1. Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, Brinkman M, Rerat K, Koumaras B, Zhu L, Barth GM, Jaecklin T, Apostol G, von Raison F. {{Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials}}. {Sci Transl Med}. 2016; 8(321): 321ra5.
Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-CFX) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits.
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2. Curran EA, Kenny LC, Khashan AS. {{Sibling Comparisons and Confounding in Autism Epidemiological Studies-Reply}}. {JAMA Psychiatry}. 2016: 1.
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3. de Castilho LS, Abreu MH, de Oliveira RB, Souza ESME, Resende VL. {{Factors associated with mouth breathing in children with -developmental -disabilities}}. {Spec Care Dentist}. 2016.
OBJECTIVE: To investigate the prevalence and factors associated with mouth breathing among patients with developmental disabilities of a dental service. METHODS: We analyzed 408 dental records. Mouth breathing was reported by the patients’ parents and from direct observation. Other variables were as -follows: history of asthma, bronchitis, palate shape, pacifier use, thumb -sucking, nail biting, use of medications, gastroesophageal reflux, bruxism, gender, age, and diagnosis of the patient. Statistical analysis included descriptive analysis with ratio calculation and multiple logistic regression. Variables with p < 0.25 were included in the model to estimate the adjusted OR (95% CI), calculated by the forward stepwise method. Variables with p < 0.05 were kept in the model. RESULTS: Being male (p = 0.016) and use of centrally acting drugs (p = 0.001) were the variables that remained in the model. CONCLUSION: Among patients with -developmental disabilities, boys and psychotropic drug users had a greater chance of being mouth breathers. Lien vers le texte intégral (Open Access ou abonnement)
4. Fernandes FD, de La Higuera Amato CA, Cardoso C, Navas AL, Molini-Avejonas DR. {{Reading in Autism Spectrum Disorders: A Literature Review}}. {Folia Phoniatr Logop}. 2016; 67(4): 169-77.
OBJECTIVE: To review what the literature says about reading abilities of children on the autism spectrum (autism spectrum disorders, ASD) as well as to assess the results of intervention proposals. The broad ASD diagnosis used in the last decades and the resulting changes in the prevalence of these disorders have led to a relevant increase in the number of children diagnosed with ASD in the school system. The purpose of this review is to identify the different profiles of reading abilities shown by children with ASD described in the recent literature and the results of reported intervention methods. METHODS: A review of the literature was conducted in the Web of Sciences and PubMed databases with the keywords ‘autism’ AND ‘read*’ and the filter 2010-2015. All articles published in the last 5 years focusing on description of and intervention for reading abilities in individuals with ASD were included. Review articles were excluded. RESULTS: The selected 58 articles were divided into those that described reading abilities in individuals with ASD (n = 27) and those that reported intervention procedures for reading development (n = 31). CONCLUSIONS: Direct comparisons and associations were prevented due to different inclusion criteria and lack of detailed information about intervention processes. We propose tentative conclusions that should be confirmed by further studies.
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5. Gardner MR, Suplee PD, Jerome-D’Emilia B. {{Survey of Nursing Faculty Preparation for Teaching About Autism Spectrum Disorders}}. {Nurse Educ}. 2016.
The prevalence of autism spectrum disorders (ASDs) has increased significantly in children and adults. Nursing faculty’s ability to teach students about best practices in their care across the lifespan is important. This study explored nurse educators’ perceived knowledge of, and levels of comfort in, their abilities to teach nursing students about nursing care of people with ASD. Strategies are proposed to incorporate competencies for care of people with ASD into nursing curricula.
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6. Keehn B, Joseph RM. {{Exploring What’s Missing: What Do Target Absent Trials Reveal About Autism Search Superiority?}}. {J Autism Dev Disord}. 2016.
We used eye-tracking to investigate the roles of enhanced discrimination and peripheral selection in superior visual search in autism spectrum disorder (ASD). Children with ASD were faster at visual search than their typically developing peers. However, group differences in performance and eye-movements did not vary with the level of difficulty of discrimination or selection. Rather, consistent with prior ASD research, group differences were mainly the effect of faster performance on target-absent trials. Eye-tracking revealed a lack of left-visual-field search asymmetry in ASD, which may confer an additional advantage when the target is absent. Lastly, ASD symptomatology was positively associated with search superiority, the mechanisms of which may shed light on the atypical brain organization that underlies social-communicative impairment in ASD.
