Pubmed du 12/05/09

mercredi 13 mai 2009

1. Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Curr Opin Investig Drugs ;2009 (May) ;10(5):463-473.

Autism spectrum disorders is a heterogenous group of neurodevelopmental disorders, the etiology or etiologies of which remain unknown. Increasing evidence of autoimmune phenomena in individuals with autism could represent the presence of altered or inappropriate immune responses in this disorder, and this immune system dysfunction may represent novel targets for treatment. Furthermore, in recent studies, antibodies directed against the fetal brain have been detected in some mothers of children with autism ; these antibodies have the ability to alter behavioral outcomes in the offspring of animal models. A better understanding of the involvement of the immune response in early brain development, with respect to autism, may have important therapeutic implications.

2. Esbensen AJ, Greenberg JS, Seltzer MM, Aman MG. A Longitudinal Investigation of Psychotropic and Non-Psychotropic Medication Use Among Adolescents and Adults with Autism Spectrum Disorders. J Autism Dev Disord ;2009 (May 12)

Medication use was examined in 286 adolescents and adults with ASD over a 4.5 year period. A total of 70% were taking a psychotropic or non-psychotropic medication at the beginning of the study. Both the number of psychotropic and non-psychotropic medications taken, and the proportion of individuals taking these medications, increased significantly over the study period, with 81% taking at least one medication 4.5 years later. Our findings suggested a high likelihood of staying medicated over time. Thus, adolescents and adults with ASD are a highly and increasingly medicated population.

3. Grezes J, Wicker B, Berthoz S, de Gelder B. A failure to grasp the affective meaning of actions in autism spectrum disorder subjects. Neuropsychologia ;2009 (Jul) ;47(8-9):1816-1825.

The ability to grasp emotional messages in everyday gestures and respond to them is at the core of successful social communication. The hypothesis that abnormalities in socio-emotional behavior in people with autism are linked to a failure to grasp emotional significance conveyed by gestures was explored. We measured brain activity using fMRI during perception of fearful or neutral actions and showed that whereas similar activation of brain regions known to play a role in action perception was revealed in both autistics and controls, autistics failed to activate amygdala, inferior frontal gyrus and premotor cortex when viewing gestures expressing fear. Our results support the notion that dysfunctions in this network may contribute significantly to the characteristic communicative impairments documented in autism.

4. Hume K, Loftin R, Lantz J. Increasing Independence in Autism Spectrum Disorders : A Review of Three Focused Interventions. J Autism Dev Disord ;2009 (May 9)

The features of autism that inhibit the independent demonstration of skills, as well as three effective interventions for increasing independence, are explored in this review article. Independent performance may prove difficult for individuals with autism spectrum disorders (ASD) due to the core deficits of the disability, as well as executive function deficits that impact initiation and generalization. These difficulties, coupled with intervention strategies that encourage over-reliance on adult support, contribute to poor long term outcomes for adults with ASD in employment, housing, and relationship development. Self-monitoring, video modeling, and individual work systems each emphasize a shift in stimulus control from continuous adult management to an alternative stimulus and have proven successful in addressing executive function deficits and increasing independence.

5. Rout UK, Clausen P. Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders. Neurosci Res ;2009 (Jun) ;64(2):162-169.

Autism spectrum disorder (ASD) is a disease of neuro-developmental origin of uncertain etiology. The current understanding is that both genetic and environmental factors contribute to the development of ASD. Exposure to valproate, thalidomide and alcohol during gestation are amongst the environmental triggers that are associated with the development of ASD. These teratogens may disturb the ontogeny of the brain by altering the expression pattern of genes that regulate the normal development of the brain. In this study, a neuron-like PC-12 cell model was used to examine the effects of these compounds on the binding potential of 50 different transcription factors to understand the molecular mechanism/s that may be involved in the teratogenesis caused by these agents. Cells in culture were treated with low or high concentrations of teratogens within a range that are reported in the blood of individuals. A pronounced increase in GATA transcription factor binding was observed for all three teratogens. Furthermore, Western blot analysis showed that GATA-3 level in the nuclear fractions was enhanced by each of the three teratogens. Results suggest that altered gene expression pattern due to heightened GATA-3 activities in the fetral brains following exposure to these teratogens may contribute to the development of ASD.

