1. Chmielewski WX, Wolff N, Muckschel M, Roessner V, Beste C. {{Effects of multisensory integration processes on response inhibition in adolescent autism spectrum disorder}}. {Psychol Med};2016 (Jul 18):1-12.
BACKGROUND: In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD. METHOD: Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task. RESULTS: Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus. CONCLUSIONS: RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.
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2. D’Agati D, Chang AD, Wachtel LE, Reti IM. {{Treatment of Severe Self-Injurious Behavior in Autism Spectrum Disorder by Neuromodulation}}. {J ECT};2016 (Jul 16)
An increasing number of case reports and series document the safe and effective use of electroconvulsive therapy (ECT) in children, adolescents, and young adults with autism spectrum disorder who engage in severe, intractable, repetitive self-injurious behavior (SIB) without environmental or operant function. Although the treatment is very effective for such patients, they typically remain highly dependent on frequent maintenance ECT (M-ECT) to maintain suppression of the SIB achieved during the acute course. Some patients receive M-ECT as frequently as once every 5 days. Such a regimen is quite burdensome for the patient and the patient’s family, and the long-term effects of such regimens, starting as early as childhood, are unknown. In this review, we explore the expanding literature supporting the use of ECT for suppressing severe SIB associated with autism spectrum disorder. We also focus on the possible development of alternate nonconvulsive focal forms of brain stimulation, which might replace frequent M-ECT or reduce how frequently a patient needs to receive it. Although there are scarce clinical data currently available supporting these latter treatments, future studies are clearly indicated.
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3. Di Giorgio E, Frasnelli E, Rosa Salva O, Scattoni ML, Puopolo M, Tosoni D, Simion F, Vallortigara G. {{Corrigendum: Difference in Visual Social Predispositions Between Newborns at Low- and High-risk for Autism}}. {Sci Rep};2016;6:29860.
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4. Goldson E. {{Advances in Autism-2016}}. {Adv Pediatr};2016 (Aug);63(1):333-355.
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5. Li H, Zhao P, Xu Q, Shan S, Hu C, Qiu Z, Xu X. {{The autism-related gene SNRPN regulates cortical and spine development via controlling nuclear receptor Nr4a1}}. {Sci Rep};2016;6:29878.
The small nuclear ribonucleoprotein polypeptide N (SNRPN) gene, encoding the RNA-associated SmN protein, duplications or deletions of which are strongly associated with neurodevelopmental disabilities. SNRPN-coding protein is highly expressed in the brain. However, the role of SNRPN protein in neural development remains largely unknown. Here we showed that the expression of SNRPN increased markedly during postnatal brain development. Overexpression or knockdown of SNRPN in cortical neurons impaired neurite outgrowth, neuron migration, and the distribution of dendritic spines. We found that SNRPN regulated the expression level of Nr4a1, a critical nuclear receptor during neural development, in cultured primary cortical neurons. The abnormal spine development caused by SNRPN overexpression could be fully rescued by Nr4a1 co-expression. Importantly, we found that either knockdown of Nr4a1 or 3, 3′- Diindolylmethane (DIM), an Nr4a1 antagonist, were able to rescue the effects of SNRPN knockdown on neurite outgrowth of embryonic cortical neurons, providing the potential therapeutic methods for SNRPN deletion disorders. We thus concluded that maintaining the proper level of SNRPN is critical in cortical neurodevelopment. Finally, Nr4a1 may serve as a potential drug target for SNRPN-related neurodevelopmental disabilities, including Prader-Willi syndrome (PWS) and autism spectrum disorders (ASDs).
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6. Mouridsen SE, Rich B, Isager T. {{Diseases of the circulatory system among adult people diagnosed with infantile autism as children: A longitudinal case control study}}. {Res Dev Disabil};2016 (Jul 19);57:193-200.
BACKGROUND: Research dealing with adult people with autism spectrum disorders (ASD) noticeably lags behind studies of children and young individuals with ASD. AIMS: The objective of this study was to compare the prevalence and types of diseases of the circulatory system in a clinical sample of 118 adult people diagnosed with infantile autism (IA) as children with 336 sex and age matched controls from the general population. METHODS AND PROCEDURES: All participants were screened through the nationwide Danish National Hospital Register. The average observation time of both groups was 37.2 years, and mean age at follow-up was 49.6 years. OUTCOMES AND RESULTS: Of the 118 people with IA, 11 (9.3%) were registered with at least one disease of the circulatory system against 54 (16.1%) in the comparison group (p=0.09; OR=0.54; 95% CI 0.3-1.2). Ischemic heart diseases occurred significantly more frequently among people in the comparison group (p=0.02). CONCLUSIONS AND IMPLICATIONS: It is argued that diseases of the circulatory system may be underdiagnosed in people with IA because of the difficulties they face with respect to identifying and communicating symptoms of ill health. Bearing in mind that cardiovascular disease is the primary cause of death in most developed countries, it is suggested that to prevent disease and manage health conditions, health monitoring is essential in adult people with IA.
