1. Badia M, Orgaz MB, Verdugo MA, Ullan AM, Martinez M. {{Relationships between Leisure Participation and Quality of Life of People with Developmental Disabilities}}. {J Appl Res Intellect Disabil};2013 (Apr 24)
BACKGROUND: Studies of people with developmental disabilities suggest that participation in leisure activities might be a key factor for good quality of life. This study explores the relationships between objective and subjective quality of life and leisure participation of adults with developmental disabilities. MATERIALS AND METHODS: A cross-sectional design was used with a convenience sample of 125 people, aged 17-65, living in the community. Participants completed the subjective scale of Integral Quality Scale and the Leisure Assessment Inventory in the form of an individual interview. Staff completed the GENCAT Scale. RESULTS: No relationship was found between objective quality of life and leisure participation. However, correlations between some leisure participation dimensions and specific subjective quality of life domains were observed. The results establish a predictive relationship between leisure participation and material, emotional, and physical well-being. Personal and environmental variables analyzed were not found to have a moderating effect on the relationship between leisure participation and quality of life. CONCLUSIONS: These findings indicate that some aspects of leisure participation may significantly contribute to enhancing the quality of life of young people and adults with developmental disabilities living in the community.
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2. Bas VN, Cetinkaya S, Agladioglu SY, Aksoy A, Gulpinar B, Aycan Z. {{Report of the first case of precocious puberty in Rett syndrome}}. {J Pediatr Endocrinol Metab};2013 (Apr 2):1-3.
Abstract Rett syndrome is an X-linked dominant disorder frequently caused by the mutations in the methyl-CpG-binding protein 2 gene (MECP2). Its prevalence in the population is 1/15,000-20,000. Patients with Rett syndrome present apparently normal psychomotor developments during the first 6-18 months of life. Subsequently, they show a short period of developmental stagnation followed by a rapid regression in language and motor development. Precocious puberty is characterized by premature breast and pubic hair development, and advanced bone age development at 8 years of age. We present a case of Rett syndrome and precocious puberty in a 6-year-old girl. At the age of 6, the first signs of precocious puberty appeared (Tanner stage 3). Laboratory measurements were detected as follows: luteinizing hormone (LH), 0.2 mIU/mL; follicle-stimulating hormone (FSH), 1.1 mIU/mL; estradiol, 36 pg/mL; bone age, 9 years. The response to luteinizing hormone releasing hormone (gonadotropin-releasing hormone stimulation test) was characteristic for true precocious puberty (LH, 32 mIU/mL; FSH, 26 mIU/mL). This is the first reported case of precocious puberty related to Rett syndrome.
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3. Christensen J, Gronborg TK, Sorensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M. {{Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism}}. {JAMA};2013 (Apr 24);309(16):1696-1703.
IMPORTANCE: Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism. OBJECTIVE: To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring. DESIGN, SETTING, AND PARTICIPANTS: Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. MAIN OUTCOMES AND MEASURES: Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy. RESULTS: Of 655,615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate. CONCLUSIONS AND RELEVANCE: Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.
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4. Cooper M, Martin J, Langley K, Hamshere M, Thapar A. {{Autistic traits in children with ADHD index clinical and cognitive problems}}. {Eur Child Adolesc Psychiatry};2013 (Apr 25)
Traits of autistic spectrum disorders (ASD) occur frequently in attention deficit hyperactivity disorder (ADHD), but the significance of their presence in terms of phenotype and underlying neurobiology is not properly understood. This analysis aimed to determine whether higher levels of autistic traits, as measured by the Social Communication Questionnaire (SCQ), index a more severe presentation in a large, rigorously phenotyped sample of children with ADHD (N = 711). Regression analyses were used to examine association of SCQ scores with core ADHD features, clinical comorbidities and cognitive and developmental features, with adjustment for putative confounders. For outcomes showing association with total SCQ score, secondary analyses determined levels of differential association of the three ASD sub-domains. Results suggest that increasing ASD symptomatology within ADHD is associated with a more severe phenotype in terms of oppositional, conduct and anxiety symptoms, lower full-scale IQ, working memory deficits and general motor problems. These associations persisted after accounting for ADHD severity, suggesting that autistic symptomatology independently indexes the severity of comorbid impairments in the context of ADHD. Sub-domain scores did not show unique contributions to most outcomes, except that social deficits were independently associated with oppositional symptoms and repetitive behaviours independently predicted hyperactive-impulsive symptoms and motor problems. It would be worthwhile for clinicians to consider levels of socio-communicative and repetitive traits in those with ADHD who do not meet diagnostic criteria for ASD, as they index higher levels of phenotypic complexity, which may have implications for efficacy of interventions.
