1. Baum SH, Stevenson RA, Wallace MT. {{Behavioral, Perceptual, and Neural Alterations in Sensory and Multisensory Function in Autism Spectrum Disorder}}. {Prog Neurobiol};2015 (Oct 6)
Although sensory processing challenges have been noted since the first clinical descriptions of autism, it has taken until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 for sensory problems to be included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile. Because sensory information forms the building blocks for higher-order social and cognitive functions, we argue that sensory processing is not only an additional piece of the puzzle, but rather a critical cornerstone for characterizing and understanding ASD. In this review we discuss what is currently known about sensory processing in ASD, how sensory function fits within contemporary models of ASD, and what is understood about the differences in the underlying neural processing of sensory and social communication observed between individuals with and without ASD. In addition to highlighting the sensory features associated with ASD, we also emphasize the importance of multisensory processing in building perceptual and cognitive representations, and how deficits in multisensory integration may also be a core characteristic of ASD.
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2. Bennett MR, Lagopoulos J. {{Neurodevelopmental sequelae associated with gray and white matter changes and their cellular basis: A comparison between Autism Spectrum Disorder, ADHD and dyslexia}}. {Int J Dev Neurosci};2015 (Nov);46:132-143.
Many psychiatric diseases, such as major depression and schizophrenia, are accompanied by patterns of gray matter and white matter changes in the cortex that may be due to structural pathologies of synapses and their dendrites in the gray matter on the one hand and to pathologies in myelinating oligodendrocytes on the other. Here the possibility has been briefly examined that such a generalization might also hold for Autistic Spectrum Disorders (ASD). Evidence is presented that gray matter changes that accompany ASD may in fact reflect changes in synapses and subsequently of their dendrites, whereas those in the white matter reflect changes in myelination due to pathologies of oligodendrocytes. It is proposed that such structural pathologies during development provide a coherent biological model not only for the onset and course of ASD but also provide the basis for development and systematic evaluation of new treatment strategies.
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3. Bitsika V, Sharpley CF, Agnew LL, Andronicos NM. {{Age-related differences in the association between stereotypic behaviour and salivary cortisol in young males with an Autism Spectrum Disorder}}. {Physiol Behav};2015 (Oct 9);152(Pt A):238-243.
To identify if age influenced the relationship between one of the central symptoms of Autism Spectrum Disorder (ASD) and physiological stress, the association between stereotypic behaviour (SB) and stress-related cortisol concentrations was examined in a sample of 150 young males with an ASD. Parent-rated SB was significantly correlated with cortisol concentrations for boys aged 6years to 12years but not for adolescents aged 13years to 18years. This age-related difference in this association was not a function of cortisol concentrations but was related to differences in SB across these two age groups. IQ did not have a significant effect on this relationship, suggesting that age-related learning may have been a possible pathway for reduced SB during adolescence. The aspect of SB that was most powerfully related to cortisol was general repetitive behaviour rather than movements of specific body parts. Explanations of these findings are raised for further investigation.
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4. Bultas MW, McMillin SE, Zand DH. {{Reducing Barriers to Care in the Office-Based Health Care Setting for Children With Autism}}. {J Pediatr Health Care};2015 (Oct 8)
The purpose of this survey-design research study was to evaluate the usefulness of a researcher-developed tool designed to improve office-based health care services and to assess the barriers and resources affecting office-based health care services for children with autism spectrum disorder. Fifty-four health care providers (HCPs) and 59 parents participated in the study. HCPs reported child behaviors, communication, and fears as barriers to providing care, whereas parents reported child behavior, sensory issues, and feelings of a disconnect with the HCP as barriers. HCPs identified the parent as a key resource. Parent-identified resources included provider adaptations to the patient, including slowing down the delivery of care and environmental adaptations to the office. In addition, both HCPs and parents indicated that the researcher-developed tool would be useful in reducing barriers during the HCE. Reducing barriers and improving health care interactions during delivery of care for children with autism spectrum disorder has the potential to improve health outcomes.
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5. Cederlof M, Pettersson E, Sariaslan A, Larsson H, Ostberg P, Kelleher I, Langstrom N, Gumpert CH, Lundstrom S, Lichtenstein P. {{The association between childhood autistic traits and adolescent psychotic experiences is explained by general neuropsychiatric problems}}. {Am J Med Genet B Neuropsychiatr Genet};2015 (Oct 13)
Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. (c) 2015 Wiley Periodicals, Inc.
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6. Eslick GD. {{Answers regarding the link between vaccines and the development of autism: A question of appropriate study design, ethics, and bias}}. {Vaccine};2015 (Oct 13);33(42):5497.