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7. Newbigin A, Uljarevic M, Vivanti G, Dissanayake C. {{Brief Report: Empathic Responsiveness of High Functioning Children with Autism to Expressed and Anticipated Distress}}. {J Autism Dev Disord};2016 (Jul 19)
The majority of studies that have investigated empathic responsiveness of individuals with Autism spectrum disorder (ASD) have used heterogeneous groups in terms of age, cognitive level and gender which significantly impact the results. Our aim in this study was to explore responsiveness of a more homogenous sample of 21 children with ASD and 17 typically developing controls, aged 8-12 years to both overt (or expressed) and anticipated distress. In the anticipated distress task, groups were not differentiated in their response towards the experimenter who had her drawing torn. In the expressed distress task, groups were again similar in expressing concern and acting prosocially towards an experimenter who pretended to lose her watch. The theoretical and clinical implications of these findings are discussed.
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8. Niort J, Hernandez Vazquez FJ. {{Comparative study of laterality in people with fragile X syndrome, people with intellectual disabilities, and people with typical development}}. {Laterality};2016 (Jul 19):1-13.
Following on from the studies by McManus and Cornish [(1997). Fractionating handedness in mental retardation: What is the role of the cerebellum? Laterality, 2(2), 81-89] and Cornish, Pigram, and Shaw [(1997). Do anomalies of handedness exist in children with fragile-X syndrome? Laterality, 2(2), 91-101], the aim of this paper was to determine laterality in people with fragile X syndrome (FXS). The sample comprised three study groups: the first with 30 people with FXS (mean age 17.9 years), the second 34 people with various intellectual disabilities (ID, mean age 20.9 years), and the third 160 people with typical development (mean age 14.7 years). Laterality was assessed with a test adapted for this study. The results confirm the preponderance of right-handedness (93.3%) in people with FXS and present new data regarding footedness and sensory dominance (eyedness and earedness), indicating inconsistent footedness and ocular cross-dominance. Almost three-quarters (73.5%) of people with other ID were right-handed. The results corroborate those of McManus and Cornish (1997). People with FXS tend to be right-handed but have ocular cross-dominance.
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9. Pears KC, Kim HK, Fisher PA, Yoerger K. {{Increasing pre-kindergarten early literacy skills in children with developmental disabilities and delays}}. {J Sch Psychol};2016 (Aug);57:15-27.
Two hundred and nine children receiving early childhood special education services for developmental disabilities or delays who also had behavioral, social, or attentional difficulties were included in a study of an intervention to increase school readiness, including early literacy skills. Results showed that the intervention had a significant positive effect on children’s literacy skills from baseline to the end of summer before the start of kindergarten (d=.14). The intervention also had significant indirect effects on teacher ratings of children’s literacy skills during the fall of their kindergarten year (beta=.09). Additionally, when scores were compared to standard benchmarks, a greater percentage of the children who received the intervention moved from being at risk for reading difficulties to having low risk. Overall, this study demonstrates that a school readiness intervention delivered prior to the start of kindergarten may help increase children’s early literacy skills.
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10. Pecorelli A, Cervellati C, Hayek J, Valacchi G. {{OxInflammation in Rett Syndrome}}. {Int J Biochem Cell Biol};2016 (Jul 14)
Rett syndrome (RTT) is an orphan progressive neurodevelopmental disease affecting almost exclusively females (frequency 1:10,000). RTT clinical expression is typically characterized by loss of purposeful hand movements, severe mental retardation and motor impairment, breathing disorders, ataxia and increased risk of sudden death. Although the main genetic cause, i.e. mutation in the methyl-CpG binding protein 2 gene (MECP2), has been already identified, the molecular and pathogenic mechanisms by which MECP2 deficiency drives pathology in RTT remains not fully understood. A wealth of evidence from our and other laboratories suggests a potential causal relationship between MECP2 dysfunction and systemic redox imbalance, a condition that has been widely found in association with RTT. In turn, a « short-circuit » of redox pathways may contribute to the systemic immune dysfunction expressed as cytokines/chemokines dysregulation, a feature clearly emerged from two recent studies on RTT patients. In this light, the purpose of this review is to describe and to stimulate a new discussion on the idea that systemic subclinical inflammation and oxidative stress are crucial players of a detrimental vicious circle, driving the pathogenesis and clinical course of RTT.
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11. Rizzo R, Pavone P. {{Aripiprazole for the treatment of irritability and aggression in children and adolescents affected by autism spectrum disorders}}. {Expert Rev Neurother};2016 (Jul 19):1-8.
INTRODUCTION: Aripiprazole is an atypical antipsychotic approved for the treatment of irritability and aggression in children and adolescents aged 6-17 years with autism spectrum disorder. AREAS COVERED: This review will discuss the drug profile as well as available studies of aripiprazole in individuals with autism spectrum disorder as documented in prospective randomized controlled trials. Expert commentary: The heterogeneity of autism spectrum disorder has implications for assessing the effectiveness and safety of aripiprazole as it may not produce the same results in two individuals with the same diagnosis but different etiologies. Subgrouping of patients according to their overall presentation of symptoms may therefore be warranted. In addition, consideration should be given to the potential causes of irritability and aggression, such as coexisting medical conditions and environmental factors including inappropriate intervention of parents and teachers. In these cases, the identification of the underlying cause is important because the appropriate management.