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5. Dominguez LG, Velazquez JL, Galan RF. {{A model of functional brain connectivity and background noise as a biomarker for cognitive phenotypes: application to autism}}. {PLoS One};2013;8(4):e61493.
We present an efficient approach to discriminate between typical and atypical brains from macroscopic neural dynamics recorded as magnetoencephalograms (MEG). Our approach is based on the fact that spontaneous brain activity can be accurately described with stochastic dynamics, as a multivariate Ornstein-Uhlenbeck process (mOUP). By fitting the data to a mOUP we obtain: 1) the functional connectivity matrix, corresponding to the drift operator, and 2) the traces of background stochastic activity (noise) driving the brain. We applied this method to investigate functional connectivity and background noise in juvenile patients (n = 9) with Asperger’s syndrome, a form of autism spectrum disorder (ASD), and compared them to age-matched juvenile control subjects (n = 10). Our analysis reveals significant alterations in both functional brain connectivity and background noise in ASD patients. The dominant connectivity change in ASD relative to control shows enhanced functional excitation from occipital to frontal areas along a parasagittal axis. Background noise in ASD patients is spatially correlated over wide areas, as opposed to control, where areas driven by correlated noise form smaller patches. An analysis of the spatial complexity reveals that it is significantly lower in ASD subjects. Although the detailed physiological mechanisms underlying these alterations cannot be determined from macroscopic brain recordings, we speculate that enhanced occipital-frontal excitation may result from changes in white matter density in ASD, as suggested in previous studies. We also venture that long-range spatial correlations in the background noise may result from less specificity (or more promiscuity) of thalamo-cortical projections. All the calculations involved in our analysis are highly efficient and outperform other algorithms to discriminate typical and atypical brains with a comparable level of accuracy. Altogether our results demonstrate a promising potential of our approach as an efficient biomarker for altered brain dynamics associated with a cognitive phenotype.
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6. El-Baz F, Hamza RT, Ayad MS, Mahmoud NH. {{Hyperandrogenemia in male autistic children and adolescents: relation to disease severity}}. {Int J Adolesc Med Health};2013 (Apr 20):1-6.
Abstract Background: It has been suggested that autistic patients have elevated blood androgens, and although signs of precocious puberty have been reported in autistic patients, such a relation has not yet been clarified. Objectives: To assess serum androgen levels in a group of Egyptian male autistic children and adolescents and their relation to disease severity. In addition, the risk for association of androgens with autism was estimated. Methods: In comparison to 20 controls, 30 male autistic children were studied. All subjects were subjected to clinical evaluation, intelligence quotient (IQ) assessment and measurement of serum free testosterone (FT), dehydroepiandosterone (DHEA) and Delta4-androstenedione (Delta4-A). Results: Androgens were higher in autistic patients than in controls and increased with increased autistic severity. Of the patients, 11 (36.66%) had high FT, 9 (30%) had high DHEA, 12 (40%) had high Delta4-A and 8 (26.66%) showed elevation of all androgen levels. FT (OR: 38.45, 95% CI: 2.14-688.93, p=0.013) and Delta4-A (OR: 13.6, 95%CI: 2.25-22.89, p=0.04) had a significant risk for association with autism. Conclusions: Hyperandrogenemia is prevalent in autistic patients and increases with autistic severity. Thus, androgen levels should be assessed in autistic patients with signs of early puberty. Further studies are warranted regarding trials of anti-androgen therapy in such patients.