6. White S, O’Reilly H, Frith U. Big heads, small details and autism. Neuropsychologia ;2009 (Apr) ;47(5):1274-1281.

Autism is thought to be associated with a bias towards detail-focussed processing. While the cognitive basis remains controversial, one strong hypothesis is that there are high processing costs associated with changing from local into global processing. A possible neural mechanism underlying this processing style is abnormal neural connectivity ; specifically reduced structural or functional connectivity between brain regions might lead to good exemplar-based processing but poor generalisation. Abnormal neural connectivity has also been suggested to account for the increased incidence of macrocephaly in autism (increased head/brain size). The present study therefore investigated the effect of head size on the ability to switch between global and local processing in autism. 49 high-functioning 7-12 year olds with autism (12 with macrocephaly) were compared to 25 normally developing children in their performance on a Local-Global Switching task. Those children with autism who also had macrocephaly showed a greater processing cost when switching into global processing, or ’zooming out’, than both the remaining children with autism and the control children. A second experiment revealed that macrocephaly in the context of normal development is not associated with difficulty switching into global processing but rather occurs in children who are physically large. Macrocephaly in the context of autism may therefore be a biological marker of abnormal neural connectivity, and of a local processing bias.

7. Wilbarger JL, McIntosh DN, Winkielman P. Startle modulation in autism : Positive affective stimuli enhance startle response. Neuropsychologia ;2009 (Apr) ;47(5):1323-1331.

Behavioral evidence suggests that emotion processing deficits in individuals with autism spectrum disorders (ASD) may occur at the level of basic (early, rapid, automatic) affective processes. Consistently, neurological evidence indicates that key brain areas associated with basic affective processing are atypical in ASD. The current study sought to better specify these deficits by comparing different components of basic affective processing in 14 adolescents and adults with ASD and 14 typical controls matched for age and verbal ability. Participants viewed affective pictures, and their responses were assessed with (i) affective eyeblink startle modulation, an indicator of the brain’s aversive motivational system ; (ii) facial electromyography, an online indicator of implicit valence appraisal ; and (iii) self-report, an indicator of overt valence appraisal. The results show that in contrast to the typical pattern, in which exposure to negative stimuli increases startle whereas exposure to positive stimuli decreases startle, individuals with ASD showed startle potentiation to both positive and negative stimuli. Atypical potentiation during positive stimuli occurred despite individuals with ASD demonstrating appropriate implicit valence appraisals, reflected in their facial EMG responses, and appropriate overt appraisals, reflected in their self-reported ratings of the stimuli. Potentiation of startle to both positive and negative stimuli suggests a disruption in basic affective processes in ASD at the level of the early motivational response. This atypical pattern of responses has implications for understanding social and emotion deficits in ASD and calls for further investigation of basic affective processes.

8. Yoo HK, Chung S, Hong JP, Kim BN, Cho SC. Microsatellite marker in gamma - aminobutyric acid - a receptor beta 3 subunit gene and autism spectrum disorders in Korean trios. Yonsei Med J ;2009 (Apr 30) ;50(2):304-306.

This study aimed to identify the association between gamma-aminobutyric acid-A (GABA-A) receptor subunit beta3 (GABRB3) gene and autism spectrum disorders (ASD) in Korea. Fifty-eight children with ASD [47 boys (81.0%), 5.5 +/- 4.1 years old], 46 family trios, and 86 healthy control subjects [71 males (82.6%), 33.6 +/- 9.3 years old] were recruited. Transmission disequilibrium test revealed that, 183 bp long allele in GABRB3 gene was preferentially transmitted in families with ASD (p = 0.025), whereas a population-based case-control study, however, showed no association between ASD and GABRB3 microsatellite polymorphism. Our data provide preliminary evidence that GABRB3 gene is associated with ASD in Korea.


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