1. Badia M, Orgaz MB, Verdugo MA, Ullan AM, Martinez M. {{Relationships between Leisure Participation and Quality of Life of People with Developmental Disabilities}}. {J Appl Res Intellect Disabil}. 2013; 26(6): 533-45.
BACKGROUND: Studies of people with developmental disabilities suggest that participation in leisure activities might be a key factor for good quality of life. This study explores the relationships between objective and subjective quality of life and leisure participation of adults with developmental disabilities. MATERIALS AND METHODS: A cross-sectional design was used with a convenience sample of 125 people, aged 17-65, living in the community. Participants completed the subjective scale of Integral Quality Scale and the Leisure Assessment Inventory in the form of an individual interview. Staff completed the GENCAT Scale. RESULTS: No relationship was found between objective quality of life and leisure participation. However, correlations between some leisure participation dimensions and specific subjective quality of life domains were observed. The results establish a predictive relationship between leisure participation and material, emotional, and physical well-being. Personal and environmental variables analyzed were not found to have a moderating effect on the relationship between leisure participation and quality of life. CONCLUSIONS: These findings indicate that some aspects of leisure participation may significantly contribute to enhancing the quality of life of young people and adults with developmental disabilities living in the community.
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2. Bagni C, Oostra BA. {{Fragile X syndrome: From protein function to therapy}}. {Am J Med Genet A}. 2013; 161(11): 2809-21.
Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The FMR1 gene contains a CGG repeat present in the 5′-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The disease is a result of lack of expression of the fragile X mental retardation protein leading to severe symptoms, including intellectual disability, hyperactivity, and autistic-like behavior. The FMR1 protein (FMRP) has a number of functions. The translational dysregulation of a subset of mRNAs targeted by FMRP is probably the major contribution to FXS. FMRP is also involved in mRNA transport to synapses where protein synthesis occurs. For some FMRP-bound mRNAs, FMRP is a direct modulator of mRNA stability either by sustaining or preventing mRNA decay. Increased knowledge about the role of FMRP has led to the identification of potential treatments for fragile X syndrome that were often tested first in the different animal models. This review gives an overview about the present knowledge of the function of FMRP and the therapeutic strategies in mouse and man. (c) 2013 Wiley Periodicals, Inc.
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3. Bolte EE, Diehl JJ. {{Measurement tools and target symptoms/skills used to assess treatment response for individuals with autism spectrum disorder}}. {J Autism Dev Disord}. 2013; 43(11): 2491-501.
This study examined the measurement tools and target symptoms/skills used to assess treatment response during Autism Spectrum Disorder (ASD) intervention trials from 2001 through 2010. Data from 195 prospective trials were analyzed. There were 289 unique measurement tools, of which 61.6 % were used only once, and 20.8 % were investigator-designed. Only three tools were used in more than 2 % of the studies, and none were used in more than 7 % of studies. Studies investigated an average of 11.4 tool-symptom combinations per trial, with as many as 45 in one study. These results represent a lack of consistency in outcome measurements in ASD intervention trials. These findings highlight the need to set guidelines for appropriate outcome measurement in the ASD field.
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4. Bornstein MH, Hendricks C. {{Screening for developmental disabilities in developing countries}}. {Soc Sci Med}. 2013; 97: 307-15.
Despite waxing international interest in child disability, little information exists about the situation of children with disabilities in developing countries. Using a culture-free screen for child disability from the 2005-2007 Multiple Indicator Cluster Survey, this study reports percentages of children in 16 developing countries who screened positive for cognitive, language, sensory, and motor disabilities, covariation among disabilities, deviation contrasts that compare each country to the overall effect of country (including effects of age and gender and their interactions), and associations of disabilities with the Human Development Index. Developmental disabilities vary by child age and country, and younger children in developing countries with lower standards of living are more likely to screen positive for disabilities. The discussion of these findings revolves around research and policy implications.
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5. Braam W, Keijzer H, Struijker Boudier H, Didden R, Smits M, Curfs L. {{CYP1A2 polymorphisms in slow melatonin metabolisers: a possible relationship with autism spectrum disorder?}}. {J Intellect Disabil Res}. 2013; 57(11): 993-1000.
Background In some of our patients with intellectual disabilities (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment. In these patients melatonin levels at noon were extremely high (>50 pg/ml). We hypothesise that the disappearing effectiveness is associated with slow metabolisation of melatonin because of a single nucleotide polymorphism (SNP) of CYP1A2. Method In this pilot study we analysed DNA extracted from saliva samples of 15 consecutive patients with disappearing effectiveness of melatonin. Saliva was collected at noon and 4 pm for measuring melatonin levels. Results In all patients’ salivary melatonin levels at noon were >50 or melatonin half time was >5 h. A SNP was found in eight of 15 patients. The allele *1C was found in two patients and in six patients the *1F allele was found. Conclusions Of 15 patients with disappearing effectiveness of melatonin, seven were diagnosed with autism spectrum disorder, and in four of them a SNP was found. The other eight patients were known with a genetic syndrome. In six of them behaviour was considered to be autistic-type and in three of them a SNP was found. This finding may give a new direction for research into the genetic background of autism.
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6. Brimberg L, Sadiq A, Gregersen PK, Diamond B. {{Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder}}. {Mol Psychiatry}. 2013; 18(11): 1171-7.
It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder.
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7. Brock J, Bzishvili S, Reid M, Hautus M, Johnson BW. {{Brief report: atypical neuromagnetic responses to illusory auditory pitch in children with autism spectrum disorders}}. {J Autism Dev Disord}. 2013; 43(11): 2726-31.
Atypical auditory perception is a widely recognised but poorly understood feature of autism. In the current study, we used magnetoencephalography to measure the brain responses of 10 autistic children as they listened passively to dichotic pitch stimuli, in which an illusory tone is generated by sub-millisecond inter-aural timing differences in white noise. Relative to control stimuli that contain no inter-aural timing differences, dichotic pitch stimuli typically elicit an object related negativity (ORN) response, associated with the perceptual segregation of the tone and the carrier noise into distinct auditory objects. Autistic children failed to demonstrate an ORN, suggesting a failure of segregation; however, comparison with the ORNs of age-matched typically developing controls narrowly failed to attain significance. More striking, the autistic children demonstrated a significant differential response to the pitch stimulus, peaking at around 50 ms. This was not present in the control group, nor has it been found in other groups tested using similar stimuli. This response may be a neural signature of atypical processing of pitch in at least some autistic individuals.
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8. Butterly F, Percy C, Ward G. {{Brief Report: Do Service Dog Providers Placing Dogs with Children with Developmental Disabilities Use Outcome Measures and, If So, What Are they?}}. {J Autism Dev Disord}. 2013; 43(11): 2720-5.
The aim of this study was to identify the outcomes expected and assessed by those providing service dogs to children with developmental disabilities. Seventeen registered service dog providers were invited to complete a mixed methods online survey. Five providers, who prepared dogs to work with a wide range of conditions and behaviours, mainly Asperger’s syndrome, autism and communication disorders, completed the survey. All five participants reported that they expected to see positive changes as a consequence of the service dog placement, in both the recipient child and their family, including improvements in attention span and language skills, as well as increased familial cohesion. Survey responses indicated that not all desired outcomes were routinely assessed. The range of assessments used were interviews, intake conversations, pre-placement questionnaires, child social dairies filled in by parents, follow up surveys after placement, and child observation by parents. No specifically named valid and reliable clinical or research measures were referred to, showing an emphasis on assessments from parents and service dog providers. It is not clear whether pre-intervention assessments are repeated systematically at follow-up, which could show robust intervention effects. There is scope for professionals in developmental disability to work with service dog providers to improve the evidence base in this field.
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9. Byers ES, Nichols S, Voyer SD. {{Challenging stereotypes: sexual functioning of single adults with high functioning autism spectrum disorder}}. {J Autism Dev Disord}. 2013; 43(11): 2617-27.
This study examined the sexual functioning of single adults (61 men, 68 women) with high functioning autism and Asperger syndrome living in the community with and without prior relationship experience. Participants completed an on-line questionnaire assessing autism symptoms, psychological functioning, and various aspects of sexual functioning. In general participants reported positive sexual functioning. Participants without prior relationship experience were significantly younger and more likely to be male and identify as heterosexual. They reported significantly higher sexual anxiety, lower sexual arousability, lower dyadic desire, and fewer positive sexual cognitions. The men reported better sexual function than did the women in a number of areas. These results counter negative societal perceptions about the sexuality of high functioning individuals on the autism spectrum.
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10. Careaga M, Hansen RL, Hertz-Piccotto I, Van de Water J, Ashwood P. {{Increased anti-phospholipid antibodies in autism spectrum disorders}}. {Mediators Inflamm}. 2013; 2013: 935608.
Autism spectrum disorders (ASD) are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD) controls and children with developmental delays (DD) other than ASD. We found that levels of anti-cardiolipin, beta 2-glycoprotein 1, and anti-phosphoserine antibodies were elevated in children with ASD compared with age-matched TD and DD controls. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD.
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11. Cascio C, Gribbin M, Gouttard S, Smith RG, Jomier M, Field S, Graves M, Hazlett HC, Muller K, Gerig G, Piven J. {{Fractional anisotropy distributions in 2- to 6-year-old children with autism}}. {J Intellect Disabil Res}. 2013; 57(11): 1037-49.
Background Increasing evidence suggests that autism is a disorder of distributed neural networks that may exhibit abnormal developmental trajectories. Characterisation of white matter early in the developmental course of the disorder is critical to understanding these aberrant trajectories. Methods A cross-sectional study of 2- to 6-year-old children with autism was conducted using diffusion tensor imaging combined with a novel statistical approach employing fractional anisotropy distributions. Fifty-eight children aged 18-79 months were imaged: 33 were diagnosed with autism, 8 with general developmental delay, and 17 were typically developing. Fractional anisotropy values within global white matter, cortical lobes and the cerebellum were measured and transformed to random F distributions for each subject. Each distribution of values for a region was summarised by estimating delta, the estimated mean and standard deviation of the approximating F for each distribution. Results The estimated delta parameter, , was significantly decreased in individuals with autism compared to the combined control group. This was true in all cortical lobes, as well as in the cerebellum, but differences were most robust in the temporal lobe. Predicted developmental trajectories of across the age range in the sample showed patterns that partially distinguished the groups. Exploratory analyses suggested that the variability, rather than the central tendency, component of was the driving force behind these results. Conclusions While preliminary, our results suggest white matter in young children with autism may be abnormally homogeneous, which may reflect poorly organised or differentiated pathways, particularly in the temporal lobe, which is important for social and emotional cognition.
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12. Chapleau CA, Lane J, Pozzo-Miller L, Percy AK. {{Evaluation of current pharmacological treatment options in the management of rett syndrome: from the present to future therapeutic alternatives}}. {Curr Clin Pharmacol}. 2013; 8(4): 358-69.
Neurodevelopmental disorders are a large family of conditions of genetic or environmental origin that are characterized by deficiencies in cognitive and behavioral functions. The therapeutic management of individuals with these disorders is typically complex and is limited to the treatment of specific symptoms that characterize each disorder. The neurodevelopmental disorder Rett syndrome (RTT) is the leading cause of severe intellectual disability in females. Mutations in the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MECP2), located on the X chromosome, have been confirmed in more than 95% of individuals meeting diagnostic criteria for classical RTT. RTT is characterized by an uneventful early infancy followed by stagnation and regression of growth, motor, language, and social skills later in development. This review will discuss the genetics, pathology, and symptoms that distinguish RTT from other neurodevelopmental disorders associated with intellectual disability. Because great progress has been made in the basic and clinical science of RTT, the goal of this review is to provide a thorough assessment of current pharmacotherapeutic options to treat the symptoms associated with this disorder. Furthermore, we will highlight recent discoveries made with novel pharmacological interventions in experimental preclinical phases, and which have reversed pathological phenotypes in mouse and cell culture models of RTT and may result in clinical trials.
