1. Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, Brian J, Arnold LE, Capano L, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Hadjiyannakis S, Peleg N, Odrobina D, McAuliffe-Bellin S, Zakroysky P, Marler S, Wagner A, Wong T, Macklin EA, Veenstra-VanderWeele J. {{Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial}}. {JAMA Psychiatry}. 2016.
Importance: Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use. Objective: To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. Design, Setting, and Participants: A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. Interventions: Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. Main Outcomes and Measures: The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. Results: Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P = .005). Conclusions and Relevance: Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. Trial Registration: clinicaltrials.gov Identifier: NCT01825798.
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2. Anzulewicz A, Sobota K, Delafield-Butt JT. {{Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism}}. {Sci Rep}. 2016; 6: 31107.
Autism is a developmental disorder evident from infancy. Yet, its clinical identification requires expert diagnostic training. New evidence indicates disruption to motor timing and integration may underpin the disorder, providing a potential new computational marker for its early identification. In this study, we employed smart tablet computers with touch-sensitive screens and embedded inertial movement sensors to record the movement kinematics and gesture forces made by 37 children 3-6 years old with autism and 45 age- and gender-matched children developing typically. Machine learning analysis of the children’s motor patterns identified autism with up to 93% accuracy. Analysis revealed these patterns consisted of greater forces at contact and with a different distribution of forces within a gesture, and gesture kinematics were faster and larger, with more distal use of space. These data support the notion disruption to movement is core feature of autism, and demonstrate autism can be computationally assessed by fun, smart device gameplay.
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3. Buchele G, Becker C, Cameron ID, Auer R, Rothenbacher D, Konig HH, Rapp K. {{Fracture risk in people with developmental disabilities: results of a large claims data analysis}}. {Osteoporos Int}. 2016.
Age- and sex-specific fracture rates of 18,000 people with developmental disabilities aged 0-69 years were compared to the general population. Age-standardized incidence of femoral fracture was 4.8- and 7.1-fold higher in women and men, respectively. Comparable fracture risks to the general population occurred 10-15 years earlier in females and 20-40 years earlier in males. INTRODUCTION: Previous studies suggested that fracture risks in people with developmental disabilities (DD) may be higher than in people in the general population. However, there are no current sufficiently large studies to compare age- and sex-specific fracture rates of single fracture types. METHODS: People with DD and incident fractures were identified by routine data of a health insurance company. Fractures in the general population were derived from the official fracture statistics. Age-specific and age-standardized fracture incidences were analyzed. To compare fracture risks in people with DD with that of the general population incidence ratios were calculated. RESULTS: Between 2008 and 2010, 148 femoral fractures and 469 other fractures were observed in nearly 18,000 people with DD aged 0-69 years. The three most frequent fracture types leading to hospital admission were fractures of the femur, lower leg/ankle, and shoulder/arm. For femoral fractures, a particularly high risk was observed in children and adolescents with DD. In adults with DD, the risk of femoral fractures increased with increasing age. Even if the youngest age category was not considered, the age-standardized incidence was 4.8- and 7.1-fold higher in women and men, respectively. For all other fracture types, except fractures of forearm/hand and of pelvis, people with DD had also higher fracture incidences than the general population. CONCLUSIONS: People with DD have a high fracture burden. Comparable risks of femoral fracture, for example, occurred about 10-15 years earlier in females and even 20-40 years earlier in males with DD than in the general population.
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4. Cantiani C, Choudhury NA, Yu YH, Shafer VL, Schwartz RG, Benasich AA. {{From Sensory Perception to Lexical-Semantic Processing: An ERP Study in Non-Verbal Children with Autism}}. {PLoS One}. 2016; 11(8): e0161637.