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7. Hammer M, Krueger-Burg D, Tuffy LP, Cooper BH, Taschenberger H, Goswami SP, Ehrenreich H, Jonas P, Varoqueaux F, Rhee JS, Brose N. {{Perturbed Hippocampal Synaptic Inhibition and gamma-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism}}. {Cell Rep};2015 (Oct 7)
Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of gamma-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches.
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8. Heller T, Gibbons HM, Fisher D. {{Caregiving and Family Support Interventions: Crossing Networks of Aging and Developmental Disabilities}}. {Intellect Dev Disabil};2015 (Oct);53(5):329-345.
This scoping review addressed the following questions: (a) What types of caregiver interventions are being done in both aging and developmental disability research? (b) How are these interventions similar and different? (c) What kinds of outcomes do these interventions have? (d) What innovative approaches are these interventions using? and (e) What can each field (developmental disabilities and gerontology) learn from the other based on this review? The disability review spanned 20 years (1992-2012), resulting in 14 studies; the aging review spanned 5 years (2008-2012), resulting in 55 studies. Data from the final selected studies were then extracted and compared on research design, type of intervention (governmental programs, small-group psychosocial, and other), and outcomes. Generally, in both fields, family-support interventions benefited participants’ well-being and improved service access and satisfaction. Increased partnership between the fields of aging and developmental disabilities is critical to future scholarship in caregiving for both populations.
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9. Iossifov I, Levy D, Allen J, Ye K, Ronemus M, Lee YH, Yamrom B, Wigler M. {{Low load for disruptive mutations in autism genes and their biased transmission}}. {Proc Natl Acad Sci U S A};2015 (Oct 13);112(41):E5600-5607.
We previously computed that genes with de novo (DN) likely gene-disruptive (LGD) mutations in children with autism spectrum disorders (ASD) have high vulnerability: disruptive mutations in many of these genes, the vulnerable autism genes, will have a high likelihood of resulting in ASD. Because individuals with ASD have lower fecundity, such mutations in autism genes would be under strong negative selection pressure. An immediate prediction is that these genes will have a lower LGD load than typical genes in the human gene pool. We confirm this hypothesis in an explicit test by measuring the load of disruptive mutations in whole-exome sequence databases from two cohorts. We use information about mutational load to show that lower and higher intelligence quotients (IQ) affected individuals can be distinguished by the mutational load in their respective gene targets, as well as to help prioritize gene targets by their likelihood of being autism genes. Moreover, we demonstrate that transmission of rare disruptions in genes with a lower LGD load occurs more often to affected offspring; we show transmission originates most often from the mother, and transmission of such variants is seen more often in offspring with lower IQ. A surprising proportion of transmission of these rare events comes from genes expressed in the embryonic brain that show sharply reduced expression shortly after birth.
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10. Izadi-Najafabadi S, Mirzakhani-Araghi N, Miri-Lavasani N, Nejati V, Pashazadeh-Azari Z. {{Implicit and explicit motor learning: Application to children with Autism Spectrum Disorder (ASD)}}. {Res Dev Disabil};2015 (Oct 9);47:284-296.
AIMS AND OBJECTIVES: This study aims to determine whether children with Autism Spectrum Disorder (ASD) are capable of learning a motor skill both implicitly and explicitly. METHODS: In the present study, 30 boys with ASD, aged 7-11 with IQ average of 81.2, were compared with 32 typical IQ- and age-matched boys on their performance on a serial reaction time task (SRTT). Children were grouped by ASD and typical children and by implicit and explicit learning groups for the SRTT. RESULTS: Implicit motor learning occurred in both children with ASD (p=.02) and typical children (p=.01). There were no significant differences between groups (p=.39). However, explicit motor learning was only observed in typical children (p=.01) not children with ASD (p=.40). There was a significant difference between groups for explicit learning (p=.01). DISCUSSION: The results of our study showed that implicit motor learning is not affected in children with ASD. Implications for implicit and explicit learning are applied to the CO-OP approach of motor learning with children with ASD.