13. Creasey N, Finlay F. {{Question 2: Do weighted blankets improve sleep in children with an autistic spectrum disorder?}}. {Arch Dis Child}. 2013; 98(11): 919-20.
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14. Crisp S, Meyer E, Gregory A, Archer H, Hayflick S, Kurian MA, de Silva R. {{A rett-look-alike with brain iron accumulation}}. {J Neurol Neurosurg Psychiatry}. 2013; 84(11): e2.
A 31-year old female presented with progressive loss of motor and social skills, on a background of previously static global developmental delay. Her history and examination were consistent with atypical Rett syndrome, but MECP2 sequencing failed to demonstrate a pathogenic mutation. Magnetic resonance imaging (MRI) of brain in adulthood revealed a pattern of iron accumulation in the basal ganglia and cerebral peduncles characteristic of the newly described entity of beta-propeller protein-associated neurodegeneration (BPAN).(1-3) Genetic analysis confirmed the presence of a novel mutation in the associated WDR45 gene on the X-chromosome. Video data demonstrating the patient’s phenotype, detailed MRI findings and their discrimination from other forms of brain iron accumulation are presented. Classically, the clinical features of BPAN are global developmental delay in childhood and neurological degeneration in adulthood, with progressive dystonia, parkinsonism and dementia.(2) However, our patient presented predominantly with a Rett-like phenotype, features of which may be present in approximately 25% of BPAN cases.(2) The proportion of patients with atypical Rett syndrome, particularly those with negative conventional genetic tests, who actually have BPAN remains to be established. Like Rett syndromes, this disorder is more common in females consistent with sensitivity to X-inactivation.(1) The phenotypic variability may be attributable to variation in the pattern of inactivation.
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15. Dajani R, Koo SE, Sullivan GJ, Park IH. {{Investigation of Rett syndrome using pluripotent stem cells}}. {J Cell Biochem}. 2013; 114(11): 2446-53.
Rett syndrome (RTT) is one of most prevalent female neurodevelopmental disorders. De novo mutations in X-linked MECP2 are mostly responsible for RTT. Since the identification of MeCP2 as the underlying cause of RTT, murine models have contributed to understanding the pathophysiology of RTT and function of MeCP2. Reprogramming is a procedure to produce induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors. iPSCs obtain similar features as embryonic stem cells and are capable of self-renewing and differentiating into cells of all three layers. iPSCs have been utilized in modeling human diseases in vitro. Neurons differentiated from RTT-iPSCs showed the recapitulation of RTT phenotypes. Despite the early success, genetic and epigenetic instability upon reprogramming and ensuing maintenance of iPSCs raise concerns in using RTT-iPSCs as an accurate in vitro model. Here, we update the current iPSC-based RTT modeling, and its concerns and challenges.
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16. Edvardson S, Ashikov A, Jalas C, Sturiale L, Shaag A, Fedick A, Treff NR, Garozzo D, Gerardy-Schahn R, Elpeleg O. {{Mutations in SLC35A3 cause autism spectrum disorder, epilepsy and arthrogryposis}}. {J Med Genet}. 2013; 50(11): 733-9.
BACKGROUND: The heritability of autism spectrum disorder is currently estimated at 55%. Identification of the molecular basis of patients with syndromic autism extends our understanding of the pathogenesis of autism in general. The objective of this study was to find the gene mutated in eight patients from a large kindred, who suffered from autism spectrum disorder, arthrogryposis and epilepsy. METHODS AND RESULTS: By linkage analysis and exome sequencing, we identified deleterious mutations in SLC35A3 in these patients. SLC35A3 encodes the major Golgi uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter. In Golgi vesicles isolated from patient fibroblasts the transport of the respective nucleotide sugar was significantly reduced causing a massive decrease in the content of cell surface expressed highly branched N-glycans and a concomitant sharp increase of lower branched glycoforms. CONCLUSIONS: Spontaneous mutation in SLC35A3 has been discovered in cattle worldwide, recapitulating the human phenotype with arthrogryposis and additional skeletal defects known as Complex Vertebral Malformation syndrome. The skeletal anomalies in the mutant cattle and in our patients, and perhaps even the neurological symptoms are likely the consequence of the lack of high-branched N-glycans and the concomitant abundance of lower-branched glycoforms at the cell surface. This pattern has previously been associated with growth arrest and induction of differentiation. With this study, we add SLC35A3 to the gene list of autism spectrum disorders, and underscore the crucial importance of UDP-GlcNAc in the regulation of the N-glycan branching pathway in the Golgi apparatus.
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17. Eussen ML, Van Gool AR, Verheij F, De Nijs PF, Verhulst FC, Greaves-Lord K. {{The association of quality of social relations, symptom severity and intelligence with anxiety in children with autism spectrum disorders}}. {Autism}. 2013; 17(6): 723-35.
Limited quality of social relations, milder symptom severity and higher intelligence were shown to account for higher anxiety levels in autism spectrum disorders. The current study replicated and extended earlier findings by combining these three determinants of anxiety in autism spectrum disorders in one study. The sample consisted of 134 school-aged children with autism spectrum disorders, of whom 58 (43%) had a co-morbid anxiety disorder according to the Diagnostic Interview Schedule for Children-Parent version. In this sample, we tested associations between these determinants and anxiety univariately and multivariately to clarify the unique contribution of all determinants. Since we hypothesized that the association between limited quality of social relations and anxiety would be amplified by low symptom severity and/or high intelligence, we additionally tested for moderating effects. We found that higher anxiety levels were associated with a lower quality of social relations and lower symptom severity. In this mainly high-functioning sample, intelligence was not related to anxiety levels. No moderation effects were found. Since lower quality of social relations and lower symptom severity are associated with higher anxiety levels in children with autism spectrum disorders, therapeutic interventions aimed at reducing anxiety in autism spectrum disorders should pay attention to improving social relations, and presumably children with a lower symptom severity could benefit most from such interventions.
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18. Ey E, Torquet N, Le Sourd AM, Leblond CS, Boeckers TM, Faure P, Bourgeron T. {{The Autism ProSAP1/Shank2 mouse model displays quantitative and structural abnormalities in ultrasonic vocalisations}}. {Behav Brain Res}. 2013; 256: 677-89.
Mouse ultrasonic vocalisations have been often used as a paradigm to extrapolate vocal communication defects observed in patients with autism spectrum disorders (ASD). The role of these vocalisations as well as their development, structure and informational content, however, remain largely unknown. In the present study, we characterised in depth the emission of pup and adult ultrasonic vocalisations of wild-type mice and their ProSAP1/Shank2(-/-) littermates lacking a synaptic scaffold protein mutated in ASD. We hypothesised that the vocal behaviour of ProSAP1/Shank2(-/-) mice not only differs from the vocal behaviour of their wild-type littermates in a quantitative way, but also presents more qualitative abnormalities in temporal organisation and acoustic structure. We first quantified the rate of emission of ultrasonic vocalisations, and analysed the organisation of vocalisations sequences using Markov models. We subsequently measured duration and peak frequency characteristics of each ultrasonic vocalisation, to characterise their acoustic structure. In wild-type mice, we found a high level of organisation in sequences of ultrasonic vocalisations, suggesting a communicative function in this complex system. Very limited significant sex-related variations were detected in their usage and acoustic structure, even in adult mice. In adult ProSAP1/Shank2(-/-) mice, we found abnormalities in the call usage and the structure of ultrasonic vocalisations. Both ProSAP1/Shank2(-/-) male and female mice uttered less vocalisations with a different call distribution and at lower peak frequency in comparison with wild-type littermates. This study provides a comprehensive framework to characterise abnormalities of ultrasonic vocalisations in mice and confirms that ProSAP1/Shank2(-/-) mice represent a relevant model to study communication defects.
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19. Freeth M, Sheppard E, Ramachandran R, Milne E. {{A Cross-Cultural Comparison of Autistic Traits in the UK, India and Malaysia}}. {J Autism Dev Disord}. 2013; 43(11): 2569-83.
The disorder of autism is widely recognised throughout the world. However, the diagnostic criteria and theories of autism are based on research predominantly conducted in Western cultures. Here we compare the expression of autistic traits in a sample of neurotypical individuals from one Western culture (UK) and two Eastern cultures (India and Malaysia), using the Autism-spectrum Quotient (AQ) in order to identify possible cultural differences in the expression of autistic traits. Behaviours associated with autistic traits were reported to a greater extent in the Eastern cultures than the Western culture. Males scored higher than females and science students scored higher than non-science students in each culture. Indian students scored higher than both other groups on the Imagination sub-scale, Malaysian students scored higher than both other groups on the Attention Switching sub-scale. The underlying factor structures of the AQ for each population were derived and discussed.
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20. Ghanizadeh A. {{Atomoxetine for treating ADHD symptoms in autism: a systematic review}}. {J Atten Disord}. 2013; 17(8): 635-40.
Objective: This study systematically reviews the current literature on the administration of atomoxetine for treating children and adolescents with comorbidity on autism spectrum disorder (ASD) and ADHD. Method: PubMed/Medline and Google Scholar databases were electronically searched to find the published trials on atomoxetine and ASD. Results: Six articles reported the clinical trials of atomoxetine for treatment of ADHD symptoms in patients with autism or pervasive development disorders. Only one study that was placebo-controlled crossover pilot trial reported that it is effective. Atomoxetine may be effective in high-functioning patients with autism or patients with low severity. Those with high severity of ASD may be more vulnerable to the adverse effects of atomoxetine. Conclusion: There are not enough controlled clinical trials for showing the efficacy of atomoxetine for treatment of ADHD symptoms in autism. Although evidence suggests potential efficacy of atomoxetine, the current evidences are not conclusive.
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21. Gibson J, Adams C, Lockton E, Green J. {{Social communication disorder outside autism? A diagnostic classification approach to delineating pragmatic language impairment, high functioning autism and specific language impairment}}. {J Child Psychol Psychiatry}. 2013; 54(11): 1186-97.
BACKGROUND: Developmental disorders of language and communication present considerable diagnostic challenges due to overlapping of symptomatology and uncertain aetiology. We aimed to further elucidate the behavioural and linguistic profile associated with impairments of social communication occurring outside of an autism diagnosis. METHODS: Six to eleven year olds diagnosed with pragmatic language impairment (PLI), high functioning autism (HFA) or specific language impairment (SLI) were compared on measures of social interaction with peers (PI), restricted and repetitive behaviours/interests (RRBIs) and language ability. Odds ratios (OR) from a multinomial logistic regression were used to determine the importance of each measure to diagnostic grouping. MANOVA was used to investigate differences in subscale scores for the PI measure. RESULTS: Greater degrees of PI difficulties (OR = 1.22, 95% CI = 1.05-1.41), RRBI (OR = 1.23, 95% CI = 1.06-1.42) and expressive language ability (OR = 1.16, 95% CI = 1.03-1.30) discriminated HFA from PLI. PLI was differentiated from SLI by elevated PI difficulties (OR = 0.82, 95% CI = 0.70-0.96) and higher expressive language ability (OR = 0.88, 95% CI = 0.77-0.98), but indistinguishable from SLI using RRBI (OR = 1.01, 95% CI=0.94-1.09). A significant effect of group on PI subscales was observed (theta = 1.38, F(4, 56) = 19.26, p < .01) and PLI and HFA groups shared a similar PI subscale profile. CONCLUSIONS: Results provide empirical support for a conceptualisation of PLI as a developmental impairment distinguishable from HFA by absence of RRBIs and by the presence of expressive language difficulties. PI difficulties appear elevated in PLI compared with SLI, but may be less pervasive than in HFA. Findings are discussed with reference to the proposed new category of ‘social communication disorder’ in DSM-5.
