1. Asakai H, Weskamp S, Eastaugh L, d’Udekem Y, Pflaumer A. {{Atrioventricular block after ASD closure}}. {Heart Asia}. 2016; 8(2): 26-31.
OBJECTIVE: Secundum atrial septal defect (ASD) is a common congenital heart defect. There is limited data on both early and late atrioventricular (AV) block post ASD closure. The aim of this study was to determine the incidence and risk factors of AV block associated with ASD closure. METHODS: A retrospective analysis of all patients who underwent ASD closure either with a device or surgical method at the Royal Children’s Hospital Melbourne between 1996 and 2010 was performed. Baseline demographics, procedural details and follow-up data were collected from medical records. RESULTS: A total of 378 patients were identified; 242 in the device group and 136 in the surgical group. Fourteen patients (3.7%) had AV block (1 with second degree and 13 with first degree) at a median follow-up of 28 months; 11/242 (4.5%) in the device group and 3/135 (2.2%) in the surgical group (p=0.39). Six patients had new-onset AV block after ASD closure. In the device subgroup, patients with AV block at follow-up had a larger indexed device size compared with those without (22 (15-31) vs 18(7-38), p=0.02). Multivariate analysis revealed the presence of AV block either pre procedure or post procedure to be the only variables associated with late AV block. CONCLUSIONS: Late AV block in patients with repaired ASD is rare and most likely independent of the technique used. In the device subgroup, the only risk factor identified to be associated with late AV block was the presence of either preprocedural or postprocedural AV block, so long-term follow-up for these patients should be provided.
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2. Corbett BA, Bales KL, Swain D, Sanders K, Weinstein TA, Muglia LJ. {{Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development}}. {J Neurodev Disord}. 2016; 8: 32.
BACKGROUND: Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin (OT) and cortisol are key neuromodulators of biological and behavioral responses, show a synergistic effect, and have been implicated in the neuropathological profile in ASD. However, they are rarely investigated together. The purpose of the pilot study was to evaluate the relationship between cortisol and OT in children with ASD under baseline and physiological stress (hydrocortisone challenge) conditions. Arginine vasopressin (AVP), structurally similar to OT, was also examined. METHODS: A double-blind, placebo-controlled, randomly assigned, crossover design was employed in 25 children 8-to-12 years with ASD (N = 14) or typical development (TD, N = 11). A low dose of hydrocortisone and placebo were administered via liquid suspension. Analysis of variance (ANOVA) was used to examine the within-subject factor « Condition » (hydrocortisone/placebo) and « Time » (pre and post) and the between-subject factor « Group » (ASD vs. TD). Pearson correlations examined the relationship between hormone levels and clinical profile. RESULTS: There was a significant Time x Condition x Group interaction F (1.23) = 4.18, p = 0.05 showing a rise in OT during the experimental condition (hydrocortisone) and a drop during the placebo condition for the TD group but not the ASD group. There were no group differences for AVP. Hormone levels were associated with social profiles. CONCLUSIONS: For the TD group, an inverse relationship was observed. OT increased during physiological challenge suggesting that OT played a stress-buffering role during cortisol administration. In contrast for the ASD group, OT remained unchanged or decreased during both the physiological challenge and the placebo condition, suggesting that OT failed to serve as a stress buffer under conditions of physiological stress. While OT has been tied to the social ability of children with ASD, the diminished moderating effect of OT on cortisol may also play a contributory role in the heightened stress often observed in children with ASD. These results contribute to our understanding of the growing complexity of the effects of OT on social behavior as well as the functional interplay and differential regulation OT may have on stress modulation.
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3. Deserno MK, Borsboom D, Begeer S, Geurts HM. {{Multicausal systems ask for multicausal approaches: A network perspective on subjective well-being in individuals with autism spectrum disorder}}. {Autism}. 2016.
