Pubmed du 10/04/09

mardi 14 avril 2009

1. Campbell JM, Marino CA. Brief Report : Sociometric Status and Behavioral Characteristics of Peer Nominated Buddies for a Child with Autism. J Autism Dev Disord ;2009 (Apr 9)

We examined social and behavioral correlates of children selected by their peers to serve as peer buddies for an unfamiliar child with autism (CWA). Participants were 293 children from two public elementary schools who completed social status, behavioral, and peer buddy nomination measures. Peer buddy nominations for a CWA were related to : (a) perceived unpopularity ; (b) being viewed as helpful and smart ; and (c) lacking influence regarding popularity within the classroom. In contrast, peer buddy nominations for a typical boy were related to being viewed as popular, helpful, and self-confident. Students may select a social niche for CWA based on principles of peer homophily. Limitations and suggestions for future research are discussed.

2. Corbett BA, Schupp CW, Levine S, Mendoza S. Comparing cortisol, stress, and sensory sensitivity in children with autism. Autism Res ;2009 (Feb) ;2(1):39-49.

Previously we reported that children with autism show significant variability in cortisol. The current investigation was designed to extend these findings by exploring plausible relationships between cortisol and psychological measures of stress and sensory functioning. Salivary cortisol values for diurnal rhythms and response to stress in children with and without autism were compared to parent-report measures of child stress, the Stress Survey Schedule (SSS), sensory functioning, Short Sensory Profile (SSP), and Parenting Stress Index. In autism, a negative relationship between morning cortisol and the SSS revealed that higher observed symptoms of stress were related to lower cortisol. Lower cortisol is seen in conditions of chronic stress and in social situations characterized by unstable social relationships. Sensory sensitivity painted a more complicated picture, in that some aspects of SSP were associated with higher while others were associated with lower cortisol. We propose that increased sensory sensitivity may enhance the autistic child’s susceptibility to the influence of zeitgeibers reflected in variable cortisol secretion. Evening cortisol was positively associated with SSS such that the higher the level of evening cortisol, the higher the child’s parent-reported daily stress, especially to changes, such as in daily routine. Regarding the response to stress, the psychological and parent variables did not differentiate the groups ; rather, discrete subgroups of cortisol responders and nonresponders were revealed in both the autism and neurotypical children. The results support a complex interplay between physiological and behavioral stress and sensory sensitivity in autism and plausible developmental factors influencing stress reactivity across the groups.

3. Grandgeorge M, Hausberger M, Tordjman S, Deleau M, Lazartigues A, Lemonnier E. Environmental factors influence language development in children with autism spectrum disorders. PLoS ONE ;2009 ;4(4):e4683.

BACKGROUND : While it is clearly admitted that normal behavioural development is determined by the interplay of genetic and environmental influences, this is much less the case for psychiatric disorders for which more emphasis has been given in the past decades on biological determinism. Thus, previous studies have shown that Autistic Spectrum Disorders (ASD) were not affected by parental style. However, animal research suggests that different behavioural traits can be differentially affected by genetic/environmental factors. METHODOLOGY/ PRINCIPAL FINDINGS : In the present study we hypothesized that amongst the ASD, language disorders may be more sensitive to social factors as language is a social act that develops under social influences. Using the Autism Diagnostic Interview-Revised, we compared the early characteristics of sensori-motor and language development in a large sample of children with ASD (n = 162) with parents belonging to different levels of education. The results showed that children raised by parents with a high level of education displayed earlier language development. Moreover, they showed earlier first words and phrases if their mother was at a high level of education, which reveals an additional gender effect. CONCLUSIONS/SIGNIFICANCE : To our knowledge this study may trigger important new lines of thought and research, help equilibrate social and purely biological perspectives regarding ASD and bring new hopes for environmentally based therapies.

4. Irwin J. Audiovisual speech perception in children with autism spectrum disorders and typical controls : Implications for development. J Acoust Soc Am ;2009 (Apr) ;125(4):2533.