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7. Guo T, Wang W, Liu B, Chen H, Yang C. {{Catechol-O-methyltransferase Val158Met polymorphism and risk of autism spectrum disorders}}. {J Int Med Res};2013 (Apr 15)
OBJECTIVE: Autism spectrum disorders (ASD) are a family of childhood-onset neurodevelopmental disorders with complex genetic mechanisms underlying their aetiology. The aim of this case-control study was to evaluate the effect of the catechol-O-methyltransferase (COMT) gene Val158Met polymorphism on ASD risk in a Chinese Han population. METHODS: The COMT gene Val158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in children (</=18 years old) with ASD and healthy control subjects. RESULTS: The frequency of the Val158/Val158 genotype in children with ASD (22/186; 11.8%) was significantly lower than in controls (38/186; 20.4%). When stratifying by select-item scores on the Autism Diagnostic Interview-Revised protocol, it was found that children with ‘current overactivity’ and ‘ever overactivity’ had a significantly lower frequency of the Val158/Val158 genotype than those without. There were no significant associations between the COMT gene Val158Met polymorphism and ASD subtypes. CONCLUSIONS: The COMT gene Val158Met polymorphism may be a biomarker for phenotypic variation in ASD, but these preliminary findings remain tentative, pending replication in larger, independent samples.
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8. Jones-Davis DM, Yang M, Rider E, Osbun NC, da Gente GJ, Li J, Katz AM, Weber MD, Sen S, Crawley J, Sherr EH. {{Quantitative Trait Loci for Interhemispheric Commissure Development and Social Behaviors in the BTBR T(+) tf/J Mouse Model of Autism}}. {PLoS One};2013;8(4):e61829.
BACKGROUND: Autism and Agenesis of the Corpus Callosum (AgCC) are interrelated behavioral and anatomic phenotypes whose genetic etiologies are incompletely understood. We used the BTBR T(+) tf/J (BTBR) strain, exhibiting fully penetrant AgCC, a diminished hippocampal commissure, and abnormal behaviors that may have face validity to autism, to study the genetic basis of these disorders. METHODS: We generated 410 progeny from an F2 intercross between the BTBR and C57BL/6J strains. The progeny were phenotyped for social behaviors (as juveniles and adults) and commisural morphology, and genotyped using 458 markers. Quantitative trait loci (QTL) were identified using genome scans; significant loci were fine-mapped, and the BTBR genome was sequenced and analyzed to identify candidate genes. RESULTS: Six QTL meeting genome-wide significance for three autism-relevant behaviors in BTBR were identified on chromosomes 1, 3, 9, 10, 12, and X. Four novel QTL for commissural morphology on chromosomes 4, 6, and 12 were also identified. We identified a highly significant QTL (LOD score = 20.2) for callosal morphology on the distal end of chromosome 4. CONCLUSIONS: We identified several QTL and candidate genes for both autism-relevant traits and commissural morphology in the BTBR mouse. Twenty-nine candidate genes were associated with synaptic activity, axon guidance, and neural development. This is consistent with a role for these processes in modulating white matter tract development and aspects of autism-relevant behaviors in the BTBR mouse. Our findings reveal candidate genes in a mouse model that will inform future human and preclinical studies of autism and AgCC.