Given the heterogeneity of autism spectrum disorder, an important limitation of much autism spectrum disorder research is that outcome measures are statistically modeled as separate dependent variables. Often, their multivariate structure is either ignored or treated as a nuisance. This study aims to lift this limitation by applying network analysis to explicate the multivariate pattern of risk and success factors for subjective well-being in autism spectrum disorder. We estimated a network structure for 27 potential factors in 2341 individuals with autism spectrum disorder to assess the centrality of specific life domains and their importance for well-being. The data included both self- and proxy-reported information. We identified social satisfaction and societal contribution as the strongest direct paths to subjective well-being. The results suggest that an important contribution to well-being lies in resources that allow the individual to engage in social relations, which influence well-being directly. Factors most important in determining the network’s structure include self-reported IQ, living situation, level of daily activity, and happiness. Number of family members with autism spectrum disorder and openness about one’s diagnosis are least important of all factors for subjective well-being. These types of results can serve as a roadmap for interventions directed at improving the well-being of individuals with autism spectrum disorder.
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4. Donaldson CK, Stauder JE, Donkers FC. {{Increased Sensory Processing Atypicalities in Parents of Multiplex ASD Families Versus Typically Developing and Simplex ASD Families}}. {J Autism Dev Disord}. 2016.
Recent studies have suggested that sensory processing atypicalities may share genetic influences with autism spectrum disorder (ASD). To further investigate this, the adolescent/adult sensory profile (AASP) questionnaire was distributed to 85 parents of typically developing children (P-TD), 121 parents from simplex ASD families (SPX), and 54 parents from multiplex ASD families (MPX). After controlling for gender and presence of mental disorders, results showed that MPX parents significantly differed from P-TD parents in all four subscales of the AASP. Differences between SPX and MPX parents reached significance in the Sensory Sensitivity subscale and also in subsequent modality-specific analyses in the auditory and visual domains. Our finding that parents with high genetic liability for ASD (i.e., MPX) had more sensory processing atypicalities than parents with low (i.e., SPX) or no (i.e., P-TD) ASD genetic liability suggests that sensory processing atypicalities may contribute to the genetic susceptibility for ASD.
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5. Ego C, Bonhomme L, Orban de Xivry JJ, Da Fonseca D, Lefevre P, Masson GS, Deruelle C. {{Behavioral characterization of prediction and internal models in adolescents with autistic spectrum disorders}}. {Neuropsychologia}. 2016.
Autism has been considered as a deficit in prediction of the upcoming event or of the sensory consequences of our own movements. To test this hypothesis, we recorded eye movements from high-functioning autistic adolescent and from age-matched controls during a blanking paradigm. In this paradigm, adolescent were instructed to follow a moving target with their eyes even during its transient disappearance. Given the absence of visual information during the blanking period, eye movements during this period are solely controlled on the basis of the prediction of the ongoing target motion. Typical markers of predictive eye movements such as the number and accuracy of predictive saccades and the predictive reacceleration before target reappearance were identical in the two populations. In addition, the synergy of predictive saccades and smooth pursuit observed during the blanking periods, which is a marker for the quality of internal models about target/eye motions, was comparable between these two populations. These results suggest that, in our large population of high-functioning autistic adolescent, both predictive abilities and internal models are left intact in Autism, at least for low-level sensorimotor transformation.
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6. Estes ML, McAllister AK. {{Maternal immune activation: Implications for neuropsychiatric disorders}}. {Science}. 2016; 353(6301): 772-7.
Epidemiological evidence implicates maternal infection as a risk factor for autism spectrum disorder and schizophrenia. Animal models corroborate this link and demonstrate that maternal immune activation (MIA) alone is sufficient to impart lifelong neuropathology and altered behaviors in offspring. This Review describes common principles revealed by these models, highlighting recent findings that strengthen their relevance for schizophrenia and autism and are starting to reveal the molecular mechanisms underlying the effects of MIA on offspring. The role of MIA as a primer for a much wider range of psychiatric and neurologic disorders is also discussed. Finally, the need for more research in this nascent field and the implications for identifying and developing new treatments for individuals at heightened risk for neuroimmune disorders are considered.