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7. Kirby AV. {{Parent Expectations Mediate Outcomes for Young Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
Understanding the complex relationships among factors that may predict the outcomes of young adults with autism spectrum disorder (ASD) is of utmost importance given the increasing population undergoing and anticipating the transition to adulthood. With a sample of youth with ASD (n = 1170) from the National Longitudinal Transition Study-2, structural equation modeling techniques were used to test parent expectations as a mediator of young adult outcomes (i.e., employment, residential independence, social participation) in a longitudinal analysis. The mediation hypothesis was confirmed; family background and functional performance variables significantly predicted parent expectations which significantly predicted outcomes. These findings add context to previous studies examining the role of parent expectations on young adult outcomes and inform directions for family-centered interventions and future research.
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8. Lorenz T, Frischling C, Cuadros R, Heinitz K. {{Autism and Overcoming Job Barriers: Comparing Job-Related Barriers and Possible Solutions in and outside of Autism-Specific Employment}}. {PLoS One}. 2016; 11(1): e0147040.
The aim of this study was to discover how individuals with autism succeed in entering the job market. We therefore sought to identify expected and occurred barriers, keeping them from taking up and staying in employment as well as to identify the solutions used to overcome these barriers. Sixty-six employed individuals with autism-17 of them with autism-specific employment-participated in an online survey. Results showed a variety of possible barriers. Individuals in autism-specific employment named formality problems-problems with organizational and practical process-related aspects of the job entry-most frequently while individuals in non-autism-specific employment mentioned social problems-obstacles concerning communication and human interaction-most. In terms of solutions, both groups used their own resources as much as external help, but differed in their specific strategies. In addition, correlations of an autism-specific employment with general and occupational self-efficacy as well as life and job satisfaction were examined. Possible implications of the results are discussed with regard to problem solving behavior and the use of strengths.
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9. Schendel DE, Parner E. {{Sibling Comparisons and Confounding in Autism Epidemiological Studies}}. {JAMA Psychiatry}. 2016: 1.
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10. Schipul SE, Just MA. {{Diminished neural adaptation during implicit learning in autism}}. {Neuroimage}. 2016; 125: 332-41.
Neuroimaging studies have shown evidence of disrupted neural adaptation during learning in individuals with autism spectrum disorder (ASD) in several types of tasks, potentially stemming from frontal-posterior cortical underconnectivity (Schipul et al., 2012). The aim of the current study was to examine neural adaptations in an implicit learning task that entails participation of frontal and posterior regions. Sixteen high-functioning adults with ASD and sixteen neurotypical control participants were trained on and performed an implicit dot pattern prototype learning task in a functional magnetic resonance imaging (fMRI) session. During the preliminary exposure to the type of implicit prototype learning task later to be used in the scanner, the ASD participants took longer than the neurotypical group to learn the task, demonstrating altered implicit learning in ASD. After equating task structure learning, the two groups’ brain activation differed during their learning of a new prototype in the subsequent scanning session. The main findings indicated that neural adaptations in a distributed task network were reduced in the ASD group, relative to the neurotypical group, and were related to ASD symptom severity. Functional connectivity was reduced and did not change as much during learning for the ASD group, and was related to ASD symptom severity. These findings suggest that individuals with ASD show altered neural adaptations during learning, as seen in both activation and functional connectivity measures. This finding suggests why many real-world implicit learning situations may pose special challenges for ASD.
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11. Steinhausen HC, Mohr Jensen C, Lauritsen MB. {{A systematic review and meta-analysis of the long-term overall outcome of autism spectrum disorders in adolescence and adulthood}}. {Acta Psychiatr Scand}. 2016.
OBJECTIVE: A systematic review and meta-analysis of studies reporting on the overall outcome in terms of a global measure of adjustment in children with autistic disorders followed up in adolescence and adulthood. METHOD: PubMed, PsycINFO, and EMBASE were systematically searched on 3rd of August 2015. Included studies were analyzed using random-effects models estimating event rates (%) and 95% confidence intervals (95%CI). RESULTS: From 4350 records identified in the search, 15 studies covering 12 unique samples and a total of N = 828 individuals with autistic disorders were included in the analyses. An estimated 19.7% (95%CI: 14.2-26.6) had a good outcome, 31.1% (95%CI: 23.2-40.4%) a fair outcome, and 47.7% (95%CI: 36.6-59.0) a poor outcome. The meta-analysis showed strong evidence for heterogeneity. The subtype of childhood autism is a significant moderating factor on the risk of having a poor outcome at follow-up, whereas age at follow-up showed statistically significant but inconsistent associations with outcome status. CONCLUSION: The long-term outcome of almost half of all individuals with autistic disorders is poor. The subtype of autism in childhood may be a predictor for specific long-term outcomes, but in general, little is known about the pathways and predictors.
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12. Sy JR, Green L, Gratz O, Ervin T. {{An Evaluation of the Effects of a Mild Delayed Verbal Punisher on Choice of an Immediate Reinforcer by Children With Autism}}. {Behav Modif}. 2016.