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9. Khanna R, Jariwala K, Bentley JP. {{Psychometric properties of the EuroQol Five Dimensional Questionnaire (EQ-5D-3L) in caregivers of autistic children}}. {Qual Life Res};2013 (Apr 25)
PURPOSE: This study aimed to ascertain the psychometric properties of EuroQol Five Dimensional Questionnaire (EQ-5D-3L) in primary caregivers of children with autism. The convergent validity, discriminant validity, known-groups validity, internal consistency reliability, and floor and ceiling effects of EQ-5D-3L were analyzed. METHODS: A cross-sectional design was used for study purposes. Through an online survey, relevant study information was collected from 316 primary caregivers of children with autism. Study participants were from families of children with autism living in the United States who were registered with the Interactive Autism Network. Convergent validity of the EQ-5D-3L was assessed through its correlation with other measures of similar constructs. Discriminant validity was assessed by observing the correlation of EQ-5D-3L domains with theoretically unrelated constructs. Known-groups validity was tested by comparing EQ-5D-3L index and visual analog scale (VAS) scores across levels of autism severity among the care recipients. Internal consistency reliability of EQ-5D-3L was tested. Lastly, floor and ceiling effects of EQ-5D-3L were assessed. RESULTS: More than 60 % of participants reported problems of ‘anxiety/depression.’ Convergent and discriminant validity of the EQ-5D-3L was good. Significant correlation (convergent validity) was observed among EQ-5D-3L index and VAS and (SF-12v2) physical component summary and mental component summary scores. Caregivers’ EQ-5D-3L index and VAS scores varied by levels of autism severity among care recipients, providing evidence of known-groups validity. Reliability assessed through Cronbach’s alpha was less than satisfactory; however, corrected item-total correlations were adequate. CONCLUSIONS: The EQ-5D-3L is a psychometrically sound tool to elicit health state preferences among caregivers of children with autism.
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10. Kopecky K, Broder-Fingert S, Iannuzzi D, Connors S. {{The Needs of Hospitalized Patients With Autism Spectrum Disorders: A Parent Survey}}. {Clin Pediatr (Phila)};2013 (Apr 25)
Objective. This survey assessed the in-hospital needs of patients diagnosed with autism spectrum disorders (ASDs). Methods. Parents were recruited to complete a 21-item survey about the needs of their child with an ASD while in the hospital. ASD diagnosis was reported by parents at the time of the survey. The results of the survey were analyzed and evaluated in 3 distinct categories of need. Results. We documented a range of responses associated with ASD-specific needs during hospitalization. Common concerns included child safety and the importance of acknowledging individual communication methods. Conclusions. In a population of children with ASDs, parents report a diverse range of needs while in the hospital. These data support the concept that a pragmatic assessment of individual communication and sensory differences is likely to be essential in the development of an appropriate inpatient care plan.
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11. Meador KJ, Loring DW. {{Risks of in utero exposure to valproate}}. {JAMA};2013 (Apr 24);309(16):1730-1731.
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12. Mosca-Boidron AL, Valduga M, Thauvin-Robinet C, Lagarde N, Marle N, Henry C, Pinoit JM, Huet F, Beri-Deixheimer M, Ragon C, Gueneau L, Payet M, Callier P, Mugneret F, Jonveaux P, Faivre L. {{Additional Evidence to Support the Role of the 20q13.33 Region in Susceptibility to Autism}}. {Am J Med Genet A};2013 (Apr 23)
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13. Orsmond GI, Shattuck PT, Cooper BP, Sterzing PR, Anderson KA. {{Social Participation Among Young Adults with an Autism Spectrum Disorder}}. {J Autism Dev Disord};2013 (Apr 25)
Investigating social participation of young adults with an autism spectrum disorder (ASD) is important given the increasing number of youth aging into young adulthood. Social participation is an indicator of life quality and overall functioning. Using data from the National Longitudinal Transition Study 2, we examined rates of participation in social activities among young adults who received special education services for autism (ASD group), compared to young adults who received special education for intellectual disability, emotional/behavioral disability, or a learning disability. Young adults with an ASD were significantly more likely to never see friends, never get called by friends, never be invited to activities, and be socially isolated. Among those with an ASD, lower conversation ability, lower functional skills, and living with a parent were predictors of less social participation.