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7. Hashimoto RI, Itahashi T, Ohta H, Yamada T, Kanai C, Nakamura M, Watanabe H, Kato N. {{Altered Effects of Perspective-Taking on Functional Connectivity during Self- and Other-Referential Processing in Adults with Autism Spectrum Disorder}}. {Soc Neurosci}. 2016.
In interactive social situations, it is often crucial to be able to take another person’s perspective when evaluating one’s own or another person’s specific trait; individuals with ASD critically lack this social skill. To examine how perspective-dependent self- and other-evaluation processes modulate functional connectivity in ASD, we conducted an fMRI study in which 26 high-functioning adults with ASD and 24 typically developed (TD) controls were asked to decide whether an adjective describing a personality trait correctly described the participant himself/herself (« self ») or the participant’s mother (« other ») by taking either the first (1P) or third person (3P) perspective. We observed that functional connectivity between the left sensorimotor cortex and the left middle cingulate cortex was enhanced in TD taking the 3P perspective, this enhancement was significantly reduced in ASD, and the degree of reduction was significantly correlated with the severity of autistic traits. Furthermore, the self-reference effect on functional connectivity between the left inferior frontal cortex and frontopolar cortices was significantly enhanced in TD taking the 3P perspective, whereas such effect was reversed in ASD. These findings indicate altered effects of perspective on the functional connectivity, which may underlie the deficits in social interaction and communication observed in individuals with ASD.
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8. Lehan Mackin M, Loew N, Gonzalez A, Tykol H, Christensen T. {{Parent Perceptions of Sexual Education Needs for Their Children With Autism}}. {J Pediatr Nurs}. 2016.
Primary responsibility for sexual education for adolescents with autism spectrum disorder falls on parents who have reported a lack of professional and material support. The purpose of this study was to 1) describe parent perceptions of sexual education needs of their children aged 14-20 with an autism spectrum disorder diagnosis and 2) determine parent-preferred mechanisms of delivery for tailored educational intervention strategies. DESIGN AND METHODS: The study aims were accomplished by a qualitative research design using focus groups and telephone interviews assisted by a structured interview guide. Study methods and analysis were guided by social marketing principles. RESULTS: A total of 15 parents (5 participated in 1 focus group and 10 completed individual interviews) acknowledged their primary role in providing sexual education for their children and confirmed a need for resources to assist them in this role. All parents in this study found that some level of sexual education was necessary and important and that all children had been introduced to sexual information but in varying degrees. Topic preferences included those that would increase the recognition of healthy relationships, provide a measure of self-protection, and ameliorate undesirable consequences of sexual activity. Parents were knowledgeable about how their children best learned and suggested future interventions use technology interfaces with engaging displays and allow for individualized content. CONCLUSION AND IMPLICATIONS: These findings highlight a need for additional research and enhanced clinical services to ensure that adolescents with autism spectrum disorder have their informational needs met, are able to avoid risks, and have the greatest capacity for a healthy sexuality as they transition to adulthood.
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9. Lucariello M, Vidal E, Vidal S, Saez M, Roa L, Huertas D, Pineda M, Dalfo E, Dopazo J, Jurado P, Armstrong J, Esteller M. {{Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype}}. {Hum Genet}. 2016.