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22. Gogolinska A, Nowak W. {{Molecular basis of lateral force spectroscopy nano-diagnostics: computational unbinding of autism related chemokine MCP-1 from IgG antibody}}. {J Mol Model}. 2013; 19(11): 4773-80.
Monocyte-chemoattractant protein-1 (MCP-1), also known as CCL2, is a potent chemoattractant of T cells and monocytes, involved in inflammatory and angio-proliferative brain and retinal diseases. Higher expression of MCP-1 is observed in metastatic tumors. Unusual levels of MCP-1 in the brain may be correlated with autism. Immunochemistry where atomic force microscope (AFM) tips functionalized with appropriate antibodies against MCP-1 are used could in principle support medical diagnostics. Useful signals from single molecule experiments may be generated if interaction forces are large enough. The chemokine-antibody unbinding force depends on a relative motion of the interacting fragments of the complex. In this paper the stability of the medically important MCP-1- immunoglobulin G antibody Fab fragment complex has been studied using steered molecular dynamics (SMD) computer simulations with the aim to model possible arrangements of nano-diagnostics experiments. Using SMD we confirm that molecular recognition in MCP1-IgG is based mainly on six pairs of residues: Glu39A – Arg98H, Lys56A – Asp52H, Asp65A – Arg32L, Asp68A – Arg32L, Thr32A – Glu55L, Gln61A – Tyr33H. The minimum external force required for mechanical dissociation of the complex depends on a direction of the force. The pulling of the MCP-1 antigen in the directions parallel to the antigen-antibody contact plane requires forces about 20 %-40 % lower than in the perpendicular one. Fortunately, these values are large enough that the fast lateral force spectroscopy may be used for effective nano-diagnostics purposes. We show that molecular modeling is a useful tool in planning AFM force spectroscopy experiments.
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23. Green J, Wan MW, Guiraud J, Holsgrove S, McNally J, Slonims V, Elsabbagh M, Charman T, Pickles A, Johnson M. {{Intervention for infants at risk of developing autism: a case series}}. {J Autism Dev Disord}. 2013; 43(11): 2502-14.
Theory and evidence suggest the potential value of prodromal intervention for infants at risk of developing autism. We report an initial case series (n = 8) of a parent-mediated, video-aided and interaction-focused intervention with infant siblings of autistic probands, beginning at 8-10 months of age. We outline the theory and evidence base behind this model and present data on feasibility, acceptability and measures ranging from parent-infant social interaction, to infant atypical behaviors, attention and cognition. The intervention proves to be both feasible and acceptable to families. Measurement across domains was successful and on larger samples promise to be an effective test of whether such an intervention in infancy will modify emergent atypical developmental trajectories in infants at risk for autism.
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24. Green SA, Rudie JD, Colich NL, Wood JJ, Shirinyan D, Hernandez L, Tottenham N, Dapretto M, Bookheimer SY. {{Overreactive brain responses to sensory stimuli in youth with autism spectrum disorders}}. {J Am Acad Child Adolesc Psychiatry}. 2013; 52(11): 1158-72.
OBJECTIVES: Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimuli, is both highly prevalent and extremely impairing in youth with autism spectrum disorders (ASD), yet little is known about the neurological bases of SOR. This study aimed to examine the functional neural correlates of SOR by comparing brain responses to sensory stimuli in youth with and without ASD. METHOD: A total of 25 high-functioning youth with ASD and 25 age- and IQ-equivalent typically developing (TD) youth were presented with mildly aversive auditory and visual stimuli during a functional magnetic resonance imaging (fMRI) scan. Parents provided ratings of children’s SOR and anxiety symptom severity. RESULTS: Compared to TD participants, ASD participants displayed greater activation in primary sensory cortical areas as well as amygdala, hippocampus, and orbital-frontal cortex. In both groups, the level of activity in these areas was positively correlated with level of SOR severity as rated by parents, over and above behavioral ratings of anxiety. CONCLUSIONS: This study demonstrates that youth with ASD show neural hyper-responsivity to sensory stimuli, and that behavioral symptoms of SOR may be related to both heightened responsivity in primary sensory regions as well as areas related to emotion processing and regulation.
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25. Grofer Klinger L, Ence W, Meyer A. {{Caregiver-mediated approaches to managing challenging behaviors in children with autism spectrum disorder}}. {Dialogues Clin Neurosci}. 2013; 15(2): 225-33.
A significant proportion of children with autism spectrum disorder (ASD) are referred to mental health centers due to the presence of challenging behaviors. Because challenging behaviors in children and adolescents with ASD often result from underlying social and communication difficulties and comorbid anxiety, traditional caregiver-mediated behavior intervention techniques developed for children with disruptive behavior disorders may need to be adapted for this population. Behavioral interventions that target communication skills, social skills, anxiety, and sensory responsiveness in children with ASD may be needed. Notably, while best practice necessitates the involvement of caregivers in treating children and adolescents with ASD, few randomized control studies have examined the effectiveness of caregiver-implemented interventions in reducing challenging behaviors. This review summarizes the current literature with regard to caregiver-mediated behavioral interventions for children with ASD, and suggests areas for intervention development and research.
26. Gunnes N, Suren P, Bresnahan M, Hornig M, Lie KK, Lipkin WI, Magnus P, Nilsen RM, Reichborn-Kjennerud T, Schjolberg S, Susser ES, Oyen AS, Stoltenberg C. {{Interpregnancy interval and risk of autistic disorder}}. {Epidemiology}. 2013; 24(6): 906-12.
BACKGROUND: A recent California study reported increased risk of autistic disorder in children conceived within a year after the birth of a sibling. METHODS: We assessed the association between interpregnancy interval and risk of autistic disorder using nationwide registry data on pairs of singleton full siblings born in Norway. We defined interpregnancy interval as the time from birth of the first-born child to conception of the second-born child in a sibship. The outcome of interest was autistic disorder in the second-born child. Analyses were restricted to sibships in which the second-born child was born in 1990-2004. Odds ratios (ORs) were estimated by fitting ordinary logistic models and logistic generalized additive models. RESULTS: The study sample included 223,476 singleton full-sibling pairs. In sibships with interpregnancy intervals <9 months, 0.25% of the second-born children had autistic disorder, compared with 0.13% in the reference category (>/=36 months). For interpregnancy intervals shorter than 9 months, the adjusted OR of autistic disorder in the second-born child was 2.18 (95% confidence interval 1.42-3.26). The risk of autistic disorder in the second-born child was also increased for interpregnancy intervals of 9-11 months in the adjusted analysis (OR = 1.71 [95% CI = 1.07-2.64]). CONCLUSIONS: Consistent with a previous report from California, interpregnancy intervals shorter than 1 year were associated with increased risk of autistic disorder in the second-born child. A possible explanation is depletion of micronutrients in mothers with closely spaced pregnancies.
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27. Hagebeuk EE, Duran M, Abeling NG, Vyth A, Poll-The BT. {{S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation}}. {J Inherit Metab Dis}. 2013; 36(6): 967-72.
Rett syndrome is a neurodevelopmental disorder characterized by cognitive and locomotor regression and stereotypic hand movements. The disorder is caused by mutations in the X chromosomal MECP2 a gene encoding methyl CpG-binding protein. It has been associated with disturbances of cerebral folate homeostasis, as well as with speculations on a compromised DNA-methylation. Folinic acid is the stable form of folate. Its derived intermediate 5-MTHF supports the conversion of homocysteine to methionine, the precursor of S-adenosylmethionine (SAM). This in turn donates its methyl group to various acceptors, including DNA, thereby being converted to S-adenosylhomocysteine (SAH). The SAM/SAH ratio reflects the methylation potential. The goal of our study was to influence DNA methylation processes and ameliorate the clinical symptoms in Rett syndrome. Therefore we examined the hypothesis that folinic acid supplementation, besides increasing cerebrospinal fluid (CSF) 5-MTHF (p = 0.003), influences SAM and SAH and their ratio. In our randomized, double-blind crossover study on folinic acid supplementation, ten female Rett patients received both folinic acid and placebo for 1 year each. It was shown that both SAM and SAH levels in the CSF remained unchanged following folinic acid administration (p = 0.202 and p = 0.097, respectively) in spite of a rise of plasma SAM and SAH (p = 0.007; p = 0.009). There was no significant change in the SAM/SAH ratio either in plasma or CSF. The apparent inability of Rett patients to upregulate SAM and SAH levels in the CSF may contribute to the biochemical anomalies of the Rett syndrome. Our studies warrant further attempts to promote DNA methylation in the true region of interest, i.e. the brain.
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28. Hall DA, O’Keefe JA. {{Clinical neurogenetics: fragile x-associated tremor/ataxia syndrome}}. {Neurol Clin}. 2013; 31(4): 1073-84.
This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene. It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings. Symptomatic treatment is beneficial in some patients. The inheritance is X-linked and family members may be at risk for other fragile X-associated disorders. This information is useful to neurologists, general practitioners, and geneticists.
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29. Hani HB, Gonzalez-Barrero AM, Nadig AS. {{Children’s referential understanding of novel words and parent labeling behaviors: similarities across children with and without autism spectrum disorders}}. {J Child Lang}. 2013; 40(5): 971-1002.
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30. Hanley M, McPhillips M, Mulhern G, Riby DM. {{Spontaneous attention to faces in Asperger syndrome using ecologically valid static stimuli}}. {Autism}. 2013; 17(6): 754-61.
Previous eye tracking research on the allocation of attention to social information by individuals with autism spectrum disorders is equivocal and may be in part a consequence of variation in stimuli used between studies. The current study explored attention allocation to faces, and within faces, by individuals with Asperger syndrome using a range of static stimuli where faces were either viewed in isolation or viewed in the context of a social scene. Results showed that faces were viewed typically by the individuals with Asperger syndrome when presented in isolation, but attention to the eyes was significantly diminished in comparison to age and IQ-matched typical viewers when faces were viewed as part of social scenes. We show that when using static stimuli, there is evidence of atypicality for individuals with Asperger syndrome depending on the extent of social context. Our findings shed light on the previous explanations of gaze behaviour that have emphasised the role of movement in atypicalities of social attention in autism spectrum disorders and highlight the importance of consideration of the realistic portrayal of social information for future studies.
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31. Harper A, Dyches TT, Harper J, Roper SO, South M. {{Respite care, marital quality, and stress in parents of children with autism spectrum disorders}}. {J Autism Dev Disord}. 2013; 43(11): 2604-16.
Parents of children with autism spectrum disorders (ASD) are at risk for having higher stress and lower marital quality than other parents. Survey data regarding respite care, marital quality, and daily hassles and uplifts were obtained from 101 mother-father dyads who were together raising at least one child with ASD (total # of children = 118). Number of hours of respite care was positively related to improved marital quality for both husbands and wives, such that a 1-h increase in weekly respite care was associated with a one-half standard deviation increase in marital quality. This relationship was significantly mediated by perceived daily stresses and uplifts in both husbands and wives. More respite care was associated with increased uplifts and reduced stress; increased uplifts were associated with improved marital quality; and more stress was associated with reduced marital quality. The number of children in the family was associated with greater stress, and reduced relational quality and daily uplifts. Results suggest policymakers and practitioners should develop supports for providing respite for families raising children with ASD.