Different combinations of immediate and delayed consequences differentially affect choice. Basic research has found that nonhuman animals are more likely to choose an alternative that produces an immediate reinforcer that is followed by a delayed punisher as the delay to punishment increases. The purpose of the current effort was to examine the choices of three individuals with autism when they were given the choice between receiving a larger amount of preferred food followed by a mild, delayed verbal punisher and a smaller amount of the preferred food. A secondary purpose was to determine whether signal presence and duration would affect the efficacy of the punisher (i.e., whether children would be more likely to select the smaller reward that was not followed by a delayed punisher). Results were idiosyncratic across children and highlight the need to evaluate choice under multiple arrangements.
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13. Tonge NA, Rodebaugh TL, Fernandez KC, Lim MH. {{Self-reported social skills impairment explains elevated autistic traits in individuals with generalized social anxiety disorder}}. {J Anxiety Disord}. 2015; 38: 31-6.
Screening for autism in individuals with generalized social anxiety disorder (GSAD) is complicated by symptom overlap between GSAD and autism spectrum disorder (ASD). We examined the prevalence of self-reported autistic traits within a sample of participants with a diagnosis of GSAD (n=37) compared to individuals without a GSAD diagnosis (NOSAD; n=26). Of the GSAD sample participants, 70.84% self-reported autistic traits above a cut-off of 65 on the Autism Quotient-Short (AQ-S) and reported significantly more autistic traits on 3 of 5 AQ-S subscales compared to the NOSAD group. Diagnosis uniquely predicted variation in the social skills subscale above and beyond the other subscales and other predictors. Furthermore, variation in the social skills subscale largely explained group differences on the other subscales. Our results suggest caution in utilizing measures like the AQ-S with clinical populations characterized by social difficulties such as individuals with a GSAD diagnosis.
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14. Uljarevic M, Lane A, Kelly A, Leekam S. {{Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder}}. {Autism Res}. 2016.
This study aimed to identify sensory subtypes in older children and adolescents with Autism Spectrum Disorders (ASD) and examine the relationship of sensory subtypes with anxiety levels in this group. Mothers of 57 children and adolescents with ASD aged 11-17 years (Mean age = 14 years. 2.4 months, SD = 1.81) completed the short sensory profile and Spence anxiety scales. Model-based cluster analysis was applied to sensory profile scores to identify sensory subtypes. Three sensory subtypes, sensory adaptive (N = 19), sensory moderate (N = 29) and sensory severe (N = 9) were identified. The results indicated that the differences between the subtypes were well characterised by the severity of sensory symptoms and were not attributable to sensory modality or varying types of sensory-related behaviors. Children and adolescents from the adaptive subtype had significantly lower anxiety scores when compared with other two subtypes. There were no differences between subtypes based on chronological age, expressive language, or severity of autism diagnostic features as measured by the social communication questionnaire (SCQ total score). This is the first study to identify the existence of sensory subtypes among older children and adolescents with ASD and explore their association with anxiety levels. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Vohra R, Madhavan S, Sambamoorthi U. {{Emergency Department Use Among Adults with Autism Spectrum Disorders (ASD)}}. {J Autism Dev Disord}. 2016.
A cross-sectional analyses using Nationwide Emergency Department Sample (2006-2011) was conducted to examine the trends, type of ED visits, and mean total ED charges for adults aged 22-64 years with and without ASD (matched 1:3). Around 0.4 % ED visits (n = 25,527) were associated with any ASD and rates of such visits more than doubled from 2006 to 2011 (2549-6087 per 100,000 admissions). Adults with ASD visited ED for: primary psychiatric disorder (15 %ASD vs. 4.2 %noASD), primary non-psychiatric disorder (16 %ASD vs. 14 %noASD), and any injury (24 %ASD vs. 28 %noASD). Mean total ED charges for adults with ASD were 2.3 times higher than for adults without ASD. Findings emphasize the need to examine the extent of frequent ED use in this population.
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16. Wei H, Ma Y, Liu J, Ding C, Hu F, Yu L. {{Proteomic analysis of cortical brain tissue from the BTBR mouse model of autism: Evidence for changes in STOP and myelin-related proteins}}. {Neuroscience}. 2016; 312: 26-34.