Classical Rett syndrome (RTT) is a neurodevelopmental disorder where most of cases carry MECP2 mutations. Atypical RTT variants involve mutations in CDKL5 and FOXG1. However, a subset of RTT patients remains that do not carry any mutation in the described genes. Whole exome sequencing was carried out in a cohort of 21 female probands with clinical features overlapping with those of RTT, but without mutations in the customarily studied genes. Candidates were functionally validated by assessing the appearance of a neurological phenotype in Caenorhabditis elegans upon disruption of the corresponding ortholog gene. We detected pathogenic variants that accounted for the RTT-like phenotype in 14 (66.6 %) patients. Five patients were carriers of mutations in genes already known to be associated with other syndromic neurodevelopmental disorders. We determined that the other patients harbored mutations in genes that have not previously been linked to RTT or other neurodevelopmental syndromes, such as the ankyrin repeat containing protein ANKRD31 or the neuronal acetylcholine receptor subunit alpha-5 (CHRNA5). Furthermore, worm assays demonstrated that mutations in the studied candidate genes caused locomotion defects. Our findings indicate that mutations in a variety of genes contribute to the development of RTT-like phenotypes.
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10. Mansour S, Rozenblat V, Fuller-Tyszkiewicz M, Paganini C, Treasure J, Krug I. {{Emotions mediate the relationship between autistic traits and disordered eating: A new autistic-emotional model for eating pathology}}. {Psychiatry Res}. 2016; 245: 119-26.
The aim of the study was to assess the extent of overlap between autistic traits, body dissatisfaction and disordered eating and to explore the mediating effects of negative attitudes towards emotional expression and emotion dysregulation. The sample comprised 416 university students (82% females, 17-48 years [M=19.76, SD=3.85]), who completed an online questionnaire assessing eating attitudes and behaviours (including dieting, bulimia and oral control), body dissatisfaction, and autistic traits (including the Autism Quotient [AQ] and its related subscales as well as the Empathising Quotient). Attitudes towards emotional expression and emotion regulation were also assessed. Results revealed that eating pathology correlated highly with all AQ subscales, with the exception of the attention to detail subscale. However, there was no significant relationship between empathising and eating pathology. Path-analyses indicated that emotion dysregulation, but not negative attitudes towards emotional expression, was a significant mediator of the relationship between AQ, body dissatisfaction and eating pathology. Direct relationships were also obtained for the AQ-bulimia and the AQ-oral control paths. Prevention and early intervention programs for eating pathology would likely benefit from addressing abnormalities in emotion processes in individuals who score highly on measures of autistic traits.
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11. Pin TW, Chan WL, Chan CL, Foo KH, Fung KH, Li LK, Tsang TC. {{Clinical transition for adolescents with developmental disabilities in Hong Kong: a pilot study}}. {Hong Kong Med J}. 2016.
INTRODUCTION: Children with developmental disabilities usually move from the paediatric to adult health service after the age of 18 years. This clinical transition is fragmented in Hong Kong. There are no local data for adolescents with developmental disabilities and their families about the issues they face during the clinical transition. This pilot study aimed to explore and collect information from adolescents with developmental disabilities and their caregivers about their transition from paediatric to adult health care services in Hong Kong. METHODS: This exploratory survey was carried out in two special schools in Hong Kong. Convenient samples of adolescents with developmental disabilities and their parents were taken. The questionnaire was administered by interviewers in Cantonese. Descriptive statistics were used to analyse the answers to closed-ended questions. Responses to open-ended questions were summarised. RESULTS: In this study, 22 parents (mean age +/- standard deviation: 49.9 +/- 10.0 years) and 13 adolescents (19.6 +/- 1.0 years) completed the face-to-face questionnaire. The main diagnoses of the adolescents were cerebral palsy (59%) and cognitive impairment (55%). Of the study parents, 77% were reluctant to transition. For the 10 families who did move to adult care, 60% of the parents were not satisfied with the services. The main reasons were reluctant to change and dissatisfaction with the adult medical service. The participants emphasised their need for a structured clinical transition service to support them during this challenging time. CONCLUSIONS: This study is the first in Hong Kong to present preliminary data on adolescents with developmental disabilities and their families during transition from paediatric to adult medical care. Further studies are required to understand the needs of this population group during clinical transition.