For typically developing perceivers, visual speech information influences what listeners hear. For example, when the place of articulation of visual and auditory speech tokens are incongruent, perceivers often report hearing a visually influenced response (the McGurk effect ; McGurk and MacDonald, 1976). To better understand the role of visual speech information in development, children with autism spectrum disorders (ASD), children with typical development and adults with typical development were assessed on : (1) sensitivity to mismatched auditory and visual speech (McGurk) ; (2) visual gain in the presence of auditory noise ; and (3) detection of auditory and visual asynchrony. Implications for the development of audiovisual speech processing in typically developing children and adults and children with ASD will be discussed. [Work supported by NIH.].

5. Judson MC, Bergman MY, Campbell DB, Eagleson KL, Levitt P. Dynamic gene and protein expression patterns of the autism-associated met receptor tyrosine kinase in the developing mouse forebrain. J Comp Neurol ;2009 (Apr 10) ;513(5):511-531.

The establishment of appropriate neural circuitry depends on the coordination of multiple developmental events across space and time. These events include proliferation, migration, differentiation, and survival-all of which can be mediated by hepatocyte growth factor (HGF) signaling through the Met receptor tyrosine kinase. We previously found a functional promoter variant of the MET gene to be associated with autism spectrum disorder, suggesting that forebrain circuits governing social and emotional function may be especially vulnerable to developmental disruptions in HGF/Met signaling. However, little is known about the spatiotemporal distribution of Met expression in the forebrain during the development of such circuits. To advance our understanding of the neurodevelopmental influences of Met activation, we employed complementary Western blotting, in situ hybridization, and immunohistochemistry to comprehensively map Met transcript and protein expression throughout perinatal and postnatal development of the mouse forebrain. Our studies reveal complex and dynamic spatiotemporal patterns of expression during this period. Spatially, Met transcript is localized primarily to specific populations of projection neurons within the neocortex and in structures of the limbic system, including the amygdala, hippocampus, and septum. Met protein appears to be principally located in axon tracts. Temporally, peak expression of transcript and protein occurs during the second postnatal week. This period is characterized by extensive neurite outgrowth and synaptogenesis, supporting a role for the receptor in these processes. Collectively, these data suggest that Met signaling may be necessary for the appropriate wiring of forebrain circuits, with particular relevance to the social and emotional dimensions of behavior.

6. Ke X, Tang T, Hong S, Hang Y, Zou B, Li H, Zhou Z, Ruan Z, Lu Z, Tao G, Liu Y. White matter impairments in autism, evidence from voxel-based morphometry and diffusion tensor imaging. Brain Res ;2009 (Apr 10) ;1265:171-177.

This study explored white matter abnormalities in a group of Chinese children with high functioning autism (HFA). Twelve male children with HFA and ten matched typically developing children underwent diffusion tensor imaging (DTI) as well three-dimensional T1-weighted MRI for voxel-based morphometry (VBM). We found a significant decrease of the white matter density in the right frontal lobe, left parietal lobe and right anterior cingulate and a significant increase in the right frontal lobe, left parietal lobe and left cingulate gyrus in the HFA group compared with the control group. The HFA group also had decreased FA in the frontal lobe and left temporal lobe. By combining DT-MRI FA and MRI volumetric analyses based on the VBM model, the results showed consistent white matter abnormalities in a group of Chinese children with HFA.

7. Koegel RL, Vernon TW, Koegel LK. Improving Social Initiations in Young Children with Autism Using Reinforcers with Embedded Social Interactions. J Autism Dev Disord ;2009 (Apr 9)

Children with autism often exhibit low levels of social engagement, decreased levels of eye contact, and low social affect. However, both the literature and our direct clinical observations suggest that some components of intervention procedures may result in improvement in child-initiated social areas. Using an ABAB research design with three children with autism, this study systematically assessed whether embedding social interactions into reinforcers, delivered during language intervention, would lead to increased levels of child-initiated social behaviors. We compared this condition with a language intervention condition that did not embed social interactions into the reinforcers. Results indicated that embedding social interactions into the reinforcers resulted in increases in child-initiated social engagement during communication, improved nonverbal dyadic orienting, and improvements in general child affect. Theoretical and applied implications are discussed.

