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. Bhanushali AA, Mandsaurwala A, Das BR. {{Homozygous c.1160C>T (P38L) in the MECP2 gene in a female Rett syndrome patient}}. {J Clin Neurosci}. 2016.
Rett syndrome is a severe X-linked dominant neurodevelopmental disorder. Mutations in the MECP2 gene on chromosome Xq28 have been shown to be the cause of Rett syndrome. Sequencing of the MECP2 gene in a patient with clinical suspicion of Rett syndrome revealed c.1160C>T (P387L) in exon 4 of the MECP2 gene homozygously. Females with Rett syndrome are usually heterozygous for a mutation in MECP2. Uniparental disomy as a probable cause for the homozygous presence of this mutation was ruled out by quantitative fluorescence-polymerase chain reaction. Moreover to our knowledge this mutation has only been reported in males with X-linked mental retardation (MRX). We hypothesize that the presence of this mutation c.1160C>T (P387L) in the homozygous form is responsible for the Rett syndrome-like phenotype seen in this patient. This novel report reveals for the first time the homozygous presence of a mutation which has hitherto only been reported in males with MRX.
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3. Butera G, Lovin N, Paola Basile D, Carminati M. {{Goose-neck snare-assisted transcatheter ASD closure: A safety procedure for large and complex ASDs}}. {Catheter Cardiovasc Interv}. 2016.
OBJECTIVE: To report on a new technique that increases the safety of percutaneous atrial septal defect (ASD) closure using a goose-neck snare system. BACKGROUND: ASD transcatheter closure is a widespread procedure. However, in some cases, ASDs may be large and with soft rims. In these situation, a potential risk exists for device malposition or embolization. METHODS: When transesophageal echocardiography (TEE) evaluation and balloon sizing showed large defects with floppy rims the chosen Amplatzer device was implanted in a standard way. In large defects with floppy rims, before release a 5-mm goose-neck snare with its 4 Fr catheter was placed across the delivery cable and fixed to catch the screwing mechanism of implanted Amplatzer device. The delivery cable was unscrewed and the device reached its final position without any tension. If the position was considered satisfactory the device was released from the goose-neck snare. RESULTS: Thirteen patients had a snare-assisted ASD transcatheter closure. Median device size was 24 mm (range 14-38 mm). Retrieval or repositioning of the device using the goose-neck snare was performed in four cases: in three patients, because of device malposition after delivery cable release and in one patient, because of unsuitability of closure of a second significant defect. Furthermore, in two subjects with multiple ASDs, a second fenestration looked quite significant with the device still attached to the delivery cable while it appeared smaller after release. CONCLUSIONS: Snare-assisted Amplatzer ASD device placement is a new method for ASD percutaneous closure and adds safety to the procedure. (c) 2016 Wiley Periodicals, Inc.
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4. Curran EA, Kenny LC, Khashan AS. {{Sibling Comparisons and Confounding in Autism Epidemiological Studies-Reply}}. {JAMA Psychiatry}. 2016: 1.
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5. 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)
6. Doehring P, Volkmar FR. {{Knowledge Gaps in ASD Research: Short and Long Term Implications for Policy}}. {J Autism Dev Disord}. 2016.
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7. Jain A, Marshall J, Buikema A, Bancroft T, Kelly JP, Newschaffer C. {{Correction of Description of MMR Vaccine Receipt Coding and Minor Errors in MMR Vaccine and Autism Study}}. {JAMA}. 2016; 315(2): 202-4.
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8. 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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9. 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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10. Kreider CM, Bendixen RM, Young ME, Prudencio SM, McCarty C, Mann WC. {{Social networks and participation with others for youth with learning, attention, and autism spectrum disorders: Reseaux sociaux et participation avec les autres, chez des adolescents ayant des troubles d’apprentissage, de l’attention et du spectre de l’autisme}}. {Can J Occup Ther}. 2016; 83(1): 14-26.
BACKGROUND: Social participation involves activities and roles providing interactions with others, including those within their social networks. PURPOSE: This study sought to characterize social networks and participation with others for 36 youth, ages 11 to 16 years, with (n = 19) and without (n = 17) learning disability, attention disorder, or high-functioning autism. METHOD: Social networks were measured using methods of personal network analysis. The Children’s Assessment of Participation and Enjoyment With Whom dimension scores were used to measure participation with others. Youth from the clinical group were interviewed regarding their experiences within their social networks. FINDINGS: Group differences were observed for six social network variables and in the proportion of overall, physical, recreational, social, and informal activities engaged with family and/or friends. Qualitative findings explicated strategies used in building, shaping, and maintaining social networks. IMPLICATIONS: Social network factors should be considered when seeking to understand social participation.
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11. Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A. {{Gut microbiota in autism and mood disorders}}. {World J Gastroenterol}. 2016; 22(1): 361-8.
The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.
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12. Schendel DE, Parner E. {{Sibling Comparisons and Confounding in Autism Epidemiological Studies}}. {JAMA Psychiatry}. 2016: 1.
