1. Bravo Oro A, Vazquez Briseno J, Cuello Garcia CA, Calderon Sepulveda RF, Hernandez Villalobos AM, Esmer Sanchez C. {{Early manifestations of autism spectrum disorders. Experience of 393 cases in a child neurological centre}}. {Neurologia};2011 (Nov 15)
INTRODUCTION: The Autism Spectrum Disorders are group of conditions characterised by qualitative impairments in social communication; in the interaction and imagination; with a restricted range of interests and stereotyped repetitive behaviours. Frequently, there is a delay in the age of detection, and therefore in starting multidisciplinary evaluations and interventions, which may result in a worst prognosis and an impaired quality of life for both children and parents. The aim of our study was to described some clinical and epidemiological data including the age of detection and main initial complaints present in children with autism disorders from a paediatric neurology center. PATIENTS AND METHODS: A total of 393 medical records of consecutive cases with a diagnosis of Autism Spectrum Disorders were reviewed. RESULTS: Autism was diagnosed in 82.1% of the cases, unspecified pervasive disorder in 9.9%, and Asperger syndrome in 4.8%. Sixty percent of autistic children presented with a language disorder as their main complaint. The average age of detection was 4 years. CONCLUSIONS: Compared with other countries, age of detection is delayed. A Primary Care based screening and surveillance are required in order to improve prognosis and quality of life of children with an Autism Spectrum Disorder.
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2. Chen BY, Zou XB, Zhang J, Deng HZ, Li JY, Li LY, Tang C, Zou YY. {{[Copy-number variations of SHANK3 and related clinical phenotypes in children with autism]}}. {Zhonghua Er Ke Za Zhi};2011 (Aug);49(8):607-611.
OBJECTIVE: To explore possible relationship between copy-number variations (CNVs) in 15q11-13, 16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification (MLPA) and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism. METHODS: The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-IV, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains. RESULTS: Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANK3 microdeletion, accounting for approximately 2% (2/109) of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation. CONCLUSIONS: SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANK3 microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism.
3. Chen YZ, Matsushita M, Girirajan S, Lisowski M, Sun E, Sul Y, Bernier R, Estes A, Dawson G, Minshew N, Shellenberg GD, Eichler EE, Rieder MJ, Nickerson DA, Tsuang DW, Tsuang MT, Wijsman EM, Raskind WH, Brkanac Z. {{Evidence for involvement of GNB1L in autism}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Nov 16)
Structural variations in the chromosome 22q11.2 region mediated by nonallelic homologous recombination result in 22q11.2 deletion (del22q11.2) and 22q11.2 duplication (dup22q11.2) syndromes. The majority of del22q11.2 cases have facial and cardiac malformations, immunologic impairments, specific cognitive profile and increased risk for schizophrenia and autism spectrum disorders (ASDs). The phenotype of dup22q11.2 is frequently without physical features but includes the spectrum of neurocognitive abnormalities. Although there is substantial evidence that haploinsufficiency for TBX1 plays a role in the physical features of del22q11.2, it is not known which gene(s) in the critical 1.5 Mb region are responsible for the observed spectrum of behavioral phenotypes. We identified an individual with a balanced translocation 46,XY,t(1;22)(p36.1;q11.2) and a behavioral phenotype characterized by cognitive impairment, autism, and schizophrenia in the absence of congenital malformations. Using somatic cell hybrids and comparative genomic hybridization (CGH) we mapped the chromosome-22 breakpoint within intron 7 of the GNB1L gene. Copy number evaluations and direct DNA sequencing of GNB1L in 271 schizophrenia and 513 autism cases revealed dup22q11.2 in two families with autism and private GNB1L missense variants in conserved residues in three families (P = 0.036). The identified missense variants affect residues in the WD40 repeat domains and are predicted to have deleterious effects on the protein. Prior studies provided evidence that GNB1L may have a role in schizophrenia. Our findings support involvement of GNB1L in ASDs as well. (c) 2011 Wiley Periodicals, Inc.
