1. Berkowicz SR, Featherby TJ, Qu Z, Giousoh A, Borg NA, Heng JI, Whisstock JC, Bird PI. {{Brinp1 (-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density}}. {Mol Autism}. 2016; 7: 22.
BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly conserved in vertebrates, and continuously expressed in the neocortex, hippocampus, olfactory bulb and cerebellum from mid-embryonic development through to adulthood. METHODS: Brinp1 knock-out (Brinp1 (-/-)) mice were generated by Cre-recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were characterised by behavioural phenotyping, immunohistochemistry and expression analysis of the developing and adult brain. RESULTS: Absence of Brinp1 during development results in a behavioural phenotype resembling autism spectrum disorder (ASD), in which knock-out mice show reduced sociability and changes in vocalisation capacity. In addition, Brinp1 (-/-) mice exhibit hyper-locomotor activity, have impaired short-term memory, and exhibit poor reproductive success. Brinp1 (-/-) mice show increased density of parvalbumin-expressing interneurons in the adult mouse brain. Brinp1 (-/-) mice do not show signs of altered neural precursor proliferation or increased apoptosis during late embryonic brain development. The expression of the related neuronal migration genes Astn1 and Astn2 is increased in the brains of Brinp1 (-/-) mice, suggesting that they may ameliorate the effects of Brinp1 loss. CONCLUSIONS: Brinp1 plays an important role in normal brain development and function by influencing neuronal distribution within the cortex. The increased cortical PV-positive interneuron density and altered behaviour of Brinp1 (-/-) mice resemble features of a subset of human neurological disorders; namely autism spectrum disorder (ASD) and the hyperactivity aspect of attention deficit hyperactivity disorder (ADHD).
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2. Crawford H, Moss J, Oliver C, Elliott N, Anderson GM, McCleery JP. {{Visual preference for social stimuli in individuals with autism or neurodevelopmental disorders: an eye-tracking study}}. {Mol Autism}. 2016; 7: 24.
BACKGROUND: Recent research has identified differences in relative attention to competing social versus non-social video stimuli in individuals with autism spectrum disorder (ASD). Whether attentional allocation is influenced by the potential threat of stimuli has yet to be investigated. This is manipulated in the current study by the extent to which the stimuli are moving towards or moving past the viewer. Furthermore, little is known about whether such differences exist across other neurodevelopmental disorders. This study aims to determine if adolescents with ASD demonstrate differences in attentional allocation to competing pairs of social and non-social video stimuli, where the actor or object either moves towards or moves past the viewer, in comparison to individuals without ASD, and to determine if individuals with three genetic syndromes associated with differing social phenotypes demonstrate differences in attentional allocation to the same stimuli. METHODS: In study 1, adolescents with ASD and control participants were presented with social and non-social video stimuli in two formats (moving towards or moving past the viewer) whilst their eye movements were recorded. This paradigm was then employed with groups of individuals with fragile X, Cornelia de Lange, and Rubinstein-Taybi syndromes who were matched with one another on chronological age, global adaptive behaviour, and verbal adaptive behaviour (study 2). RESULTS: Adolescents with ASD demonstrated reduced looking-time to social versus non-social videos only when stimuli were moving towards them. Individuals in the three genetic syndrome groups showed similar looking-time but differences in fixation latency for social stimuli moving towards them. Across both studies, we observed within- and between-group differences in attention to social stimuli that were moving towards versus moving past the viewer. CONCLUSIONS: Taken together, these results provide strong evidence to suggest differential visual attention to competing social versus non-social video stimuli in populations with clinically relevant, genetically mediated differences in socio-behavioural phenotypes.
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3. Dickinson A, Bruyns-Haylett M, Smith R, Jones M, Milne E. {{Superior orientation discrimination and increased peak gamma frequency in autism spectrum conditions}}. {J Abnorm Psychol}. 2016; 125(3): 412-22.
While perception is recognized as being atypical in individuals with autism spectrum conditions (ASC), the underlying mechanisms for such atypicality are unclear. Here we test the hypothesis that individuals with ASC will show enhanced orientation discrimination compared with neurotypical observers. This prediction is based both on anecdotal report of superior discriminatory skills in ASC and also on evidence in the auditory domain that some individuals with ASC have superior pitch discrimination. In order to establish whether atypical perception might be mediated by an imbalance in the ratio of neural excitation and inhibition (E:I ratio), we also measured peak gamma frequency, which provides an indication of neural inhibition levels. Using a rigorous thresholding method, we found that orientation discrimination thresholds for obliquely oriented stimuli were significantly lower in participants with ASC. Using EEG to measure the visually induced gamma band response, we also found that peak gamma frequency was higher in participants with ASC, relative to a well-matched control group. These novel results suggest that neural inhibition may be increased in the occipital cortex of individuals with ASC. Implications for existing theories of an imbalance in the E:I ratio of ASC are discussed. (PsycINFO Database Record
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4. Egilson ST, Olafsdottir LB, Leosdottir T, Saemundsen E. {{Quality of life of high-functioning children and youth with autism spectrum disorder and typically developing peers: Self- and proxy-reports}}. {Autism}. 2016.
