1. Anshu K, Nair AK, Kumaresan UD, Kutty BM, Srinath S, Laxmi TR. {{Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder}}. {Autism Res}. 2017.
Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. Our work validates the use of the VPA model in the quest for evaluating suitable therapeutic targets for improving attentional performance.
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2. Benner S, Yamasue H. {{Clinical potential of oxytocin in autism spectrum disorder: current issues and future perspectives}}. {Behav Pharmacol}. 2017.
The effects of oxytocin on social cognition and behavior have recently attracted considerable attention. In particular, oxytocin has been proposed as a novel therapeutic for psychiatric disorders with social deficits such as autism spectrum disorders. This review provides a brief overview of behavioral and neural responses to oxytocin manipulations in humans and animal models. Although the differences in findings between human and animal studies should be interpreted carefully, shared behavioral phenotypes have been recognized, such as social bonding, social responses, and recognition and usage of social cues. Previous literature suggests that the neural effects of oxytocin in humans and animals overlap in the prefrontal, limbic, and paralimbic cortices. Oxytocin-induced alterations in these regions may indicate a fundamental basis for how oxytocin modulates social behaviors and facilitate the discovery of new pharmaceutical targets for treating social deficits.
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3. Capal JK, Horn PS, Murray DS, Byars AW, Bing NM, Kent B, Bucher LA, Williams ME, O’Kelley S, Pearson DA, Sahin M, Krueger DA. {{Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex}}. {Pediatr Neurol}. 2017.
BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder with high prevalence of associated autism spectrum disorder (ASD). Our primary objectives were to determine early predictors of autism risk to identify children with TSC in most need of early interventions. The Autism Observation Scale for Infants (AOSI) was evaluated as a measure of ASD-associated behaviors in infants with TSC at age 12 months and its ability to predict ASD at 24 months. METHODS: Children ages 0 to 36 months with TSC were enrolled in the TSC Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study to identify biomarkers of ASD. The AOSI was administered at age 12 months and the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R) at 24 months. Developmental functioning was assessed using the Mullen Scales of Early Learning. Children were classified as ASD or non-ASD according to the ADOS-2. RESULTS: Analysis included 79 children who had been administered the AOSI at 12 months and ADOS-2 and ADI-R at 24 months. The ASD group had a mean AOSI total score at 12 months significantly higher than the non-ASD group (11.8 +/- 7.4 vs 6.3 +/- 4.7; P < 0.001). An AOSI total score cutoff of 13 provided a specificity of 0.89 to detect ASD with the ADOS-2. AOSI total score at 12 months was similarly associated with exceeding cutoff scores on the ADI-R. CONCLUSIONS: The AOSI is a useful clinical tool in determining which infants with TSC are at increased risk for developing ASD. Lien vers le texte intégral (Open Access ou abonnement)
4. Crespi BJ. {{Shared sociogenetic basis of honey bee behavior and human risk for autism}}. {Proc Natl Acad Sci U S A}. 2017.
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5. Delhey L, Kilinc EN, Yin L, Slattery J, Tippett M, Wynne R, Rose S, Kahler S, Damle S, Legido A, Goldenthal MJ, Frye RE. {{Bioenergetic variation is related to autism symptomatology}}. {Metab Brain Dis}. 2017.
Autism spectrum disorder (ASD) has been associated with mitochondrial dysfunction but few studies have examined the relationship between mitochondrial function and ASD symptoms. We measured Complex I and IV and citrate synthase activities in 76 children with ASD who were not receiving vitamin supplementation or medication. We also measured language using the Preschool Language Scales or Clinical Evaluation of Language Fundamentals, adaptive behavior using the Vineland Adaptive Behavioral Scale, social function using the Social Responsiveness Scale and behavior using Aberrant Behavior Checklist, Childhood Behavior Checklist and the Ohio Autism Clinical Impression Scale. Children with ASD demonstrated significantly greater variation in mitochondrial activity compared to controls with more than expected ASD children having enzyme activity outside of the normal range for Citrate Synthase (24%), Complex I (39%) and Complex IV (11%). Poorer adaptive skills were associated with Complex IV activity lower or higher than average and lower Complex I activity. Poorer social function and behavior was associated with relatively higher Citrate Synthase activity. Similar to previous studies we find both mitochondrial underactivity and overactivity in ASD. This study confirms an expanded variation in mitochondrial activity in ASD and demonstrates, for the first time, that such variations are related to ASD symptoms.