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4. Deutsch SI, Urbano MR, Burket JA, Herndon AL, Winebarger EE. {{Pharmacotherapeutic Implications of the Association Between Genomic Instability at Chromosome 15q13.3 and Autism Spectrum Disorders}}. {Clin Neuropharmacol};2011 (Nov 16)
ABSTRACT: Recurrent microdeletions of chromosome 15q13.3 are causally associated with autism spectrum disorders (ASDs), suggesting that haploinsufficiency of CHRNA7, the gene that codes for the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) subunit, is an etiological mechanism. Independent of these genetic data, given the location of alpha7 nAChRs on gamma-aminobutyric acid-inhibitory neurons and their role in maintaining central inhibitory tone, a compelling pharmacological rationale exists for therapeutically targeting the alpha7 nAChR in persons with ASDs. Given the availability of positive allosteric modulators of nicotinic acetylcholine receptors and selective agonists for the alpha7 nAChR (eg, choline derived from dietary administration of cytidine 5’diphosphocholine and anabasine derivatives), it is possible to conduct « proof of concept » clinical trials, exploring the effects of alpha7 nAChR agonist interventional strategies on domains of psychopathology, such as attention, cognition, and memory, in persons with ASDs.
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5. Efstratopoulou M, Janssen R, Simons J. {{Differentiating children with Attention-Deficit/Hyperactivity Disorder, Conduct Disorder, Learning Disabilities and Autistic Spectrum Disorders by means of their motor behavior characteristics}}. {Res Dev Disabil};2012 (Jan);33(1):196-204.
The study was designed to investigate the discriminant validity of the Motor Behavior Checklist (MBC) for distinguishing four group of children independently classified with Attention-Deficit/Hyperactivity Disorder, (ADHD; N=22), Conduct Disorder (CD; N=17), Learning Disabilities (LD; N=24) and Autistic Spectrum Disorders (ASD; N=20). Physical education teachers used the MBC for children to rate their pupils based on their motor related behaviors. A multivariate analysis revealed significant differences among the groups on different problem scales. The results indicated that the MBC for children may be effective in discriminating children with similar disruptive behaviors (e.g., ADHD, CD) and autistic disorders, based on their motor behavior characteristics, but not children with Learning Disabilities (LD), when used by physical education teachers in school settings.
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6. Hammond JL, Hirt M, Hall SS. {{Effects of computerized match-to-sample training on emergent fraction-decimal relations in individuals with fragile X syndrome}}. {Res Dev Disabil};2012 (Jan);33(1):1-11.
Individuals diagnosed with fragile X syndrome (FXS), the most common known form of inherited intellectual disability, are reported to exhibit considerable deficits in mathematical skills that are often attributed to brain-based abnormalities associated with the syndrome. We examined whether participants with FXS would display emergent fraction-decimal relations following brief, intensive match-to-sample training on baseline relations. The performance profiles on tests of symmetry and transitivity/equivalence of 11 participants with FXS, aged 10-23 years, following baseline match-to-sample training were compared to those of 11 age- and IQ-matched controls with idiopathic developmental disability. The results showed that both groups of participants showed significant improvements in the baseline (trained) relations, as expected. However, participants with FXS failed to show significant improvements in the (untrained) symmetry and transitivity/equivalence relations compared to those in the control group. A categorical analysis of the data indicated that five participants with FXS and eight controls showed at least « intermediate » emergence of symmetry relations, whereas one individual with FXS and three controls showed at least intermediate emergence of transitivity/equivalence relations. A correlation analysis of the data indicated that improvements in the symmetry relations were significantly associated with improvements in the transitivity/equivalence relations in the control group (r=.69, p=.018), but this was not the case in the FXS group (r=.34, p>.05). Participant IQ was significantly associated with improvements in the symmetry relations in individuals with FXS (r=.60, p=.049), but not in controls (r=.21, p>.05). Taken together, these results suggest that brief, computerized match-to-sample training may produce emergent mathematical relations for a subset of children with FXS and developmental disabilities. However, the ability of individuals with FXS to form transitivity/equivalence relations may be impaired relative to those with idiopathic developmental disabilities, which may be attributed to neurodevelopmental variables associated with the syndrome.
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7. Kataoka S, Takuma K, Hara Y, Maeda Y, Ago Y, Matsuda T. {{Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid}}. {Int J Neuropsychopharmacol};2011 (Nov 18):1-13.
Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice. Mice exposed to VPA at embryonic day 12.5 (E12.5), but not at E9 and E14.5, displayed social interaction deficits, anxiety-like behaviour and memory deficits at age 4-8 wk. In contrast to male mice, the social interaction deficits (a decrease in sniffing behaviour) were not observed in female mice at age 8 wk. The exposure to VPA at E12.5 decreased the number of Nissl-positive cells in the middle and lower layers of the prefrontal cortex and in the lower layers of the somatosensory cortex at age 8 wk. Furthermore, VPA exposure caused a transient increase in acetylated histone levels in the embryonic brain, followed by an increase in apoptotic cell death in the neocortex and a decrease in cell proliferation in the ganglionic eminence. In contrast, prenatal exposure to valpromide at E12.5 did not affect the behavioural, biochemical and histological parameters. Furthermore, these findings suggest that VPA-induced histone hyperacetylation plays a key role in cortical pathology and abnormal autism-like behaviours in mice.
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8. Kjellmer L, Hedvall A, Fernell E, Gillberg C, Norrelgen F. {{Language and communication skills in preschool children with autism spectrum disorders: Contribution of cognition, severity of autism symptoms, and adaptive functioning to the variability}}. {Res Dev Disabil};2012 (Jan);33(1):172-180.
This study examined the contribution of cognitive function, severity of autism, and adaptive functioning to the variability in language and communication skills in 129 preschool children (aged 24-63 months) with autism spectrum disorder (ASD). Participants were selected from a representative research cohort of 208 preschool children on the basis of caregiver completion of the MacArthur-Bates Communicative Development Inventories (CDI). The children were classified into three cognitive groups: (a) Normal intelligence; (b) Developmental delay; and (c) Intellectual disability. Autism symptom severity was measured by the Autistic Behavior Checklist (ABC), and adaptive functioning by the Daily Living Skills (DLS) and Socialization (Soc) subscales from the Vineland Adaptive Behavior Scales. For each of five CDI variables (Phrases understood, Words understood, Words produced, Gestures and actions, and Language use), the contribution of cognition, severity of autism symptoms, and adaptive functioning to the variability was examined. Cognition and age explained about half or more of the variance in the four verbal language CDI variables, but only about one fourth of the variance in the non-verbal communication variable Gestures and actions. Severity of autism symptoms and the two adaptive measures (DLS and Soc) each only accounted for a few percent more of the variance in the four CDI language variables; however, for Gestures and actions, an additional 11-21% of the variance was accounted for. In conclusion, for children with ASD, receptive and expressive language is mainly related to cognitive level, whereas non-verbal communication skills seem to also be related to severity of autism symptoms and adaptive functioning.
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9. Lee HS, Kim MJ, Lim CK, Cho JW, Song IO, Kang IS. {{Multiple displacement amplification for preimplantation genetic diagnosis of fragile X syndrome}}. {Genet Mol Res};2011;10(4):2851-2859.
Preimplantation genetic diagnosis (PGD) has become an assisted reproductive technique for couples that have genetic risks. Despite the many advantages provided by PGD, there are several problems, including amplification failure, allele drop-out and amplification inefficiency. We evaluated multiple displacement amplification (MDA) for PGD of the fragile X syndrome. Whole genome amplification was performed using MDA. MDA products were subjected to fluorescent PCR of fragile X mental retardation-1 (FMR1) CGG repeats, amelogenin and two polymorphic markers. In the pre-clinical tests, the amplification rates of the FMR1 CGG repeat, DXS1215 and FRAXAC1 were 84.2, 87.5 and 75.0%, respectively, while the allele dropout rates were 31.3, 57.1 and 50.0%, respectively. In two PGD treatment cycles, 20 embryos among 30 embryos were successfully diagnosed as 10 normal embryos, four mutated embryos and six heterozygous carriers. Three healthy embryos were transferred to the uterus; however, no clinical pregnancy was achieved. Our data indicate that MDA and fluorescent PCR with four loci can be successfully applied to PGD for fragile X syndrome. Advanced methods for amplification of minuscule amounts of DNA could improve the sensitivity and reliability of PGD for complicated single gene disorders.
