Pubmed du 10/02/09

mercredi 11 février 2009

1. Boddaert N, Zilbovicius M, Philipe A, Robel L, Bourgeois M, Barthelemy C, Seidenwurm D, Meresse I, Laurier L, Desguerre I, Bahi-Buisson N, Brunelle F, Munnich A, Samson Y, Mouren MC, Chabane N. MRI findings in 77 children with non-syndromic autistic disorder. PLoS ONE ;2009 ;4(2):e4415.

BACKGROUND : The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences. Our main objective was to evaluate the prevalence of brain abnormalities in a large group of children with a non-syndromic autistic disorder (AD) using T1, T2 and FLAIR MRI sequences. METHODOLOGY : MRI inspection of 77 children and adolescents with non-syndromic AD (mean age 7.4+/-3.6) was performed. All met the DSM-IV and ADI -R criteria for autism. Based on recommended clinical and biological screenings, we excluded patients with infectious, metabolic or genetic diseases, seizures or any other neurological symptoms. Identical MRI inspections of 77 children (mean age 7.0+/-4.2) without AD, developmental or neurological disorders were also performed. All MRIs were acquired with a 1.5-T Signa GE (3-D T1-FSPGR, T2, FLAIR coronal and axial sequences). Two neuroradiologists independently inspected cortical and sub-cortical regions. MRIs were reported to be normal, abnormal or uninterpretable. PRINCIPAL FINDINGS : MRIs were judged as uninterpretable in 10% (8/77) of the cases. In 48% of the children (33/69 patients), abnormalities were reported. Three predominant abnormalities were observed, including white matter signal abnormalities (19/69), major dilated Virchow-Robin spaces (12/69) and temporal lobe abnormalities (20/69). In all, 52% of the MRIs were interpreted as normal (36/69 patients). CONCLUSIONS : An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in non-syndromic autism. These results could contribute to further etiopathogenetic research into autism.

2. Bowler DM, Limoges E, Mottron L. Different Verbal Learning Strategies in Autism Spectrum Disorder : Evidence from the Rey Auditory Verbal Learning Test. J Autism Dev Disord ;2009 (Feb 10)

The Rey Auditory Verbal Learning Test, which requires the free recall of the same list of 15 unrelated words over 5 trials, was administered to 21 high-functioning adolescents and adults with autism spectrum disorder (ASD) and 21 matched typical individuals. The groups showed similar overall levels of free recall, rates of learning over trials and subjective organisation of their recall. However, the primacy portion of the serial position curve of the ASD participants showed slower growth over trials than that of the typical participants. The implications of this finding for our understanding of memory in ASD are discussed.

3. Gokcen S, Bora E, Erermis S, Kesikci H, Aydin C. Theory of mind and verbal working memory deficits in parents of autistic children. Psychiatry Res ;2009 (Feb 4)

The objective of this study was to investigate the potential values of executive function and social cognition deficits as endophenotypes of autism. While theory of mind (ToM) is generally accepted as a unitary concept, some have suggested that ToM may be separated into two components (mental state reasoning and decoding). In this study, both aspects of ToM and verbal working memory abilities were investigated with relatively demanding tasks. The authors used a neurocognitive battery to compare the executive function and social cognition skills of 76 parents of autistic probands with 41 parents of healthy children. Both groups were matched for IQ, age and gender. Index parents had verbal working memory deficits. They had also low performance on a mental state reasoning task. Index parents had difficulties in reasoning about others’ emotions. In contrast to findings in the control group, low performance of mental state reasoning ability was not associated with working memory deficit in index parents. Social cognition and working memory impairments may represent potential endophenotypes, related to an underlying vulnerability for autistic spectrum disorders.

4. Kuusikko S, Haapsamo H, Jansson-Verkasalo E, Hurtig T, Mattila ML, Ebeling H, Jussila K, Bolte S, Moilanen I. Emotion Recognition in Children and Adolescents with Autism Spectrum Disorders. J Autism Dev Disord ;2009 (Feb 10)

We examined upper facial basic emotion recognition in 57 subjects with autism spectrum disorders (ASD) (M = 13.5 years) and 33 typically developing controls (M = 14.3 years) by using a standardized computer-aided measure (The Frankfurt Test and Training of Facial Affect Recognition, FEFA). The ASD group scored lower than controls on the total scores of FEFA and perceived ambiguous stimuli more often as a negative emotion. The older ASD group (>/=12 years) performed better than the younger ASD group (<12 years) on the blended emotions of FEFA. The results support the findings that individuals with ASD have difficulties in emotion recognition. However, older subjects with ASD seem to have better skills than younger subjects with ASD.

5. Lind SE, Bowler DM. Language and Theory of Mind in Autism Spectrum Disorder : The Relationship Between Complement Syntax and False Belief Task Performance. J Autism Dev Disord ;2009 (Feb 10)

This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of "hacking out" solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a "memory for complements" task, a measure of receptive vocabulary, and traditional location change and unexpected contents false belief tasks. Consistent with predictions, the correlation between complement syntax score and location change task performance was significantly stronger within the ASD group than within the comparison group. However, contrary to predictions, complement syntax score was not significantly correlated with unexpected contents task performance within either group. Possible explanations for this pattern of results are considered.