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11. Micalizzi L, Ronald A, Saudino KJ. {{A Genetically Informed Cross-Lagged Analysis of Autistic-Like Traits and Affective Problems in Early Childhood}}. {J Abnorm Child Psychol};2015 (Oct 12)
A genetically informed cross-lagged model was applied to twin data to explore etiological links between autistic-like traits and affective problems in early childhood. The sample comprised 310 same-sex twin pairs (143 monozygotic and 167 dizygotic; 53 % male). Autistic-like traits and affective problems were assessed at ages 2 and 3 using parent ratings. Both constructs were related within and across age (r = 0.30-0.53) and showed moderate stability (r = 0.45-0.54). Autistic-like traits and affective problems showed genetic and environmental influences at both ages. Whereas at age 2, the covariance between autistic-like traits and affective problems was entirely due to environmental influences (shared and nonshared), at age 3, genetic factors also contributed to the covariance between constructs. The stability paths, but not the cross-lagged paths, were significant, indicating that there is stability in both autistic-like traits and affective problems but they do not mutually influence each other across age. Stability effects were due to genetic, shared, and nonshared environmental influences. Substantial novel genetic and nonshared environmental influences emerge at age 3 and suggest change in the etiology of these constructs over time. During early childhood, autistic-like traits tend to occur alongside affective problems and partly overlapping genetic and environmental influences explain this association.
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12. Mutluer T, Karakoc Demirkaya S, Abali O. {{Assessment of sleep problems and related risk factors observed in Turkish children with Autism spectrum disorders}}. {Autism Res};2015 (Oct 13)
Sleep problems are common and difficult to manage in children with autism spectrum disorders (ASD). Another major adverse impact of sleep problems is that they exacerbate behavioral problems. To assess sleep problems and possible behavioral risk factors in detail, we aimed to compare sleep habits of children with ASD, with healthy children. The relationship between sleep difficulties and concomitant behavioral problems such as repetitive behaviors, hyperactivity, and social withdrawal were also examined. Hundred and seventeen children and adolescents including 64 with the diagnosis of ASD and 53 healthy subjects were enrolled in the study. Diagnostic Interview for ASD was performed according to DSM-IV-TR. Socio-demographical data form and childhood autism rating scale were filled by researchers. Aberrant behavior checklist (ABC), child behavior checklist and pediatric sleep questionnaire (PSQ) were completed by the parents of the children. Children with ASD had higher frequency of sleep problems, snoring, breathing problems, behavioral problems compared with healthy children (for all parameters; P < 0.001). A positive correlation was identified between the total score of PSQ and the total score of ABC (P < 0.05, Spearman correlation coefficient: 0.347). Sleep latency was prolonged in children with ASD compared with healthy subjects (P < 0.001). In accordance with the current literature, children with ASD were subject to sleep problems significantly more than the control group. Identified risk factors for sleep problems in ASD children were behavioral factors such as stereotypies, self-mutilation, hyperactivity, and social withdrawal. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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13. O’Leary HM, Marschik PB, Khwaja OS, Ho E, Barnes KV, Clarkson TW, Bruck NM, Kaufmann WE. {{Detecting autonomic response to pain in Rett syndrome}}. {Dev Neurorehabil};2015 (Oct 12):1-7.
OBJECTIVE: To quantify pain response in girls affected by Rett syndrome (RTT) using electrodermal activity (EDA), a measure of skin conductance, reflecting sympathetic activity known to be modulated by physical and environmental stress. METHODS: EDA increase, heart rate (HR) increase and Face Legs Activity Cry Consolability (FLACC) values calculated during venipuncture (invasive) and vital signs collection (non-invasive) events were compared with values calculated during a prior baseline and a RTT clinical severity score (CSS). RESULTS: EDA and HR increase were significantly higher than baseline during venipuncture only and not significantly correlated with FLACC or CSS. EDA increase was the most sensitive measure of pain response. CONCLUSIONS: These preliminary findings revealed that motor impairment might bias non-verbal pain scales, underscore the importance of using autonomic measures when assessing pain and warrant further investigation into the utility of using EDA to objectively quantify RTT pain response to inform future RTT pain management.
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14. Park CY, Halevy T, Lee DR, Sung JJ, Lee JS, Yanuka O, Benvenisty N, Kim DW. {{Reversion of FMR1 Methylation and Silencing by Editing the Triplet Repeats in Fragile X iPSC-Derived Neurons}}. {Cell Rep};2015 (Oct 13);13(2):234-241.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from a CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Here, we report a strategy for CGG repeat correction using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced pluripotent stem cells derived from FXS patients. Following gene correction in FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in neural precursor cells and mature neurons. Strikingly, after removal of the CGG repeats, the upstream CpG island of the FMR1 promoter showed extensive demethylation, an open chromatin state, and transcription initiation. These results suggest a silencing maintenance mechanism for the FMR1 promoter that is dependent on the existence of the CGG repeat expansion. Our strategy for deletion of trinucleotide repeats provides further insights into the molecular mechanisms of FXS and future therapies of trinucleotide repeat disorders.
