1. Branigan HP, Tosi A, Gillespie-Smith K. {{Spontaneous Lexical Alignment in Children With an Autistic Spectrum Disorder and Their Typically Developing Peers}}. {J Exp Psychol Learn Mem Cogn};2016 (Apr 14)
It is well established that adults converge on common referring expressions in dialogue, and that such lexical alignment is important for successful and rewarding communication. The authors show that children with an autistic spectrum disorder (ASD) and chronological- and verbal-age-matched typically developing (TD) children also show spontaneous lexical alignment. In a card game, both groups tended to refer to an object using the same name as their partner had previously used for the same or a different token of the object. This tendency to align on a pragmatically conditioned aspect of language did not differ between ASD and TD groups, and was unaffected by verbal/chronological age, or (in the ASD group) Theory of Mind or social functioning. The authors suggest that lexical priming can lead to automatic lexical alignment in both ASD and TD children’s dialogue. Their results further suggest that ASD children’s conversational impairments do not involve an all-encompassing deficit in linguistic imitation. (PsycINFO Database Record
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2. Cappuccio G, Vitiello F, Casertano A, Fontana P, Genesio R, Bruzzese D, Ginocchio VM, Mormile A, Nitsch L, Andria G, Melis D. {{New insights in the interpretation of array-CGH: autism spectrum disorder and positive family history for intellectual disability predict the detection of pathogenic variants}}. {Ital J Pediatr};2016;42(1):39.
BACKGROUND: Array-CGH (aCGH) is presently used into routine clinical practice for diagnosis of patients with intellectual disability (ID), multiple congenital anomalies (MCA), and autism spectrum disorder (ASD). ACGH could detect small chromosomal imbalances, copy number variations (CNVs), and closely define their size and gene content. ACGH detects pathogenic imbalances in 14-20 % of patients with ID. The aims of this study were: to establish clinical clues potentially associated with pathogenic CNVs and to identify cytogenetic indicators to predict the pathogenicity of the variants of uncertain significance (VOUS) in a large cohort of paediatric patients. METHODS: We enrolled 214 patients referred for either: ID, and/or ASD and/or MCA to genetic services at the Federico II University of Naples, Department of Translational Medicine. For each patient we collected clinical and imaging data. All the patients were tested with aCGH or as first-tier test or as part of a wider diagnostic work-up. RESULTS: Pathologic data were detected in 65 individuals (30 %) and 46 CNVs revealed a known syndrome. The pathological CNVs were usually deletions showing the highest gene-dosage content. The positive family history for ID/ASD/MCA and ASD were good indicators for detecting pathological chromosomal rearrangements. Other clinical features as eyes anomalies, hearing loss, neurological signs, cutaneous dyscromia and endocrinological problems seem to be potential predictors of pathological CNVs. Among patients carrying VOUS we analyzed genetic features including CNVs size, presence of deletion or duplication, genic density, multiple CNVs, to clinical features. Higher gene density was found in patients affected by ID. This result suggest that higher gene content has more chances to include pathogenic gene involved and causing ID in these patients. CONCLUSION: Our study suggest the use of aCGH as first-tier test in patients with neurdevelopmental phenotypes. The inferred results have been used for building a flow-chart to be applied for children with ID.