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6. Kam TE, Suk HI, Lee SW. {{Multiple functional networks modeling for autism spectrum disorder diagnosis}}. {Hum Brain Mapp}. 2017.
Despite countless studies on autism spectrum disorder (ASD), diagnosis relies on specific behavioral criteria and neuroimaging biomarkers for the disorder are still relatively scarce and irrelevant for diagnostic workup. Many researchers have focused on functional networks of brain activities using resting-state functional magnetic resonance imaging (rsfMRI) to diagnose brain diseases, including ASD. Although some existing methods are able to reveal the abnormalities in functional networks, they are either highly dependent on prior assumptions for modeling these networks or do not focus on latent functional connectivities (FCs) by considering discriminative relations among FCs in a nonlinear way. In this article, we propose a novel framework to model multiple networks of rsfMRI with data-driven approaches. Specifically, we construct large-scale functional networks with hierarchical clustering and find discriminative connectivity patterns between ASD and normal controls (NC). We then learn features and classifiers for each cluster through discriminative restricted Boltzmann machines (DRBMs). In the testing phase, each DRBM determines whether a test sample is ASD or NC, based on which we make a final decision with a majority voting strategy. We assess the diagnostic performance of the proposed method using public datasets and describe the effectiveness of our method by comparing it to competing methods. We also rigorously analyze FCs learned by DRBMs on each cluster and discover dominant FCs that play a major role in discriminating between ASD and NC. Hum Brain Mapp, 2017. (c) 2017 Wiley Periodicals, Inc.
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7. Matthews NL, Malligo A, Smith CJ. {{Toward the identification of adaptive functioning intervention targets for intellectually-able, transition-aged youth with autism: An examination of caregiver responses on the Vineland-II}}. {Autism Res}. 2017.
Little is known about specific adaptive functioning impairments in intellectually-able individuals with autism spectrum disorder. In adolescents (n = 22) and young adults (n = 22) matched on composite IQ scores, this study examined profiles of cognitive and adaptive functioning, and caregiver responses on individual Vineland-II items. Adaptive functioning standard scores were significantly lower than IQ scores, and the adult group had significantly lower adaptive functioning standard scores than the adolescent group. Examination of caregiver responses to individual Vineland-II items identified more than 100 potential intervention targets. Differences favoring the adult group were observed on only 16 items across all three adaptive functioning domains, suggesting that little skill development is occurring during the transition to adulthood. Future research will examine the relevance of identified intervention targets to optimal outcomes. Autism Res 2017,. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Adolescents and young adults with autism spectrum disorder (ASD) without intellectual disability demonstrated impaired adaptive functioning skills (i.e., age appropriate skills necessary for independent living). Development of adaptive functioning skills appears to slow with age among individuals without intellectual disability. Findings clarify the specific adaptive functioning skills that transition-aged youth with ASD have difficulty completing independently and will inform the development of interventions to increase the likelihood of independent living in adulthood.
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8. Rashid M, Hodgetts S, Nicholas D. {{Building Employer Capacity to Support Meaningful Employment for Persons with Developmental Disabilities: A Grounded Theory Study of Employment Support Perspectives}}. {J Autism Dev Disord}. 2017.
To explore strategies to build employer capacity to support people with DD in meaningful employment from perspective of employment support workers. A grounded theory study was conducted with 34 employment support individuals. A theoretical sampling approach was used to identify and recruit participants from multiple sites in Ontario and Alberta. Three main themes, with seven sub-themes, emerged: (1) experiences of supporting employment finding for people with DD, (2) institutional influences on employee experiences, and (3) attitudes, assumptions and stigma. Several recommendations related to building employer capacity were offered. Our findings provide insight on specific elements and strategies that can support building employer capacity for persons with DD.