Studies have shown parents to report lower quality of life for their children with autism spectrum disorder than children’s self-report scores and the same applies for data on typically developing children. Our objectives were to: (1) explore how high-functioning children with autism spectrum disorder rate their quality of life compared with paired controls without autism spectrum disorder; (2) explore how parents of high-functioning children with autism spectrum disorder rate their children’s quality of life compared with parents of paired controls; and (3) compare child self-reports of quality of life with their parent’s proxy-reports for both groups of children. Data were collected with the Icelandic self- and proxy-reported versions of the KIDSCREEN-27. Reports of 96 children with autism spectrum disorder, 211 controls and their parents were included in the analyses. Compared with controls, children with autism spectrum disorder had lower means on all quality of life dimensions. Parents of children with autism spectrum disorder evaluated their children’s quality of life lower on all dimensions than did parents of controls. On four out of five dimensions, children with autism spectrum disorder reported better quality of life than did their parents. Despite differences in ratings children with autism spectrum disorder and their parents agreed on the most problematic dimensions, namely,social support and peersandphysical well-being Our results highlight the importance of seeking the viewpoints of both children and their parents.
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5. Factor RS, Condy EE, Farley JP, Scarpa A. {{Brief Report: Insistence on Sameness, Anxiety, and Social Motivation in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
While the function of restricted repetitive behaviors (RRBs) in autism spectrum disorder (ASD) is unclear, RRBs may function as anxiety reduction strategies (Joosten et al. J Autism Dev Disord 39(3):521-531, 2009. Moreover, anxiety in ASD is associated with low social motivation (Swain et al. J Autism Dev Disord, 2015. The present study examined social motivation as a mediator between anxiety and RRBs in a sample of 44 children (2-17 years old; 80 % male) with ASD. The relationship between anxiety and IS, but not other RRBs, was partially mediated by social motivation. These findings suggest anxiety is linked to social motivation deficits in children with ASD, which may increase ritualized behaviors and difficulties with changes in routine. Implications are discussed for differing functions and treatment of RRB domains.
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6. Fried R, Joshi G, Bhide P, Pope A, Galdo M, Koster A, Chan J, Faraone SV, Biederman J. {{A study of the neuropsychological correlates in adults with high functioning autism spectrum disorders}}. {Acta Neuropsychiatr}. 2016: 1-10.
OBJECTIVE: To examine the unique neuropsychological presentation in adults with high functioning autism spectrum disorders (HF-ASD) by comparison with adults with attention deficit hyperactivity disorder (ADHD). METHODS: Adults with ASD referred to a specialty clinic (n=26) were compared to two non-ASD groups with (n=52) and without (n=52) ADHD of similar age and sex. RESULTS: No differences in IQ were found. Subjects with HF-ASD were significantly more impaired than both comparison groups in processing speed, cognitive flexibility and sight words. Subjects with HF-ASD were more impaired than controls in working memory, but not the ADHD group. CONCLUSION: These findings suggest that there may be specific neuropsychological correlates of HF-ASD differing from ADHD that could have significant implications for identifying individuals at risk for ASD.
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7. Huang CT, Chiang CH, Hung CY. {{Young children with autism spectrum disorders imitate in the context of others’ prior intention}}. {Autism}. 2016.
Many studies have shown that children with autism spectrum disorder have some understanding of intentions behind others’ goal-directed actions on objects. It is not clear whether they understand intentions at a high level of abstraction reliant on the context in which the actions occur. This study tested their understanding of others’ prior intentions with typically developing and developmentally delayed children. We replicated Carpenter et al.’s test of the ability to understand prior intentions embedded in the social situation with an additional context of no prior intention. Results showed that when the experimenter’s intention was made known before the demonstration, children without autism spectrum disorder performed not only better than the autism spectrum disorder children but also better than themselves when there was no information about prior intention. No between-condition difference was found in the autism spectrum disorder group. It thus appears that children with autism spectrum disorder have difficulty decoupling intentions from the context of the situation. The present findings, together with previous evidence for the intactness of the ability to understand and to imitate goal-directed actions, suggest that asymmetrical imitation performance occurs at different levels of understanding of intention by children with autism spectrum disorder.
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8. Joshi G, Wozniak J, Faraone SV, Fried R, Chan J, Furtak S, Grimsley E, Conroy K, Kilcullen JR, Woodworth KY, Biederman J. {{A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder}}. {J Clin Psychopharmacol}. 2016.
