1. Adolfsson M, Simmeborn Fleischer A. {{Applying the ICF to identify requirements for students with Asperger syndrome in higher education}}. {Dev Neurorehabil}. 2013.
Abstract Higher education requires more than academic skills and everyday student-life can be stressful. Students with Asperger syndrome (AS) may need support to manage their education due to difficulties in social functioning. Objective: As preparation for the development of a structured tool to guide student and coordinator dialogues at Swedish universities, this study aimed to identify ICF categories that reflect requirements in everyday student-life for students with AS. Methods: Using descriptive qualitative approach, information in documents reflecting the perspectives of university students, international classifications, user/health organisations and education authorities were linked to ICF codes. Results: In total, 114 ICF categories were identified, most of which related to learning, tasks and demands, communication and interactions. Conclusion: Students with AS need varying accommodations to be successful in higher education. In the future, ICF-based code sets, including demands on student roles, can be used as checklists to describe functioning and needs for support.
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2. Beighley JS, Matson JL, Rieske RD, Adams HL. {{Food selectivity in children with and without an autism spectrum disorder: Investigation of diagnosis and age}}. {Res Dev Disabil}. 2013; 34(10): 3497-503.
Feeding problems are common in children with autism spectrum disorders (ASDs), with food selectivity being the most frequently reported. Selectivity based on type and/or texture of food is of concern in those with ASD. Variations in symptom presentation of food selectivity in children with different autism spectrum diagnoses across childhood have not often been investigated. Parent-report of food selectivity was examined in 525 children age 2-18 years diagnosed with autistic disorder, PDD-NOS, Asperger’s disorder, atypical development, and typical development using information garnered from the Autism Spectrum Disorder-Comorbidity for Children (ASD-CC), a tool to assess emotional issues and comorbid psychopathology. Individuals with an ASD were reported to have significantly more food selectivity than both the atypically developing group and the typically developing group. In addition, the ASD groups, when looked at together, showed a decrease in food selectivity across childhood with significant decrease in the Asperger’s disorder group.
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3. Brimberg L, Sadiq A, Gregersen PK, Diamond B. {{Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder}}. {Mol Psychiatry}. 2013.
It is believed that in utero environmental factors contribute to autism spectrum disorder (ASD). The goal of this study was to demonstrate, using the largest cohort reported so far, that mothers of an ASD child have an elevated frequency of anti-brain antibodies and to assess whether brain reactivity is associated with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of an ASD child from Simon Simplex Collection and plasma of 653 unselected women of child-bearing age for anti-brain antibodies using immunohistology on mouse brain. Positive and negative plasma from mothers with an ASD child were analyzed for anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic Resource Exchange with multiplex families displayed an 8.8% prevalence of anti-brain antibodies in the mothers of these families. Fifty-three percent of these mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies compared with 13.4% of mothers of an ASD child without anti-brain antibodies and 15% of control women of child-bearing age. The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus. This study provides robust evidence that brain-reactive antibodies are increased in mothers of an ASD child and may be associated with autoimmunity. The current study serves as a benchmark and justification for studying the potential pathogenicity of these antibodies on the developing brain. The detailed characterization of the specificity of these antibodies will provide practical benefits for the management and prevention of this disorder.Molecular Psychiatry advance online publication, 20 August 2013; doi:10.1038/mp.2013.101.
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4. Campbell NG, Zhu CB, Lindler KM, Yaspan BL, Kistner-Griffin E, Consortium NA, Hewlett WA, Tate CG, Blakely RD, Sutcliffe JS. {{Rare coding variants of the adenosine A3 receptor are increased in autism: on the trail of the serotonin transporter regulome}}. {Mol Autism}. 2013; 4(1): 28.