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12. Richards M, Mossey J, Robins DL. {{Parents’ Concerns as They Relate to Their Child’s Development and Later Diagnosis of Autism Spectrum Disorder}}. {J Dev Behav Pediatr}. 2016.
OBJECTIVE: Data from a toddler screening study were used to examine: (1) categories of concerns regarding the development of their child reported by parents prior to diagnostic evaluation, (2) congruence of parent concerns with their child’s later diagnosis, (3) the extent to which parent concern(s) were associated with the therapies their child received and types of specialists consulted, and (4) the association between the number of parental concern categories and clinical measures. METHOD: Toddlers who screened positive for autism spectrum disorder (ASD) during well-child checkups received a diagnostic evaluation and parents completed a history questionnaire (n = 532; 274 ASD, 258 non-ASD). Parents’ concerns about their child’s development, therapy received, and specialists consulted were coded into discrete categories. RESULTS: Most parents (>90%) reported concerns about their child’s development. The most common concern in both the ASD and non-ASD groups was speech/communication (78.6%). Significant differences were found between diagnostic groups in the speech/communication, restricted/repetitive behaviors, social, behavioral, and medical concern categories. Parent concerns were associated with therapies received and specialists consulted. The number of concern categories was positively associated with several ASD scores. CONCLUSION: The developmental concerns expressed by parents of undiagnosed toddlers were highly consistent with the diagnosis the child later received. Based in part on their areas of concern, parents made contact with the appropriate professionals and their children received some therapy prior to diagnosis. Finally, parents who reported concerns across different areas endorsed more symptoms during screening. Results emphasize the need for providers to elicit and take seriously parent concerns during the referral and diagnostic processes.
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13. Suh J, Orinstein A, Barton M, Chen CM, Eigsti IM, Ramirez-Esparza N, Fein D. {{Ratings of Broader Autism Phenotype and Personality Traits in Optimal Outcomes from Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
The study examines whether « optimal outcome » (OO) children, despite no longer meeting diagnostic criteria for Autism Spectrum Disorder (ASD), exhibit personality traits often found in those with ASD. Nine zero acquaintance raters evaluated Broader Autism Phenotype (BAP) and Big Five personality traits of 22 OO individuals, 27 high functioning individuals with ASD (HFA), and 23 typically developing (TD) peers. HFA children displayed higher ratings than their peers on all BAP traits. OO were indistinguishable from TD, with the exception of greater extraversion (e.g., increased talkativeness), a potential tendency to be less emotionally stable, and pragmatic language deficits such as getting sidetracked in conversation. Overall, OO individuals are not showing BAP characteristics, but may be subject to other mild ADHD-like characteristics.
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14. Wei H, Ma Y, Ding C, Jin G, Liu J, Chang Q, Hu F, Yu L. {{Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder}}. {Neurochem Res}. 2016.
Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. The BTBR T + Itpr3 tf (BTBR) mice have emerged as a well characterized and widely used mouse model of a range of ASD-like phenotype, showing deficiencies in social behaviors and unusual ultrasonic vocalizations as well as increased repetitive self-grooming. However, the inherited neurobiological changes that lead to ASD-like behaviors in these mice are incompletely known and still under active investigation. The aim of this study was to further evaluate the structure and neurotransmitter release of the glutamatergic synapse in BTBR mice. C57BL/6J (B6) mice were used as a control strain because of their high level of sociability. The important results showed that the evoked glutamate release in the cerebral cortex of BTBR mice was significantly lower than in B6 mice. And the level of vesicle docking-related protein Syntaxin-1A was reduced in BTBR mice. However, no significant changes were observed in the number of glutamatergic synapse, level of synaptic proteins, density of dendritic spine and postsynaptic density between BTBR mice and B6 mice. Overall, our results suggest that abnormal vesicular glutamate activity may underlie the ASD relevant pathology in the BTBR mice.