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13. Shah P, Bird G, Cook R. {{Face processing in autism: Reduced integration of cross-feature dynamics}}. {Cortex}. 2015; 75: 113-9.
Characteristic problems with social interaction have prompted considerable interest in the face processing of individuals with Autism Spectrum Disorder (ASD). Studies suggest that reduced integration of information from disparate facial regions likely contributes to difficulties recognizing static faces in this population. Recent work also indicates that observers with ASD have problems using patterns of facial motion to judge identity and gender, and may be less able to derive global motion percepts. These findings raise the possibility that feature integration deficits also impact the perception of moving faces. To test this hypothesis, we examined whether observers with ASD exhibit susceptibility to a new dynamic face illusion, thought to index integration of moving facial features. When typical observers view eye-opening and -closing in the presence of asynchronous mouth-opening and -closing, the concurrent mouth movements induce a strong illusory slowing of the eye transitions. However, we find that observers with ASD are not susceptible to this illusion, suggestive of weaker integration of cross-feature dynamics. Nevertheless, observers with ASD and typical controls were equally able to detect the physical differences between comparison eye transitions. Importantly, this confirms that observers with ASD were able to fixate the eye-region, indicating that the striking group difference has a perceptual, not attentional origin. The clarity of the present results contrasts starkly with the modest effect sizes and equivocal findings seen throughout the literature on static face perception in ASD. We speculate that differences in the perception of facial motion may be a more reliable feature of this condition.
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14. 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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15. 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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16. Van Der Miesen AI, Hurley H, De Vries AL. {{Gender dysphoria and autism spectrum disorder: A narrative review}}. {Int Rev Psychiatry}. 2016: 1-11.
The current literature shows growing evidence of a link between gender dysphoria (GD) and autism spectrum disorder (ASD). This study reviews the available clinical and empirical data. A systematic search of the literature was conducted using the following databases: PubMed, Web of Science, PsycINFO and Scopus; utilizing different combinations of the following search terms: autism, autism spectrum disorder (ASD), Asperger’s disorder (AD), co-morbidity, gender dysphoria (GD), gender identity disorder (GID), transgenderism and transsexualism. In total, 25 articles and reports were selected and discussed. Information was grouped by found co-occurrence rates, underlying hypotheses and implications for diagnosis and treatment. GD and ASD were found to co-occur frequently – sometimes characterized by atypical presentation of GD, which makes a correct diagnosis and determination of treatment options for GD difficult. Despite these challenges there are several case reports describing gender affirming treatment of co-occurring GD in adolescents and adults with ASD. Various underlying hypotheses for the link between GD and ASD were suggested, but almost all of them lack evidence.
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17. 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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18. Yang L, Faraone SV, Zhang-James Y. {{Autism spectrum disorder traits in Slc9a9 knock-out mice}}. {Am J Med Genet B Neuropsychiatr Genet}. 2016.
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders which begin in childhood and persist into adulthood. They cause lifelong impairments and are associated with substantial burdens to patients, families, and society. Genetic studies have implicated the sodium/proton exchanger (NHE) nine gene, Slc9a9, to ASDs and attention-deficit/hyperactivity disorder(ADHD). Slc9a9 encodes, NHE9, a membrane protein of the late recycling endosomes. The recycling endosome plays an important role in synapse development and plasticity by regulating the trafficking of membrane neurotransmitter receptors and transporters. Here we tested the hypothesis that Slc9a9 knock-out (KO) mice would show ADHD-like and ASD-like traits. Ultrasonic vocalization (USV) recording showed that Slc9a9 KO mice emitted fewer calls and had shorter call durations, which suggest communication impairment. Slc9a9 KO mice lacked a preference for social novelty, but did not show deficits in social approach; Slc9a9 KO mice spent more time self-grooming, an indicator for restricted and repetitive behavior. We did not observe hyperactivity or other behavior impairments which are commonly comorbid with ASDs in human, such as anxiety-like behavior. Our study is the first animal behavior study that links Slc9a9 to ASDs. By eliminatingNHE9 activity, it provides strong evidence that lack of Slc9a9leads to ASD-like behaviors in mice and provides the field with a new mouse model of ASDs. (c) 2016 Wiley Periodicals, Inc.
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19. Zhao X, Zhang P, Fu L, Maes JH. {{Attentional biases to faces expressing disgust in children with autism spectrum disorders: an exploratory study}}. {Sci Rep}. 2016; 6: 19381.
Previous studies on attentional bias towards emotional faces in individuals with autism spectrum disorders (ASD) provided mixed results. This might be due to differences in the examined attentional bias components and emotional expressions. This study assessed three bias components, hypervigilance, disengagement, and avoidance, using faces with a disgust, happy, or neutral expression in a dot-probe and external cuing task in 18 children with ASD and 21 typically developing (TD) children. The children with ASD initially displayed hypervigilance towards the disgust faces, followed by a general tendency to avoid looking back at the spatial location at which any face, irrespective of its emotional expression, had been presented. These results highlight the importance of differentiating between attentional bias components in research on ASD.