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. However, the widely accepted biomarkers for autism are still lacking. In this study, we carried out a quantitative proteomic profiling study of cortical brain tissue from BTBR T(+)Itpr3(tf) (BTBR) mice, a mouse model that displays an autism-like phenotype. Using isobaric tag for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS, a total of 3611 proteins were quantitated in mouse cortices. As compared to C57BL/6J (B6) mice, 126 differentially expressed proteins were found in the brain from BTBR mice. The functional annotation and categories of differentially expressed proteins were analyzed. Especially, the stable tubule only polypeptide (STOP) protein and myelin-related proteins down-regulated significantly in BTBR mice were confirmed by Western blotting. Furthermore, the BTBR mice displayed reduced levels of staining with ferric alum in comparison to B6 controls, indicative of myelin disruption. Finally, we propose that reduced STOP expression in the brain could be involved in the mediation of autism-like behaviors through impairments of myelination in oligodendrocytes and synaptic function in neurons. Manipulation of STOP protein could be a promising avenue for therapeutic interventions to autism.
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17. Yalcin O, Kaymak G, Erdogan A, Tanidir C, Karacetin G, Kilicoglu AG, Mutlu C, Adaletli H, Gunes H, Bahali K, Ayik B, Uneri OS. {{A Retrospective Investigation of Clozapine Treatment in Autistic and Nonautistic Children and Adolescents in an Inpatient Clinic in Turkey}}. {J Child Adolesc Psychopharmacol}. 2016.
OBJECTIVE: The aim of this retrospective study is to examine the clinical outcomes and safety of clozapine in children and adolescents with schizophrenia or other psychotic disorders/autism spectrum disorder (ASD) or affective disorders. METHODS: The inpatient and outpatient files of all children and adolescents treated with clozapine over a period of 34 months (from October 2011 to July 2014) were reviewed. Demographic and clinical data were examined to describe clinical and metabolic findings, dosing, and tolerability of clozapine treatment in youth with schizophrenia, other psychotic disorders, ASD, or bipolar disorder. RESULTS: The 37 pediatric patients included 26 patients with schizophrenia or other psychotic disorders, 7 patients with ASD complicated by schizophrenia or other psychotic disorders or affective disorders, and 4 patients with ASD only. In all groups (n = 37) there was a significant reduction (p < 0.001) in Brief Psychiatric Rating Scale (BPRS) points after clozapine treatment during the inpatient period (38.78 +/- 27.75 days). In patients with schizophrenia or other psychotic disorders co-occurring with ASD or not (n = 31), there was a significant improvement in psychotic symptoms according to Positive and Negative Syndrome Scale (PANSS) total scores and subscores (p < 0.001). Of the 26 patients with schizophrenia or other psychotic disorders, 8 (30.8%) showed a positive response (>30% symptom reduction on BPRS). In patients with ASD complicated by schizophrenia or other psychotic disorders or bipolar disorders (n = 7), there was a significant reduction (p = 0.017) in BPRS scores after clozapine treatment. The discontinuation rate for clozapine was 10.8%, and the most frequently observed side effect was hypersalivation (54.1%). Neutropenia associated with clozapine was observed in only one patient (2.7%). CONCLUSIONS: Clozapine seems to be effective and safe in children and adolescents with schizophrenia or other psychotic disorders co-occuring with ASD or not. There is a need for further studies for determining the efficacy of clozapine in children and adolescents with bipolar affective disorder or ASD.
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18. Zaman S, Yazdani U, Deng Y, Li W, Gadad BS, Hynan L, Karp D, Roatch N, Schutte C, Nathan Marti C, Hewitson L, German DC. {{A Search for Blood Biomarkers for Autism: Peptoids}}. {Sci Rep}. 2016; 6: 19164.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, and restricted, repetitive patterns of behavior. In order to identify individuals with ASD and initiate interventions at the earliest possible age, biomarkers for the disorder are desirable. Research findings have identified widespread changes in the immune system in children with autism, at both systemic and cellular levels. In an attempt to find candidate antibody biomarkers for ASD, highly complex libraries of peptoids (oligo-N-substituted glycines) were screened for compounds that preferentially bind IgG from boys with ASD over typically developing (TD) boys. Unexpectedly, many peptoids were identified that preferentially bound IgG from TD boys. One of these peptoids was studied further and found to bind significantly higher levels (>2-fold) of the IgG1 subtype in serum from TD boys (n = 60) compared to ASD boys (n = 74), as well as compared to older adult males (n = 53). Together these data suggest that ASD boys have reduced levels (>50%) of an IgG1 antibody, which resembles the level found normally with advanced age. In this discovery study, the ASD1 peptoid was 66% accurate in predicting ASD.
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19. Zamzow RM, Ferguson BJ, Stichter JP, Porges EC, Ragsdale AS, Lewis ML, Beversdorf DQ. {{Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study}}. {Psychopharmacology (Berl)}. 2016.
RATIONALE: Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. OBJECTIVES: The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug’s effects. METHODS: In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. RESULTS: Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. CONCLUSIONS: Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.