6. Nelson D, Amplo K. Care of the autistic patient in the perioperative area. Aorn J ;2009 (Feb) ;89(2):391-397.

7. Oosterling IJ, Swinkels SH, van der Gaag RJ, Visser JC, Dietz C, Buitelaar JK. Comparative Analysis of Three Screening Instruments for Autism Spectrum Disorder in Toddlers at High Risk. J Autism Dev Disord ;2009 (Feb 10)

Several instruments have been developed to screen for autism spectrum disorders (ASD) in high-risk populations. However, few studies compare different instruments in one sample. Data were gathered from the Early Screening of Autistic Traits Questionnaire, Social Communication Questionnaire, Communication and Symbolic Behavior Scales-Developmental Profile, Infant-Toddler Checklist and key items of the Checklist for Autism in Toddlers in 238 children (mean age = 29.6 months, SD = 6.4) at risk for ASD. Discriminative properties are compared in the whole sample and in two age groups separately (8-24 months and 25-44 months). No instrument or individual item shows satisfying power in discriminating ASD from non-ASD, but pros and cons of instruments and items are discussed and directions for future research are proposed.

8. Scahill L, Bearss K. The rise in autism and the mercury myth. J Child Adolesc Psychiatr Nurs ;2009 (Feb) ;22(1):51-53.

9. Sokhadze E, Baruth J, Tasman A, Sears L, Mathai G, El-Baz A, Casanova MF. Event-related Potential Study of Novelty Processing Abnormalities in Autism. Appl Psychophysiol Biofeedback ;2009 (Feb 6)

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.

10. Tabares-Seisdedos R, Rubenstein JL. Chromosome 8p as a potential hub for developmental neuropsychiatric disorders : implications for schizophrenia, autism and cancer. Mol Psychiatry ;2009 (Feb 10)

Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p ; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson’s and Alzheimer’s disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.Molecular Psychiatry advance online publication, 10 February 2009 ; doi:10.1038/mp.2009.2.

11. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A ;2009 (Feb 10) ;106(6):2029-2034.

Rett Syndrome (RTT) is a severe form of X-linked mental retardation caused by mutations in the gene coding for methyl CpG-binding protein 2 (MECP2). Mice deficient in MeCP2 have a range of physiological and neurological abnormalities that mimic the human syndrome. Here we show that systemic treatment of MeCP2 mutant mice with an active peptide fragment of Insulin-like Growth Factor 1 (IGF-1) extends the life span of the mice, improves locomotor function, ameliorates breathing patterns, and reduces irregularity in heart rate. In addition, treatment with IGF-1 peptide increases brain weight of the mutant mice. Multiple measurements support the hypothesis that RTT results from a deficit in synaptic maturation in the brain : MeCP2 mutant mice have sparse dendritic spines and reduced PSD-95 in motor cortex pyramidal neurons, reduced synaptic amplitude in the same neurons, and protracted cortical plasticity in vivo. Treatment with IGF-1 peptide partially restores spine density and synaptic amplitude, increases PSD-95, and stabilizes cortical plasticity to wild-type levels. Our results thus strongly suggest IGF-1 as a candidate for pharmacological treatment of RTT and potentially of other CNS disorders caused by delayed synapse maturation.

12. Wachtel LE, Contrucci-Kuhn SA, Griffin M, Thompson A, Dhossche DM, Reti IM. ECT for self-injury in an autistic boy. Eur Child Adolesc Psychiatry ;2009 (Feb 5)

OBJECTIVE : Self-injurious behavior presents a significant challenge in autism, and first-line psychopharmacological and behavioral interventions have limited efficacy in some patients. These intractable cases may be responsive to electroconvulsive therapy. CLINICAL PICTURE : This article presents an eight-year-old boy with autism, mental retardation, prominent mood lability and a five-year history of extreme self-injurious behavior towards his head, averaging 109 self-injurious attempts hourly. The patient was at high risk for serious head trauma, and required usage of bilateral arm restraints and protective equipment (i.e., padding on shoulders, arms, and legs). All areas of daily functioning were profoundly impacted by dangerous self-injury. TREATMENT : Fifteen bilateral ECT treatments resulted in excellent mood stabilization and reduction of self-injury to 19 attempts hourly, and maintenance ECT was pursued. The patient was able to return to developmentally-appropriate educational and social activities. CONCLUSION : ECT should be considered in the treatment algorithm of refractory cases of severe self-injury in autism.

13. Williams DM, Happe F. What Did I Say ? Versus What Did I Think ? Attributing False Beliefs to Self Amongst Children With and Without Autism. J Autism Dev Disord ;2009 (Feb 10)

The task used most widely to assess recognition of false belief in self and others is the ’Smarties’ unexpected contents task. Amongst individuals with and without autism, the Self and Other-person test questions of this task are of an equivalent level of difficulty. However, a potential confound with this task may allow the Self test question to be passed without false belief competence. Three groups of participants (with autism, developmental disability and typical development) undertook a new unexpected contents task which did not suffer from this confound. The main finding was that participants with autism performed significantly less well on the Self test question than the Other-person test question on this new task. Individuals with autism may have greater difficulty representing their own beliefs than the beliefs of other people.


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