Pubmed du 11/06/10

vendredi 18 juin 2010

1. Iseri E, Guney E, Ceylan MF, Yucel A, Aral A, Bodur S, Sener S. Increased Serum Levels of Epidermal Growth Factor in Children with Autism. J Autism Dev Disord (Jun 11)

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral nervous system. In this study we hypothesized that EGF may play a role in the pathophysiology of autism and examined serum EGF levels in children with autism. We measured serum levels of EGF in the 27 autistic children and 28 age- matched normal controls. The serum levels of EGF in the subjects with autism were significantly higher than those of normal control subjects. However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. This is the first report demonstrating the increased serum levels of EGF in children with autism. This study suggests that increased levels of EGF might have an importance in the pathophysiology of autism.

2. Jegatheesan B. Muslim children with autism learn to pray. J Dev Behav Pediatr (Jun) ;31(5):458-459.

3. Kim EK, Neggers YH, Shin CS, Kim E, Kim EM. Alterations in lipid profile of autistic boys : a case control study. Nutr Res (Apr) ;30(4):255-260.

We hypothesize that autism is associated with alterations in the plasma lipid profile and that some lipid fractions in autistic boys may be significantly different than those of healthy boys. A matched case control study was conducted with 29 autistic boys (mean age, 10.1 +/- 1.3 years) recruited from a school for disabled children and 29 comparable healthy boys from a neighboring elementary school in South Korea. Fasting plasma total cholesterol (T-Chol), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), the LDL/HDL ratio, and 1-day food intakes were measured. Multiple regression analyses were performed to assess the association between autism and various lipid fractions. The mean TG level (102.4 +/- 52.4 vs 70.6 +/- 36.3 ; P = .01) was significantly higher, whereas the mean HDL-C level (48.8 +/- 11.9 vs 60.5 +/- 10.9 mg/dL ; P = .003) was significantly lower in cases as compared to controls. There was no significant difference in T-Chol and LDL-C levels between cases and controls. The LDL/HDL ratio was significantly higher in cases as compared to controls. Multiple regression analyses indicated that autism was significantly associated with plasma TG (beta = 31.7 +/- 11.9 ; P = .01), HDL (beta = -11.6 +/- 2.1 ; P = .0003), and the LDL/HDL ratio (beta = 0.40 +/- 0.18 ; P = .04). There was a significant interaction between autism and TG level in relation to plasma HDL level (P = .02). Fifty-three percent of variation in the plasma HDL was explained by autism, plasma TG, LDL/HDL ratio, and the interaction between autism and plasma TG level. These results indicate the presence of dyslipidemia in boys with autism and suggest a possibility that dyslipidemia might be a marker of association between lipid metabolism and autism.

4. Matsuo M, Maeda T, Sasaki K, Ishii K, Hamasaki Y. Frequent association of autism spectrum disorder in patients with childhood onset epilepsy. Brain Dev (Jun 11)

Autism spectrum disorder (ASD) has a close relationship with epilepsy. This study retrospectively examined patients with epilepsy associated with ASD. Among the 519 patients with epilepsy, 79 patients (15.2%) had ASD. Sixty-two patients had idiopathic ASD and 17 had secondary ASD. The epilepsy patients with idiopathic ASD were retrospectively analyzed. There were 47 males and 15 females, ranging from 2 to 43years of age (median 11years). The most frequent age at the onset of seizures was 4years, and 85% occurred before 10. ASD was detected after the onset of epilepsy in 29 cases (46.8%), and eight of them had been overlooked for more than five years. Most of these were high-functioning ASD cases. The most frequent type of seizure was a complex partial seizure (CPS ; 68%). Paroxysmal activities on EEG were localized in the frontal area in about half of the cases. Multiple anti-epileptic drugs were used in 33.8% cases (two in 17.7%, three in 16.1%), and 67.3% of the patients were seizure-free for more than two years. An amelioration of the autistic symptoms occurred after epilepsy treatment in five cases (8%). CPS with frontal paroxysms occurring from one to nine years of age seems to be characteristic of epilepsy associated with ASD.

5. Sahyoun CP, Belliveau JW, Mody M. White matter integrity and pictorial reasoning in high-functioning children with autism. Brain Cogn (Jun 11)

The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups’ response times (RT) on a pictorial reasoning task under three conditions : visuospatial, V, semantic, S, and V+S, a hybrid condition allowing language use to facilitate visuospatial transformations. Diffusion-weighted images were collected from HFA and CTRL participants, matched on age and IQ, and significance maps were computed for group differences in fractional anisotropy (FA) and in RT-FA association for each condition. Typically developing children showed increased FA within frontal white matter and the superior longitudinal fasciculus (SLF). HFA showed increased FA within peripheral white matter, including the ventral temporal lobe. Additionally, RT-FA relationships in the semantic condition (S) implicated white matter near the STG and in the SLF within the temporal and frontal lobes to a greater extent in CTRL. Performance in visuospatial reasoning (V, V+S), in comparison, was related to peripheral parietal and superior precentral white matter in HFA, but to the SLF, callosal, and frontal white matter in CTRL. Our results appear to support a preferential use of linguistically-mediated pathways in reasoning by typically developing children, whereas autistic cognition may rely more on visuospatial processing networks.