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32. Hermann I, Haser V, van Elst LT, Ebert D, Muller-Feldmeth D, Riedel A, Konieczny L. {{Automatic metaphor processing in adults with Asperger syndrome: a metaphor interference effect task}}. {Eur Arch Psychiatry Clin Neurosci}. 2013; 263 Suppl 2: 177-87.
This paper investigates automatic processing of novel metaphors in adults with Asperger Syndrome (AS) and typically developing controls. We present an experiment combining a semantic judgment task and a recognition task. Four types of sentences were compared: Literally true high-typical sentences, literally true low-typical sentences, apt metaphors, and scrambled metaphors (literally false sentences which are not readily interpretable as metaphors). Participants were asked to make rapid decisions about the literal truth of such sentences. The results revealed that AS and control participants showed significantly slower RTs for metaphors than for scrambled metaphors and made more mistakes in apt metaphoric sentences than in scrambled metaphors. At the same time, there was higher recognition of apt metaphors compared with scrambled metaphors. The findings indicate intact automatic metaphor processing in AS and replicate previous findings on automatic metaphor processing in typically developing individuals.
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33. Hodgetts S, Nicholas D, Zwaigenbaum L, McConnell D. {{Parents’ and professionals’ perceptions of family-centered care for children with autism spectrum disorder across service sectors}}. {Soc Sci Med}. 2013; 96: 138-46.
Family-centered care (FCC) has been linked with improved parent and child outcomes, yet its implementation can be challenging due to family, professional, organizational and systemic factors and policies. This study aims to increase knowledge and understanding of how families with children with autism spectrum disorder (ASD) experience FCC in Alberta, Canada. 152 parents with a child with ASD completed the Measure of Processes of Care, separately for each utilized service sector, and 146 professionals working with persons with ASD completed the Measure of Processes of Care – Service Providers. Additionally, in-depth interviews were conducted with a sub-sample of 19 parents, purposefully sampled for diversity in child and family characteristics. Data were collected in 2011. Descriptive and inferential statistics were used to analyze quantitative data. Interview transcripts were analyzed using grounded theory constant comparison methods, yielding a data generated theoretical model depicting families’ experiences with FCC over time and across service sectors. There were no statistically significant differences in FCC scores across service sectors, but statistically significant differences in FCC scores between parents’ and professionals’ were found. Qualitative data revealed positive experiences and perceptions of receiving FCC from professionals « on the ground » across sectors, but negative experiences and perceptions of FCC at the systems level (i.e., administration, funders). These broad experiences emerged as a core theme « System of Exclusion », which integrated the key themes: (1) « The Fight », (2) « Roles and Restrictions of Care », and (3) « Therapeutic Rapport ». Professionals and service providers can use findings to ensure that services reflect current conceptualizations of FCC, and decision and policy makers can use findings to recognize systemic barriers to implementing FCC and inform policy change.
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34. Jacquemont S, Berry-Kravis E, Hagerman R, von Raison F, Gasparini F, Apostol G, Ufer M, Des Portes V, Gomez-Mancilla B. {{The challenges of clinical trials in fragile X syndrome}}. {Psychopharmacology (Berl)}. 2013.
RATIONALE: Advances in understanding the underlying mechanisms of conditions such as fragile X syndrome (FXS) and autism spectrum disorders have revealed heterogeneous populations. Recent trials of novel FXS therapies have highlighted several challenges including subpopulations with possibly differential therapeutic responses, the lack of specific outcome measures capturing the full range of improvements of patients with FXS, and a lack of biomarkers that can track whether a specific mechanism is responsive to a new drug and whether the response correlates with clinical improvement. OBJECTIVES: We review the phenotypic heterogeneity of FXS and the implications for clinical research in FXS and other neurodevelopmental disorders. RESULTS: Residual levels of fragile X mental retardation protein (FMRP) expression explain in part the heterogeneity in the FXS phenotype; studies indicate a correlation with both cognitive and behavioral deficits. However, this does not fully explain the extent of phenotypic variance observed or the variability of drug response. Post hoc analyses of studies involving the selective mGluR5 antagonist mavoglurant and the GABAB agonist arbaclofen have uncovered significant therapeutic responses following patient stratification according to FMR1 promoter methylation patterns or baseline severity of social withdrawal, respectively. Future studies designed to quantify disease modification will need to develop new strategies to track changes effectively over time and in multiple symptom domains. CONCLUSION: Appropriate selection of patients and outcome measures is central to optimizing future clinical investigations of these complex disorders.
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35. Karanth P, Chandhok TS. {{Impact of early intervention on children with autism spectrum disorders as measured by inclusion and retention in mainstream schools}}. {Indian J Pediatr}. 2013; 80(11): 911-9.
OBJECTIVES: To follow up the school/educational status of children with a primary diagnosis of Autism Spectrum Disorders (ASD), who had been enrolled in an Early Intervention (EI) program for 1-3 y, before the age of 6. METHODS: Data was collected through a questionnaire covering three specific areas-the families’ success in following the recommendation given on completion of the EI program, issues in schooling and feedback on the EI program. The contact modes included email, post, telephonic interviews and face-to-face interviews. RESULTS: One hundred and two of the 296 children responded to the questionnaire. The responses were analyzed to identify, the number of families who had completed the program and were able to follow through with the recommendation given on completion of the EI program, difficulties faced if any, family feedback on the program and the additional help that they would have liked to receive. The reasons for failure to comply with the recommendations were analyzed. Of the 102 children who responded seven had dropped out midway through the program and 10 had discontinued after one year. Of the remaining 85 who completed the program, 71 were advised mainstreaming (83.5 %) and 14 were advised special school (16.5 %). Sixty-five of the 71 children, who were advised to enroll their child in the mainstream, were in regular school. 76.5 % of the children who completed the EI program were integrated in regular schools, 2 to 7 y after having completed the program. CONCLUSIONS: EI helps in enrolment and retention of substantial numbers of children with ASD in mainstream schools.
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36. Kenworthy L, Wallace GL, Birn R, Milleville SC, Case LK, Bandettini PA, Martin A. {{Aberrant neural mediation of verbal fluency in autism spectrum disorders}}. {Brain Cogn}. 2013; 83(2): 218-26.
OBJECTIVE: Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD). METHOD: We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n=17, mean verbal IQ=117) and neurotypical (NT; n=20, mean verbal IQ=112) adolescent and young adult males (12-23years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency. RESULTS: Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in cortico-striatal circuits previously linked to repetitive behaviors (Langen, Durston, Kas, van Engeland, & Staal, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand. CONCLUSIONS: These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses.
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37. Kerekes N, Brandstrom S, Lundstrom S, Rastam M, Nilsson T, Anckarsater H. {{ADHD, autism spectrum disorder, temperament, and character: Phenotypical associations and etiology in a Swedish childhood twin study}}. {Compr Psychiatry}. 2013; 54(8): 1140-7.
OBJECTIVE: To explore the links between neurodevelopmental disorders – attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) – and personality in a population-based, genetically sensitive study of children. METHOD: A population-based sample of 1886 twins aged 9 and 12, enriched for childhood mental health problems, was recruited from the Child and Adolescent Twin Study in Sweden (CATSS). Parents were interviewed over the telephone using the Autism-Tics, AD/HD and other Comorbidities (A-TAC) inventory, and in a second step they rated their children according to the Junior Temperament and Character Inventory (JTCI). RESULTS: ADHD was strongly correlated with novelty seeking, while ASD was correlated positively with harm avoidance and negatively with reward dependence. The strongest associations between personality traits and neurodevelopmental disorders were negative correlations between the character dimensions of self-directedness and cooperativeness and ADHD and ASD alike. Cross-twin cross-trait correlations between ADHD, ASD, and personality dimensions in monozygotic twins were more than double those in dizygotic twins, indicating a strong genetic effect behind the phenotypic covariation between neurodevelopmental disorders and personality. CONCLUSIONS: Neurodevelopmental disorders are linked specifically to particular temperament profiles and generally to hampered development of the self-governing strategies referred to as « character. » Poor self-agency and cooperation may be core functional outcomes in the separation of children with handicapping conditions from those with traits only reminiscent of neurodevelopmental disorders. The associations between neurodevelopmental disorders and personality are at least partly due to genetic effects influencing both conditions. As a consequence, personality must be broadly considered in neuropsychiatry, just as neuropsychiatric disorders and their genetic, neurodevelopmental, and cognitive susceptibilities have to be in personality research and clinical treatment.
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38. Kirkovski M, Enticott PG, Fitzgerald PB. {{A review of the role of female gender in autism spectrum disorders}}. {J Autism Dev Disord}. 2013; 43(11): 2584-603.
This paper reviews the literature exploring gender differences associated with the clinical presentation of autism spectrum disorders (ASD). The potentially mediating effect of comorbid psychopathology, biological and neurodevelopmental implications on these gender differences is also discussed. A vastly heterogeneous condition, while females on the lower-functioning end of the spectrum appear to be more severely affected, an altered clinical manifestation of the disorder among high-functioning females may consequently result in many being un or misdiagnosed. To date, there is strong bias in the literature towards the clinical presentation of ASD in males. It is imperative that future research explores gender differences across the autism spectrum, in order to improve researchers’, clinicians’ and the publics’ understanding of this debilitating disorder.
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39. Knight O, Bebbington A, Siafarikas A, Woodhead H, Girdler S, Leonard H. {{Pubertal trajectory in females with Rett syndrome: A population-based study}}. {Brain Dev}. 2013; 35(10): 912-20.
Background: Rett syndrome is a severe genetic neurodevelopmental disorder mainly affecting females. The aim of this study was to describe pubertal development in a population-based cohort of females with Rett syndrome. Methods: To assess pubertal trajectory we used six waves of data provided by parents of girls and women, recruited through the Australian population-based Rett Syndrome Database. The age at which adrenarche, thelarche or menarche occurred was used as the parameter for time to event (survival) analysis. The relationships between BMI, mutation type and the trajectories were investigated, using Cox proportional hazards. Results: One quarter of girls reached adrenarche by 9.6years, half by 11years and three quarters by 12.6years. Half reached menarche by 14years (range 8-23). Being underweight was associated with later age at adrenarche, thelarche and menarche, while higher BMI (overweight) was associated with earlier onset. In general, girls with C-terminal deletions and early truncating mutations reached pubertal stages earlier and those with the p.R168X mutation reached them later. Conclusion: The pubertal course in Rett syndrome may be abnormal, sometimes with early adrenarche but delayed menarche. These features may be genotype dependent and may have varying relationships with growth and bone acquisition.
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40. Knight V, McKissick BR, Saunders A. {{Erratum to: A Review of Technology-Based Interventions to Teach Academic Skills to Students with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2013; 43(11): 2649.
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41. Knight V, McKissick BR, Saunders A. {{A review of technology-based interventions to teach academic skills to students with autism spectrum disorder}}. {J Autism Dev Disord}. 2013; 43(11): 2628-48.
A comprehensive review of the literature was conducted for articles published between 1993 and 2012 to determine the degree to which technology-based interventions can be considered an evidence-based practice to teach academic skills to individuals with Autism Spectrum Disorder (ASD). Criteria developed by Horner et al. (Except Child 71:165-178, 2005) and Gersten et al. (Except Child 71:149-164, 2005) were used to determine the quality of single-subject research studies and group experimental research studies respectively. A total of 25 studies met inclusion criteria. Of these studies, only three single-subject studies and no group studies met criteria for quality or acceptable studies. Taken together, the results suggest that practitioners should use caution when teaching academic skills to individuals with ASD using technology-based interventions. Limitations and directions for future research are discussed.
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42. Kohane IS, Eran A. {{Can we measure autism?}}. {Sci Transl Med}. 2013; 5(209): 209ed18.
Newly released definitions of autism spectrum disorder demonstrate the need for precise diagnoses informed by the integration of clinical, molecular, and biochemical characteristics in a patient-information commons.