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10. Lunsky Y, Elserafi J. {{Antipsychotic medication prescription patterns in adults with developmental disabilities who have experienced psychiatric crisis}}. {Res Dev Disabil};2012 (Jan);33(1):32-38.
Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics taking 2 or more antipsychotics at once. Predictors of multiple antipsychotic use included gender, residence, psychiatric diagnosis and previous hospitalizations. Implications of medication prescriptions to this vulnerable population are discussed.
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11. Piven J, Rabins P. {{Autism Spectrum Disorders in Older Adults: Toward Defining a Research Agenda}}. {J Am Geriatr Soc};2011 (Nov 8)
Autism spectrum disorders (ASDs) are among the most common of the severe developmental disabilities, yet little is known about older adults with ASDs-in particular, how the disabilities and dependencies that result from aging interact with those resulting from ASDs. The aging of the population in Western countries, the increasing rate of diagnosis of ASDs, and the burgeoning use of services for ASDs are converging to create a large, growing influx of older adults with ASDs that could impose tremendous humanistic and economic burdens on the healthcare system and society. An understanding of the epidemiological, biological, psychological, and social aspects of ASDs in older adults is essential for preparing to meet their needs, but studies on ASDs in these individuals are practically nonexistent. This article outlines observations and recommendations of a multidisciplinary expert group convened in March 2010 to characterize gaps in knowledge regarding ASDs in older adults and defines research directions to help individuals, the healthcare system, and society prepare for meeting the needs of this population. The proposed research agenda could help improve the lives of older adults with ASDs and inform research and clinical practice involving younger individuals with ASDs.
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12. Szatmari P, Liu XQ, Goldberg J, Zwaigenbaum L, Paterson AD, Woodbury-Smith M, Georgiades S, Duku E, Thompson A. {{Sex differences in repetitive stereotyped behaviors in autism: Implications for genetic liability}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Nov 16)
The implications of the well known sex differences in the prevalence of autism spectrum disorder (ASD) are not well understood. The aim of this paper was to investigate whether these differences might be associated with differences in genetic liability. Individuals with ASD (970 families, 2,028 individuals) were recruited as part of the Autism Genome Project (AGP). The families were differentiated into families containing a female (either female-female or male-female) and those with only males. If the sex with the lower prevalence is associated with a greater genetic liability necessary to cross sex-specific thresholds, the males from female containing families should be more severely affected than males from male only families. Affected subjects from the different types of families with ASD were sampled and compared on the social reciprocity and repetitive behavior scores from the Autism Diagnostic Interview-Revised (ADI-R). In general, females had lower repetitive behavior scores than males. More importantly, males from female containing families had higher repetitive behavior scores than males from male-male families. No such differences were apparent on the social reciprocity scores. These results support the hypothesis of a multiple threshold model of genetic liability of ASD with females having a higher liability for affectation status, at least on the repetitive behavior dimension of the disorder. These data also support the dissociation of the different phenotypic dimensions of ASD in terms of its genetic architecture. The implications of these results for linkage and association studies are discussed. (c) 2011 Wiley Periodicals, Inc.
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13. Ward KM, Windsor R, Atkinson JP. {{A process evaluation of the Friendships and Dating Program for adults with developmental disabilities: Measuring the fidelity of program delivery}}. {Res Dev Disabil};2012 (Jan);33(1):69-75.
Adults with intellectual and developmental disabilities are frequently abused in dating and partnered relationships. The Friendships and Dating Program (FDP) was developed to prevent violence in dating and partnered relationships and to teach social skills needed to develop healthy, meaningful relationships among this population. A pilot study indicated the FDP resulted in a statistically significant increase in social network size and a significant decrease in instances of interpersonal violence. This study focused on utilizing a Process Evaluation Model (PEM) to document the level of treatment fidelity in the delivery of the 20 session FDP for adults with intellectual and developmental disabilities delivered by community agency personnel. The PEM also documented the amount of content delivered to the participants during each session. Results indicated that direct service personnel delivered the program with a high level of fidelity. Additionally, participants engaged at high rates over the course of the 10-week program. Further, the results indicated the FDP topics and methods of delivery were appropriate for adults with intellectual and developmental disabilities. Programs should use a Process Evaluation Model (PEM) and methods as a routine quality control mechanism to assess provision of salient participant procedures.
