1. Berger NI, Ingersoll B. {{A Further Investigation of Goal-Directed Intention Understanding in Young Children with Autism Spectrum Disorders}}. {Journal of autism and developmental disorders}. 2014 Jul 8.
Findings from research investigating goal-directed intention understanding in children with autism spectrum disorders (ASD) have been equivocal, in part because of the varying methodologies used across studies. This study compares both object-oriented and social-communicatively cued goal-directed intention understanding in children with ASD and typically-developing children. Relative to matched controls, children with ASD did not exhibit deficits in object-oriented intention understanding. While children with ASD also demonstrated the ability to understand intention when cued by social-communication indicators, typically-developing children differentiated between intentional and unintentional acts at a significantly greater level. Group differences in performance were eliminated if only trials in which children attended to the experimenter’s face were considered. Results suggest that children with ASD have intact object-oriented intention understanding abilities, and are able to use social-communicative cues to understand intention. However, their ability to demonstrate social-communicatively cued intention understanding is limited by a lack of attention to relevant social-communicative information.
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2. Braat S, Kooy RF. {{Insights into GABAergic System Deficits in Fragile X Syndrome Lead to Clinical Trials}}. {Neuropharmacology}. 2014 Jul 9.
An increasing number of studies implicate the GABAAergic system in the pathophysiology of the fragile X syndrome, a frequent cause of intellectual disability and autism. Animal models have proven invaluable in unravelling the molecular mechanisms underlying the disorder. Multiple defects in this inhibitory system have been identified in Fmr1 knockout mice, including altered expression of various components, aberrant GABAA receptor-mediated signalling, altered GABA concentrations and anatomical defects in GABAergic neurons. Aberrations compatible with those described in the mouse model were detected in dfmr1 deficient Drosophila melanogaster, a validated fly model for the fragile X syndrome. Treatment with drugs that ameliorate the GABAAergic deficiency in both animal models have demonstrated that the GABAA receptor is a promising target for the treatment of fragile X patients. Based on these preclinical studies, clinical trials in patients have been initiated.
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3. Goffin D, Zhou ZJ. {{The neural circuit basis of Rett syndrome}}. {Frontiers in biology}. 2012 Oct;7(5):428-35.
Rett syndrome is an Autism Spectrum Disorder caused by mutations in the gene encoding methyl-CpG binding protein (MeCP2). Following a period of normal development, patients lose learned communication and motor skills, and develop a number of symptoms including motor disturbances, cognitive impairments and often seizures. In this review, we discuss the role of MeCP2 in regulating synaptic function and how synaptic dysfunctions lead to neuronal network impairments and alterations in sensory information processing. We propose that Rett syndrome is a disorder of neural circuits as a result of non-linear accumulated dysfunction of synapses at the level of individual cell populations across multiple neurotransmitter systems and brain regions.
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4. Heard TT, Ramgopal S, Picker J, Lincoln SA, Rotenberg A, Kothare SV. {{EEG abnormalities & seizures in genetically diagnosed Fragile X Syndrome}}. {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience}. 2014 Jul 9.
We describe the seizure and EEG characteristics in a population of children with known Fragile X. The medical records of 135 genetically confirmed FXS patients receiving care in a Fragile X clinic and their available EEG reports were reviewed. The mean age was 5.94 years old including 18 males and 1 female. The mean age was 4-9 years old with an age range of 15 months to 13 years old. Twenty-two patients (16.3%) in the series had parent-reported behavior suspicious of seizures. Sixteen patients (14.1%, 1 female) had at least one EEG recorded for evaluation of clinical events suspicious for seizure, and three patients (2.2%) had an EEG in the context of a polysomnography for diagnosing sleep apnea. The mean age at EEG evaluation was 6.0 years (standard deviation 3.8 years). EEG findings included slowing of background rhythm (n=9) and epileptiform discharges (n=7). Four patients had normal EEGs (n=4). Six patients (4.4% of the sample population) were diagnosed with epilepsy by both clinical seizure semiology and documented EEG abnormalities. Thirteen patients (68.4% of total) had episodes of staring and behavioral arrest with no EEG correlate, indicating non-epileptic events. Of the eight patients who underwent a repeat EEG, five patients had showed normalization in the posterior dominant rhythm over time, two patients had unchanged findings and one patient had worsening of his EEG. Our data warrant further prospective validation.