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43. Kover ST, McDuffie AS, Hagerman RJ, Abbeduto L. {{Receptive vocabulary in boys with autism spectrum disorder: cross-sectional developmental trajectories}}. {J Autism Dev Disord}. 2013; 43(11): 2696-709.
In light of evidence that receptive language may be a relative weakness for individuals with autism spectrum disorder (ASD), this study characterized receptive vocabulary profiles in boys with ASD using cross-sectional developmental trajectories relative to age, nonverbal cognition, and expressive vocabulary. Participants were 49 boys with ASD (4-11 years) and 80 typically developing boys (2-11 years). Receptive vocabulary, assessed with the Peabody Picture Vocabulary Test, was a weakness for boys with ASD relative to age and nonverbal cognition. Relative to expressive vocabulary, assessed with the Expressive Vocabulary Test, receptive vocabulary increased at a lower rate for boys with ASD. Vocabulary trajectories in ASD are distinguished from typical development; however, nonverbal cognition largely accounts for the patterns observed.
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44. Lam YG. {{Re-examining the cognitive phenotype in autism: A study with young Chinese children}}. {Res Dev Disabil}. 2013.
Deficits consistently found in autism include an impaired « theory of mind », weak central coherence, and deficits in executive function. The current study examined whether this traditional cluster of symptoms existed in a group of Chinese-speaking children with autism. Sixteen high-functioning, non-retarded children with autism were matched to 16 typically developing (TD) children on gender, non-verbal IQ and age. Non-verbal IQ’s of all participants were measured using the Raven Progressive Matrices. Each participant was tested individually on measures of « theory of mind », central coherence and executive function. Results indicated that most, but not all, participants with autism performed significantly poorer on two standard measures of first-order « theory of mind, » although there was no significant difference on two other measures of that domain. As expected, they performed significantly worse on executive function tasks. However, the hypothesis of weak central coherence in autism was not substantiated. There was no evidence that these three cognitive impairments co-existed in individuals with autism. More likely, each of these deficits appears singly or in pair instead of forming a cluster.
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45. Lampi KM, Hinkka-Yli-Salomaki S, Lehti V, Helenius H, Gissler M, Brown AS, Sourander A. {{Parental age and risk of autism spectrum disorders in a finnish national birth cohort}}. {J Autism Dev Disord}. 2013; 43(11): 2526-35.
Aim of the study was to examine the associations between parental age and autism spectrum disorders (ASD). Data were based on the FIPS-A (Finnish Prenatal Study of Autism and Autism Spectrum Disorders), a case-control study with a total of 4,713 cases with childhood autism (n = 1,132), Asperger’s syndrome (n = 1,785) or other pervasive developmental disorder (PDD) (n = 1,796), which were ascertained from the Finnish Hospital Discharge Register. Controls were selected from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses. Advanced paternal age (35-49 years) was associated with childhood autism in offspring, whereas advanced maternal age was associated with both Asperger’s syndrome and PDD in offspring (35 years or more and 40 years or more, respectively). Teenage motherhood (19 years or less) was associated with PDD in offspring. The main finding was that maternal and paternal ages were differentially associated with ASD subtypes. In addition to advanced parental age, teenage pregnancy seems to incur a risk for PDD in offspring.
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46. Lebarton ES, Iverson JM. {{Fine motor skill predicts expressive language in infant siblings of children with autism}}. {Dev Sci}. 2013; 16(6): 815-27.
We investigated whether fine motor and expressive language skills are related in the later-born siblings of children with autism (heightened-risk, HR infants) who are at increased risk for language delays. We observed 34 HR infants longitudinally from 12 to 36 months. We used parent report and standardized observation measures to assess fine motor skill from 12 to 24 months in HR infants (Study 1) and its relation to later expressive vocabulary at 36 months in HR infants (Study 2). In Study 1, we also included 25 infants without a family history of autism to serve as a normative comparison group for a parent-report fine motor measure. We found that HR infants exhibited fine motor delays between 12 and 24 months and expressive vocabulary delays at 36 months. Further, fine motor skill significantly predicted expressive language at 36 months. Fine motor and expressive language skills are related early in development in HR infants, who, as a group, exhibit risk for delays in both. Our findings highlight the importance of considering fine motor skill in children at risk for language impairments and may have implications for early identification of expressive language difficulties.
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47. Mehta SQ, Golshani P. {{Clinical neurogenetics: autism spectrum disorders}}. {Neurol Clin}. 2013; 31(4): 951-68.
Autism spectrum disorders are neurodevelopmental disorders characterized by deficits in social interactions, communication, and repetitive or restricted interests. There is strong evidence that de novo or inherited genetic alterations play a critical role in causing Autism Spectrum Disorders, but non-genetic causes, such as in utero infections, may also play a role. Magnetic resonance imaging based and autopsy studies indicate that early rapid increase in brain size during infancy could underlie the deficits in a large subset of subjects. Clinical studies show benefits for both behavioral and pharmacological treatment strategies. Genotype-specific treatments have the potential for improving outcome in the future.
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48. Milne SL, McDonald JL, Comino EJ. {{Adaptive function in preschoolers in relation to developmental delay and diagnosis of autism spectrum disorders: Insights from a clinical sample}}. {Autism}. 2013; 17(6): 743-53.
This study aims to explore the relationship between developmental ability, autism and adaptive skills in preschoolers. Adaptive function was assessed in 152 preschoolers with autism, with and without developmental delay, and without autism, with and without developmental delay. Their overall adaptive function, measured by the general adaptive composite on the Adaptive Behaviour Assessment System, was closely correlated to developmental ability as measured by the general quotient on the Griffith Mental Development Scales. Children with autism performed significantly less well on both scales. Domain scores discriminated between children with and without autism, with poorer performance on both the social and practical domain scores for children with autism, even when controlling for the effects of development. Children with average development, both with and without autism, had lower adaptive skills than expected for their developmental level. The importance of considering domain scores as well as the general adaptive composite when determining support needs is emphasised.
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49. Mohiuddin S, Ghaziuddin M. {{Psychopharmacology of autism spectrum disorders: A selective review}}. {Autism}. 2013; 17(6): 645-54.
While there is no cure for autism spectrum disorder, psychopharmacologic agents are often used with behavioral and educational approaches to treat its comorbid symptoms of hyperactivity, irritability, and aggression. Studies suggest that at least 50% of persons with autism spectrum disorder receive psychotropic medications during their life span. This selective review examines recent studies about the use of psychotropic medications in persons with autism spectrum disorder. The aim was to focus on randomized controlled trials conducted from 1990 to 2010 on this topic. A comprehensive literature search was performed using PubMed and Cochrane databases. Out of 105 studies identified for the review, only 24 were randomized controlled trials. Thus, despite the common use of these medications in autism spectrum disorder, more controlled studies are needed to determine their long-term efficacy and safety.
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50. Nadeau J, Sulkowski ML, Ung D, Wood JJ, Lewin AB, Murphy TK, May JE, Storch EA. {{Treatment of comorbid anxiety and autism spectrum disorders}}. {Neuropsychiatry (London)}. 2011; 1(6): 567-78.
Clinically significant anxiety occurs frequently among individuals with autism spectrum disorders (ASDs) and is linked to increased psychosocial, familial, behavioral and academic impairment beyond the core autism symptoms when present. Although efforts are underway to establish empirically supported treatments for anxiety among individuals with ASDs, this remains an emerging research area. This literature review summarizes available information on the efficacy of pharmacological and psychosocial approaches for treating anxiety and repetitive behaviors in children, adolescents and adults with ASDs. Specifically, we evaluate evidence for the use of cognitive-behavioral therapy and selective serotonin-reuptake inhibitors. Evidence is growing in support of using cognitive-behavioral therapy to treat anxiety in youths with ASDs; however, mixed evidence exists for its application in treating repetitive behaviors, as well as the use of selective serotonin-reuptake inhibitors for anxiety in youths with ASDs. We conclude the article with a discussion of the strength of current information and next steps in research.
51. O’Keefe N, Lindell AK. {{Reduced interhemispheric interaction in non-autistic individuals with normal but high levels of autism traits}}. {Brain Cogn}. 2013; 83(2): 183-9.
People with autism spectrum disorder (ASD) show superior performance for tasks requiring detail-focused processing. Atypical neural connectivity and reduced interhemispheric communication are posited to underlie this cognitive advantage. Given recent conceptualization of autism as a continuum, we sought to investigate whether people with normal but high levels of autism like traits (AQ) also exhibit reduced hemispheric interaction. Sixty right-handed participants completed the AQ questionnaire (Baron-Cohen, Wheelwright, Skinner, Martin, & Clubley, 2001) and a lateralised letter matching task that assessed unilateral and bilateral performance in response to simple (physical) and complex (identity) matches. Whereas people with low self-rated AQ scores showed a bilateral advantage for the more complex task, indicating normal interhemispheric interaction, people in the high AQ group failed to show a bilateral gain for the computationally demanding stimuli. This finding of disrupted interhemispheric interaction converges with a dimensional conceptualisation of ASD, suggesting that the structural anomalies of ASD extend to non-autistic individuals with high levels of autism traits.
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52. Orsmond GI, Shattuck PT, Cooper BP, Sterzing PR, Anderson KA. {{Social participation among young adults with an autism spectrum disorder}}. {J Autism Dev Disord}. 2013; 43(11): 2710-9.
Investigating social participation of young adults with an autism spectrum disorder (ASD) is important given the increasing number of youth aging into young adulthood. Social participation is an indicator of life quality and overall functioning. Using data from the National Longitudinal Transition Study 2, we examined rates of participation in social activities among young adults who received special education services for autism (ASD group), compared to young adults who received special education for intellectual disability, emotional/behavioral disability, or a learning disability. Young adults with an ASD were significantly more likely to never see friends, never get called by friends, never be invited to activities, and be socially isolated. Among those with an ASD, lower conversation ability, lower functional skills, and living with a parent were predictors of less social participation.
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53. Pisano S, Milone A, Gemo I, Masi G. {{High-functioning autism spectrum disorder associated with CHARGE syndrome: a case report}}. {Clin Dysmorphol}. 2013.
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54. Poljac E, Wagemans J. {{Reduced accuracy and sensitivity in the perception of emotional facial expressions in individuals with high autism spectrum traits}}. {Autism}. 2013; 17(6): 668-80.
Autism spectrum disorder (ASD) is among other things characterized by specific impairments in emotion processing. It is not clear, however, to what extent the typical decline in affective functioning is related to the specific autistic traits. We employed The Autism Spectrum-Quotient (AQ) to quantify autistic traits in a group of 500 healthy individuals and investigate whether we could detect similar difficulties in the perception of emotional expressions in a broader autistic phenotype. The group with high AQ score was less accurate and needed higher emotional content to recognize emotions of anger, disgust, and sadness. Our findings demonstrate a selective impairment in identification of emotional facial expressions in healthy individuals that is primarily related to the extent of autistic traits.
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55. R GK, S JC, Le Couteur A, Gould J, Wing L, Maljaars J, Noens I, van Berckelaer-Onnes I, S RL. {{Diagnosing Autism Spectrum Disorder: who will get a DSM-5 diagnosis?}}. {J Child Psychol Psychiatry}. 2013; 54(11): 1242-50.
