1. {{Prevalence of autism spectrum disorders – autism and developmental disabilities monitoring network, 14 sites, United States, 2008}}. {MMWR Surveill Summ};2012 (Mar 30);61(3):1-19.
Problem/Condition: Autism spectrum disorders (ASDs) are a group of developmental disabilities characterized by impairments in social interaction and communication and by restricted, repetitive, and stereotyped patterns of behavior. Symptoms typically are apparent before age 3 years. The complex nature of these disorders, coupled with a lack of biologic markers for diagnosis and changes in clinical definitions over time, creates challenges in monitoring the prevalence of ASDs. Accurate reporting of data is essential to understand the prevalence of ASDs in the population and can help direct research. Period Covered: 2008. Description of System: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that estimates the prevalence of ASDs and describes other characteristics among children aged 8 years whose parents or guardians reside within 14 ADDM sites in the United States. ADDM does not rely on professional or family reporting of an existing ASD diagnosis or classification to ascertain case status. Instead, information is obtained from children’s evaluation records to determine the presence of ASD symptoms at any time from birth through the end of the year when the child reaches age 8 years. ADDM focuses on children aged 8 years because a baseline study conducted by CDC demonstrated that this is the age of identified peak prevalence. A child is included as meeting the surveillance case definition for an ASD if he or she displays behaviors (as described on a comprehensive evaluation completed by a qualified professional) consistent with the American Psychiatric Association’s Diagnostic and Statistical Manual-IV, Text Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions: Autistic Disorder; Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS, including Atypical Autism); or Asperger Disorder. The first phase of the ADDM methodology involves screening and abstraction of comprehensive evaluations completed by professional providers at multiple data sources in the community. Multiple data sources are included, ranging from general pediatric health clinics to specialized programs for children with developmental disabilities. In addition, many ADDM sites also review and abstract records of children receiving special education services in public schools. In the second phase of the study, all abstracted evaluations are reviewed by trained clinicians to determine ASD case status. Because the case definition and surveillance methods have remained consistent across all ADDM surveillance years to date, comparisons to results for earlier surveillance years can be made. This report provides updated ASD prevalence estimates from the 2008 surveillance year, representing 14 ADDM areas in the United States. In addition to prevalence estimates, characteristics of the population of children with ASDs are described, as well as detailed comparisons of the 2008 surveillance year findings with those for the 2002 and 2006 surveillance years. Results: For 2008, the overall estimated prevalence of ASDs among the 14 ADDM sites was 11.3 per 1,000 (one in 88) children aged 8 years who were living in these communities during 2008. Overall ASD prevalence estimates varied widely across all sites (range: 4.8-21.2 per 1,000 children aged 8 years). ASD prevalence estimates also varied widely by sex and by racial/ethnic group. Approximately one in 54 boys and one in 252 girls living in the ADDM Network communities were identified as having ASDs. Comparison of 2008 findings with those for earlier surveillance years indicated an increase in estimated ASD prevalence of 23% when the 2008 data were compared with the data for 2006 (from 9.0 per 1,000 children aged 8 years in 2006 to 11.0 in 2008 for the 11 sites that provided data for both surveillance years) and an estimated increase of 78% when the 2008 data were compared with the data for 2002 (from 6.4 per 1,000 children aged 8 years in 2002 to 11.4 in 2008 for the 13 sites that provided data for both surveillance years). Because the ADDM Network sites do not make up a nationally representative sample, these combined prevalence estimates should not be generalized to the United States as a whole. Interpretation: These data confirm that the estimated prevalence of ASDs identified in the ADDM network surveillance populations continues to increase. The extent to which these increases reflect better case ascertainment as a result of increases in awareness and access to services or true increases in prevalence of ASD symptoms is not known. ASDs continue to be an important public health concern in the United States, underscoring the need for continued resources to identify potential risk factors and to provide essential supports for persons with ASDs and their families. Public Health Action: Given substantial increases in ASD prevalence estimates over a relatively short period, overall and within various subgroups of the population, continued monitoring is needed to quantify and understand these patterns. With 5 biennial surveillance years completed in the past decade, the ADDM Network continues to monitor prevalence and characteristics of ASDs and other developmental disabilities for the 2010 surveillance year. Further work is needed to evaluate multiple factors contributing to increases in estimated ASD prevalence over time. ADDM Network investigators continue to explore these factors, with a focus on understanding disparities in the identification of ASDs among certain subgroups and on how these disparities have contributed to changes in the estimated prevalence of ASDs. CDC is partnering with other federal and private partners in a coordinated response to identify risk factors for ASDs and to meet the needs of persons with ASDs and their families.
