1. Beacher FD, Minati L, Baron-Cohen S, Lombardo MV, Lai MC, Gray MA, Harrison NA, Critchley HD. {{Autism Attenuates Sex Differences in Brain Structure: A Combined Voxel-Based Morphometry and Diffusion Tensor Imaging Study}}. {AJNR Am J Neuroradiol};2011 (Dec 15)
BACKGROUND AND PURPOSE:It has been proposed that autism spectrums condition may represent a form of extreme male brain (EMB), a notion supported by psychometric, behavioral, and endocrine evidence. Yet, limited data are presently available evaluating this hypothesis in terms of neuroanatomy. Here, we investigated sex-related anatomic features in adults with AS, a « pure » form of autism not involving major developmental delay.MATERIALS AND METHODS:Males and females with AS and healthy controls (n = 28 and 30, respectively) were recruited. Structural MR imaging was performed to measure overall gray and white matter volume and to assess regional effects by means of VBM. DTI was used to investigate the integrity of the main white matter tracts.RESULTS:Significant interactions were found between sex and diagnosis in total white matter volume, regional gray matter volume in the right parietal operculum, and fractional anisotropy (FA) in the body of the CC, cingulum, and CR. Post hoc comparisons indicated that the typical sexual dimorphism found in controls, whereby males have larger FA and total white matter volume, was absent or attenuated in participants with AS.CONCLUSIONS:Our results point to a fundamental role of the factors that underlie sex-specific brain differentiation in the etiology of autism.
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2. Juneja M, Jain R, Singhal S, Mishra D. {{Availing Services for Developmental Disabilities: Parental Experiences from a Referral Center in Developing Country}}. {Indian J Pediatr};2011 (Dec 17)
OBJECTIVES: To identify the problems faced by parents of children with developmental disabilities in availing rehabilitative services and to find their satisfaction level. METHODS: This study was carried out at a Child Development Clinic (CDC) located in Northern India. Children with developmental disabilities, who were availing services at CDC for at least last 3 mo and had at least 3 follow-up visits, were enrolled. A questionnaire pertaining to the socio-demographic profile, problems faced in availing services and satisfaction level was filled by the parents of the enrolled children. RESULTS: During the study period, 161 parents filled the questionnaire. 77.6% had some problems in getting the services, the major being difficulty in commuting (50%) and financial constraint (21.7%). More than 80% parents use public transport to reach CDC with 19% travelling more than 50 Km. 29.8% had difficulty in bringing their child to the clinic, either due to severe behavioral problems or physical disability. However, majority of the families were well satisfied with the services as 95% of them graded their satisfaction level at 3 or more on the scale of 0-5. CONCLUSIONS: Parents of children with developmental disabilities face many problems in getting rehabilitative services. They travel long distances, face hardships in carrying their child, and lose their day’s earnings, apart from spending time and money for their child’s therapy. However, most of the parents are well satisfied with the services.
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3. Kumar A, Swanwick CC, Johnson N, Menashe I, Basu SN, Bales ME, Banerjee-Basu S. {{A brain region-specific predictive gene map for autism derived by profiling a reference gene set}}. {PLoS One};2011;6(12):e28431.
Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heterogeneity of ASD to derive a predictive map of candidate genes by an integrated bioinformatics approach. Using a reference set of 84 Rare and Syndromic candidate ASD genes (AutRef84), we built a composite reference profile based on both functional and expression analyses. First, we created a functional profile of AutRef84 by performing Gene Ontology (GO) enrichment analysis which encompassed three main areas: 1) neurogenesis/projection, 2) cell adhesion, and 3) ion channel activity. Second, we constructed an expression profile of AutRef84 by conducting DAVID analysis which found enrichment in brain regions critical for sensory information processing (olfactory bulb, occipital lobe), executive function (prefrontal cortex), and hormone secretion (pituitary). Disease specificity of this dual AutRef84 profile was demonstrated by comparative analysis with control, diabetes, and non-specific gene sets. We then screened the human genome with the dual AutRef84 profile to derive a set of 460 potential ASD candidate genes. Importantly, the power of our predictive gene map was demonstrated by capturing 18 existing ASD-associated genes which were not part of the AutRef84 input dataset. The remaining 442 genes are entirely novel putative ASD risk genes. Together, we used a composite ASD reference profile to generate a predictive map of novel ASD candidate genes which should be prioritized for future research.