BACKGROUND: Introduction of proposed criteria for DSM-5 Autism Spectrum Disorder (ASD) has raised concerns that some individuals currently meeting diagnostic criteria for Pervasive Developmental Disorder (PDD; DSM-IV-TR/ICD-10) will not qualify for a diagnosis under the proposed changes. To date, reports of sensitivity and specificity of the new criteria have been inconsistent across studies. No study has yet considered how changes at the ‘sub domain’ level might affect overall sensitivity and specificity, and few have included individuals of different ages and ability levels. METHODS: A set of DSM-5 ASD algorithms were developed using items from the Diagnostic Interview for Social and Communication Disorders (DISCO). The number of items required for each DSM-5 subdomain was defined either according to criteria specified by DSM-5 (Initial Algorithm), a statistical approach (Youden J Algorithm), or to minimise the number of false positives while maximising sensitivity (Modified Algorithm). The algorithms were designed, tested and compared in two independent samples (Sample 1, N = 82; Sample 2, N = 115), while sensitivity was assessed across age and ability levels in an additional dataset of individuals with an ICD-10 PDD diagnosis (Sample 3, N = 190). RESULTS: Sensitivity was highest in the Initial Algorithm, which had the poorest specificity. Although Youden J had excellent specificity, sensitivity was significantly lower than in the Modified Algorithm, which had both good sensitivity and specificity. Relaxing the domain A rules improved sensitivity of the Youden J Algorithm, but it remained less sensitive than the Modified Algorithm. Moreover, this was the only algorithm with variable sensitivity across age. All versions of the algorithm performed well across ability level. CONCLUSIONS: This study demonstrates that good levels of both sensitivity and specificity can be achieved for a diagnostic algorithm adhering to the DSM-5 criteria that is suitable across age and ability level.
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56. Ramirez JM, Ward CS, Neul JL. {{Breathing challenges in Rett Syndrome: Lessons learned from humans and animal models}}. {Respir Physiol Neurobiol}. 2013; 189(2): 280-7.
Breathing disturbances are a major challenge in Rett Syndrome (RTT). These disturbances are more pronounced during wakefulness; but irregular breathing occurs also during sleep. During the day patients can exhibit alternating bouts of hypoventilation and irregular hyperventilation. But there is significant individual variability in severity, onset, duration and type of breathing disturbances. Research in mouse models of RTT suggests that different areas in the ventrolateral medulla and pons give rise to different aspects of this breathing disorder. Pre-clinical experiments in mouse models that target different neuromodulatory and neurotransmitter receptors and MeCP2 function within glia cells can partly reverse breathing abnormalities. The success in animal models raises optimism that one day it will be possible to control or potentially cure the devastating symptoms also in human patients with RTT.
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57. Ricci S, Businaro R, Ippoliti F, Lo Vasco VR, Massoni F, Onofri E, Troili GM, Pontecorvi V, Morelli M, Rapp Ricciardi M, Archer T. {{Altered cytokine and BDNF levels in autism spectrum disorder}}. {Neurotox Res}. 2013; 24(4): 491-501.
The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were observed, regardless of age and gender. Comparisons were made with age- and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder.
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58. Ruiz-Robledillo N, Moya-Albiol L. {{Self-reported health and cortisol awakening response in parents of people with asperger syndrome: The role of trait anger and anxiety, coping and burden}}. {Psychol Health}. 2013; 28(11): 1246-64.
Caring for offspring with autism spectrum disorders entails high levels of stress for a long period of time and is associated with several types of health complaints. Few studies have focused on specific effects of particular disorders in the spectrum. This study was carried out with the aim of evaluating the global health of parents of people with Asperger syndrome (N = 53) compared to those of typically developing children (N = 54) through self-reported measures (medication consumption and somatic symptoms) and biological markers (cortisol awakening response [CAR]). Additionally, we analysed various psychological variables as potential predictors of caregiver health. We found that caregivers take more medication and have worse self-reported health than controls, but there were no significant differences in CAR between the groups. However, after controlling for negative affect, differences between groups in CAR reached significance. With regards to predictor variables, anxiety trait, cognitive-coping style, burden and anger temperament were significantly associated with caregiver’s self-reported health. These findings underline the need to develop interventions that foster improvements in the health of caregivers, reduce their burden and enhance their quality of life.
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59. Sacrey LA, Bryson SE, Zwaigenbaum L. {{Prospective examination of visual attention during play in infants at high-risk for autism spectrum disorder: A longitudinal study from 6 to 36 months of age}}. {Behav Brain Res}. 2013; 256: 441-50.
Regulation of visual attention is essential to learning about one’s environment. Children with autism spectrum disorder (ASD) exhibit impairments in regulating their visual attention, but little is known about how such impairments develop over time. This prospective longitudinal study is the first to describe the development of components of visual attention, including engaging, sustaining, and disengaging attention, in infants at high-risk of developing ASD (each with an older sibling with ASD). Non-sibling controls and high-risk infant siblings were filmed at 6, 9, 12, 15, 18, 24, and 36 months of age as they engaged in play with small, easily graspable toys. Duration of time spent looking at toy targets before moving the hand toward the target and the duration of time spent looking at the target after grasp were measured. At 36 months of age, an independent, gold standard diagnostic assessment for ASD was conducted for all participants. As predicted, infant siblings subsequently diagnosed with ASD were distinguished by prolonged latency to disengage (‘sticky attention’) by 12 months of age, and continued to show this characteristic at 15, 18, and 24 months of age. The results are discussed in relation to how the development of visual attention may impact later cognitive outcomes of children diagnosed with ASD.
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60. Sasson NJ, Nowlin RB, Pinkham AE. {{Social cognition, social skill, and the broad autism phenotype}}. {Autism}. 2013; 17(6): 655-67.
Social-cognitive deficits differentiate parents with the « broad autism phenotype » from non-broad autism phenotype parents more robustly than other neuropsychological features of autism, suggesting that this domain may be particularly informative for identifying genetic and brain processes associated with the phenotype. The current study examined whether the social-cognitive deficits associated with the broad autism phenotype extend to the general population and relate to reduced social skill. A total of 74 undergraduates completed the Broad Autism Phenotype Questionnaire, three standardized social-cognitive tasks, and a live social interaction with an unfamiliar research assistant. Social broad autism phenotype traits were significantly associated with deficits in social cognition and reduced social skill. In addition, the relationship between social broad autism phenotype traits and social skill was partially mediated by social cognition, suggesting that the reduced interpersonal ability associated with the broad autism phenotype occurs in part because of poorer social-cognitive ability. Together, these findings indicate that the impairments in social cognition and social skill that characterize autism spectrum disorder extend in milder forms to the broad autism phenotype in the general population and suggest a framework for understanding how social broad autism phenotype traits may manifest in diminished social ability.
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61. Schaaf CP, Gonzalez-Garay ML, Xia F, Potocki L, Gripp KW, Zhang B, Peters BA, McElwain MA, Drmanac R, Beaudet AL, Caskey CT, Yang Y. {{Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism}}. {Nat Genet}. 2013; 45(11): 1405-8.
Prader-Willi syndrome (PWS) is caused by the absence of paternally expressed, maternally silenced genes at 15q11-q13. We report four individuals with truncating mutations on the paternal allele of MAGEL2, a gene within the PWS domain. The first subject was ascertained by whole-genome sequencing analysis for PWS features. Three additional subjects were identified by reviewing the results of exome sequencing of 1,248 cases in a clinical laboratory. All four subjects had autism spectrum disorder (ASD), intellectual disability and a varying degree of clinical and behavioral features of PWS. These findings suggest that MAGEL2 is a new gene causing complex ASD and that MAGEL2 loss of function can contribute to several aspects of the PWS phenotype.
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62. Schendel DE, Bresnahan M, Carter KW, Francis RW, Gissler M, Gronborg TK, Gross R, Gunnes N, Hornig M, Hultman CM, Langridge A, Lauritsen MB, Leonard H, Parner ET, Reichenberg A, Sandin S, Sourander A, Stoltenberg C, Suominen A, Suren P, Susser E. {{The International Collaboration for Autism Registry Epidemiology (iCARE): Multinational Registry-Based Investigations of Autism Risk Factors and Trends}}. {J Autism Dev Disord}. 2013; 43(11): 2650-63.
The International Collaboration for Autism Registry Epidemiology (iCARE) is the first multinational research consortium (Australia, Denmark, Finland, Israel, Norway, Sweden, USA) to promote research in autism geographical and temporal heterogeneity, phenotype, family and life course patterns, and etiology. iCARE devised solutions to challenges in multinational collaboration concerning data access security, confidentiality and management. Data are obtained by integrating existing national or state-wide, population-based, individual-level data systems and undergo rigorous harmonization and quality control processes. Analyses are performed using database federation via a computational infrastructure with a secure, web-based, interface. iCARE provides a unique, unprecedented resource in autism research that will significantly enhance the ability to detect environmental and genetic contributions to the causes and life course of autism.
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63. Schneider D, Slaughter VP, Bayliss AP, Dux PE. {{A temporally sustained implicit theory of mind deficit in autism spectrum disorders}}. {Cognition}. 2013; 129(2): 410-7.
Eye movements during false-belief tasks can reveal an individual’s capacity to implicitly monitor others’ mental states (theory of mind – ToM). It has been suggested, based on the results of a single-trial-experiment, that this ability is impaired in those with a high-functioning autism spectrum disorder (ASD), despite neurotypical-like performance on explicit ToM measures. However, given there are known attention differences and visual hypersensitivities in ASD it is important to establish whether such impairments are evident over time. In addition, investigating implicit ToM using a repeated trial approach allows an assessment of whether learning processes can reduce the ASD impairment in this ability, as is the case with explicit ToM. Here we investigated the temporal profile of implicit ToM in individuals with ASD and a control group. Despite similar performance on explicit ToM measures, ASD-diagnosed individuals showed no evidence of implicit false-belief tracking even over a one-hour period and many trials, whereas control participants did. These findings demonstrate that the systems involved in implicit and explicit ToM are distinct and hint that impaired implicit false-belief tracking may play an important role in ASD. Further, they indicate that learning processes do not alleviate this impairment across the presentation of multiple trials.
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64. Sheinkopf SJ, Neal-Beevers AR, Levine TP, Miller-Loncar C, Lester B. {{Parasympathetic response profiles related to social functioning in young children with autistic disorder}}. {Autism Res Treat}. 2013; 2013: 868396.
Psychophysiology studies of heart rate and heart rate variability can be employed to study regulatory processes in children with autism. The objective of this study was to test for differences in respiratory sinus arrhythmia (RSA; a measure of heart rate variability) and to examine the relationship between physiologic responses and measures of social behavior. Participants included 2- to 6-year-old children with Autistic Disorder and children without autism. Heart rate and RSA were derived from ECG recordings made during a baseline period and then a stranger approach paradigm. Social and adaptive behavior was assessed by parent report. Groups did not differ in mean heart rate or RSA at baseline or in response to social challenge. However, children with autism were more likely to show a physiologic response to intrusive portions of the stranger approach than to less intrusive portions of this procedure. Nonautistic children were equally likely to respond to intrusive and less intrusive social events. Within the autistic group, physiologic response to the intrusive stranger approach corresponded to higher ratings of social adaptive behaviors. These results suggest that physiologic responses to social challenge may help understand differences in social behavioral outcomes in children with autism.
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65. Shin CJ, Saeed S. {{Toothbrushing barriers for people with developmental disabilities: a pilot study}}. {Spec Care Dentist}. 2013; 33(6): 269-74.
PURPOSE: The aims of this study were: (1) to determine which step in tooth brushing is most difficult for individuals with developmental disabilities and (2) to determine if oral hygiene instruction improves technique. MATERIAL AND METHODS: Once per week for 6 weeks, disclosing solution was applied to the teeth of 14 subjects who were observed individually in their tooth brushing technique. Fourteen distinct steps were measured on a 4-point Likert scale. Plaque score was measured after brushing. RESULTS: The step causing greatest difficulty was « able to brush off residual, identified plaque. » Steps that showed greatest improvement were « open toothpaste » and « place toothpaste on brush. » The change in plaque score from the initial visit to the final visit was not statistically significant. CONCLUSION: Oral hygiene instruction in a group and individual setting increased compliance in the initial steps of tooth brushing.