BACKGROUND: Recent discoveries highlight rare genetic variation as an important class of autism spectrum disorder (ASD) risk factors, and that such variants can implicate biological networks for further investigation. Altered serotonin (5-HT) signaling has been implicated in ASD for over 50 years, and we and others have identified multiple, rare, ASD-associated variants in the 5-HT transporter (SERT, SLC6A4) gene that lead to elevated 5-HT re-uptake and perturbed regulation. We hypothesized that loci encoding SERT regulatory proteins harbor genetic variants that impact SERT function and/or regulation and therefore could contribute to ASD risk. The adenosine A3 receptor (A3AR) regulates SERT via protein kinase G (PKG) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways leading to enhanced SERT surface expression and catalytic activity, respectively. METHODS: To test our SERT network hypothesis, we asked whether a relative increase of rare functional variants in the A3AR gene (ADORA3) was present in cases vs. controls. Discovery Sanger sequencing of ADORA3 exons and flanking DNA in a case-control sample, and subsequent analysis of a comparison sample using whole exome sequence data were conducted to test for increased functional variants in cases. We evaluated the functional impact of two variants from the discovery sample on A3AR signaling and SERT activity. RESULTS: Sequencing discovery showed an overall increase in rare coding variants in cases vs. controls (P=0.013). While a comparison sample from exome sequence did not show a significant enrichment (P=0.071), combined analysis strengthened evidence for association of rare, functional variants in ASD (P=0.0025). Two variants discovered in ASD cases (Leu90Val and Val171Ile) lie in or near the ligand-binding pocket, and Leu90Val was enriched individually in cases (P=0.040). In vitro analysis of cells expressing Val90 A3AR revealed elevated basal cGMP levels compared with cells expressing the wildtype receptor. Additionally, the specific A3AR agonist N6-(3-iodobenzyl)-N-methyl-5′-carbamoyladenosine (IB-MECA) induced increased cGMP levels across the full time course studied in Val90 A3AR cells, as compared with the wildtype receptor expressing cells. In Val90 A3AR/SERT co-transfected cells, IB-MECA stimulation elevated SERT activity over that seen with the wildtype receptor, with a delayed recovery of 5-HT uptake activity to baseline levels. By comparison, the Ile171 A3AR variant was unable to support IB-MECA stimulation of SERT. Although both Val90 and Ile171 were present in greater numbers in these ASD cases, segregation analysis in carrier families showed incomplete penetrance, consistent with other documented rare ASD risk alleles. CONCLUSIONS: Our results validate the hypothesis that the SERT regulatory network harbors rare, functional variants that impact SERT activity and regulation in ASD, and encourages further investigation of this network as a site for additional functional variation that may impact ASD risk.
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5. Corradi A, Fadda M, Piton A, Patry L, Marte A, Rossi P, Cadieux-Dion M, Gauthier J, Lapointe L, Mottron L, Valtorta F, Rouleau GA, Fassio A, Benfenati F, Cossette P. {{SYN2 is an Autism Predisposing Gene: Loss-of-function Mutations Alter Synaptic Vesicle Cycling and Axon Outgrowth}}. {Hum Mol Genet}. 2013.
An increasing number of genes predisposing to autism spectrum disorders (ASD) has been identified, many of which are implicated in synaptic function. This « synaptic autism pathway » notably includes disruption of SYN1 that is associated with epilepsy, autism and abnormal behavior in both human and mice models. Synapsins constitute a multigene family of neuron-specific phosphoproteins (SYN1-3) present in the majority of synapses where they are implicated in the regulation of neurotransmitter release and synaptogenesis. Synapsins I and II, the major Syn isoforms in the adult brain, display partially overlapping functions and defects in both isoforms are associated with epilepsy and autistic-like behavior in mice. In this study, we show that nonsense (A94fs199X) and missense (Y236S and G464R) mutations in SYN2 are associated with ASD in humans. The phenotype is apparent in males. Female carriers of SYN2 mutations are unaffected, suggesting that SYN2 is another example of autosomal sex-limited expression in ASD. When expressed in SYN2 knockout neurons, wild type human Syn II fully rescues the SYN2 knockout phenotype, whereas the nonsense mutant is not expressed and the missense mutants are virtually unable to modify the SYN2 knockout phenotype. These results identify for the first time SYN2 as a novel predisposing gene for ASD and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies ASD.
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6. Cutting J. {{Autism and the brain: neurophenomenological interpretation}}. {Cogn Neuropsychiatry}. 2013.
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7. D’Elia L, Valeri G, Sonnino F, Fontana I, Mammone A, Vicari S. {{A Longitudinal Study of the Teacch Program in Different Settings: The Potential Benefits of Low Intensity Intervention in Preschool Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2013.
We conducted a longitudinal study of 30 preschool children with autism spectrum disorders (ASDs) to evaluate the potential benefits of the Treatment and Education of Autistic and related Communication Handicapped Children (TEACCH). Fifteen children following a low intensity TEACCH program were assessed four times for autism severity, adaptive functioning, language skills, maladaptive behaviors and parental stress and compared with a control group of 15 children following a non-specific approach. Findings suggest that a low intensity home and school TEACCH program may provide benefits for children with ASD by reducing autistic symptoms and maladaptive behaviors. Furthermore, a decrease in parental stress indicates that parents’ involvement in the rehabilitation program is a crucial factor and contributes greatly to treatment efficacy.