2. Allen KD, Burke RV, Howard MR, Wallace DP, Bowen SL. {{Use of Audio Cuing to Expand Employment Opportunities for Adolescents with Autism Spectrum Disorders and Intellectual Disabilities}}. {J Autism Dev Disord};2012 (Mar 29)
We evaluated audio cuing to facilitate community employment of individuals with autism and intellectual disability. The job required promoting products in retail stores by wearing an air-inflated WalkAround((R)) costume of a popular commercial character. Three adolescents, ages 16-18, were initially trained with video modeling. Audio cuing was then used by an attendant who delivered prompts regarding when to perform job skills. The two interventions were evaluated in an interrupted time series withdrawal design during training and then again in an actual job setting. Results show video modeling was not effective. However, the audio cuing produced job performances well above the designated criteria during training and when on the job. These changes were replicated with each participant, demonstrating clear experimental control. The changes proved statistically significant as well. Participants and parents reported high job satisfaction. The challenges of competitive employment for individuals with autism and intellectual disabilities are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
3. Chow ML, Pramparo T, Winn ME, Barnes CC, Li HR, Weiss L, Fan JB, Murray S, April C, Belinson H, Fu XD, Wynshaw-Boris A, Schork NJ, Courchesne E. {{Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages}}. {PLoS Genet};2012 (Mar);8(3):e1002592.
Autism is a highly heritable neurodevelopmental disorder, yet the genetic underpinnings of the disorder are largely unknown. Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association, linkage, and expression studies have not identified genetic factors that explain this trajectory. Few studies have had sufficient statistical power to investigate whole-genome gene expression and genotypic variation in the autistic brain, especially in regions that display the greatest growth abnormality. Previous functional genomic studies have identified possible alterations in transcript levels of genes related to neurodevelopment and immune function. Thus, there is a need for genetic studies involving key brain regions to replicate these findings and solidify the role of particular functional pathways in autism pathogenesis. We therefore sought to identify abnormal brain gene expression patterns via whole-genome analysis of mRNA levels and copy number variations (CNVs) in autistic and control postmortem brain samples. We focused on prefrontal cortex tissue where excess neuron numbers and cortical overgrowth are pronounced in the majority of autism cases. We found evidence for dysregulation in pathways governing cell number, cortical patterning, and differentiation in young autistic prefrontal cortex. In contrast, adult autistic prefrontal cortex showed dysregulation of signaling and repair pathways. Genes regulating cell cycle also exhibited autism-specific CNVs in DNA derived from prefrontal cortex, and these genes were significantly associated with autism in genome-wide association study datasets. Our results suggest that CNVs and age-dependent gene expression changes in autism may reflect distinct pathological processes in the developing versus the mature autistic prefrontal cortex. Our results raise the hypothesis that genetic dysregulation in the developing brain leads to abnormal regional patterning, excess prefrontal neurons, cortical overgrowth, and neural dysfunction in autism.