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15. Wei H, Sun S, Li Y, Yu S. {{Reduced plasma levels of microtubule-associated STOP/MAP6 protein in autistic patients}}. {Psychiatry Res}. 2016; 245: 116-8.
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits and repetitive behaviors with restricted interests. A previous quantitative proteomic profiling study demonstrated that microtubule-associated stable tubule only polypeptide (STOP; also known as MAP6) protein was significant reduced in the cerebral cortex from BTBR mouse model of autism compared to the C57BL/6J mice. In the present study, the result showed that the concentration of STOP/MAP6 protein was significantly reduced in the plasma of autistic subjects than that in healthy controls. Finally, a possible mechanism of STOP/MAP6 protein in the pathogenesis of autism was proposed.
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16. Yui K, Tanuma N, Yamada H, Kawasaki Y. {{Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder}}. {Int J Dev Neurosci}. 2016.
Individuals with autism spectrum disorders (ASD) have impaired detoxification capacity. Investigatingthe neurobiological bases ofimpaired antioxidant capacity is thus a research priority in the pathophysiology of ASD.We measuredthe urinary levels of hexanoyl-lysine (HEL) which is a new oxidative stressbiomarker, total antioxidant power (TAP) and DNA methylation biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the plasma levels of superoxide dismutase (SOD), which is a major antioxidant enzyme. We examined whether the urinary levels of these enzymes and biomarkers may be related to symptoms of social impairment in 20individuals with ASD (meanage,11.1+/-5.2years) and 12 age- and gender-matched healthy controls (meanage,14.3+/-6.2years). Symptoms of social impairment wereassessed using the Social Responsiveness Scale (SRS). The dietary TAP of the fruit juice, chocolate, cookies, biscuits, jam and marmalade was significantly higher in the ASD group than in the control group, although the intake of nutrients was not significantly different between the groups. The urinary TAP levels were significantly lower in the ASD group than in the control group. There were no significantly differences in urinary HEL and 8-OHdG levels between the ASD and control groups. The SRS scores were significantly higher in the ASD group than in the control group. Stepwise regression analysis revealed that urinary TAP levels and plasma SOD levels can differences in the biomarkers and the SRS scores between the ASD group and the control group. The endogenous antioxidant capacity may be deficient without altered urinary HEL and 8-OHdG levels in individuals with ASD. The plasma SOD levels may be related to reduced endogenous antioxidant capacity.
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17. Zorio DA, Jackson CM, Liu Y, Rubel EW, Wang Y. {{Cellular Distribution of the Fragile X Mental Retardation Protein in the Mouse Brain}}. {J Comp Neurol}. 2016.
The fragile X mental retardation protein (FMRP) plays an important role in normal brain development. Absence of FMRP results in abnormal neuronal morphologies in a selected manner throughout the brain, leading to intellectual deficits and sensory dysfunction in the fragile X syndrome (FXS). Despite FMRP importance for proper brain function, its overall expression pattern in the mammalian brain at the resolution of individual neuronal cell groups is not known. In this study, we used FMR1 knockout and isogenic wild type mice to systematically map the distribution of FMRP expression in the entire mouse brain. Using immunocytochemistry and cellular quantification analyses, we identified a large number of prominent cell groups expressing high levels of FMRP at the subcortical levels, in particular sensory and motor neurons in the brainstem and thalamus. In contrast, many cell groups in the midbrain and hypothalamus exhibit low FMRP levels. More importantly, we describe differential patterns of FMRP distribution in both cortical and subcortical brain regions. Almost all major brain areas contain high and low levels of FMRP cell groups adjacent to each other or between layers of the same cortical areas. These differential patterns indicate that FMRP expression appears to be specific to individual neuronal cell groups instead of being associated with all neurons in distinct brain regions as previously considered. Taken together, these findings support the notion of FMRP differential neuronal regulation and strongly implicate the contribution of fundamental sensory and motor processing at subcortical levels to FXS pathology. This article is protected by copyright. All rights reserved.