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14. Petazzi P, Sandoval J, Szczesna K, Jorge OC, Roa L, Sayols S, Gomez A, Huertas D, Esteller M. {{Dysregulation of the long non-coding RNA transcriptome in a Rett syndrome mouse model}}. {RNA Biol};2013 (Apr 17);10(7)
Mecp2 is a transcriptional repressor protein that is mutated in Rett syndrome, a neurodevelopmental disorder that is the second most common cause of mental retardation in women. It has been shown that the loss of the Mecp2 protein in Rett syndrome cells alters the transcriptional silencing of coding genes and microRNAs. Herein, we have studied the impact of Mecp2 impairment in a Rett syndrome mouse model on the global transcriptional patterns of long non-coding RNAs (lncRNAs). Using a microarray platform that assesses 41,232 unique lncRNA transcripts, we have identified the aberrant lncRNA transcriptome that is present in the brain of Rett syndrome mice. The study of the most relevant lncRNAs altered in the assay highlighted the upregulation of the AK081227 and AK087060 transcripts in Mecp2-null mice brains. Chromatin immunoprecipitation demonstrated the Mecp2 occupancy in the 5′-end genomic loci of the described lncRNAs and its absence in Rett syndrome mice. Most importantly, we were able to show that the overexpression of AK081227 mediated by the Mecp2 loss was associated with the downregulation of its host coding protein gene, the gamma-aminobutyric acid receptor subunit Rho 2 (Gabrr2). Overall, our findings indicate that the transcriptional dysregulation of lncRNAs upon Mecp2 loss contributes to the neurological phenotype of Rett syndrome and highlights the complex interaction between ncRNAs and coding-RNAs.
15. Reiff M, Bernhardt BA, Mulchandani S. {{Genomic variation: what does it mean?}}. {LDI Issue Brief};2013 (Feb-Mar);18(4):1-4.
New technologies have given us the ability to detect genomic variation at resolutions 50-100 times greater than earlier tests. The good news is that we can now detect variations that help explain developmental delays, autism, or multiple congenital anomalies in up to 20% of children. The bad news is that we can also detect small missing or extra pieces of chromosomes that remain unexplained: that is, we don’t know whether they have any clinical significance at all. The rapid pace of technological change may have outpaced the lab’s ability to interpret, providers’ abilities to explain, and patients’ abilities to understand the test results. This Issue Brief summarizes a series of studies examining the uncertainties revolving around chromosomal microarray testing, which has become the new standard of practice in genetic testing of children with unexplained anomalies.
16. Turygin NC, Matson JL, Adams H, Belva B. {{The effect of DSM-5 criteria on externalizing, internalizing, behavioral and adaptive symptoms in children diagnosed with autism}}. {Dev Neurorehabil};2013 (Apr 25)
Objective: Diagnostic criteria for autism spectrum disorders (ASDs) are changing with the fifth edition of the Diagnostic and Statistical Manual (DSM-5), which simplifies the diagnostic categories into social/emotional deficits and repetitive and restricted behavior. ASDs have been closely linked to a variety of other disorders, in particular externalizing disorders such as ADHD, and internalizing disorders including anxiety disorders and obsessive compulsive disorder. The present study examines the externalizing, internalizing, behavioral and adaptive symptoms of children with ASD. Method: Children diagnosed with the DSM-IV who do not meet diagnostic criteria for DSM-5 and were compared to a non-ASD sample and a sample of those who meet the new criteria. Differences were examined between the three experimental groups with respect to internalizing, externalizing, behavioral severity and adaptive behavior. Results: No significant differences were observed between the DSM-5 and DSM-IV groups with respect to composite and subscale scores on the externalizing, behavior severity index and adaptive behavior domains of the Behavior Assessment System for Children, Second Edition. Conclusions: Significantly more impairment was evident for both ASD groups compared to the no-ASD group.