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66. Siniscalco D, Sapone A, Giordano C, Cirillo A, de Magistris L, Rossi F, Fasano A, Bradstreet JJ, Maione S, Antonucci N. {{Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders}}. {J Autism Dev Disord}. 2013; 43(11): 2686-95.
Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3-9 years; mean age: 6.06 +/- 1.52 vs. 6.14 +/- 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean +/- SE of arbitrary units: 0.34 +/- 0.03 vs. 0.23 +/- 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean +/- SE of arbitrary units: 33.5 +/- 1.32 vs. 6.70 +/- 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care.
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67. Sochocky N, Milin R. {{Second Generation Antipsychotics in Asperger’s Disorder and High Functioning Autism: A Systematic Review of the Literature and Effectiveness of Meta-Analysis}}. {Curr Clin Pharmacol}. 2013; 8(4): 370-9.
Objective: Second generation antipsychotics (SGA) have gained increased evidence for the treatment of irritability and aggression in children and adolescents with lower functioning autistic disorder. Individuals with Asperger’s Disorder (AD) and High Functioning Autism (HFA) experience significant emotional and behavioral problems and psychiatric comorbidity. There is a need to review the published literature on SGA treatment efficacy in the AD and HFA populations to provide more effective treatment choices for these subgroups. Methods: We conducted a systematic review and meta-analysis of the recent English literature on SGA use in children and adolescents (ages 0-24 years) with AD and HFA using the Medline/PubMed and PsychINFO computerized databases. Key search words were ‘Asperger’, ‘high functioning autism’, ‘autism spectrum disorders (ASD)’, and ‘pervasive developmental disorder (PDD)’ in combination with ‘second generation antipsychotics’, ‘aripiprazole; ‘olanzapine’, ‘quetiapine’, ‘risperidone’, or ‘ziprasidone’. Results: Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with >/=25% of their subjects having an IQ>/=71 were included in our review. Eleven original studies met our inclusion parameters for review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of the studies reported weight gain as a potentially concerning adverse effect. Conclusion: There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.
68. Stein TP, Schluter MD, Steer RA, Ming X. {{Autism and phthalate metabolite glucuronidation}}. {J Autism Dev Disord}. 2013; 43(11): 2677-85.
Exposure to environmental chemicals may precipitate autism spectrum disorders (ASD) in genetically susceptible children. Differences in the efficiency of the glucuronidation process may substantially modulate substrate concentrations and effects. To determine whether the efficiency of this pathway is compromised in children with ASD, we measured the efficiency of glucuronidation for a series of metabolites derived from the commonly used plasticizer, diethylhexyl phthalate. Spot urines were collected and analyzed for the fraction of each metabolite conjugated by isotope dilution-liquid chromatography mass spectrometry-mass spectrometry. The degree of glucuronidation was lower with the ASD group. The glucuronidation pathway may differ in some children with ASD.
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69. Stevens SA, Nash K, Koren G, Rovet J. {{Autism characteristics in children with fetal alcohol spectrum disorders}}. {Child Neuropsychol}. 2013; 19(6): 579-87.
Background: Children with fetal alcohol spectrum disorders (FASD) exhibit difficulties in many cognitive and behavioral domains and also have high comorbidity with other disorders such as attention deficit/hyperactivity disorder (ADHD) and conduct disorder as well as autism. Although the FASD profile is shown to be distinct from ADHD and conduct disorder, far less is known about the commonalities with autism. The current study used a parent-rated questionnaire containing an autism subscale to explore the autistic-like features that children with FASD exhibit. Methods: Studied were 25 children with FASD (age: M = 10.3 years) and 17 normal controls (NCs; age: M = 10.2 years). As part of a larger study, all parents/caregivers completed the Social Skills Improvement System (SSIS; Gresham & Elliot, 2008), which in addition to evaluating social skills and behavior problems globally, includes an Autism subscale. Results: Between-group comparisons showed the FASD group not only scored significantly lower in social skills and significantly higher in behavior problems than the NC group but children with FASD also scored significantly higher on the Autism subscale. Item analysis revealed they showed the most difficulty in terms of social and communicative functioning and the least in repetitive and restrictive behaviors. Conclusion: Current findings signify that FASD and autism share similarities with regard to social and communicative functioning. These findings, which further our knowledge of the FASD phenotype, may be useful in specifying the particular interventions these children need.
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70. Tabolacci E, Chiurazzi P. {{Epigenetics, fragile X syndrome and transcriptional therapy}}. {Am J Med Genet A}. 2013; 161(11): 2797-808.
Epigenetics refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic mechanisms therefore include all transcriptional controls that determine how genes are expressed during development and differentiation, but also in individual cells responding to environmental stimuli. The purpose of this review is to examine the basic principles of epigenetic mechanisms and their contribution to human disorders with a particular focus on fragile X syndrome (FXS), the most common monogenic form of developmental cognitive impairment. FXS represents a prototype of the so-called repeat expansion disorders due to « dynamic » mutations, namely the expansion (known as « full mutation ») of a CGG repeat in the 5’UTR of the FMR1 gene. This genetic anomaly is accompanied by epigenetic modifications (mainly DNA methylation and histone deacetylation), resulting in the inactivation of the FMR1 gene. The presence of an intact FMR1 coding sequence allowed pharmacological reactivation of gene transcription, particularly through the use of the DNA demethylating agent 5′-aza-2′-deoxycytydine and/or inhibitors of histone deacetylases. These treatments suggested that DNA methylation is dominant over histone acetylation in silencing the FMR1 gene. The importance of DNA methylation in repressing FMR1 transcription is confirmed by the existence of rare unaffected males carrying unmethylated full mutations. Finally, we address the potential use of epigenetic approaches to targeted treatment of other genetic conditions. (c) 2013 Wiley Periodicals, Inc.
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71. Tebartz van Elst L, Pick M, Biscaldi M, Fangmeier T, Riedel A. {{High-functioning autism spectrum disorder as a basic disorder in adult psychiatry and psychotherapy: psychopathological presentation, clinical relevance and therapeutic concepts}}. {Eur Arch Psychiatry Clin Neurosci}. 2013; 263 Suppl 2: 189-96.
Autism spectrum disorder (ASD) is characterized by deficits in social cognition and competence, communication, highly circumscribed interests and a strong desire for routines. Besides, there are specific abnormalities in perception and language. Typical symptoms are already present in early childhood. Traditionally autism has been regarded as a severe form of neurodevelopmental disorder which goes along with overtly abnormal language, learning difficulties and low IQ in the majority of cases. However, over the last decades, it has become clear that there are also many patients with high-functioning variants of ASD. These are patients with normal language at a superficial level of description and normal and sometimes above average intelligence. In high-functioning variants of the disease, they may run unrecognized until late in adult life. High-functioning ASD is associated with a very high prevalence of comorbid classical psychiatric disorders such as depression, anxiety, ADHD, tics, psychotic symptoms or emotionally unstable syndromes. In many such cases, there is a causal relationship between ASD and the comorbid psychiatric conditions in that the specific ASD symptoms result in chronic conflicts, misunderstandings and failure in private and vocational relationships. These problems in turn often lead to depression, anxiety and sometimes psychosis-like stress reactions. In this constellation, ASD has to be regarded as a basic disorder with causal relevance for secondary psychiatric syndromes. In this paper, we summarize the classical presentation of high-functioning ASD in adult psychiatry and psychotherapy and suggest a nosological model to classify different ASD conditions instead. To conclude, we outline first treatment concepts in out- and in-patient settings.
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72. Terrett G, Rendell PG, Raponi-Saunders S, Henry JD, Bailey PE, Altgassen M. {{Episodic future thinking in children with autism spectrum disorder}}. {J Autism Dev Disord}. 2013; 43(11): 2558-68.
The capacity to imagine oneself experiencing future events has important implications for effective daily living but investigation of this ability in autism spectrum disorder (ASD) is limited. This study investigated future thinking in 30 children with high functioning ASD (IQ > 85) and 30 typically developing children. They completed the Adapted Autobiographical Interview, a measure which required participants to describe personal past events (indexing episodic memory) and plausible future events (indexing episodic future thinking). The results showed that there are ASD-related deficits in future thinking, and also provided preliminary evidence regarding cognitive mechanisms that may (and may not) contribute to these difficulties. The theoretical and practical implications of these results are discussed.
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73. Tunc-Ozcan E, Ullmann TM, Shukla PK, Redei EE. {{Low-Dose Thyroxine Attenuates Autism-Associated Adverse Effects of Fetal Alcohol in Male Offspring’s Social Behavior and Hippocampal Gene Expression}}. {Alcohol Clin Exp Res}. 2013; 37(11): 1986-95.
BACKGROUND: Fetal alcohol spectrum disorder (FASD) is characterized by neurodevelopmental anomalies manifesting in cognitive and behavioral deficits in the offspring with diverse severities. Social behavior is affected in FASD, and these deficits overlap with those of autism spectrum disorder (ASD). Identifying some of the molecular characteristics related to ASD in an animal model of FASD could ultimately provide details on the underlying molecular mechanisms of both disorders that could lead to novel treatments. METHODS: Pregnant Sprague-Dawley rats received the following diets: control (C; ad libitum standard laboratory chow), nutritional control pair-fed (PF), ethanol (EtOH), or an EtOH diet supplemented with 0.3, 1.5, or 7.5 mg thyroxine (T4)/l in the diet. Social behavior and memory were tested in the adult offspring. Plasma total T4, free T3 (fT3), and thyroid-stimulating hormone (TSH) levels were measured. Hippocampal expression of Gabrb3, Ube3a, Nr2b, Rasgrf1, and Dio3 were measured by RT-qPCR and protein levels of Mecp2 and Slc25a12 by Western blotting. RESULTS: Adult male offspring of EtOH dams showed elevated fT3 and low TSH levels. Adult male, but not female, offspring of EtOH dams exhibited social behavior and memory deficits. Expression of autism candidates, Gabrb3, Ube3a, Mecp2, and Slc25a12, was significantly increased in the hippocampus of male offspring of EtOH dams. Hippocampal Nr2b and Dio3 were also increased, while Rasgrf1 was decreased in the same population. Peripheral thyroid function, social behavioral deficits, and altered expression of the above genes were normalized by simultaneous administration of 0.3 mg/l T4 in the EtOH diet. CONCLUSIONS: Our data suggest that social interaction deficits of FASD share molecular mechanism with ASD by showing altered hippocampal expression of several ASD candidate genes. Social interaction deficits as well as the gene expression changes in the offspring of EtOH-consuming dams can be reversed by low dose of thyroid hormone supplementation to the mothers.
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74. van Steensel FJ, Deutschman AA, Bogels SM. {{Examining the Screen for Child Anxiety-Related Emotional Disorder-71 as an assessment tool for anxiety in children with high-functioning autism spectrum disorders}}. {Autism}. 2013; 17(6): 681-92.
The psychometric properties of a questionnaire developed to assess symptoms of anxiety disorders (SCARED-71) were compared between two groups of children: children with high-functioning autism spectrum disorder and comorbid anxiety disorders (ASD-group; n = 115), and children with anxiety disorders (AD-group; n = 122). Anxiety disorders were established with a semi-structured interview (ADIS-C/P), using child- as well as parent-report. Internal consistency, construct validity, sensitivity, specificity, and discriminant validity of the SCARED-71 was investigated. Results revealed that the psychometric properties of the SCARED-71 for the ASD-group were quite comparable to the AD-group, however, the discriminant validity of the SCARED-71 child-report was less in the ASD-group. Raising the parental cutoffs of the SCARED-71 resulted in higher specificity rates, which suggests that research should focus more on establishing alternative cutoffs for the ASD-population.