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5. Kondapalli KC, Prasad H, Rao R. {{An inside job: how endosomal Na(+)/H(+) exchangers link to autism and neurological disease}}. {Frontiers in cellular neuroscience}. 2014;8:172.
Autism imposes a major impediment to childhood development and a huge emotional and financial burden on society. In recent years, there has been rapidly accumulating genetic evidence that links the eNHE, a subset of Na(+)/H(+) exchangers that localize to intracellular vesicles, to a variety of neurological conditions including autism, attention deficit hyperactivity disorder (ADHD), intellectual disability, and epilepsy. By providing a leak pathway for protons pumped by the V-ATPase, eNHE determine luminal pH and regulate cation (Na(+), K(+)) content in early and recycling endosomal compartments. Loss-of-function mutations in eNHE cause hyperacidification of endosomal lumen, as a result of imbalance in pump and leak pathways. Two isoforms, NHE6 and NHE9 are highly expressed in brain, including hippocampus and cortex. Here, we summarize evidence for the importance of luminal cation content and pH on processing, delivery and fate of cargo. Drawing upon insights from model organisms and mammalian cells we show how eNHE affect surface expression and function of membrane receptors and neurotransmitter transporters. These studies lead to cellular models of eNHE activity in pre- and post-synaptic neurons and astrocytes, where they could impact synapse development and plasticity. The study of eNHE has provided new insight on the mechanism of autism and other debilitating neurological disorders and opened up new possibilities for therapeutic intervention.
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6. Oginsky MF, Cui N, Zhong W, Johnson CM, Jiang C. {{Alterations in the cholinergic system of brainstem neurons in a mouse model of Rett Syndrome}}. {American journal of physiology Cell physiology}. 2014 Jul 9.
Rett syndrome (RTT) is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine (NE) system originating mainly in the locus coeruleus (LC) is defective in RTT and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate and acetylcholine (Ach), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post- and presynaptic Ach inputs. We found that the post-synaptic currents of nicotinic acetylcholine receptors (nAchR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the WT. Single cell PCR analysis showed a decrease in the expression of alpha3, alpha4, alpha7 and beta3 subunits and an increase in the alpha5 and alpha6 subunits in the mutant mice. The alpha5 subunit was present in many of the LC neurons with slow decay nAchR currents. The nicotinic modulation of spontaneous GABAA-ergic IPSCs in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAchR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current clamp studies showed that the modulation of LC neurons by Ach input was reduced moderately in Mecp2-null mice despite the major decrease in nAchR currents suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons.
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7. Quint EH. {{Menstrual and Reproductive Issues in Adolescents With Physical and Developmental Disabilities}}. {Obstetrics and gynecology}. 2014 Jul 7.
Most obstetrician-gynecologists will encounter adolescents with disabilities in their practice, because developmental and physical disabilities are common in young patients (8.4%). Reproductive health issues such as puberty, sexuality, and menstruation can be more complicated for teenagers with disabilities and their families as a result of concerns surrounding menstrual hygiene, abuse risk, vulnerability, changes in seizure pattern, and altered mood. Teenagers with disabilities have gynecologic health care needs similar to those of their peers as well as unique needs related to their physical and cognitive issues. The gynecologic health visit for a teenager with disabilities should include an evaluation of the teenager’s reproductive knowledge as well as an assessment of her abuse and coercion risk and her ability to consent to sexual activity. The menstrual history is focused on the effects of menstrual cycles on her daily life. Diagnostic testing is not different from other adolescents. Hormonal treatment is often requested by the patient and her family to alleviate abnormal bleeding, cyclic mood changes, dysmenorrhea, or a combination of these, to assist with menstrual hygiene, and to provide contraception. Menstrual manipulation can be used to induce complete amenorrhea, regulate cycles, or decrease regular menstrual flow. However, treatment risks and side effects may have a different effect on the lives of these adolescents. The comfort level of health care providers to respond to the special concerns of adolescents with disabilities is low, and several barriers exist. This review addresses the complex issues of puberty, menstruation, sexuality, abuse, and safety highlighting the distinctive needs of this population. The options and decisions around menstrual manipulation are highlighted in detail.
