1. Berry-Kravis E, Sumis A, Hervey C, Mathur S. {{Clinic-based retrospective analysis of psychopharmacology for behavior in fragile x syndrome}}. {Int J Pediatr}. 2012; 2012: 843016.
Fragile X syndrome (FXS) is associated with behavior that limits functioning, including distractibility, hyperactivity, impulsivity, hyperarousal, anxiety, mood dysregulation, and aggression. Medication response and side effect data were reviewed retrospectively for 257 patients (age 14 +/- 11 years, range 4-60 years, 203 M, 54 F) attending an FXS clinic. Treatment success rates were defined as the percentage of positive response in the form of documented clinical report of improvement in the behavior(s) being targeted over at least a 6-month period on the medication, without side effects requiring medication discontinuance, while failures were defined as discontinuance of medication due to lack of clinical effectiveness or side effects. Success rate for treatment of targeted behaviors with trials of individual medications was 55% for stimulants, 53% for antidepressants, 62% for alpha2-agonists, and 54% for antipsychotics. With sequential trials of different medications in the same class, success rate improved to 73-77%. Side effect-related failures were highest for antipsychotics. Systematic psychopharmacologic intervention targeted to behavioral symptoms appears helpful in the majority of patients with FXS.
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2. Bozdagi O, Sakurai T, Dorr N, Pilorge M, Takahashi N, Buxbaum JD. {{Haploinsufficiency of cyfip1 produces fragile x-like phenotypes in mice}}. {PLoS One}. 2012; 7(8): e42422.
BACKGROUND: Copy number variation (CNV) at the 15q11.2 region, which includes a gene that codes for CYFIP1 (cytoplasmic FMR1 interacting protein 1), has been implicated in autism, intellectual disability and additional neuropsychiatric phenotypes. In the current study we studied the function of Cyfip1 in synaptic physiology and behavior, using mice with a disruption of the Cyfip1 gene. METHODOLOGY/PRINCIPAL FINDINGS: We observed that in Cyfip1 heterozygous mice metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) induced by paired-pulse low frequency stimulation (PP-LFS) was significantly increased in comparison to wildtype mice. In addition, mGluR-LTD was not affected in the presence of protein synthesis inhibitor in the Cyfip1 heterozygous mice, while the same treatment inhibited LTD in wildtype littermate controls. mGluR-agonist (RS)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD was also significantly increased in hippocampal slices from Cyfip1 heterozygous mice and again showed independence from protein synthesis only in the heterozygous animals. Furthermore, we observed that the mammalian Target of Rapamycin (mTOR) inhibitor rapamycin was only effective at reducing mGluR-LTD in wildtype animals. Behaviorally, Cyfip1 heterozygous mice showed enhanced extinction of inhibitory avoidance. Application of both mGluR5 and mGluR1 antagonist to slices from Cyfip1 heterozygous mice reversed the increase in DHPG-induced LTD in these mice. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that haploinsufficiency of Cyfip1 mimics key aspects of the phenotype of Fmr1 knockout mice and are consistent with the hypothesis that these effects are mediated by interaction of Cyfip1 and Fmrp in regulating activity-dependent translation. The data provide support for a model where CYFIP1 haploinsufficiency in patients results in intermediate phenotypes increasing risk for neuropsychiatric disorders.
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3. Gan SM, Tung LC, Yeh CY, Wang CH. {{ICF-CY based assessment tool for children with autism}}. {Disabil Rehabil}. 2012.
Purpose: The objectives of this study was to develop an International Classification of Functioning, Disability and Health-Children and Youth (ICF-CY) based questionnaire for children with autism, investigate the inter-rater reliability of the questionnaire and assess functional performance in children with autism. Method: The ICF-CY based questionnaire for children with autism comprised 118 items was designed with reference the ICF-CY structure. The study protocol was divided into two parts. In the first part, the inter-rater reliability of the questionnaire was investigated using information from 26 children (aged 3-6 years) with autism and using the intra-class correlation coefficients to estimate reliability. The second part of the study aimed to assess functional performance of another independent sample (136 children, aged 3-6 years) utilizing the questionnaire. Mean scores were compared by nonparametric statistic. Results: The inter-rater reliability for each domains of the questionnaire was found to be moderate to high (intra-class correlation coefficients ranged from 0.72 to 0.97). Children with autism had major problems in voice and speech functions. They had high dependency when executing individual activities of learning and applied knowledge. They also required maximal assistance while engaging in social activities related to conversation and major life categories. Conclusions: This preliminary study shows that ICF-CY based questionnaire has good reliability and can reflect the functional profile of preschool children with autism. However, further study is needed to confirm other psychometric characteristics. [Box: see text].
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4. Hasan KM, Walimuni IS, Frye RE. {{Global Cerebral and Regional Multimodal Neuroimaging Markers of the Neurobiology of Autism: Development and Cognition}}. {J Child Neurol}. 2012.
Quantitative magnetic resonance imaging (MRI) studies of the microstructure and macrostructure in children with autism report contradictory results due, in part, to the autistic population heterogeneity from factors such as variation in intellect and inadequately accounting for age-related changes in brain development. In this report, the authors compared global and regional volumetry, relaxometry, anisotropy, and diffusometry of gray and white matter in 10 autism spectrum disorder children relative to the age-related trajectories obtained from 38 typically developing controls while controlling for nonverbal intellect using a validated quantitative MRI method. The normalized hippocampus volume increased with age in both autistic and typically developing individuals with limbic structures larger in autistic patients. Hippocampus volume, but not diffusivity or relaxation time, was larger in autistic children. Hippocampus volume was inversely correlated with nonverbal intellect across control individuals. The pattern of hippocampal abnormalities suggests a disturbance in early brain development in autistic children independent of intellect.