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3. Cerquera C, Rumia J, Herrera JM, Moreno V, Bargallo N, Valldeoriola F. {{A single case report of MR-guided focused ultrasound thalamotomy for tremor in fragile X-associated tremor/ataxia}}. {Parkinsonism Relat Disord};2016 (Apr 4)
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4. Chevreul K, Gandre C, Brigham KB, Lopez-Bastida J, Linertova R, Oliva-Moreno J, Serrano-Aguilar P, Posada-de-la-Paz M, Taruscio D, Schieppati A, Iskrov G, Gulacsi L, von der Schulenburg JM, Kanavos P, Persson U, Fattore G. {{Social/economic costs and health-related quality of life in patients with fragile X syndrome in Europe}}. {Eur J Health Econ};2016 (Apr 12)
OBJECTIVE: To estimate the social/economic costs of fragile X syndrome (FXS) in Europe and to assess the health-related quality of life (HRQOL) of patients and caregivers. METHODS: A cross-sectional study was conducted in a sample of European countries. Patients were recruited through patients’ associations. Data on their resource use and absence from the labour market were retrospectively obtained from an online questionnaire. Costs were estimated by a bottom-up approach and the EuroQol-5 Domain (EQ-5D) questionnaire was used to measure patients’ and caregivers’ HRQOL. RESULTS: Five countries were included in the analysis. The mean annual cost of FXS per patient varied from euro4951 in Hungary to euro58,862 in Sweden. Direct non-healthcare costs represented the majority of costs in all countries but there were differences in the share incurred by formal and informal care among those costs. Costs were also shown to differ between children and adults. Mean EQ-5D utility score for adult patients varied from 0.52 in France (n = 42) to 0.73 in Hungary (n = 2), while for caregivers this score was consistently inferior to 0.87. CONCLUSION: Our findings underline that, although its prevalence is low, FXS is costly from a societal perspective. They support the development of tailored policies to reduce the consequences of FXS on both patients and their relatives.
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5. Chong WH, Kua SM. {{Parenting Self-Efficacy Beliefs in Parents of Children With Autism: Perspectives From Singapore}}. {Am J Orthopsychiatry};2016 (Apr 14)
Substantial empirical evidence has highlighted the psychological stress and negative well-being of parents whose children are diagnosed with autism. It has further indicated a need for understanding the mechanisms through which these parents come to successfully meet the challenges of caregiving for these children whose condition are often characterized by persistent behavioral, social, and communication problems. This qualitative study aims to bridge the research gap in 3 ways. First, we sought to understand the ways in which mothers of children having autism foster their parenting self-efficacy (PSE) when caring for their child. Second, we sought to identify additional PSE sources. Third, we attempted to understand how these mothers successfully manage negative experiences that were often in the way of their parenting efforts. Ten mothers with children between 7 and 9 years of age were interviewed. Bandura’s social-cognitive framework guided the analyses of the sources of PSE (Bandura, 1997). Mastery experiences were identified as the most critical PSE source, and the physiological and affective states of the mothers were second most important in shaping their PSE. Vicarious experiences and verbal persuasion did not emerge as salient sources. « Support in parenting » was also found to be significant in fostering the mothers’ perceived capability. Furthermore, we noted that while multiple negative experiences were encountered, these mothers tended to frame their experiences in adaptive ways to allow them to use these as feedback for subsequent parenting endeavors to booster their perceived capability. Implications for future research were discussed in the light of these findings. (PsycINFO Database Record
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6. Cook J. {{From movement kinematics to social cognition: the case of autism}}. {Philos Trans R Soc Lond B Biol Sci};2016 (May 5);371(1693)
The way in which we move influences our ability to perceive, interpret and predict the actions of others. Thus movements play an important role in social cognition. This review article will appraise the literature concerning movement kinematics and motor control in individuals with autism, and will argue that movement differences between typical and autistic individuals may contribute to bilateral difficulties in reciprocal social cognition.
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7. Elder JH, Brasher S, Alexander B. {{Identifying the Barriers to Early Diagnosis and Treatment in Underserved Individuals with Autism Spectrum Disorders (ASD) and Their Families: A Qualitative Study}}. {Issues Ment Health Nurs};2016 (Apr 12):1-9.
Clinical accounts indicate that disparities exist among families of children with Autism Spectrum Disorders (ASD), and that these disparities impede timely diagnosis and intervention. Furthermore, families living in rural areas are more likely to have reduced access to proper care and use alternative, unproven, and potentially harmful treatments. The purpose of this project was to begin addressing these needs by engaging providers and families of children with ASD living in rural and typically underserved areas. The investigators established a Community Advisory Board (CAB) of ASD professionals (e.g., community-based healthcare and service providers, director of a center for disabilities, psychologist, autism researcher, and special education professional). Next, they conducted four focus groups comprised of a total of 35 major stakeholders (e.g., individuals with ASD, parents of individuals with ASD, community-based healthcare and service providers, school teachers) to determine potential resources, barriers to early diagnosis/treatment, and alternative treatment use in children with ASD. Focus group sessions were audio-recorded, transcribed verbatim, and analyzed by three trained independent coders. Community participants identified several barriers to early diagnosis and intervention, as well as a variety of alternative treatments used in children with ASD. Thematic analysis of focus group transcripts showed several overarching themes regarding barriers to early diagnosis and treatment. Findings from this study have implications for practice and future research.