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15. Sacco R, Gabriele S, Persico AM. {{Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis}}. {Psychiatry Res};2015 (Sep 28)
Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use.
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16. Scott M, Falkmer M, Girdler S, Falkmer T. {{Viewpoints on Factors for Successful Employment for Adults with Autism Spectrum Disorder}}. {PLoS One};2015;10(10):e0139281.
This article explores the key factors for successful employment from the viewpoints of adults with autism spectrum disorder (ASD) and employers. Two groups of individuals participated in this study, 40 adults with ASD and 35 employers. Q method was used to understand and contrast the viewpoints of the two groups. Data were analysed using by-person varimax rotation factor analysis. Results showed that although both groups appear committed to the employment process, the difference in their understanding regarding the type of workplace support required, job expectations and productivity requirements continues to hinder successful employment. These results highlight the need to facilitate communication between employees and employers to ensure a clear understanding of the needs of both groups are met. The use of an ASD-specific workplace tool may assist in facilitating the necessary communication between these two groups.
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17. Solomon O, Heritage J, Yin L, Maynard DW, Bauman ML. {{‘What Brings Him Here Today?’: Medical Problem Presentation Involving Children with Autism Spectrum Disorders and Typically Developing Children}}. {J Autism Dev Disord};2015 (Oct 13)
Conversation and discourse analyses were used to examine medical problem presentation in pediatric care. Healthcare visits involving children with ASD and typically developing children were analyzed. We examined how children’s communicative and epistemic capabilities, and their opportunities to be socialized into a competent patient role are interactionally achieved. We found that medical problem presentation is designed to contain a ‘pre-visit’ account of the interactional and epistemic work that children and caregivers carry out at home to identify the child’s health problems; and that the intersubjective accessibility of children’s experiences that becomes disrupted by ASD presents a dilemma to all participants in the visit. The article examines interactional roots of unmet healthcare needs and foregone medical care of people with ASD.
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18. Tsuchiya Y, Minami Y, Umemura Y, Watanabe H, Ono D, Nakamura W, Takahashi T, Honma S, Kondoh G, Matsuishi T, Yagita K. {{Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse}}. {Genes Cells};2015 (Oct 12)
Methyl-CpG-binding protein 2 (Mecp2) is an X-linked gene encoding a methylated DNA-binding nuclear protein which regulates transcriptional activity. The mutation of MECP2 in humans is associated with Rett syndrome (RTT), a neurodevelopmental disorder. Patients with RTT frequently show abnormal sleep patterns and sleep-associated problems, in addition to autistic symptoms, raising the possibility of circadian clock dysfunction in RTT. In this study, we investigated circadian clock function in Mecp2-deficient mice. We successfully generated both male and female Mecp2-deficient mice on the wild-type C57BL/6 background and PER2Luciferase (PER2Luc ) knock-in background using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Generated Mecp2-deficient mice recapitulated reduced activity in mouse models of RTT, and their activity rhythms were diminished in constant dark conditions. Furthermore, real-time bioluminescence imaging showed that the amplitude of PER2Luc -driven circadian oscillation was significantly attenuated in Mecp2-deficient SCN neurons. On the other hand, in vitro circadian rhythm development assay using Mecp2-deficient mouse embryonic stem cells (ESCs) did not show amplitude changes of PER2Luc bioluminescence rhythms. Together, these results show that Mecp2 deficiency abrogates the circadian pacemaking ability of the SCN, which may be a therapeutic target to treat the sleep problems of patients with RTT.
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19. Turville C, Golden I. {{Autism and vaccination: The value of the evidence base of a recent meta-analysis}}. {Vaccine};2015 (Oct 13);33(42):5494-5496.
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20. Vokalova L, Durdiakova J, Ostatnikova D. {{Topoisomerases interlink genetic network underlying autism}}. {Int J Dev Neurosci};2015 (Aug 11)
DNA topoisomerases belong to the group of proteins that play an important role in the organizational dynamics of the human genome. Their enzymatic activity solves topological strain rising from DNA supercoiling occurring during transcription. DNA topoisomerases are especially important for transcription of genes involved in neurodevelopment. Disruption of topoisomerase activity in animal models resulted in impaired neurodevelopment and changed brain architecture. Recent research revealed that topoisomerases induced expression of the same group of genes as those associated with autism. Transcriptional inhibition of neuronal genes during critical stages of brain development may be responsible for pathology of neurodevelopmental disorders such as autism. In this review we aim to outline the role of topoisomerase in neurodevelopment and its possible linkage to neuropathology of autism.
