1. Baecker T, Mangus K, Pfaender S, Chhabra R, Boeckers TM, Grabrucker AM. {{Loss of COMMD1 and copper overload disrupt zinc homeostasis and influence an autism-associated pathway at glutamatergic synapses}}. {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}. 2014 Jul 10.
Recent studies suggest that synaptic pathology in autism spectrum disorder (ASD) might be caused by the disruption of a signaling pathway at excitatory glutamatergic synapses, which can be influenced by environmental factors. Some factors, such as prenatal zinc deficiency, dysfunction of metallothioneins as well as deletion of COMMD1, all affect brain metal-ion homeostasis and have been associated with ASD. Given that COMMD1 regulates copper levels and that copper and zinc have antagonistic properties, here, we followed the idea that copper overload might induce a local zinc deficiency affecting key players of a putative ASD pathway such as ProSAP/Shank proteins as reported before. Our results show that increased copper levels indeed interfere with intracellular zinc concentrations and affect synaptic ProSAP/Shank levels, which similarly are altered by manipulation of copper and zinc levels through overexpression and knockdown of COMMD1. In line with this, acute and prenatal copper overload lead to local zinc deficiencies in mice. Pups exposed to prenatal copper overload furthermore show a reduction in ProSAP/Shank protein levels in the brain as well as a decreased NMDAR subunit 1 concentration. Thus, it might be likely that brain metal ion status influences a distinct pathway in excitatory synapses associated with genetic forms of ASD.
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2. Caffarelli C, Hayek J, Pitinca MD, Nuti R, Gonnelli S. {{A Comparative Study of Dual-X-ray Absorptiometry and Quantitative Ultrasonography for the Evaluating Bone Status in Subjects with Rett Syndrome}}. {Calcified tissue international}. 2014 Jul 11.
Rett syndrome, an X-linked neurodevelopmental disorder primarily affecting girls, is frequently characterized by a reduced bone mineral density (BMD) with an increased risk of fragility fractures. The aim of the study was to assess bone status by DXA technique and by quantitative ultrasound (QUS) in subjects with Rett syndrome and to evaluate which DXA or QUS parameters better correlate with clinical features. In 156 Rett subjects (mean age 13.6 +/- 8.2 years) and in 62 controls, we measured BMD at femoral neck (BMD-FN) and at total femur (BMD-TF). Apparent volumetric bone mineral density (vBMAD) was also calculated. In all subjects, QUS parameters at phalanges by Bone Profiler-IGEA (amplitude-dependent speed of sound: AD-SoS and bone transmission time: BTT) were evaluated. We found that both DXA parameters and QUS parameters were significantly lower in Rett subjects than in controls. All clinical characteristics were positively correlated to BMD-FN, BMD-TF, AD-SoS, and BTT (p < 0.001) but not with vBMAD-FN. All ultrasonographic parameters were significantly correlated to BMD-FN and BMD-TF, whereas vBMAD-FN showed only positive significant correlation with densitometric parameters (p < 001). In Rett subjects BMD-FN was predicted primarily by weight and movement capacity, whereas vBMAD-FN was predicted by weight, height, and calcium intake. Moreover, AD-SoS was predicted by weight, height, and age, while BTT was predicted only by height. In conclusion, in our study the performance of QUS at phalanges was similar to those of BMD at femur, therefore, both areal BMD at femur and QUS at phalanges (AD-SoS and BTT) may be equally useful in the evaluation of skeletal status in Rett patients.
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3. Gabriele S, Sacco R, Cerullo S, Neri C, Urbani A, Tripi G, Malvy J, Barthelemy C, Bonnet-Brihault F, Persico AM. {{Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study}}. {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals}. 2014 Jul 10:1-8.