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4. Ladha S. {{Getting to the bottom of autism spectrum and related disorders: MBD5 as a key contributor}}. {Clin Genet};2011 (Dec 15)
References: 1. Talkowski ME, Mullegama SV, Rosenfeld JA et al. Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder. American Journal of Human Genetics 2011: 89, 551-563. 2. van Bon BW, Koolen DA, Brueton L et al. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype. Eur. J. Hum. Genet. 2010: 18, 163-1703. 3. Laget S, Joulie M, Le Masson F, et al. The human proteins MBD5 and MBD6 associate with heterochromatin but they do not bind methylated DNA. PLoS ONE 2010: 5, e11982. Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder Talkowski ME, Mullegama SV, Rosenfeld JA et al. American Journal of Human Genetics 2011: 89, 551-563.
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5. Lee BK, Gardner RM, Dal H, Svensson A, Galanti MR, Rai D, Dalman C, Magnusson C. {{Brief Report: Maternal Smoking During Pregnancy and Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (Dec 16)
Prenatal exposure to tobacco smoke is suggested as a potential risk factor for autism spectrum disorders (ASD). Previous epidemiological studies of this topic have yielded mixed findings. We performed a case-control study of 3,958 ASD cases and 38,983 controls nested in a large register-based cohort in Sweden. ASD case status was measured using a multisource case ascertainment system. In adjusted results, we found that maternal smoking during pregnancy is not associated with increased risk of ASD regardless of presence or absence of comorbid intellectual disability. Apparent associations were attributable to confounding by sociodemographic characteristics of parents such as education, income, and occupation.
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6. McCauley MD, Wang T, Mike E, Herrera J, Beavers DL, Huang TW, Ward CS, Skinner S, Percy AK, Glaze DG, Wehrens XH, Neul JL. {{Pathogenesis of lethal cardiac arrhythmias in mecp2 mutant mice: implication for therapy in rett syndrome}}. {Sci Transl Med};2011 (Dec 14);3(113):113ra125.
Rett syndrome is a neurodevelopmental disorder typically caused by mutations in methyl-CpG-binding protein 2 (MECP2) in which 26% of deaths are sudden and of unknown cause. To explore the hypothesis that these deaths may be due to cardiac dysfunction, we characterized the electrocardiograms in 379 people with Rett syndrome and found that 18.5% show prolongation of the corrected QT interval (QTc), an indication of a repolarization abnormality that can predispose to the development of an unstable fatal cardiac rhythm. Male mice lacking MeCP2 function, Mecp2(Null/Y), also have prolonged QTc and show increased susceptibility to induced ventricular tachycardia. Female heterozygous null mice, Mecp2(Null/+), show an age-dependent prolongation of QTc associated with ventricular tachycardia and cardiac-related death. Genetic deletion of MeCP2 function in only the nervous system was sufficient to cause long QTc and ventricular tachycardia, implicating neuronally mediated changes to cardiac electrical conduction as a potential cause of ventricular tachycardia in Rett syndrome. The standard therapy for prolonged QTc in Rett syndrome, beta-adrenergic receptor blockers, did not prevent ventricular tachycardia in Mecp2(Null/Y) mice. To determine whether an alternative therapy would be more appropriate, we characterized cardiomyocytes from Mecp2(Null/Y) mice and found increased persistent sodium current, which was normalized when cells were treated with the sodium channel-blocking anti-seizure drug phenytoin. Treatment with phenytoin reduced both QTc and sustained ventricular tachycardia in Mecp2(Null/Y) mice. These results demonstrate that cardiac abnormalities in Rett syndrome are secondary to abnormal nervous system control, which leads to increased persistent sodium current. Our findings suggest that treatment in people with Rett syndrome would be more effective if it targeted the increased persistent sodium current to prevent lethal cardiac arrhythmias.