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8. Foss-Feig JH, McGugin RW, Gauthier I, Mash LE, Ventola P, Cascio CJ. {{A functional neuroimaging study of fusiform response to restricted interests in children and adolescents with autism spectrum disorder}}. {J Neurodev Disord};2016;8:15.
BACKGROUND: While autism spectrum disorder (ASD) is characterized by both social communication deficits and restricted and repetitive patterns of behavior and interest, literature examining possible neural bases of the latter class of symptoms is limited. The fusiform face area (FFA) is a region in the ventral temporal cortex that not only shows preferential responsiveness to faces but also responds to non-face objects of visual expertise. Because restricted interests in ASD are accompanied by high levels of visual expertise, the objective of this study was to determine the extent to which this region responds to images related to restricted interests in individuals with ASD, compared to individuals without ASD who have a strong hobby or interest. METHODS: Children and adolescents with and without ASD with hobbies or interests that consumed a pre-determined minimum amount of time were identified, and the intensity, frequency, and degree of interference of these interests were quantified. Each participant underwent functional magnetic resonance imaging (fMRI) while viewing images related to their personal restricted interests (in the ASD group) or strong interest or hobby (in the comparison group). A generalized linear model was used to compare the intensity and spatial extent of fusiform gyrus response between groups, controlling for the appearance of faces in the stimuli. RESULTS: Images related to interests and expertise elicited response in FFA in both ASD and typically developing individuals, but this response was more robust in ASD. CONCLUSIONS: These findings add neurobiological support to behavioral observations that restricted interests are associated with enhanced visual expertise in ASD, above and beyond what would be expected for simply a strong interest. Further, the results suggest that brain regions associated with social functioning may not be inherently less responsive in ASD, but rather may be recruited by different environmental stimuli. This study contributes to our understanding of the neural basis of restricted interests in ASD and may provide clues toward developing novel interventions.
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9. Ha VS, Whittaker A. {{‘Closer to my world’: Children with autism spectrum disorder tell their stories through photovoice}}. {Glob Public Health};2016 (Apr 13):1-18.
One of the challenges in doing research with individuals with autism spectrum disorder (ASD) is the difficulty in communication. This study employed a modified form of photovoice with a group of young people with ASD in Hanoi, Vietnam, to provide a means of meaningful participation in research about their lives, experiences, and needs. We describe the process of conducting photovoice with nine children with ASD from June 2011 to May 2012, many of whom had limited verbal communication skills. More than 2100 photos were taken by children. Undertaking photovoice with children with ASD required some modification of the method. In particular we consider the difficulties in analysing and interpreting the photographs produced by children with ASD. Due to the ambiguities of the visual images produced we found content analysis of photographs alone was inadequate. There was a discrepancy between our initial interpretations of the photographs and our understandings derived from information from interviews with children, parents, carers, and our own observations. Our study points to the need to understand context through multiple methods and the potential of photovoice as a means to mediate communication and participation in research for groups with communication difficulties.
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10. Hamilton J, Stevens G, Girdler S. {{Becoming a Mentor: The Impact of Training and the Experience of Mentoring University Students on the Autism Spectrum}}. {PLoS One};2016;11(4):e0153204.
While it is widely recognised that the number of young adults diagnosed with Autism Spectrum Disoders (ASD) is increasing, there is currently limited understanding of effective support for the transition to adulthood. One approach gaining increasing attention in the university sector is specialised peer mentoring. The aim of this inductive study was to understand the impact of peer mentor training on seven student mentors working with university students with an ASD. Kirkpatrick’s model framed a mixed methods evaluation of the mentors’ training and description of their experience. Overall, the training was well received by the mentors, who reported on average a 29% increase in their ASD knowledge following the training. Results from the semi-structured interviews conducted three months after the training, found that mentors felt that the general ASD knowledge they gained as part of their training had been essential to their role. The mentors described how their overall experience had been positive and reported that the training and support provided to them was pivotal to their ability to succeed in as peer mentors to students with ASD. This study provides feedback in support of specialist peer-mentoring programs for university students and can inform recommendations for future programs and research.