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9. Chee DYT, Lee HCY, Patomella AH, Falkmer T. {{Investigating the driving performance of drivers with and without autism spectrum disorders under complex driving conditions}}. {Disabil Rehabil}. 2017: 1-8.
PURPOSE: The aim of this study was to investigate the driving performance of drivers with autism spectrum disorders under complex driving conditions. METHOD: Seventeen drivers with autism spectrum disorders and 18 typically developed drivers participated in a driving simulator trial. Prior to the assessment, participants completed the Driving Behaviour Questionnaire and measurements of cognitive and visual-motor ability. The driving simulation involved driving in an urban area with dense traffic and unpredictable events. RESULTS: In comparison with the typically developed group, drivers with autism spectrum disorders reported significantly more lapses in driving, committed more mistakes on the driving simulator, and were slower to react in challenging situations, such as driving through intersections with abrupt changes in traffic lights. However, they were also less likely to tailgate other vehicles, as measured by time-to-collision between vehicles, on the driving simulator. CONCLUSIONS: The performances of licensed drivers with autism spectrum disorders appeared to be safer in respect to car-following distance but were poorer in their response to challenging traffic situations. Driver education for individuals with autism spectrum disorders should focus on quick identification of hazards, prompt execution of responses, and effective allocation of attention to reduce lapses in driving. Implications for rehabilitation Drivers with autism spectrum disorders reported significantly more lapses during driving. Drivers with autism spectrum disorders were observed to be poorer in traffic scenarios requiring critical response. Driver education for individuals with autism spectrum disorders should focus on managing anxiety and effective attention allocation while driving. Driving simulators can be used as a safe means for training critical response to challenging traffic scenarios.
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10. Reisinger DL, Roberts JE. {{Differential Relationships of Anxiety and Autism Symptoms on Social Skills in Young Boys With Fragile X Syndrome}}. {Am J Intellect Dev Disabil}. 2017; 122(5): 359-73.
Social skills are critical for academic, social, and psychological success of children with both typical and atypical development. Boys with fragile X syndrome (FXS) are at high risk for social skill impairments, given intellectual impairments and secondary conditions. The present study examines the impact of adaptive behavior, autism symptoms, and anxiety symptoms to social skills at the composite and subdomain level in boys with FXS across age. This cross-sectional study included boys with FXS (3-14 years) contrasted to age-matched typical control boys. Results revealed that social skills are generally within developmental expectations, with adaptive behavior as the primary predictor. Anxiety and autism symptoms emerged as additive risk factors, particularly in the areas of responsibility and self-control.
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11. Rivard M, Mercier C, Mestari Z, Terroux A, Mello C, Begin J. {{Psychometric Properties of the Beach Center Family Quality of Life in French-Speaking Families With a Preschool-Aged Child Diagnosed With Autism Spectrum Disorder}}. {Am J Intellect Dev Disabil}. 2017; 122(5): 439-52.
The Beach Center Family Quality of Life Scale (Beach Center FQOL) is used to evaluate and develop family-centered intervention services. However, its use with families of children with autism spectrum disorder (ASD) and in non-English speaking populations requires further investigation. The present study sought to assess the psychometric properties of a French translation of this scale on 452 parents of children aged 5 and under who were recently diagnosed with ASD. The resulting Satisfaction and Importance scales presented excellent internal consistency at the scale level and acceptable internal consistency at the subscale level. Theoretical model positing 5 dimensions of FQOL generally fit the data acceptably. Satisfaction ratings were found to be sensitive to changes and were negatively correlated with parenting stress.
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12. Giacometti G, Ferreri C, Sansone A, Chatgilialoglu C, Marzetti C, Spyratou E, Georgakilas AG, Marini M, Abruzzo PM, Bolotta A, Ghezzo A, Minguzzi R, Posar A, Visconti P. {{High predictive values of RBC membrane-based diagnostics by biophotonics in an integrated approach for Autism Spectrum Disorders}}. {Sci Rep}. 2017; 7(1): 9854.