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12. Sajith SG, Liew SF, Tor PC. {{Response to Electroconvulsive Therapy in Patients With Autism Spectrum Disorder and Intractable Challenging Behaviors Associated With Symptoms of Catatonia}}. {J ECT};2016 (Jul 16)
BACKGROUND: There are several reports of electroconvulsive therapy (ECT) used in autism spectrum disorder (ASD) in the context of catatonic symptoms. We describe response to ECT in two adults with ASD and intellectual disability with intractable aggression and self-injurious behaviors associated with catatonic symptoms who had not responded to standard interventions. METHOD: Unilateral ECT at a frequency of 3 times a week was given followed by weekly maintenance ECT. RESULTS: Patients’ catatonic symptoms included episodes of agitation and echophenomena. Electroconvulsive therapy resulted in significant improvement in their behavior problems but 1 patient relapsed when the ECT was discontinued or frequency of treatment reduced. The second patient required 2 courses of ECT before improvement which was maintained on weekly ECT. CONCLUSIONS: Electroconvulsive therapy could be a potentially beneficial intervention in patients with ASD and severe challenging behaviors associated with catatonic symptoms including agitated or excited forms of catatonia.
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13. von dem Hagen EA, Bright N. {{High autistic trait individuals do not modulate gaze behaviour in response to social presence but look away more when actively engaged in an interaction}}. {Autism Res};2016 (Jul 19)
Autism is characterised by difficulties in social functioning, notably in interactions with other people. Yet, most studies addressing social difficulties have used static images or, at best, videos of social stimuli, with no scope for real interaction. Here, we study one crucial aspect of social interactions-gaze behaviour-in an interactive setting. First, typical individuals were shown videos of an experimenter and, by means of a deception procedure, were either led to believe that the experimenter was present via a live video-feed or was pre-recorded. Participants’ eye movements revealed that when passively viewing an experimenter they believed to be « live, » they looked less at that person than when they believed the experimenter video was pre-recorded. Interestingly, this reduction in viewing behaviour in response to the believed « live » presence of the experimenter was absent in individuals high in autistic traits, suggesting a relative insensitivity to social presence alone. When participants were asked to actively engage in a real-time interaction with the experimenter, however, high autistic trait individuals looked significantly less at the experimenter relative to low autistic trait individuals. The results reinforce findings of atypical gaze behaviour in individuals high in autistic traits, but suggest that active engagement in a social interaction may be important in eliciting reduced looking. We propose that difficulties with the spatio-temporal dynamics associated with real social interactions rather than underlying difficulties processing the social stimulus itself may drive these effects. The results underline the importance of developing ecologically valid methods to investigate social cognition. Autism Res 2016. (c) 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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14. Weber AR, Ostendorf A. {{Teaching NeuroImages: A central theta EEG rhythm in Rett syndrome can masquerade as seizure}}. {Neurology};2016 (Jul 19);87(3):e29-30.
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15. Ypma RJ, Moseley RL, Holt RJ, Rughooputh N, Floris DL, Chura LR, Spencer MD, Baron-Cohen S, Suckling J, Bullmore ET, Rubinov M. {{Default Mode Hypoconnectivity Underlies a Sex-Related Autism Spectrum}}. {Biol Psychiatry Cogn Neurosci Neuroimaging};2016 (Jul);1(4):364-371.
BACKGROUND: Females and males differ significantly in the prevalence and presentation of autism spectrum conditions. One theory of this effect postulates that autistic traits lie on a sex-related continuum in the general population, and autism represents the extreme male end of this spectrum. This theory predicts that any feature of autism in males should 1) be present in autistic females, 2) differentiate between the sexes in the typical population, and 3) correlate with autistic traits. We tested these three predictions for default mode network (DMN) hypoconnectivity during the resting state, one of the most robustly found neurobiological differences in autism. METHODS: We analyzed a primary dataset of adolescents (N = 121, 12-18 years of age) containing a relatively large number of females and a replication multisite dataset including children, adolescents, and adults (N = 980, 6-58 years of age). We quantified the average connectivity between DMN regions and tested for group differences and correlation with behavioral performance using robust regression. RESULTS: We found significant differences in DMN intraconnectivity between female controls and females with autism (p = .001 in the primary dataset; p = .009 in the replication dataset), and between female controls and male controls (p = .036 in the primary dataset; p = .002 in the replication dataset). We also found a significant correlation between DMN intraconnectivity and performance on a mentalizing task (p = .001) in the primary dataset. CONCLUSIONS: Collectively, these findings provide the first evidence for DMN hypoconnectivity as a behaviorally relevant neuroimaging phenotype of the sex-related spectrum of autistic traits, of which autism represents the extreme case.