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5. Kouijzer ME, van Schie HT, Gerrits BJ, Buitelaar JK, de Moor JM. {{Is EEG-biofeedback an Effective Treatment in Autism Spectrum Disorders? A Randomized Controlled Trial}}. {Appl Psychophysiol Biofeedback}. 2012.
EEG-biofeedback has been reported to reduce symptoms of autism spectrum disorders (ASD) in several studies. However, these studies did not control for nonspecific effects of EEG-biofeedback and did not distinguish between participants who succeeded in influencing their own EEG activity and participants who did not. To overcome these methodological shortcomings, this study evaluated the effects of EEG-biofeedback in ASD in a randomized pretest-posttest control group design with blinded active comparator and six months follow-up. Thirty-eight participants were randomly allocated to the EEG-biofeedback, skin conductance (SC)-biofeedback or waiting list group. EEG- and SC-biofeedback sessions were similar and participants were blinded to the type of feedback they received. Assessments pre-treatment, post-treatment, and after 6 months included parent ratings of symptoms of ASD, executive function tasks, and 19-channel EEG recordings. Fifty-four percent of the participants significantly reduced delta and/or theta power during EEG-biofeedback sessions and were identified as EEG-regulators. In these EEG-regulators, no statistically significant reductions of symptoms of ASD were observed, but they showed significant improvement in cognitive flexibility as compared to participants who managed to regulate SC. EEG-biofeedback seems to be an applicable tool to regulate EEG activity and has specific effects on cognitive flexibility, but it did not result in significant reductions in symptoms of ASD. An important finding was that no nonspecific effects of EEG-biofeedback were demonstrated.
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6. Mostafa GA, Al-Ayadhi LY. {{Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity}}. {J Neuroinflammation}. 2012; 9(1): 201.
ABSTRACT: BACKGROUND: Aside from the skeletal health affection, vitamin D deficiency has been implicated as a potential environmental factor triggering for some autoimmune disorders. Vitamin D might play a role in the regulation of the production of auto-antibodies. Immunomodulatory effects of vitamin D may act not only through modulation of T-helper cell function, but also through induction of CD4+CD25high regulatory T-cells. We are the first to investigate the relationship between serum levels of 25-hydroxy vitamin D and anti-myelin-associated glycoprotein (anti-MAG) auto-antibodies in autistic children. METHODS: Serum levels of 25-hydroxy vitamin D and anti-MAG auto-antibodies were measured in 50 autistic children, aged between 5 and 12 years, and 30 healthy-matched children. Serum 25-hydroxy vitamin D levels 10–30 ng/mL and < 10 ng/mL were defined as vitamin D insufficiency and deficiency, respectively. RESULTS: Autistic children had significantly lower serum levels of 25-hydroxy vitamin D than healthy children (P < 0.001) with 40% and 48% being vitamin D deficient and insufficient, respectively. Serum 25-hydroxy vitamin D had significant negative correlations with Childhood Autism Rating Scale (P < 0.001). Increased levels of serum anti-MAG auto-antibodies were found in 70% of autistic patients. Serum 25-hydroxy vitamin D levels had significant negative correlations with serum levels of anti-MAG auto-antibodies (P < 0.001). CONCLUSIONS: Vitamin D deficiency was found in some autistic children and this deficiency may contribute to the induction of the production of serum anti-MAG auto-antibodies in these children. However, future studies looking at a potential role of vitamin D in the pathophysiology and treatment of autism are warranted.
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7. Salowitz NM, Eccarius P, Karst J, Carson A, Schohl K, Stevens S, Van Hecke AV, Scheidt RA. {{Brief Report: Visuo-spatial Guidance of Movement during Gesture Imitation and Mirror Drawing in Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2012.
Thirteen autistic and 14 typically developing children (controls) imitated hand/arm gestures and performed mirror drawing; both tasks assessed ability to reorganize the relationship between spatial goals and the motor commands needed to acquire them. During imitation, children with autism were less accurate than controls in replicating hand shape, hand orientation, and number of constituent limb movements. During shape tracing, children with autism performed accurately with direct visual feedback, but when viewing their hand in a mirror, some children with autism generated fewer errors than controls whereas others performed much worse. Large mirror drawing errors correlated with hand orientation and hand shape errors in imitation, suggesting that visuospatial information processing deficits may contribute importantly to functional motor coordination deficits in autism.
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8. Takahashi J, Gyoba J. {{Self-rated autistic-like traits and capacity of visual working memory}}. {Psychol Rep}. 2012; 110(3): 879-90.
The effect on the capacity of visual working memory of spatial complexity (as defined by Garner’s principle) in rotation and reflection transformation was examined in persons differing along the Autism Spectrum Quotient (AQ), using a change-detection task. On each trial, nine line segments were arrayed in simple, medium, and complex configurations, which were presented in memory and test displays. 27 participants (8 men, 19 women; M age = 22.3 yr., SD = 2.7) were asked whether the orientations of stimuli between two displays were the same or different. On the basis of their AQ scores out of 50 (M AQ scores = 20.9, SD = 6.3), the participants were divided into groups with high (n = 13; M AQ scores = 26.2, SD = 4.1) and low (n = 12; M AQ scores = 15.3, SD = 2.7) self-reported autistic-like traits (High and Low AQ groups, 2 excluded for scores at the median). The results showed that spatial complexity affects the capacity of visual working memory for the Low AQ group but not for the High AQ group, suggesting the functional dissociation of spatial configuration and visual working memory in the High AQ group.