Membranes attract attention in medicine, concerning lipidome composition and fatty acid correlation with neurological diseases. Hyperspectral dark field microscopy (HDFM), a biophotonic imaging using reflectance spectra, provides accurate characterization of healthy adult RBC identifying a library of 8 spectral end-members. Here we report hyperspectral RBC imaging in children affected by Autism Spectrum Disorder (ASD) (n = 21) compared to healthy age-matched subjects (n = 20), investigating if statistically significant differences in their HDFM spectra exist, that can comprehensively map a membrane impairment involved in disease. A significant difference concerning one end-member (spectrum 4) was found (P value = 0.0021). A thorough statistical treatment evidenced: i) diagnostic performance by the receiving operators curve (ROC) analysis, with cut-offs and very high predictive values (P value = 0.0008) of spectrum 4 for identifying disease; ii) significant correlations of spectrum 4 with clinical parameters and with the RBC membrane deficit of the omega-3 docosahexaenoic acid (DHA) in ASD patients; iii) by principal component analysis, very high affinity values of spectrum 4 to the factor that combines behavioural parameters and the variable « cc » discriminating cases and controls. These results foresee the use of biophotonic methodologies in ASD diagnostic panels combining with molecular elements for a correct neuronal growth.
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13. Lewis KE, Sharan K, Takumi T, Yadav VK. {{Skeletal Site-specific Changes in Bone Mass in a Genetic Mouse Model for Human 15q11-13 Duplication Seen in Autism}}. {Sci Rep}. 2017; 7(1): 9902.
Children suffering from autism have been reported to have low bone mineral density and increased risk for fracture, yet the cellular origin of the bone phenotype remains unknown. Here we have utilized a mouse model of autism that duplicates 6.3 Mb region of chromosome 7 (Dp/+) corresponding to a region of chromosome 15q11-13, duplication of which is recurrent in humans to characterize the bone phenotype. Paternally inherited Dp/+ (patDp/+) mice showed expected increases in the gene expression in bone, normal postnatal growth and body weight acquisition compared to the littermate controls. Four weeks-old patDp/+ mice develop a low bone mass phenotype in the appendicular but not the axial skeleton compared to the littermate controls. This low bone mass in the mutant mice was secondary to a decrease in the number of osteoblasts and bone formation rate while the osteoclasts remained relatively unaffected. Further in vitro cell culture experiments and gene expression analysis revealed a major defect in the proliferation, differentiation and mineralization abilities of patDp/+ osteoblasts while osteoclast differentiation remained unchanged compared to controls. This study therefore characterizes the structural and cellular bone phenotype in a mouse model of autism that can be further utilized to investigate therapeutic avenues to treat bone fractures in children with autism.
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14. Maddox BB, Cleary P, Kuschner ES, Miller JS, Armour AC, Guy L, Kenworthy L, Schultz RT, Yerys BE. {{Lagging skills contribute to challenging behaviors in children with autism spectrum disorder without intellectual disability}}. {Autism}. 2017: 1362361317712651.
Many children with autism spectrum disorder display challenging behaviors. These behaviors are not limited to those with cognitive and/or language impairments. The Collaborative and Proactive Solutions framework proposes that challenging behaviors result from an incompatibility between environmental demands and a child’s « lagging skills. » The primary Collaborative and Proactive Solutions lagging skills-executive function, emotion regulation, language, and social skills-are often areas of weakness for individuals with autism spectrum disorder. The purpose of this study was to evaluate whether these lagging skills are associated with challenging behaviors in youth with autism spectrum disorder without intellectual disability. Parents of 182 youth with autism spectrum disorder (6-15 years) completed measures of their children’s challenging behaviors, executive function, language, emotion regulation, and social skills. We tested whether the Collaborative and Proactive Solutions lagging skills predicted challenging behaviors using multiple linear regression. The Collaborative and Proactive Solutions lagging skills explained significant variance in participants’ challenging behaviors. The Depression (emotion regulation), Inhibit (executive function), and Sameness (executive function) scales emerged as significant predictors. Impairments in emotion regulation and executive function may contribute substantially to aggressive and oppositional behaviors in school-age youth with autism spectrum disorder without intellectual disability. Treatment for challenging behaviors in this group may consider targeting the incompatibility between environmental demands and a child’s lagging skills.