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11. Igelstrom KM, Webb TW, Graziano MS. {{Functional Connectivity Between the Temporoparietal Cortex and Cerebellum in Autism Spectrum Disorder}}. {Cereb Cortex};2016 (Apr 12)
The neural basis of autism spectrum disorder (ASD) is not yet understood. ASD is marked by social deficits and is strongly associated with cerebellar abnormalities. We studied the organization and cerebellar connectivity of the temporoparietal junction (TPJ), an area that plays a crucial role in social cognition. We applied localized independent component analysis to resting-state fMRI data from autistic and neurotypical adolescents to yield an unbiased parcellation of the bilateral TPJ into 11 independent components (ICs). A comparison between neurotypical and autistic adolescents showed that the organization of the TPJ was not significantly altered in ASD. Second, we used the time courses of the TPJ ICs as spatially unbiased « seeds » for a functional connectivity analysis applied to voxels within the cerebellum. We found that the cerebellum contained a fine-grained, lateralized map of the TPJ. The connectivity of the TPJ subdivisions with cerebellar zones showed one striking difference in ASD. The right dorsal TPJ showed markedly less connectivity with the left Crus II. Disturbed cerebellar input to this key region for cognition and multimodal integration may contribute to social deficits in ASD. The findings might also suggest that the right TPJ and/or left Crus II are potential targets for noninvasive brain stimulation therapies.
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12. Kurita T, Kikuchi M, Yoshimura Y, Hiraishi H, Hasegawa C, Takahashi T, Hirosawa T, Furutani N, Higashida H, Ikeda T, Mutou K, Asada M, Minabe Y. {{Atypical Bilateral Brain Synchronization in the Early Stage of Human Voice Auditory Processing in Young Children with Autism}}. {PLoS One};2016;11(4):e0153077.
Autism spectrum disorder (ASD) has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical interhemispheric circuitry. In the context of ASD, alterations in both peripheral and central auditory processes have also attracted a great deal of interest because these changes appear to represent pathophysiological processes; therefore, many prior studies have focused on atypical auditory responses in ASD. The auditory evoked field (AEF), recorded by magnetoencephalography, and the synchronization of these processes between right and left hemispheres was recently suggested to reflect various cognitive abilities in children. However, to date, no previous study has focused on AEF synchronization in ASD subjects. To assess global coordination across spatially distributed brain regions, the analysis of Omega complexity from multichannel neurophysiological data was proposed. Using Omega complexity analysis, we investigated the global coordination of AEFs in 3-8-year-old typically developing (TD) children (n = 50) and children with ASD (n = 50) in 50-ms time-windows. Children with ASD displayed significantly higher Omega complexities compared with TD children in the time-window of 0-50 ms, suggesting lower whole brain synchronization in the early stage of the P1m component. When we analyzed the left and right hemispheres separately, no significant differences in any time-windows were observed. These results suggest lower right-left hemispheric synchronization in children with ASD compared with TD children. Our study provides new evidence of aberrant neural synchronization in young children with ASD by investigating auditory evoked neural responses to the human voice.
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13. Mangatt M, Wong K, Anderson B, Epstein A, Hodgetts S, Leonard H, Downs J. {{Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome}}. {Orphanet J Rare Dis};2016;11(1):39.
