnement)
20. Vernon TW, Miller AR, Ko JA, Wu VL. {{Social Tools And Rules for Teens (The START Program): Program Description and Preliminary Outcomes of an Experiential Socialization Intervention for Adolescents with Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Feb 9)
Experiential learning is an essential process in the development of core social competencies. Unfortunately, adolescents with autism spectrum disorders often do not possess the prerequisite skillset and motivation to sustain the level of social immersion needed to benefit from this learning process. These persisting social vulnerabilities can limit their long-term relational success and associated quality of life, creating a need for comprehensive social programming. This paper describes a multi-component socialization intervention that simultaneously targets motivational, conceptual, and skill deficits using a hybrid experiential/didactic treatment approach. Evidence of social competence improvements was noted in survey and live conversational measures, indicating that the START program may hold promise as a method for improving the social success of participating adolescents with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
21. Wehman P, Brooke V, Brooke AM, Ham W, Schall C, McDonough J, Lau S, Seward H, Avellone L. {{Employment for adults with autism spectrum disorders: A retrospective review of a customized employment approach}}. {Res Dev Disabil};2016 (Feb 5);53-54:61-72.
Over the past few decades, there has been an increase in prevalence of children with autism spectrum disorders (ASD), and those children are now becoming young adults in need of competitive integrated employment (CIE). Customized employment (CE) is one pathway to employment that has been successful for other individuals with developmental disabilities (DD), though research has been very limited on the effectiveness with individuals with ASD. This paper provides a retrospective review of 64 individuals with ASD who came to our program from 2009 to 2014 for supported employment services as referred by the state vocational rehabilitation services agency. Employment specialists engaged in situational assessment, discovery, job development, customized job descriptions, on-site training and support, positive behavioral supports, and job retention techniques. The employment specialists were responsible for tracking their actual time spent working directly with or for the jobseeker with autism spectrum disorders (ASD). All vocational rehabilitation clients with ASD served during this time successfully secured CIE, and maintained their employment with ongoing supports, with intensity of support time decreasing over time. The majority (63/64, 98.4%) of individuals successfully secured CIE through the use of supported employment, in 72 unique employment positions. Of the majority of the individuals who secured employment, 77% (50) individuals indicated that they had never worked before and additional 18% (12) reported having short intermittent histories of employment. Despite this lack of employment experience, in all cases the jobseeker directed the job search and ultimately the job selection.
Lien vers le texte intégral (Open Access ou abonnement)
22. Xie Z, Jones A, Deeney JT, Hur SK, Bankaitis VA. {{Inborn Errors of Long-Chain Fatty Acid beta-Oxidation Link Neural Stem Cell Self-Renewal to Autism}}. {Cell Rep};2016 (Feb 9);14(5):991-999.
Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid beta-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (an enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism.
Lien vers le texte intégral (Open Access ou abonnement)
23. Yoganathan S, Arunachal G, Sudhakar SV, Rajaraman V, Thomas M, Danda S. {{Beta Propellar Protein-Associated Neurodegeneration: A Rare Cause of Infantile Autistic Regression and Intracranial Calcification}}. {Neuropediatrics};2016 (Feb 9)
Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of single gene disorders with distinguished clinical phenotypes and definitive imaging findings. Beta propeller protein-associated neurodegeneration (BPAN) is a subentity of NBIA with X linked dominant inheritance. In this report, we describe a girl with autistic regression, seizures, intracranial calcification, iron accumulation in substantia nigra, and globi pallidi, and diagnosis of BPAN was established based on the identification of previously described disease causing variant in WD repeat domain 45 (WDR45) gene encoding for beta propeller protein. This is the first genetically proven case from India. BPAN is an underrecognized disorder and must be considered as a differential diagnosis in children with atypical Rett features and should be enlisted among the causes for autistic regression and intracranial calcification. Pediatricians must be aware of this rare entity for establishing early diagnosis, prognostication, and genetic counseling. Treatment is usually supportive. More research is needed to explore drugs in the management of BPAN that can facilitate the autophagy and promotes cytoprotection.
Lien vers le texte intégral (Open Access ou abonnement)
24. Zilkha N, Kuperman Y, Kimchi T. {{High-fat diet exacerbates cognitive rigidity and social deficiency in the BTBR mouse model of autism}}. {Neuroscience};2016 (Feb 5)
The global increase in rates of obesity has been accompanied by a similar surge in the number of autism diagnoses. Accumulating epidemiological evidence suggest a possible link between overweight and the risk for autism spectrum disorders (ASD), as well as autism severity. In laboratory animals, several studies have shown a direct link between various environmental factors, including diet-induced obesity, and the development of autism-related behaviors. However, the effect of high-fat or imbalanced diet on a pre-existing autism-like phenotype is unclear. In this study, we employed the BTBR inbred mouse strain, a well-established mouse model for autism, to directly assess the impact of inadequate fattening nutrition on the autism-related behavioral phenotype. Male mice were fed by high-fat diet (HFD) or control balanced diet (control) from weaning onwards, and tested in a series of behavioral assays as adults. In addition, we measured the hypothalamic expression levels of several genes involved in oxytocin and dopamine signaling, in search of a possible neurobiological underlying mechanism. As an internal control, we also employed similar metabolic and behavioral measures on neurotypical C57 mice. Compared to control mice, BTBR mice fed by HFD showed marked aggravation in autism-related behaviors, manifested in increased cognitive rigidity and diminished preference for social novelty. Moreover, the total autism composite (severity) score was higher in the HFD group, and positively correlated with higher body weight. Finally, we revealed negative correlations associating dopamine signaling factors in the hypothalamus, to autism-related severity and body weight. In contrast, we found no significant effects of HFD on autism-related behaviors of C57 mice, though the metabolic effects of the diet were similar for both strains. Our results indicate a direct causative link between diet-induced obesity and worsening of a pre-existing autism-related behavior and emphasize the need for adequate nutrition in ASD patients. Our results might also implicate the involvement of hypothalamic dopamine in mediating this effect.