Lien vers le texte intégral (Open Access ou abonnement)
4. Cornew L, Dobkins KR, Akshoomoff N, McCleery JP, Carver LJ. {{Atypical Social Referencing in Infant Siblings of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2012 (Mar 29)
Social referencing was investigated in 18-month-old siblings of children with autism spectrum disorders (ASD; « high-risk infants »). Infants were exposed to novel toys, which were emotionally tagged via adults’ facial and vocal signals. Infants’ information seeking (initiation of joint attention with an adult) and their approach/withdrawal behavior toward the toys before versus after the adults’ emotional signals was measured. Compared to both typically developing infants and high-risk infants without ASD, infants later diagnosed with ASD engaged in slower information seeking, suggesting that this aspect of referencing may be an early indicator of ASD. High-risk infants, both those who were and those who were not later diagnosed with ASD, exhibited impairments in regulating their behavior based on the adults’ emotional signals, suggesting that this aspect of social referencing may reflect an endophenotype for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
5. Freitag CM, Feineis-Matthews S, Valerian J, Teufel K, Wilker C. {{The Frankfurt early intervention program FFIP for preschool aged children with autism spectrum disorder: a pilot study}}. {J Neural Transm};2012 (Mar 30)
Different early intervention programs, developed predominantly in the US, for preschool aged children with autism spectrum disorders (ASD) have been published. Several systematic review articles including a German Health Technology Assessment on behavioural and skill-based early interventions in children with ASD reported insufficient evidence and a substantial problem of generalisability to the German context. In Germany, approx. 2-5 h early intervention is supported by social services. Here, we report the results of a 1 year pre-post pilot study on a developmentally based social pragmatic approach, the Frankfurt Early Intervention program FFIP. In FFIP, individual 2:1, behaviourally and developmentally based therapy with the child is combined with parent training and training of kindergarten teachers. Treatment frequency is 2 h/week. Outcome measures were the Vineland Adaptive Behaviour Scales II (VABS), mental age and the ADOS severity score. Improvements after 1 year were observed for the VABS socialisation scale and the mental age quotient/IQ (medium effect sizes). Results are comparable with several other studies with a similar or slightly higher therapeutic intensity implementing comparable or different early intervention methods or programs. Compared to most high-intensity programs (30-40 h/week), lower cognitive gains were observed. Results have to be replicated and assessed by a randomized-controlled study before any final conclusions can be drawn.
Lien vers le texte intégral (Open Access ou abonnement)
6. Lerner MD, Calhoun CD, Mikami AY, De Los Reyes A. {{Understanding Parent-Child Social Informant Discrepancy in Youth with High Functioning Autism Spectrum Disorders}}. {J Autism Dev Disord};2012 (Mar 29)
We investigated discrepancies between parent- and self-reported social functioning among youth with autism spectrum disorders (ASD). Three distinct samples showed discrepancies indicating that parents viewed their children as performing one standard deviation below a standardization mean, while youth viewed themselves as comparably-skilled relative to peers. Discrepancies predicted lower parental self-efficacy, and lower youth-reported hostile attributions to peers, marginally-lower depression, and decreased post-treatment social anxiety. Discrepancies predicted outcomes better than parent- or youth-report alone. Informant discrepancies may provide valuable additional information regarding child psychopathology, parental perceptions of parenting stress, and youth treatment response. Findings support a model where abnormal self-perceptions in ASD stem from inflated imputation of subjective experiences to others, and provide direction for improving interventions for youth and parents.
Lien vers le texte intégral (Open Access ou abonnement)
7. Mattila ML, Jussila K, Linna SL, Kielinen M, Bloigu R, Kuusikko-Gauffin S, Joskitt L, Ebeling H, Hurtig T, Moilanen I. {{Validation of the Finnish Autism Spectrum Screening Questionnaire (ASSQ) for Clinical Settings and Total Population Screening}}. {J Autism Dev Disord};2012 (Mar 30)
We assessed the validity and determined cut-off scores for the Finnish Autism Spectrum Screening Questionnaire (ASSQ). A population sample of 8-year-old children (n = 4,408) was rated via the ASSQ by parents and/or teachers, and a subgroup of 104 children was examined via structured interview, semi-structured observation, IQ measurement, school observation, and medical records. Autism spectrum disorders (ASDs) were diagnosed following DSM-IV-TR criteria. A search for hospital-registered ASDs was performed. For Finnish higher-functioning primary school-aged, 7- to 12-year-olds, the optimal cut-off score was 30 in clinical settings and 28 in total population screening using summed ASSQ scores of parents’ and teachers’ ratings. Determining appropriate cut-off scores in ASD screening in different languages and in different cultures is of utmost importance.
Lien vers le texte intégral (Open Access ou abonnement)
8. O’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE. {{Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations}}. {Nat Genet};2012;44(4):471.