BACKGROUND: Initially described as an early onset seizure variant of Rett syndrome, the CDKL5 disorder is now considered as an independent entity. However, little is currently known about the full spectrum of comorbidities that affect these patients and available literature is limited to small case series. This study aimed to use a large international sample to examine the prevalence in this disorder of comorbidities of epilepsy, gastrointestinal problems including feeding difficulties, sleep and respiratory problems and scoliosis and their relationships with age and genotype. Prevalence and onset were also compared with those occurring in Rett syndrome. METHODS: Data for the CDKL5 disorder and Rett syndrome were sourced from the International CDKL5 Disorder Database (ICDD), InterRett and the Australian Rett syndrome Database (ARSD). Logistic regression (multivariate and univariate) was used to analyse the relationships between age group, mutation type and the prevalence of various comorbidities. Binary longitudinal data from the ARSD and the equivalent cross-sectional data from ICDD were examined using generalized linear models with generalized estimating equations. The Kaplan-Meier method was used to estimate the failure function for the two disorders and the log-rank test was used to compare the two functions. RESULTS: The likelihood of experiencing epilepsy, GI problems, respiratory problems, and scoliosis in the CDKL5 disorder increased with age and males were more vulnerable to respiratory and sleep problems than females. We did not identify any statistically significant relationships between mutation group and prevalence of comorbidities. Epilepsy, GI problems and sleep abnormalities were more common in the CDKL5 disorder than in Rett syndrome whilst scoliosis and respiratory problems were less prevalent. CONCLUSION: This study captured a much clearer picture of the CDKL5 disorder than previously possible using the largest sample available to date. There were differences in the presentation of clinical features occurring in the CDKL5 disorder and in Rett syndrome, reinforcing the concept that CDKL5 is an independent disorder with its own distinctive characteristics.
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14. Mercer AA, Palarz KJ, Tabatadze N, Woolley CS, Raman IM. {{Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked mutations in mice}}. {Elife};2016 (Apr 14);5
Neurons of the cerebellar nuclei (CbN) transmit cerebellar signals to premotor areas. The cerebellum expresses several autism-linked genes, including Gabrb3, which encodes GABAA receptor beta3 subunits and is among the maternal alleles deleted in Angelman syndrome. We tested how this Gabrb3 m-/p+ mutation affects CbN physiology in mice, separating responses of males and females. Wild-type mice showed sex differences in synaptic excitation, inhibition, and intrinsic properties. Relative to females, CbN cells of males had smaller synaptically evoked mGluR1/5-dependent currents, slower Purkinje-mediated IPSCs, and lower spontaneous firing rates, but rotarod performances were indistinguishable. In mutant CbN cells, IPSC kinetics were unchanged, but mutant males, unlike females, showed enlarged mGluR1/5 responses and accelerated spontaneous firing. These changes appear compensatory, since mutant males but not females performed indistinguishably from wild-type siblings on the rotarod task. Thus, sex differences in cerebellar physiology produce similar behavioral output, but provide distinct baselines for responses to mutations.
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15. Paucar M, Engvall M, Gordon L, Tham E, Synofzik M, Svenningsson P. {{POLG-Associated Ataxia Presenting as a Fragile X Tremor/Ataxia Phenocopy Syndrome}}. {Cerebellum};2016 (Apr 12)
Hyperintensities in the middle cerebellar peduncles (MCP), known as the MCP sign, and progressive late-onset ataxia constitute major characteristics of the fragile X tremor/ataxia syndrome (FXTAS). Here, we describe a 60-year-old male affected by ataxia due to biallelic mutations in the mitochondrial polymerase gamma (POLG) gene in which hyperintensities of the middle cerebellar peduncles (MCP) were found. The initial suspicion of FXTAS was however ruled out by a normal CGG expansion size in the FMR1 gene. We discuss the features of late-onset POLG-A as a phenocopy of FXTAS.
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16. Shirazi E, Hosseinpoor S, Mirhosseini SM, Bidaki R. {{Childhood disintegrative disorder with seasonal total mutism: A rare clinical presentation}}. {Adv Biomed Res};2016;5:30.
Childhood disintegrative disorder (CDD) is a rare autistic-like clinical condition with unknown etiology, in that previously acquired age-appropriate language, social and adaptive abilities deteriorate significantly in 2-10-year-old healthy children, although physical and neurological evaluations display no observable abnormality. Our case is a 22-year-old female born of a consanguineous marriage, with the appearance of CDD symptoms in her fifth year of age following normal mental and physical development during her initial four years of life. Without any precipitating factor, she gradually lost her language abilities, social relational skills, affectionate behavior, adaptive capacities, peer play and meaningful interest in her surrounding, friends and family members over a period of 4 years, reaching a plateau in her ninth year of age. The unique special clinical symptom in this case is a seasonal total mutism, which after the beginning of her CDD symptoms is revealing every year covering the spring. As no additional physical or psychological change accompanies her total seasonal speech loss, it cannot be attributed to any mental condition known as having a seasonal pattern. Because in the literature CDD is presented mostly as case reports with lacking of advanced research data, describing any new case is recommended to improve the knowledge about this rare condition, especially if it displays some new unusual signs, not reported till now.