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8. Edgar JC, Khan SY, Blaskey L, Chow VY, Rey M, Gaetz W, Cannon KM, Monroe JF, Cornew L, Qasmieh S, Liu S, Welsh JP, Levy SE, Roberts TP. {{Neuromagnetic Oscillations Predict Evoked-Response Latency Delays and Core Language Deficits in Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2013.
Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a ‘core’ abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate ‘neural tone’ and an inability to rapidly return to a resting state prior to the next stimulus.
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9. Fan YT, Chen C, Chen SC, Decety J, Cheng Y. {{Empathic arousal and social understanding in individuals with autism: evidence from fMRI and ERP measurements}}. {Soc Cogn Affect Neurosci}. 2013.
Lack of empathy is a hallmark of social impairments in individuals with autism spectrum disorder (ASD). However, the concept empathy encompasses several socio-emotional and behavioral components underpinned by interacting brain circuits. This study examined empathic arousal and social understanding in individuals with ASD and matched controls by combining pressure pain thresholds (PPT) with functional magnetic resonance imaging (study 1) and electroencephalography/event-related potentials and eye-tracking responses (study 2) to empathy-eliciting stimuli depicting physical bodily injuries. Results indicate that participants with ASD had lower PPT than controls. When viewing body parts being accidentally injured, increased hemodynamic responses in the somatosensory cortex (SI/SII) but decreased responses in the anterior mid-cingulate and anterior insula as well as heightened N2 but preserved late-positive potentials (LPP) were detected in ASD participants. When viewing a person intentionally hurting another, decreased hemodynamic responses in the medial prefrontal cortex and reduced LPP were observed in the ASD group. PPT was a mediator for the SI/SII response in predicting subjective unpleasantness ratings to others’ pain. Both ASD and control groups had comparable mu suppression, indicative of typical sensorimotor resonance. The findings demonstrate that, in addition to reduced pain thresholds, individuals with ASD exhibit heightened empathic arousal but impaired social understanding when perceiving others’ distress.
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10. Fisch GS. {{Autism and epistemology IV: Does autism need a theory of mind?}}. {Am J Med Genet A}. 2013.
In their article, « Does the autistic child have a ‘theory of mind’?, » Baron-Cohen et al. [1985] proposed a novel paradigm to explain social impairment in children diagnosed as autistic (AD). Much research has been undertaken since their article went to print. The purpose of this commentary is to gauge whether Theory of Mind (ToM)-or lack thereof-is a valid model for explaining abnormal social behavior in children with AD. ToM is defined as « the ability to impute mental states to oneself and to others » and « the ability to make inferences about what other people believe to be the case. » The source for their model was provided by an article published earlier by Premack and Woodruff, « Does the chimpanzee have a theory of mind? » Later research in chimpanzees did not support a ToM in primates. From the outset, ToM as a neurocognitive model of autism has had many shortcomings-methodological, logical, and empirical. Other ToM assumptions, for example, its universality in all children in all cultures and socioeconomic conditions, are not supported by data. The age at which a ToM emerges, or events that presage a ToM, are too often not corroborated. Recent studies of mirror neurons, their location and interconnections in brain, their relationship to social behavior and language, and the effect of lesions there on speech, language and social behavior, strongly suggests that a neurobiological as opposed to neurocognitive model of autism is a more parsimonious explanation for the social and behavioral phenotypes observed in autism. (c) 2013 Wiley Periodicals, Inc.
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11. Ganz JB, Goodwyn FD, Boles MM, Hong ER, Rispoli MJ, Lund EM, Kite E. {{Impacts of a PECS Instructional Coaching Intervention on Practitioners and Children with Autism}}. {Augment Altern Commun}. 2013; 29(3): 210-21.
Abstract There is a growing research literature on the potential benefits of augmentative and alternative communication (AAC) for individuals with autism; however few studies have investigated implementation of AAC within real-life contexts. Thus, the purpose of this study was to investigate the impact of training for practitioners in implementation of aided AAC, and to examine implementation of Picture Exchange Communication System (PECS) in real-life contexts. In particular, this study involved the implementation of instructional coaching to increase opportunities offered by behavioral therapists for their preschool-aged clients to use PECS to make requests. Results indicated increases in therapist implementation of AAC and client use of AAC in trained contexts, with limited generalization to untrained contexts.