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75. Vida MD, Maurer D, Calder AJ, Rhodes G, Walsh JA, Pachai MV, Rutherford MD. {{The influences of face inversion and facial expression on sensitivity to eye contact in high-functioning adults with autism spectrum disorders}}. {J Autism Dev Disord}. 2013; 43(11): 2536-48.
We examined the influences of face inversion and facial expression on sensitivity to eye contact in high-functioning adults with and without an autism spectrum disorder (ASD). Participants judged the direction of gaze of angry, fearful, and neutral faces. In the typical group only, the range of directions of gaze leading to the perception of eye contact (the cone of gaze) was narrower for upright than inverted faces. In both groups, the cone of gaze was wider for angry faces than for fearful or neutral faces. These results suggest that in high-functioning adults with ASD, the perception of eye contact is not tuned to be finer for upright than inverted faces, but that information is nevertheless integrated across expression and gaze direction.
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76. Villalon-Reina J, Jahanshad N, Beaton E, Toga AW, Thompson PM, Simon TJ. {{White matter microstructural abnormalities in girls with chromosome 22q11.2 deletion syndrome, Fragile X or Turner syndrome as evidenced by diffusion tensor imaging}}. {Neuroimage}. 2013; 81: 441-54.
Children with chromosome 22q11.2 deletion syndrome (22q11.2DS), Fragile X syndrome (FXS), or Turner syndrome (TS) are considered to belong to distinct genetic groups, as each disorder is caused by separate genetic alterations. Even so, they have similar cognitive and behavioral dysfunctions, particularly in visuospatial and numerical abilities. To assess evidence for common underlying neural microstructural alterations, we set out to determine whether these groups have partially overlapping white matter abnormalities, relative to typically developing controls. We scanned 101 female children between 7 and 14years old: 25 with 22q11.2DS, 18 with FXS, 17 with TS, and 41 aged-matched controls using diffusion tensor imaging (DTI). Anisotropy and diffusivity measures were calculated and all brain scans were nonlinearly aligned to population and site-specific templates. We performed voxel-based statistical comparisons of the DTI-derived metrics between each disease group and the controls, while adjusting for age. Girls with 22q11.2DS showed lower fractional anisotropy (FA) than controls in the association fibers of the superior and inferior longitudinal fasciculi, the splenium of the corpus callosum, and the corticospinal tract. FA was abnormally lower in girls with FXS in the posterior limbs of the internal capsule, posterior thalami, and precentral gyrus. Girls with TS had lower FA in the inferior longitudinal fasciculus, right internal capsule and left cerebellar peduncle. Partially overlapping neurodevelopmental anomalies were detected in all three neurogenetic disorders. Altered white matter integrity in the superior and inferior longitudinal fasciculi and thalamic to frontal tracts may contribute to the behavioral characteristics of all of these disorders.
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77. Visser E, Zwiers MP, Kan CC, Hoekstra L, van Opstal AJ, Buitelaar JK. {{Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders}}. {J Psychiatry Neurosci}. 2013; 38(6): 398-406.
BACKGROUND: Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. METHODS: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). RESULTS: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. LIMITATIONS: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. CONCLUSION: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.
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78. Wachtel LE, Schuldt S, Ghaziuddin N, Shorter E. {{The potential role of electroconvulsive therapy in the ‘Iron Triangle’ of pediatric catatonia, autism, and psychosis}}. {Acta Psychiatr Scand}. 2013; 128(5): 408-9.
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79. Warren Z, Vehorn A, Dohrmann E, Newsom C, Taylor JL. {{Brief report: Service implementation and maternal distress surrounding evaluation recommendations for young children diagnosed with autism}}. {Autism}. 2013; 17(6): 693-700.
There is limited evidence surrounding the ability of families of children with autism spectrum disorders to access and implement recommended interventions following diagnosis. The distress a family may encounter with regard to inability to access recommended services is also poorly understood. In this study, we present preliminary data regarding implementation of clinical recommendations following autism spectrum disorder diagnosis as well as associations of implementation with maternal functioning. In total, 75 mothers of young children diagnosed with autism spectrum disorder through a university-based preschool autism clinic returned surveys regarding access to recommended services as well as maternal mental health and distress. Results indicate that while families were able to implement numerous recommendations, specific categories of intervention were less likely to be received. Challenges implementing recommended services were not related to increased maternal distress. These results suggest that despite potential barriers toward accessing some specific recommended services following diagnosis of autism spectrum disorder, many families may be quite successful in implementing many other core recommended services and that failure to access such services may not necessarily negatively impact maternal mental health and distress.
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80. Williams BT, Gray KM. {{The relationship between emotion recognition ability and social skills in young children with autism}}. {Autism}. 2013; 17(6): 762-8.
This study assessed the relationship between emotion recognition ability and social skills in 42 young children with autistic disorder aged 4-7 years. The analyses revealed that accuracy in recognition of sadness, but not happiness, anger or fear, was associated with higher ratings on the Vineland-II Socialization domain, above and beyond the influence of chronological age, cognitive ability and autism symptom severity. These findings extend previous research with adolescents and adults with autism spectrum disorders, suggesting that sadness recognition is also associated with social skills in children with autism.
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81. Wilson CE, Gillan N, Spain D, Robertson D, Roberts G, Murphy CM, Maltezos S, Zinkstok J, Johnston K, Dardani C, Ohlsen C, Deeley PQ, Craig M, Mendez MA, Happe F, Murphy DG. {{Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an Adult Autism Spectrum Disorder Diagnostic Clinic}}. {J Autism Dev Disord}. 2013; 43(11): 2515-25.
An Autism Spectrum Disorder (ASD) diagnosis is often used to access services. We investigated whether ASD diagnostic outcome varied when DSM-5 was used compared to ICD-10R and DSM-IV-TR in a clinical sample of 150 intellectually able adults. Of those diagnosed with an ASD using ICD-10R, 56 % met DSM-5 ASD criteria. A further 19 % met DSM-5 (draft) criteria for Social Communication Disorder. Of those diagnosed with Autistic Disorder/Asperger Syndrome on DSM-IV-TR, 78 % met DSM-5 ASD criteria. Sensitivity of DSM-5 was significantly increased by reducing the number of criteria required for a DSM-5 diagnosis, or by rating ‘uncertain’ criteria as ‘present’, without sacrificing specificity. Reduced rates of ASD diagnosis may mean some ASD individuals will be unable to access clinical services.
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82. Yang JC, Chan SH, Khan S, Schneider A, Nanakul R, Teichholtz S, Niu YQ, Seritan A, Tassone F, Grigsby J, Hagerman PJ, Hagerman RJ, Olichney JM. {{Neural Substrates of Executive Dysfunction in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): a Brain Potential Study}}. {Cereb Cortex}. 2013; 23(11): 2657-66.
Executive dysfunction in fragile X-associated tremor/ataxia syndrome (FXTAS) has been suggested to mediate other cognitive impairments. In the present study, event-related potentials and neuropsychological testing were combined to investigate the brain mechanisms underlying the executive dysfunction in FXTAS. Thirty-two-channel electroencephalography was recorded during an auditory « oddball » task requiring dual responses. FXTAS patients (N= 41, mean age= 62) displayed prolonged latencies of N1 and P3 and reduced amplitudes of P2 and P3, whereas their N2 measures remained within the normal range, indicating relatively preserved early-stage auditory attention but markedly impaired late-stage attention and working memory updating processes (as indexed by P3). Topographical mapping revealed a typical parietal P3 peak preceded by a prominent fronto-central P3 in normal control subjects (N= 32), whereas FXTAS patients had decreased parietal P3 amplitude and diminished fronto-central positivities with a delayed onset ( approximately 50 ms later than controls, P < 0.002). The P3 abnormalities were associated with lower executive function test (e.g., BDS-2) scores. Smaller P3 amplitudes also correlated with increased CGG repeat length of fragile X mental retardation 1 (FMR1) gene and higher FMR1 mRNA levels. These results indicate that abnormal fronto-parietal attentional network dynamics underlie executive dysfunction, the cardinal feature of cognitive impairment in FXTAS.
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83. Yi L, Pan J, Fan Y, Zou X, Wang X, Lee K. {{Children with autism spectrum disorder are more trusting than typically developing children}}. {J Exp Child Psychol}. 2013; 116(3): 755-61.
The current study examined whether children with autism spectrum disorder (ASD) had an indiscriminate trust bias whereby they would believe any information provided by an unfamiliar adult with whom they had no interactive history. Young school-aged children with ASD and their age- and ability-matched typically developing (TD) peers participated in a simple hide-and-seek game. In the game, an experimenter with whom the children had no previous interactive history pointed to or left a marker on a box to indicate the whereabouts of a hidden reward. Results showed that although young school-aged ASD children did not blindly trust any information provided by the unfamiliar adult, they appeared to be more trusting in the adult informant than did their age- and ability-matched TD children.
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84. Yudell M, Tabor HK, Dawson G, Rossi J, Newschaffer C. {{Priorities for autism spectrum disorder risk communication and ethics}}. {Autism}. 2013; 17(6): 701-22.
Autism spectrum disorders are an issue of increasing public health significance. The incidence of autism spectrum disorders has been increasing in recent years, and they are associated with significant personal and financial impacts for affected persons and their families. In recent years, a large number of scientific studies have been undertaken, which investigate genetic and environmental risk factors for autism, with more studies underway. At present, much remains unknown regarding autism spectrum disorder risk factors, but the emerging picture of causation is in many cases complex, with multiple genes and gene-environment interactions being at play. The complexity and uncertainty surrounding autism spectrum disorder risk factors raise a number of questions regarding the ethical considerations that should be taken into account when undertaking autism spectrum disorder risk communication. At present, however, little has been written regarding autism spectrum disorder risk communication and ethics. This article summarizes the findings of a recent conference investigating ethical considerations and policy recommendations in autism spectrum disorder risk communication, which to the authors’ knowledge is the first of its kind. Here, the authors discuss a number of issues, including uncertainty; comprehension; inadvertent harm; justice; and the appropriate roles of clinicians, scientists, and the media in autism spectrum disorder risk communication.
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85. Zettergren A, Jonsson L, Johansson D, Melke J, Lundstrom S, Anckarsater H, Lichtenstein P, Westberg L. {{Associations between polymorphisms in sex steroid related genes and autistic-like traits}}. {Psychoneuroendocrinology}. 2013; 38(11): 2575-84.
Sex differences in psychiatric disorders are common, which is particularly striking in autism spectrum disorders (ASDs) that are four times more prevalent in boys. High levels of testosterone during early development have been hypothesized to be a risk factor for ASDs, supported by several studies showing fetal testosterone levels, as well as indirect measures of prenatal androgenization, to be associated with ASDs and autistic-like traits (ALTs). Further, the importance of sex steroid related genes in ASDs is supported by studies reporting associations between polymorphisms in genes involved in sex steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was to investigate possible associations between 29 single nucleotide polymorphisms (SNPs) in eight genes related to sex steroids and autistic features. Individuals included in the study belong to a subset (n=1771) from The Child and Adolescent Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs, rs2747648 located in the 3′-UTR of ESR1 encoding the estrogen receptor alpha and rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly significant associations with ALTs were found in boys and girls, respectively. The results of the present study suggest that SNPs in sex steroid related genes, known to affect gene expression (rs2747648 in ESR1) and enzymatic activity (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In conclusion, the current findings provide further support for a role of sex steroids in the pathophysiology of ASDs.