8. Lindgren KA, Folstein SE, Tomblin JB, Tager-Flusberg H. Language and reading abilities of children with autism spectrum disorders and specific language impairment and their first-degree relatives. Autism Res ;2009 (Feb) ;2(1):22-38.

Autism spectrum disorder (ASD) and specific language impairment (SLI) are developmental disorders exhibiting language deficits, but it is unclear whether they arise from similar etiologies. Language impairments have been described in family members of children with ASD and SLI, but few studies have quantified them. In this study, we examined IQ, language, and reading abilities of ASD and SLI children and their first-degree relatives to address whether the language difficulties observed in some children with ASD are familial and to better understand the degree of overlap between these disorders and their broader phenotypes. Participants were 52 autistic children, 36 children with SLI, their siblings, and their parents. The ASD group was divided into those with (ALI, n=32) and without (ALN, n=20) language impairment. Relationships between ASD severity and language performance were also examined in the ASD probands. ALI and SLI probands performed similarly on most measures while ALN probands scored higher. ALN and ALI probands’ language scores were not related to Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule algorithm scores. SLI relatives scored lowest on all measures, and while scores were not in the impaired range, relatives of ALI children scored lower than relatives of ALN children on some measures, though not those showing highest heritability in SLI. Given that ALI relatives performed better than SLI relatives across the language measures, the hypothesis that ALI and SLI families share similar genetic loading for language is not strongly supported.

9. McAlonan GM, Cheung C, Cheung V, Wong N, Suckling J, Chua SE. Differential effects on white-matter systems in high-functioning autism and Asperger’s syndrome. Psychol Med ;2009 (Apr 9):1-9.

BACKGROUND : Whether autism spectrum maps onto a spectrum of brain abnormalities and whether Asperger’s syndrome (ASP) is distinct from high-functioning autism (HFA) are debated. White-matter maldevelopment is associated with autism and disconnectivity theories of autism are compelling. However, it is unknown whether children with ASP and HFA have distinct white-matter abnormalities.MethodVoxel-based morphometry mapped white-matter volumes across the whole brain in 91 children. Thirty-six had autism spectrum disorder. A history of delay in phrase speech defined half with HFA ; those without delay formed the ASP group. The rest were typically developing children, balanced for age, IQ, gender, maternal language and ethnicity. White-matter volumes in HFA and ASP were compared and each contrasted with controls. RESULTS : White-matter volumes around the basal ganglia were higher in the HFA group than ASP and higher in both autism groups than controls. Compared with controls, children with HFA had less frontal and corpus callosal white matter in the left hemisphere ; those with ASP had less frontal and corpus callosal white matter in the right hemisphere with more white matter in the left parietal lobe. CONCLUSIONS : HFA involved mainly left hemisphere white-matter systems ; ASP affected predominantly right hemisphere white-matter systems. The impact of HFA on basal ganglia white matter was greater than ASP. This implies that aetiological factors and management options for autism spectrum disorders may be distinct. History of language acquisition is a potentially valuable marker to refine our search for causes and treatments in autism spectrum.

10. Mundy P, Sullivan L, Mastergeorge AM. A parallel and distributed-processing model of joint attention, social cognition and autism. Autism Res ;2009 (Feb) ;2(1):2-21.

The impaired development of joint attention is a cardinal feature of autism. Therefore, understanding the nature of joint attention is central to research on this disorder. Joint attention may be best defined in terms of an information-processing system that begins to develop by 4-6 months of age. This system integrates the parallel processing of internal information about one’s own visual attention with external information about the visual attention of other people. This type of joint encoding of information about self and other attention requires the activation of a distributed anterior and posterior cortical attention network. Genetic regulation, in conjunction with self-organizing behavioral activity, guides the development of functional connectivity in this network. With practice in infancy the joint processing of self-other attention becomes automatically engaged as an executive function. It can be argued that this executive joint attention is fundamental to human learning as well as the development of symbolic thought, social cognition and social competence throughout the life span. One advantage of this parallel and distributed-processing model of joint attention is that it directly connects theory on social pathology to a range of phenomena in autism associated with neural connectivity, constructivist and connectionist models of cognitive development, early intervention, activity-dependent gene expression and atypical ocular motor control.

11. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Increase in Cerebellar Neurotrophin-3 and Oxidative Stress Markers in Autism. Cerebellum ;2009 (Apr 9)

Autism is a neurodevelopmental disorder characterized by social and language deficits, ritualistic-repetitive behaviors and disturbance in motor functions. Data of imaging, head circumference studies, and Purkinje cell analysis suggest impaired brain growth and development. Both genetic predisposition and environmental triggers have been implicated in the etiology of autism, but the underlying cause remains unknown. Recently, we have reported an increase in 3-nitrotyrosine (3-NT), a marker of oxidative stress damage to proteins in autistic cerebella. In the present study, we further explored oxidative damage in the autistic cerebellum by measuring 8-hydroxydeoxyguanosine (8-OH-dG), a marker of DNA modification, in a subset of cases analyzed for 3-NT. We also explored the hypothesis that oxidative damage in autism is associated with altered expression of brain neurotrophins critical for normal brain growth and differentiation. The content of 8-OH-dG in cerebellar DNA isolated by the proteinase K method was measured using an enzyme-linked immunosorbent assay (ELISA) ; neurotrophin-3 (NT-3) levels in cerebellar homogenates were measured using NT-3 ELISA. Cerebellar 8-OH-dG showed trend towards higher levels with the increase of 63.4% observed in autism. Analysis of cerebellar NT-3 showed a significant (p = 0.034) increase (40.3%) in autism. Furthermore, there was a significant positive correlation between cerebellar NT-3 and 3-NT (r = 0.83 ; p = 0.0408). These data provide the first quantitative measure of brain NT-3 and show its increase in the autistic brain. Altered levels of brain NT-3 are likely to contribute to autistic pathology not only by affecting brain axonal targeting and synapse formation but also by further exacerbating oxidative stress and possibly contributing to Purkinje cell abnormalities.

12. Yip J, Soghomonian JJ, Blatt GJ. Decreased GAD65 mRNA levels in select subpopulations of neurons in the cerebellar dentate nuclei in autism : an in situ hybridization study. Autism Res ;2009 (Feb) ;2(1):50-59.

The laterally positioned dentate nuclei lie in a key position in the cerebellum to receive input from Purkinje cells in the lateral cerebellar hemisphere participating in both motor and cognitive functions. Although neuropathology of the four cerebellar nuclei using Nissl staining has been qualitatively reported in children and adults with autism, surprisingly the dentate nuclei appeared less affected despite reported reductions in Purkinje cells in the posterolateral cerebellar hemisphere. To determine any underlying abnormalities in the critically important GABAergic system, the rate-limiting GABA synthesizing enzyme, glutamic acid decarboxylase (GAD) type 65 was measured via in situ hybridization histochemistry in dentate somata. GAD65 mRNA labeling revealed two distinct subpopulations of neurons in adult control and autism postmortem brains : small-sized cells (about 10-12 microm in diameter, presumed interneurons) and larger-sized neurons (about 18-20 microm in diameter, likely feedback to inferior olivary neurons). A mean 51% reduction in GAD65 mRNA levels was found in the larger labeled cells in the autistic group compared with the control group (P=0.009 ; independent t-test) but not in the smaller cell subpopulation. This suggests a disturbance in the intrinsic cerebellar circuitry in the autism group potentially interfering with the synchronous firing of inferior olivary neurons, and the timing of Purkinje cell firing and inputs to the dentate nuclei. Disturbances in critical neural substrates within these key circuits could disrupt afferents to motor and/or cognitive cerebral association areas in the autistic brain likely contributing to the marked behavioral consequences characteristic of autism.











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