This study examines electrocortical activity associated with visual and auditory sensory perception and lexical-semantic processing in nonverbal (NV) or minimally-verbal (MV) children with Autism Spectrum Disorder (ASD). Currently, there is no agreement on whether these children comprehend incoming linguistic information and whether their perception is comparable to that of typically developing children. Event-related potentials (ERPs) of 10 NV/MV children with ASD and 10 neurotypical children were recorded during a picture-word matching paradigm. Atypical ERP responses were evident at all levels of processing in children with ASD. Basic perceptual processing was delayed in both visual and auditory domains but overall was similar in amplitude to typically-developing children. However, significant differences between groups were found at the lexical-semantic level, suggesting more atypical higher-order processes. The results suggest that although basic perception is relatively preserved in NV/MV children with ASD, higher levels of processing, including lexical- semantic functions, are impaired. The use of passive ERP paradigms that do not require active participant response shows significant potential for assessment of non-compliant populations such as NV/MV children with ASD.
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5. Dunlop WA, Enticott PG, Rajan R. {{Speech Discrimination Difficulties in High-Functioning Autism Spectrum Disorder Are Likely Independent of Auditory Hypersensitivity}}. {Front Hum Neurosci}. 2016; 10: 401.
Autism Spectrum Disorder (ASD), characterized by impaired communication skills and repetitive behaviors, can also result in differences in sensory perception. Individuals with ASD often perform normally in simple auditory tasks but poorly compared to typically developed (TD) individuals on complex auditory tasks like discriminating speech from complex background noise. A common trait of individuals with ASD is hypersensitivity to auditory stimulation. No studies to our knowledge consider whether hypersensitivity to sounds is related to differences in speech-in-noise discrimination. We provide novel evidence that individuals with high-functioning ASD show poor performance compared to TD individuals in a speech-in-noise discrimination task with an attentionally demanding background noise, but not in a purely energetic noise. Further, we demonstrate in our small sample that speech-hypersensitivity does not appear to predict performance in the speech-in-noise task. The findings support the argument that an attentional deficit, rather than a perceptual deficit, affects the ability of individuals with ASD to discriminate speech from background noise. Finally, we piloted a novel questionnaire that measures difficulty hearing in noisy environments, and sensitivity to non-verbal and verbal sounds. Psychometric analysis using 128 TD participants provided novel evidence for a difference in sensitivity to non-verbal and verbal sounds, and these findings were reinforced by participants with ASD who also completed the questionnaire. The study was limited by a small and high-functioning sample of participants with ASD. Future work could test larger sample sizes and include lower-functioning ASD participants.
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6. Ego C, Bonhomme L, Orban de Xivry JJ, Da Fonseca D, Lefevre P, Masson GS, Deruelle C. {{Behavioral characterization of prediction and internal models in adolescents with autistic spectrum disorders}}. {Neuropsychologia}. 2016.
Autism has been considered as a deficit in prediction of the upcoming event or of the sensory consequences of our own movements. To test this hypothesis, we recorded eye movements from high-functioning autistic adolescent and from age-matched controls during a blanking paradigm. In this paradigm, adolescent were instructed to follow a moving target with their eyes even during its transient disappearance. Given the absence of visual information during the blanking period, eye movements during this period are solely controlled on the basis of the prediction of the ongoing target motion. Typical markers of predictive eye movements such as the number and accuracy of predictive saccades and the predictive reacceleration before target reappearance were identical in the two populations. In addition, the synergy of predictive saccades and smooth pursuit observed during the blanking periods, which is a marker for the quality of internal models about target/eye motions, was comparable between these two populations. These results suggest that, in our large population of high-functioning autistic adolescent, both predictive abilities and internal models are left intact in Autism, at least for low-level sensorimotor transformation.
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7. Geier DA, Kern JK, Sykes LK, Geier MR. {{Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype}}. {Appl Clin Genet}. 2016; 9: 121-9.