Abstract The aromatic compound p-cresol (4-methylphenol) has been found elevated in the urines of Italian autistic children up to 8 years of age. The present study aims at replicating these initial findings in an ethnically distinct sample and at extending them by measuring also the three components of urinary p-cresol, namely p-cresylsulfate, p-cresylglucuronate and free p-cresol. Total urinary p-cresol, p-cresylsulfate and p-cresylglucuronate were significantly elevated in 33 French autism spectrum disorder (ASD) cases compared with 33 sex- and age-matched controls (p < 0.05). This increase was limited to ASD children aged </=8 years (p < 0.01), and not older (p = 0.17). Urinary levels of p-cresol and p-cresylsulfate were associated with stereotypic, compulsive/repetitive behaviors (p < 0.05), although not with overall autism severity. These results confirm the elevation of urinary p-cresol in a sizable set of small autistic children and spur interest into biomarker roles for p-cresol and p-cresylsulfate in autism.
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4. Gerhant A, Olajossy M, Olajossy-Hilkesberger L. {{[Neuroanatomical, genetic and neurochemical aspects of infantile autism]}}. {Psychiatria polska}. 2013 Nov-Dec;47(6):1101-11.
Infantile autism is a neurodevelopmental disorder characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. The etiopathogenetic processes of autism are extremely complex, which is reflected in the varying course and its symptomatology. Trajectories of brain development and volumes of its structures are aberrant in autistic patients. It is suggested that disturbances in sertotoninergic, gabaergic, glutaminergic, cholinergic and dopaminergic neurotransmission can be responsible for symptoms of autism as well as can disturb the development of the young brain. The objective of this article is to present the results of reasearch on neuroanatomical, neurochemical and genetic aspects of autism.
5. Grandin T. {{Review: the reason I jump: the inner voice of a thirteen-year-old boy with autism}}. {Cerebrum : the Dana forum on brain science}. 2014 Jan;2014:3.
In Temple Grandin’s review of The Reason I Jump by Naoki Higashida, she relates her own experience living with and studying autism to better understand the mind of a remarkable 13-year-old Japanese boy with severe autism. Structured as a series of questions that a nonautistic person might ask an autistic one, Naoki’s book is translated by David Mitchell (author of the novel Cloud Atlas) and his wife, Keiko Yoshida, and contains an impassioned introduction in which Mitchell discusses his experience with his own autistic child.
6. Hernandez LM, Rudie JD, Green SA, Bookheimer S, Dapretto M. {{Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics}}. {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}. 2014 Jul 11.
Neuroimaging investigations of Autism Spectrum Disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD subpopulations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data.Neuropsychopharmacology Reviews accepted article preview online, 11 July 2014; doi:10.1038/npp.2014.172.
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7. 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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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. 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.
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10. Zalla T, Sirigu A, Robic S, Chaste P, Leboyer M, Coricelli G. {{Feelings of regret and disappointment in adults with high-functioning autism}}. {Cortex; a journal devoted to the study of the nervous system and behavior}. 2014 Jun 9;58C:112-22.
Impairments in emotional processing in Autism Spectrum Disorders (ASDs) can be characterised by failure to generate and recognize self-reflective, cognitive-based emotions, such as pride, embarrassment and shame. Among this type of emotions, regret and disappointment, as well as their positive counterparts, result from a counterfactual comparison, that is the comparison between an actual value (« what is ») and a fictive value (« what might have been »). However, while disappointment is experienced when the obtained outcome is worse than the expected outcome that might have occurred from the same choice, regret occurs when one experiences an outcome that is worse than the outcome of foregone choices. By manipulating a simple gambling task, we examined subjective reports on the intensity of negative and positive emotions in a group of adults with High-Functioning Autism or Asperger syndrome (HFA/AS), and a control group matched for age, gender and educational level. Participants were asked to choose between two lotteries with different levels of risk under two conditions of outcome feedback: (i) Partial, in which only the outcome of the chosen lottery was visible, (ii) Complete, in which the outcomes of the two lotteries were simultaneously visible. By comparing partial and complete conditions, we aimed to investigate the differential effect between disappointment and regret, as well as between their positive counterparts. Relative to the control participants (CP), the group with HFA/AS reported reduced regret and no difference between regret and disappointment, along with a preserved ability to use counterfactual thinking and similar choice behaviour. Difficulties to distinguish the feeling of regret in participants with HFA/AS can be explained by diminished emotional awareness, likely associated with an abnormal fronto-limbic connectivity.