6. Self TL, Hale LS, Crumrine D. Pharmacotherapy and Children with Autism Spectrum Disorder : A Tutorial for Speech-Language Pathologists. Lang Speech Hear Serv Sch (Jun 11)

PURPOSE : The purpose of this tutorial is to provide Speech-Language Pathologists (SLPs) with general information regarding the most commonly prescribed medications for children with Autism Spectrum Disorder (ASD) (e.g., central nervous system stimulants, noradrenergic reuptake inhibitors, alpha-2 adrenergic agonists, antipsychotics, anticonvulsants, selective serotonin reuptake inhibitors, benzodiazepines) in regard to their mechanism of action, behaviors treated, and potential side effects. METHOD : This clinical resource was complied to support SLPs who need to understand the functions and effects of medications that have been prescribed to a child with ASD to whom they have or will be providing assessment and intervention services. CONCLUSIONS : SLPs play an important role in education, assessment, and treatment for children with ASD. Although there is no definitive cure for ASD, up to 70% of children with ASD are prescribed psychoactive medications to ameliorate disruptive behaviors associated with ASD such ashyperactivity, inattention, impulsivity, aggression, irritability, self-injury, obsessive compulsiveness, anxiety, and mood disorders. The entire healthcare team, including SLPs, should be involved in monitoring for efficacy, tolerability, and potential side effects when medications are prescribed.

7. Shamay-Tsoory SG, Gev E, Aharon-Peretz J, Adler N. Brain asymmetry in emotional processing in Asperger syndrome. Cogn Behav Neurol (Jun) ;23(2):74-84.

The role of brain asymmetry in emotional processing in Asperger syndrome (AS) is still largely unknown. Although the valence hypothesis predicts that positive emotions are processed preferentially by the left hemisphere and negative emotions by the right hemisphere, reports concerning laterality of emotion point to a left hemisphere advantage for complex emotion versus a right hemisphere advantage for basic emotions (the "type hypothesis"). In this study, we investigated the lateralization of basic versus complex (negative and positive) eye expressions in adults with AS in 2 consecutive experiments : in the first experiment, the performance of AS and healthy controls were compared in a divided visual field task. In the second experiment, the ability of participants with AS to identify eye expressions varying in valence and type was compared with that of patients with localized lesions in either the right or the left hemispheres. Controls were better in recognizing negative emotions presented to the left visual field and positive emotions presented to the right visual field, whereas individuals with AS failed to show this interaction effect. Lateralization of basic versus complex emotions was less evident although indeed controls identified better basic emotions presented to the right visual field. Furthermore, participants with AS exhibited a similar pattern of recognition of negative versus positive emotions to that of patients with left hemisphere damage. It is suggested that the pattern of performance of individuals with AS resembles that of patients with left hemisphere dysfunction.

8. Takumi T. A humanoid mouse model of autism. Brain Dev (Jun 11)

Even now fruit of the human genome project is available, we have difficulties to approach neuropsychiatric disorders at the molecular level. Autism is a complex psychiatric illness but has received considerable attention as a developmental brain disorder not only from basic researchers but also from society. Substantial evidence suggests that chromosomal abnormalities contribute to autism risk. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We succeeded to generate mice with a 6.3-Mb-wide interstitial duplication in mouse chromosome 7c that is highly syntenic to human 15q11-13 by using a Cre-loxP-based chromosome-engineering technique. The only paternally duplicated mice display autistic behavioral features such as poor social interaction and stereotypical behavior, and exhibit a developmental abnormality in ultrasonic vocalizations as well as anxiety. The detailed analysis focusing on a non-coding small nucleolar RNA, MBII52, within the duplicated region, revealed that the paternally duplicated mice alter the editing ratio of serotonin (5-HT) 2c receptor pre-mRNA and intracellular calcium responses by a 5-HT2c receptor specific agonist are changed in neurons. This result may explain one of molecular mechanisms of abnormal behaviors in the paternal duplicated mice. The first chromosome-engineered mouse model for human chromosome 15q11-13 duplication fulfills not only face validity of human autistic phenotypes but also construct validity based on human chromosome abnormality. This model will be a founder mouse for forward genetics of autistic disease and an invaluable tool for its therapeutic development.

9. Wright B, Sims D, Smart S, Alwazeer A, Alderson-Day B, Allgar V, Whitton C, Tomlinson H, Bennett S, Jardine J, McCaffrey N, Leyland C, Jakeman C, Miles J. Melatonin Versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies : A Randomised Controlled Crossover Trial. J Autism Dev Disord (Jun 10)

Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind, randomised, controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg. 17 children completed the study. There were no significant differences between sleep variables at baseline. Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings. The side effect profile was low and not significantly different between the two arms.

10. Young DM, Schenk AK, Yang SB, Jan YN, Jan LY. Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism. Proc Natl Acad Sci U S A (Jun 15) ;107(24):11074-11079.

Tuberous sclerosis (TSC) is an autosomally dominant neurocutaneous disease notable for its high comorbidity with autism in human patients. Studies of murine models of tuberous sclerosis have found defects in cognition and learning, but thus far have not uncovered deficits in social behaviors relevant to autism. To explore social communication and interaction in TSC2 heterozygous mice, we recorded ultrasonic vocalizations (USV) and found that although both wild-type (WT) and heterozygous pups born to WT dams showed similar call rates and patterns, baseline vocalization rates were elevated in pups born to heterozygous dams. Further analysis revealed several robust features of maternal potentiation in all but WT pups born to heterozygous dams. This lack of potentiation is suggestive of defects in mother-pup social interaction during or before the reunion period between WT pups and heterozygous dams. Intriguingly, male pups of both genotypes born to heterozygous dams showed particularly heightened call rates and burst patterns. Because our maternal retrieval experiments revealed that TSC2(+/-) dams exhibited improved defensive reactions against intruders and highly efficient pup retrieval performance, the alterations in their pups’ USVs and maternal potentiation do not appear to result from poor maternal care. These findings suggest that a pup’s interaction with its mother strongly influences the pup’s vocal communication, revealing an intriguing dependence of this social behavior on TSC2 gene dosage of both parties involved. Our study of this murine model thus uncovers social abnormalities that arise from TSC haploinsufficiency and are suggestive of autism.


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