BACKGROUND: Previous studies on genetic testing of chromosomal abnormalities in individuals diagnosed with autism spectrum disorder (ASD) found that ~80% have negative genetic test results (NGTRs) and ~20% have positive genetic test results (PGTRs), of which ~7% were probable de novo mutations (PDNMs). Research suggests that parental age is a risk factor for an ASD diagnosis. This study examined genotypic variation in ASD and its relationship to parental age and phenotype. METHODS: Phenotype was derived from detailed clinical information, and genotype was derived from high-resolution blood chromosome and blood whole-genome copy number variant genetic testing on a consecutive cohort (born: 1983-2009) of subjects diagnosed with ASD (N=218). RESULTS: Among the subjects examined, 80.3% had NGTRs and 19.7% had PGTRs, of which 6.9% had PDNMs. NGTR subjects were born more recently (the risk of PDNMs decreasing by 12% per more recent birth year) and tended to have an increased male-female ratio compared to PDNM subjects. PDNM subjects had significantly increased mean parental age and paternal age at subject’s birth (the risk of a PDNM increasing by 7%-8% per year of parental or paternal age) compared to NGTR subjects. PGTR and NGTR subjects showed significant improvements in speech/language/communication with increasing age. PGTR subjects showed significant improvements in sociability, a core feature of an ASD diagnosis, with increasing age, whereas NGTR subjects showed significant worsening in sociability with increasing age. CONCLUSION: This study helps to elucidate different phenotypic ASD subtypes and may even indicate the need for differential diagnostic classifications.
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8. Kasperek-Zimowska BJ, Zimowski JG, Biernacka K, Kucharska-Pietura K, Rybakowski F. {{Impaired social cognition processes in Asperger syndrome and anorexia nervosa. In search for endophenotypes of social cognition}}. {Psychiatr Pol}. 2016; 50(3): 533-42.
A growing number of publications indicates presence of significant deficits in social cognition in patients with anorexia nervosa (AN). These deficits appear to be comparable in qualitative and quantitative dimension with impairment of the same functions among people with Asperger syndrome (AS). The aim of this study is to identify subject areas in the field of impairment of social cognition processes among people with Asperger syndrome and anorexia nervosa taking into consideration the potential contribution of genetic pathways of oxytocin and vasopressin in the pathogenesis of these diseases. In the first part of the paper a systematic analysis of studies aimed at the evaluation of the processes of social cognition among patients with AN and AS has been carried out. The results of a significant number of studies confirm the presence of deficits in social cognition in AN and AS. In addition, among patients with AN and AS there exists a similar structure and distribution of the brain functions in regions responsible for social cognition. The second part of the paper describes the role of the oxytocin-vasopressin system (OT-AVP) in the processes of social cognition in AN and AS. Its genetic basis and the possible importance of single nucleotide polymorphisms within the genes: OXT, AVP, CD38, OXTR, AVPR1A and LNPEP have also been presented.
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9. Lehan Mackin M, Loew N, Gonzalez A, Tykol H, Christensen T. {{Parent Perceptions of Sexual Education Needs for Their Children With Autism}}. {J Pediatr Nurs}. 2016.
Primary responsibility for sexual education for adolescents with autism spectrum disorder falls on parents who have reported a lack of professional and material support. The purpose of this study was to 1) describe parent perceptions of sexual education needs of their children aged 14-20 with an autism spectrum disorder diagnosis and 2) determine parent-preferred mechanisms of delivery for tailored educational intervention strategies. DESIGN AND METHODS: The study aims were accomplished by a qualitative research design using focus groups and telephone interviews assisted by a structured interview guide. Study methods and analysis were guided by social marketing principles. RESULTS: A total of 15 parents (5 participated in 1 focus group and 10 completed individual interviews) acknowledged their primary role in providing sexual education for their children and confirmed a need for resources to assist them in this role. All parents in this study found that some level of sexual education was necessary and important and that all children had been introduced to sexual information but in varying degrees. Topic preferences included those that would increase the recognition of healthy relationships, provide a measure of self-protection, and ameliorate undesirable consequences of sexual activity. Parents were knowledgeable about how their children best learned and suggested future interventions use technology interfaces with engaging displays and allow for individualized content. CONCLUSION AND IMPLICATIONS: These findings highlight a need for additional research and enhanced clinical services to ensure that adolescents with autism spectrum disorder have their informational needs met, are able to avoid risks, and have the greatest capacity for a healthy sexuality as they transition to adulthood.