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17. Shochet IM, Saggers BR, Carrington SB, Orr JA, Wurfl AM, Duncan BM, Smith CL. {{The Cooperative Research Centre for Living with Autism (Autism CRC) Conceptual Model to Promote Mental Health for Adolescents with ASD}}. {Clin Child Fam Psychol Rev};2016 (Apr 12)
Despite an increased risk of mental health problems in adolescents with autism spectrum disorder (ASD), there is limited research on effective prevention approaches for this population. Funded by the Cooperative Research Centre for Living with Autism, a theoretically and empirically supported school-based preventative model has been developed to alter the negative trajectory and promote wellbeing and positive mental health in adolescents with ASD. This conceptual paper provides the rationale, theoretical, empirical and methodological framework of a multilayered intervention targeting the school, parents and adolescents on the spectrum. Two important interrelated protective factors have been identified in community adolescent samples, namely the sense of belonging (connectedness) to school and the capacity for self and affect regulation in the face of stress (i.e. resilience). We describe how a confluence of theories from social psychology, developmental psychology and family systems theory, along with empirical evidence (including emerging neurobiological evidence), supports the interrelationships between these protective factors and many indices of wellbeing. However, the characteristics of ASD (including social and communication difficulties, and frequently difficulties with changes and transitions, and diminished optimism and self-esteem) impair access to these vital protective factors. The paper describes how evidence-based interventions at the school level for promoting inclusive schools (using the Index for Inclusion) and interventions for adolescents and parents to promote resilience and belonging [using the Resourceful Adolescent Program (RAP)] are adapted and integrated for adolescents with ASD. This multisite proof-of-concept study will confirm whether this multilevel school-based intervention is promising, feasible and sustainable.
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18. Townend GS, Marschik PB, Smeets E, van de Berg R, van den Berg M, Curfs LM. {{Eye Gaze Technology as a Form of Augmentative and Alternative Communication for Individuals with Rett Syndrome: Experiences of Families in The Netherlands}}. {J Dev Phys Disabil};2016;28:101-112.
This paper provides a brief report on families’ experiences of eye gaze technology as one form of augmentative and alternative communication (AAC) for individuals with Rett syndrome (RTT), and the advice, training and support they receive in relation to this. An online survey exploring communication and AAC was circulated to 190 Dutch families; of the 67 questionnaires that were returned, 63 had answered questions relating to eye gaze technology. These 63 were analysed according to parameters including: experiences during trial periods and longer-term use; expert knowledge, advice and support; funding; communicative progress; and family satisfaction. 20 respondents were using or had previous experience of using an eye gaze system at the time of the survey, 28 of those with no prior experience wanted to try a system in the future. Following a trial period, 11 systems had been funded through health insurance for long-term use and two families had decided a system was not appropriate for them. Levels of support during trials and following long-term provision varied. Despite frustrations with the technology, satisfaction with the systems was higher than satisfaction with the support. The majority of families reported progress in their child’s skills with longer term use. These findings suggest that although eye gaze technologies offer potential to individuals with RTT and their families, greater input from suppliers and knowledgeable AAC professionals is essential for individuals and families to benefit maximally. Higher levels of training and support should be part of the ‘package’ when an eye gaze system is provided.