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8. Soto S, Linas K, Jacobstein D, Biel M, Migdal T, Anthony BJ. {{A review of cultural adaptations of screening tools for autism spectrum disorders}}. {Autism : the international journal of research and practice}. 2014 Jul 9.
Screening children to determine risk for Autism Spectrum Disorders has become more common, although some question the advisability of such a strategy. The purpose of this systematic review is to identify autism screening tools that have been adapted for use in cultures different from that in which they were developed, evaluate the cultural adaptation process, report on the psychometric properties of the adapted instruments, and describe the implications for further research and clinical practice. A total of 21 articles met criteria for inclusion, reporting on the cultural adaptation of autism screening in 18 countries and in nine languages. The cultural adaptation process was not always clearly outlined and often did not include the recommended guidelines. Cultural/linguistic modifications to the translated tools tended to increase with the rigor of the adaptation process. Differences between the psychometric properties of the original and adapted versions were common, indicating the need to obtain normative data on populations to increase the utility of the translated tool.
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9. van De Sande MM, van Buul VJ, Brouns FJ. {{Autism and nutrition: the role of the gut-brain axis}}. {Nutrition research reviews}. 2014 Jul 8:1-16.
Autism spectrum disorder (ASD) is characterised by deficits in the ability to socialise, communicate and use imagination, and displays of stereotypical behaviour. It is widely accepted that ASD involves a disorder in brain development. However, the real causes of the neurodevelopmental disorders associated with ASD are not clear. In this respect, it has been found that a majority of children with ASD display gastrointestinal symptoms, and an increased intestinal permeability. Moreover, large differences in microbiotic composition between ASD patients and controls have been reported. Therefore, nutrition-related factors have been hypothesised to play a causal role in the aetiology of ASD and its symptoms. Through a review of the literature, it was found that abnormalities in carbohydrate digestion and absorption could explain some of the gastrointestinal problems observed in a subset of ASD patients, although their role in the neurological and behavioural problems remains uncertain. In addition, the relationship between an improved gut health and a reduction of symptoms in some patients was evaluated. Recent trials involving gluten-free diets, casein-free diets, and pre- and probiotic, and multivitamin supplementation show contradictive but promising results. It can be concluded that nutrition and other environmental influences might trigger an unstable base of genetic predisposition, which may lead to the development of autism, at least in a subset of ASD patients. Clear directions for further research to improve diagnosis and treatment for the different subsets of the disorder are provided.
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10. Wright B, Marshall D, Collingridge Moore D, Ainsworth H, Hackney L, Adamson J, Ali S, Allgar V, Cook L, Dyson L, Littlewood E, Hargate R, McLaren A, McMillan D, Trepel D, Whitehead J, Williams C. {{Autism Spectrum Social Stories In Schools Trial (ASSSIST): study protocol for a feasibility randomised controlled trial analysing clinical and cost-effectiveness of Social Stories in mainstream schools}}. {BMJ open}. 2014;4(7):e005952.
INTRODUCTION: Current evidence suggests that Social Stories can be effective in tackling problem behaviours exhibited by children with autism spectrum disorder. Exploring the meaning of behaviour from a child’s perspective allows stories to provide social information that is tailored to their needs. Case reports in children with autism have suggested that these stories can lead to a number of benefits including improvements in social interactions and choice making in educational settings. METHODS AND ANALYSIS: The feasibility of clinical and cost-effectiveness of a Social Stories toolkit will be assessed using a randomised control framework. Participants (n=50) will be randomised to either the Social Stories intervention or a comparator group where they will be read standard stories for an equivalent amount of time. Statistics will be calculated for recruitment rates, follow-up rates and attrition. Economic analysis will determine appropriate measures of generic health and resource use categories for cost-effectiveness analysis. Qualitative analysis will ascertain information on perceptions about the feasibility and acceptability of the intervention. ETHICS AND DISSEMINATION: National Health Service Ethics Approval (NHS; ref 11/YH/0340) for the trial protocol has been obtained along with NHS Research and Development permission from Leeds and York Partnership NHS Foundation Trust. All adverse events will be closely monitored, documented and reported to the study Data Monitoring Ethics Committee. At least one article in a peer reviewed journal will be published and research findings presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN96286707.