This prospective 12-week open-label trial evaluates the tolerability and efficacy of memantine hydrochloride for the treatment of core social and cognitive deficits in adults with high-functioning autism spectrum disorder (ASD). Measures for assessment of therapeutic response included the Social Responsiveness Scale-Adult Research Version (SRS-A), disorder-specific Clinical Global Impression scales, Behavior Rating Inventory of Executive Functioning-Adult Self-Report, Diagnostic Analysis of Nonverbal Accuracy Scale, and Cambridge Neuropsychological Test Automated Battery. Eighteen adults (mean age, 28 +/- 9.5 years) with high-functioning ASD (SRS-A raw score, 99 +/- 17) were treated with memantine (mean dose, 19.7 +/- 1.2 mg/d; range, 15-20 mg), and 17 (94%) completed the trial. Treatment with memantine was associated with significant reduction on informant-rated (SRS-A, -28 +/- 25; P < 0.001) and clinician-rated (Clinical Global Impression-Improvement subscale Lien vers le texte intégral (Open Access ou abonnement)
9. Maddox BB, Miyazaki Y, White SW. {{Long-Term Effects of CBT on Social Impairment in Adolescents with ASD}}. {J Autism Dev Disord}. 2016.
Anxiety interventions involving social skills training and CBT for youth with ASD have shown promise, but few studies have examined the effects on social functioning or the maintenance of treatment gains. This study evaluated change in social skills during a randomized controlled trial of CBT and during the 1-year follow-up for 25 adolescents with ASD and anxiety. We examined the effect of pretreatment social anxiety and loneliness on treatment response. Social impairment improved during treatment and continued to improve through the 3-month follow-up. Although adolescents with higher social anxiety had greater pretreatment social impairment, they showed steeper improvement in social skills during treatment. Loneliness was not a significant predictor of change during treatment. CBT targeting social skills and anxiety can lead to long-term improvements in social functioning.
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10. Shooshtari S, Brownell M, Mills RS, Dik N, Yu DC, Chateau D, Burchill CA, Wetzel M. {{Comparing Health Status, Health Trajectories and Use of Health and Social Services between Children with and without Developmental Disabilities: A Population-based Longitudinal Study in Manitoba}}. {J Appl Res Intellect Disabil}. 2016.
BACKGROUND: Little information exists on health of children with developmental disabilities (DDs) in the Canadian province of Manitoba. METHOD: The present authors linked 12 years of administrative data and compared health status, changes in health and access to health and social services between children with (n = 1877) and without (n = 5661) DDs living in the province, matched by age, sex and region of residence. RESULTS: Children with DDs were significantly more likely than children in the matched comparison group to die before the age of 17 and have a history of respiratory illness, diabetes and injury-related hospitalizations. Children with DD also had significantly higher average number of ambulatory physician visits and higher rate of continuity of care. CONCLUSIONS: Children with DDs had poorer health status than the matched comparison group. The health disparities experienced by children with DDs persisted over time. Further population-based longitudinal research is needed in this area.
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11. Srinivasan S, O’Rourke J, Bersche Golas S, Neumeyer A, Misra M. {{Calcium and Vitamin D Supplement Prescribing Practices among Providers Caring for Children with Autism Spectrum Disorders: Are We Addressing Bone Health?}}. {Autism Res Treat}. 2016; 2016: 6763205.
Children with autism spectrum disorders (ASD) have several risk factors for low bone mineral density. The gluten-free, casein-free (GFCF) diet is a complementary therapy sometimes used in ASD that raises concerns for the adequacy of calcium and vitamin D intake. This study evaluated the prescribing practices of calcium and vitamin D supplements and the practice of checking 25-hydroxy vitamin D (25(OH)D) levels by providers in 100 children with ASD, 50 of whom were on the GFCF diet. Fifty-two percent and 46% of children on the GFCF diet were on some form of vitamin D and calcium supplements, respectively, compared to 18% and 14% of those not on this diet. Twenty-four percent of children in the GFCF group had a documented 25(OH)D level compared to none in the non-GFCF group. The data highlight a gap in calcium and vitamin D supplement prescribing practices among providers caring for children with ASD as well as a gap in the practice of checking 25(OH)D levels.
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12. Venkat A, Migyanka JM, Cramer R, McGonigle JJ. {{An Instrument to Prepare for Acute Care of the Individual with Autism Spectrum Disorder in the Emergency Department}}. {J Autism Dev Disord}. 2016.
We present an instrument to allow individuals with autism spectrum disorder, their families and/or their caregivers to prepare emergency department staff for the care needs of this patient population ahead of acute presentation.
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13. Yin CL, Chen HI, Li LH, Chien YL, Liao HM, Chou MC, Chou WJ, Tsai WC, Chiu YN, Wu YY, Lo CZ, Wu JY, Chen YT, Gau SS. {{Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder}}. {Mol Autism}. 2016; 7: 23.
BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754.