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19. Tropeano M, Howley D, Gazzellone MJ, Wilson CE, Ahn JW, Stavropoulos DJ, Murphy CM, Eis PS, Hatchwell E, Dobson RJ, Robertson D, Holder M, Irving M, Josifova D, Nehammer A, Ryten M, Spain D, Pitts M, Bramham J, Asherson P, Curran S, Vassos E, Breen G, Flinter F, Ogilvie CM, Collier DA, Scherer SW, McAlonan GM, Murphy DG. {{Microduplications at the pseudoautosomal SHOX locus in autism spectrum disorders and related neurodevelopmental conditions}}. {J Med Genet};2016 (Apr 12)
BACKGROUND: The pseudoautosomal short stature homeobox-containing (SHOX) gene encodes a homeodomain transcription factor involved in cell-cycle and growth regulation. SHOX/SHOX enhancers deletions cause short stature and skeletal abnormalities in a female-dominant fashion; duplications appear to be rare. Neurodevelopmental disorders (NDDs), such as autism spectrum disorders (ASDs), are complex disorders with high heritability and skewed sex ratio; several rare (<1% frequency) CNVs have been implicated in risk. METHODS: We analysed data from a discovery series of 90 adult ASD cases, who underwent clinical genetic testing by array-comparative genomic hybridisation (CGH). Twenty-seven individuals harboured CNV abnormalities, including two unrelated females with microduplications affecting SHOX. To determine the prevalence of SHOX duplications and delineate their associated phenotypic spectrum, we subsequently examined array-CGH data from a follow-up sample of 26 574 patients, including 18 857 with NDD (3541 with ASD). RESULTS: We found a significant enrichment of SHOX microduplications in the NDD cases (p=0.00036; OR 2.21) and, particularly, in those with ASD (p=9.18x10-7; OR 3.63) compared with 12 594 population-based controls. SHOX duplications affecting the upstream or downstream enhancers were enriched only in females with NDD (p=0.0043; OR 2.69/p=0.00020; OR 7.20), but not in males (p=0.404; OR 1.38/p=0.096; OR 2.21). CONCLUSIONS: Microduplications at the SHOX locus are a low penetrance risk factor for ASD/NDD, with increased risk in both sexes. However, a concomitant duplication of SHOX enhancers may be required to trigger a NDD in females. Since specific SHOX isoforms are exclusively expressed in the developing foetal brain, this may reflect the pathogenic effect of altered SHOX protein dosage on neurodevelopment. Lien vers le texte intégral (Open Access ou abonnement)
20. von der Luhe T, Manera V, Barisic I, Becchio C, Vogeley K, Schilbach L. {{Interpersonal predictive coding, not action perception, is impaired in autism}}. {Philos Trans R Soc Lond B Biol Sci};2016 (May 5);371(1693)
This study was conducted to examine interpersonal predictive coding in individuals with high-functioning autism (HFA). Healthy and HFA participants observed point-light displays of two agents (A and B) performing separate actions. In the ‘communicative’ condition, the action performed by agent B responded to a communicative gesture performed by agent A. In the ‘individual’ condition, agent A’s communicative action was substituted by a non-communicative action. Using a simultaneous masking-detection task, we demonstrate that observing agent A’s communicative gesture enhanced visual discrimination of agent B for healthy controls, but not for participants with HFA. These results were not explained by differences in attentional factors as measured via eye-tracking, or by differences in the recognition of the point-light actions employed. Our findings, therefore, suggest that individuals with HFA are impaired in the use of social information to predict others’ actions and provide behavioural evidence that such deficits could be closely related to impairments of predictive coding.
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21. Wang J, Li L, Shao SS, He Z, Chen YL, Kong R, Zhang XH, Gong JH, Song RR. {{Association analysis of genetic variant of rs13331 in PSD95 gene with autism spectrum disorders: A case-control study in a Chinese population}}. {J Huazhong Univ Sci Technolog Med Sci};2016 (Apr);36(2):285-288.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by high heritability. Recently, autism, the most profound form of ASD, has been increasingly attributed to synaptic abnormalities. Postsynaptic density 95 (PSD95), encoding PSD protein-95, was found essential for synaptic formation, maturation and plasticity at a PSD of excitatory synapse. It is possibly a crucial candidate gene for the pathogenesis of ASD. To identify the relationship between the rs13331 of PSD95 gene and ASD, we performed a case-control study in 212 patients and 636 controls in a Chinese population by using a polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) assay. The results showed that in genetic analysis of the heterozygous model, an association between the T allele of the rs13331 and ASD was found in the dominant model (OR=1.709, 95% CI 1.227-2.382, P=0.002) and the additive model (OR=1.409, 95% CI=1.104-1.800, P=0.006). Our data indicate that the genetic mutation C>T at the rs13331 in the PSD95 gene is strikingly associated with an increased risk of ASD.