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10. Libero LE, Burge W, Deshpande HD, Pestilli F, Kana RK. {{White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder}}. {Brain Connect}. 2016.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD, and 44 typically developing (TD) age-and-IQ-matched peers using diffusion tensor imaging (DTI). Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults, compared to TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory.
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11. Rybakowski F, Chojnicka I, Dziechciarz P, Horvath A, Janas-Kozik M, Jeziorek A, Pisula E, Piwowarczyk A, Slopien A, Sykut-Cegielska J, Szajewska H, Szczaluba K, Szymanska K, Waligorska A, Wojciechowska A, Wroniszewski M, Dunajska A. {{The role of genetic factors and pre- and perinatal influences in the etiology of autism spectrum disorders – indications for genetic referral}}. {Psychiatr Pol}. 2016; 50(3): 543-54.
Autism spectrum disorders (ASD) are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system – oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders – intellectual disability, epilepsy and dysmorphias – a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases.
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12. Rynkiewicz A, Lucka I, Grabowski K. {{Letter to Editor. Report « An investigation of the ‘female camouflage effect’ in autism using a new computerized test showing sex/gender differences during ADOS-2 ». IMFAR 2016, Baltimore, USA}}. {Psychiatr Pol}. 2016; 50(3): 663-6.
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13. Silva VF, Calomeni MR, Nunes RA, Pimentel CE, Martins GP, Oliveira Pda C, Silva PB, Silva AP. {{Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children}}. {Arq Neuropsiquiatr}. 2016; 74(8): 632-7.
This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.
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14. Soto T, Giserman Kiss I, Carter AS. {{SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5)}}. {Infant Ment Health J}. 2016.
Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development.
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15. Yui K, Tanuma N, Yamada H, Kawasaki Y. {{Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder}}. {Int J Dev Neurosci}. 2016.
Individuals with autism spectrum disorders (ASD) have impaired detoxification capacity. Investigatingthe neurobiological bases ofimpaired antioxidant capacity is thus a research priority in the pathophysiology of ASD.We measuredthe urinary levels of hexanoyl-lysine (HEL) which is a new oxidative stressbiomarker, total antioxidant power (TAP) and DNA methylation biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the plasma levels of superoxide dismutase (SOD), which is a major antioxidant enzyme. We examined whether the urinary levels of these enzymes and biomarkers may be related to symptoms of social impairment in 20individuals with ASD (meanage,11.1+/-5.2years) and 12 age- and gender-matched healthy controls (meanage,14.3+/-6.2years). Symptoms of social impairment wereassessed using the Social Responsiveness Scale (SRS). The dietary TAP of the fruit juice, chocolate, cookies, biscuits, jam and marmalade was significantly higher in the ASD group than in the control group, although the intake of nutrients was not significantly different between the groups. The urinary TAP levels were significantly lower in the ASD group than in the control group. There were no significantly differences in urinary HEL and 8-OHdG levels between the ASD and control groups. The SRS scores were significantly higher in the ASD group than in the control group. Stepwise regression analysis revealed that urinary TAP levels and plasma SOD levels can differences in the biomarkers and the SRS scores between the ASD group and the control group. The endogenous antioxidant capacity may be deficient without altered urinary HEL and 8-OHdG levels in individuals with ASD. The plasma SOD levels may be related to reduced endogenous antioxidant capacity.
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16. Zheng Z, Warren Z, Weitlauf A, Fu Q, Zhao H, Swanson A, Sarkar N. {{Brief Report: Evaluation of an Intelligent Learning Environment for Young Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
Researchers are increasingly attempting to develop and apply innovative technological platforms for early detection and intervention of autism spectrum disorder (ASD). This pilot study designed and evaluated a novel technologically-mediated intelligent learning environment with relevance to early social orienting skills. The environment was endowed with the capacity to administer social orienting cues and adaptively respond to autonomous real-time measurement of performance (i.e., non-contact gaze measurement). We evaluated the system with both toddlers with ASD (n = 8) as well as typically developing infants (n = 8). Children in both groups were able to ultimately respond accurately to social prompts delivered by the technological system. Results also indicated that the system was capable of attracting and pushing toward correct performance autonomously without user intervention.