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7. Mueller S, Keeser D, Reiser MF, Teipel S, Meindl T. {{Functional and Structural MR Imaging in Neuropsychiatric Disorders, Part 2: Application in Schizophrenia and Autism}}. {AJNR Am J Neuroradiol};2011 (Dec 15)
SUMMARY:During the past decade, the application of advanced MR imaging techniques in neuropsychiatric disorders has seen a rapid increase. Disease-specific alterations in brain function can be assessed by fMRI. Structural GM and WM properties are increasingly investigated by DTI and voxel-based approaches like VBM. These methods provide neurobiologic correlates for brain architecture and function, evaluation tools for therapeutic approaches, and potential early markers for diagnosis. Having provided insight into principles of functional and structural imaging and delineated common findings in mild cognitive impairment and Alzheimer disease in Part 1 of this review, we will now focus on autism and schizophrenia as common psychiatric disorders covering different stages of the life span. This review concludes by summarizing current applications, limitations, and future prospects in the field of MR imaging-based neuroimaging.
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8. Russo AJ, Devito R. {{Analysis of Copper and Zinc Plasma Concentration and the Efficacy of Zinc Therapy in Individuals with Asperger’s Syndrome, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and Autism}}. {Biomark Insights};2011;6:127-133.
AIM: To assess plasma zinc and copper concentration in individuals with Asperger’s Syndrome, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and autistic disorder, and to analyze the efficacy of zinc therapy on the normalization of zinc and copper levels and symptom severity in these disorders. SUBJECTS AND METHODS: Plasma from 79 autistic individuals, 52 individuals with PDD-NOS, 21 individuals with Asperger’s Syndrome (all meeting DSM-IV diagnostic criteria), and 18 age and gender similar neurotypical controls, were tested for plasma zinc and copper using inductively-coupled plasma-mass spectrometry. RESULTS: Autistic and PDD-NOS individuals had significantly elevated plasma levels of copper. None of the groups (autism, Asperger’s or PDD-NOS) had significantly lower plasma zinc concentrations. Post zinc and B-6 therapy, individuals with autism and PDD-NOS had significantly lower levels of copper, but individuals with Asperger’s did not have significantly lower copper. Individuals with autism, PDD-NOS and Asperger’s all had significantly higher zinc levels. Severity of symptoms decreased in autistic individuals following zinc and B-6 therapy with respect to awareness, receptive language, focus and attention, hyperactivity, tip toeing, eye contact, sound sensitivity, tactile sensitivity and seizures. None of the measured symptoms worsened after therapy. None of the symptoms in the Asperger’s patients improved after therapy. DISCUSSION: These results suggest an association between copper and zinc plasma levels and individuals with autism, PDD-NOS and Asperger’s Syndrome. The data also indicates that copper levels normalize (decrease to levels of controls) in individuals with autism and PDD-NOS, but not in individuals with Asperger’s. These same Asperger’s patients do not improve with respect to symptoms after therapy, whereas many symptoms improved in the autism group. This may indicate an association between copper levels and symptom severity.
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9. Whyatt CP, Craig CM. {{Motor Skills in Children Aged 7-10 Years, Diagnosed with Autism Spectrum Disorder}}. {J Autism Dev Disord};2011 (Dec 17)
This study used the Movement Assessment Battery for Children (M-ABC2) to assess motor skills in children aged 7-10 years with autism (n = 18) in comparison to two groups of age-matched typically developing children; a receptive vocabulary matched group (n = 19) and a nonverbal IQ matched group (n = 22). The results supported previous work, as indicated by a significant general motor impairment in the group with autism. However, sub-analysis of the M-ABC2 revealed that there were only 2 out of 8 subcomponent skills which showed universal significant specific deficits for the autism group; i.e. catching a ball and static balance. These results suggest that motor skill deficits associated with autism may not be pervasive but more apparent in activities demanding complex, interceptive actions or core balance ability.