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22. Weiss JA, Ting V, Perry A. {{Psychosocial correlates of psychiatric diagnoses and maladaptive behaviour in youth with severe developmental disability}}. {J Intellect Disabil Res};2016 (Apr 13)
BACKGROUND: We know little about the correlates of mental health problems in youth with severe and profound intellectual disability (ID), as most research includes these youth within larger samples that include greater proportions of mild and moderate disability. The purpose of the current study was to identify the child, family and psychosocial characteristics that were associated with the presence of psychiatric diagnoses and maladaptive behaviour in youth with severe ID. METHODS: Participants were 141 parents of youth with severe or profound levels of ID, 4 to 18 years of age. The mean age of children was 11.04 years (SD = 3.38), with 68% male and 39% with autism spectrum disorder (ASD). Parents completed a primarily online survey of child and family characteristics, negative life events, family quality of life and their own mental health. RESULTS: Logistic regression analyses revealed that youth with a psychiatric diagnosis had higher levels of adaptive behaviour and experienced more negative life events than youth without psychiatric diagnosis, while the presence of clinically significant maladaptive behaviour was related to higher levels of adaptive behaviour, parents’ mental health problems and lower family quality of life. Child age, gender, ASD status and financial hardship were not related to either outcome variable. CONCLUSIONS: Youth with severe and profound ID who experience psychosocial stressors are more likely reported to have mental health problems than youth without such stressors. It is likely that a combination of child and family based interventions, along with with policies that address larger systemic issues of social adversity, are needed to promote mental health and treat psychopathology when it arises.
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23. Yahata N, Morimoto J, Hashimoto R, Lisi G, Shibata K, Kawakubo Y, Kuwabara H, Kuroda M, Yamada T, Megumi F, Imamizu H, Nanez JE, Sr., Takahashi H, Okamoto Y, Kasai K, Kato N, Sasaki Y, Watanabe T, Kawato M. {{A small number of abnormal brain connections predicts adult autism spectrum disorder}}. {Nat Commun};2016;7:11254.
Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.
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24. Yang EJ, Ahn S, Lee K, Mahmood U, Kim HS. {{Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice}}. {PLoS One};2016;11(4):e0153298.
Exposure to valproic acid (VPA) during pregnancy has been linked with increased incidence of autism, and has repeatedly been demonstrated as a useful autism mouse model. We examined the early behavioral and anatomical changes as well as molecular changes in mice prenatally exposed to VPA (VPA mice). In this study, we first showed that VPA mice showed developmental delays as assessed with self-righting, eye opening tests and impaired social recognition. In addition, we provide the first evidence that primary cultured neurons from VPA-treated embryos present an increase in dendritic spines, compared with those from control mice. Mutations in phosphatase and tensin homolog (PTEN) gene are also known to be associated with autism, and mice with PTEN knockout show autistic characteristics. Protein expression of PTEN was decreased and the ratio of p-AKT/AKT was increased in the cerebral cortex and the hippocampus, and a distinctive anatomical change in the CA1 region of the hippocampus was observed. Taken together, our study suggests that prenatal exposure to VPA induces developmental delays and neuroanatomical changes via the reduction of PTEN level and these changes were detectable in the early days of life.
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25. Zanchetta MB, Scioscia MF, Zanchetta JR. {{Bone microarchitecture in Rett syndrome and treatment with teriparatide: a case report}}. {Osteoporos Int};2016 (Apr 11)
We present the case of a 28-year-old female Rett syndrome patient with low bone mass and a recent fracture who was successfully treated with teriparatide. Bone mineral density and microarchitecture substantially improved after treatment. Rett syndrome (RTT), an X-linked progressive neuro-developmental disorder caused by mutations in the methyl-CpG-binding 2 (MECP2) gene, has been consistently associated with low bone mass. Consequently, patients with RTT are at increased risk of skeletal fractures. Teriparatide is a bone-forming agent for the treatment of osteoporosis that has demonstrated its effectiveness in increasing bone strength and reducing the risk of fractures in postmenopausal women, but, recently, its positive action has also been reported in premenopausal women. We present the case of a 28-year-old female RTT patient with low bone mass and a recent fracture who was successfully treated with teriparatide. Both bone mass measured by DXA and microarchitecture assessed by high resolution peripheral computed tomography (HR pQCT) were substantially improved after treatment.