Lien vers le texte intégral (Open Access ou abonnement)
9. Schneider E, Mayer S, El Hajj N, Jensen LR, Kuss AW, Zischler H, Kondova I, Bontrop RE, Navarro B, Fuchs E, Zechner U, Haaf T. {{Methylation and Expression Analyses of the 7q Autism Susceptibility Locus Genes MEST, COPG2, and TSGA14 in Human and Anthropoid Primate Cortices}}. {Cytogenet Genome Res};2012 (Mar 24)
The autism susceptibility locus on human chromosome 7q32 contains the maternally imprinted MEST and the non-imprinted COPG2 and TSGA14 genes. Autism is a disorder of the ‘social brain’ that has been proposed to be due to an overbalance of paternally expressed genes. To study regulation of the 7q32 locus during anthropoid primate evolution, we analyzed the methylation and expression patterns of MEST, COPG2, and TSGA14 in human, chimpanzee, Old World monkey (baboon and rhesus macaque), and New World monkey (marmoset) cortices. In all human and anthropoid primate cortices, the MEST promoter was hemimethylated, as expected for a differentially methylated imprinting control region, whereas the COPG2 and TSGA14 promoters were completely demethylated, typical for transcriptionally active non-imprinted genes. The MEST gene also showed comparable mRNA expression levels in all analyzed species. In contrast, COPG2 expression was downregulated in the human cortex compared to chimpanzee, Old and New World monkeys. TSGA14 either showed no differential regulation in the human brain compared to chimpanzee and marmoset or a slight upregulation compared to baboon. The human-specific downregulation supports a role for COPG2 in the development of a ‘social brain’. Promoter methylation patterns appear to be more stable during evolution than gene expression patterns, suggesting that other mechanisms may be more important for inter-primate differences in gene expression.
Lien vers le texte intégral (Open Access ou abonnement)
10. Stoch YK, Williams CJ, Granich J, Hunt AM, Landau LI, Newnham JP, Whitehouse AJ. {{Are Prenatal Ultrasound Scans Associated with the Autism Phenotype? Follow-up of a Randomised Controlled Trial}}. {J Autism Dev Disord};2012 (Mar 29)
An existing randomised controlled trial was used to investigate whether multiple ultrasound scans may be associated with the autism phenotype. From 2,834 single pregnancies, 1,415 were selected at random to receive ultrasound imaging and continuous wave Doppler flow studies at five points throughout pregnancy (Intensive) and 1,419 to receive a single imaging scan at 18 weeks (Regular), with further scans only as indicated on clinical grounds. There was no significant difference in the rate of Autism Spectrum Disorder between the Regular (9/1,125, 0.8 %) and Intensive (7/1,167, 0.6 %) groups, nor a difference between groups in the level of autistic-like traits in early adulthood. There is no clear link between the frequency and timing of prenatal ultrasound scans and the autism phenotype.
Lien vers le texte intégral (Open Access ou abonnement)
11. Tassone F, Greco CM, Hunsaker MR, Seritan AL, Berman RF, Gane LW, Jacquemont S, Basuta K, Jin LW, Hagerman PJ, Hagerman RJ. {{Neuropathological, Clinical, and Molecular Pathology in Female Fragile X Premutation Carriers with and without FXTAS}}. {Genes Brain Behav};2012 (Mar 30)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Approximately 40% of older male premutation carriers, and a smaller proportion of females, are affected by FXTAS; due to the lower penetrance the characterization of the disorder in females is much less detailed. Core clinical features of FXTAS include intention tremor, cerebellar gait ataxia, and frequently parkinsonism, autonomic dysfunction, and cognitive deficits progressing to dementia in up to 50% of males. Here, we report the clinical, molecular, and neuropathological findings of eight female premutation carriers. Significantly, four of these women had dementia; of the four, three had FXTAS plus dementia. Post mortem examination revealed the presence of intranuclear inclusions in all eight cases, which included one asymptomatic premutation carrier who died from cancer. Among the four subjects with dementia, three had sufficient number of cortical amyloid plaques and neurofibrillary tangles to make Alzheimer’s disease a highly likely cause of dementia and a fourth case had dementia with cortical Lewy bodies. Dementia appears to be more common than originally reported in females with FXTAS. Although further studies are required, our observation suggests that in a portion of FXTAS cases and Alzheimer pathologies a synergistic effect on the progression of the disease may occurs.