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12. Garcia-Fernandez L, Hernandez AV, Suarez Moreno V, Fiestas F. {{[Addressing the controversy regarding the association between thimerosal-containing vaccines and autism]}}. {Rev Peru Med Exp Salud Publica}. 2013; 30(2): 268-74.
Vaccination is one of the most important public health interventions in the reduction childhood morbidity and mortality. Thimerosal is an organic mercury compound used as preservante in multi-dose vials. Often in Peru, there are waves of controversy about the safety of this type of vaccines, mainly arguing that there is an association between them and autism. As a result of these controversies, there have been some voices asking for laws banning thimerosal-containing vaccines, which would have a large impact in costs and the logistic aspects of the public vaccination programs. The aim of this article is to review the literature for the main controversies about thimerosal in vaccines and its supposed association to autism. We made an historical review about these controversies given the available scientific evidence and the statements from important international organizations. We concluded that the current available evidence do not support an association between thimerosal and childhood neurodevelopmental disorders, such as autism.
13. Garg SK, Lioy DT, Cheval H, McGann JC, Bissonnette JM, Murtha MJ, Foust KD, Kaspar BK, Bird A, Mandel G. {{Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome}}. {J Neurosci}. 2013; 33(34): 13612-20.
De novo mutations in the X-linked gene encoding the transcription factor methyl-CpG binding protein 2 (MECP2) are the most frequent cause of the neurological disorder Rett syndrome (RTT). Hemizygous males usually die of neonatal encephalopathy. Heterozygous females survive into adulthood but exhibit severe symptoms including microcephaly, loss of purposeful hand motions and speech, and motor abnormalities, which appear after a period of apparently normal development. Most studies have focused on male mouse models because of the shorter latency to and severity in symptoms, yet how well these mice mimic the disease in affected females is not clear. Very few therapeutic treatments have been proposed for females, the more gender-appropriate model. Here, we show that self-complementary AAV9, bearing MeCP2 cDNA under control of a fragment of its own promoter (scAAV9/MeCP2), is capable of significantly stabilizing or reversing symptoms when administered systemically into female RTT mice. To our knowledge, this is the first potential gene therapy for females afflicted with RTT.
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14. Ghanbari Y, Bloy L, Christopher Edgar J, Blaskey L, Verma R, Roberts TP. {{Joint Analysis of Band-Specific Functional Connectivity and Signal Complexity in Autism}}. {J Autism Dev Disord}. 2013.
Examination of resting state brain activity using electrophysiological measures like complexity as well as functional connectivity is of growing interest in the study of autism spectrum disorders (ASD). The present paper jointly examined complexity and connectivity to obtain a more detailed characterization of resting state brain activity in ASD. Multi-scale entropy was computed to quantify the signal complexity, and synchronization likelihood was used to evaluate functional connectivity (FC), with node strength values providing a sensor-level measure of connectivity to facilitate comparisons with complexity. Sensor level analysis of complexity and connectivity was performed at different frequency bands computed from resting state MEG from 26 children with ASD and 22 typically developing controls (TD). Analyses revealed band-specific group differences in each measure that agreed with other functional studies in fMRI and EEG: higher complexity in TD than ASD, in frontal regions in the delta band and occipital-parietal regions in the alpha band, and lower complexity in TD than in ASD in delta (parietal regions), theta (central and temporal regions) and gamma (frontal-central boundary regions); increased short-range connectivity in ASD in the frontal lobe in the delta band and long-range connectivity in the temporal, parietal and occipital lobes in the alpha band. Finally, and perhaps most strikingly, group differences between ASD and TD in complexity and FC appear spatially complementary, such that where FC was elevated in ASD, complexity was reduced (and vice versa). The correlation of regional average complexity and connectivity node strength with symptom severity scores of ASD subjects supported the overall complementarity (with opposing sign) of connectivity and complexity measures, pointing to either diminished connectivity leading to elevated entropy due to poor inhibitory regulation or chaotic signals prohibiting effective measure of connectivity.
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15. Gronborg TK, Schendel DE, Parner ET. {{Recurrence of Autism Spectrum Disorders in Full- and Half-Siblings and Trends Over Time: A Population-Based Cohort Study}}. {JAMA Pediatr}. 2013.
IMPORTANCE To date, this is the first population-based study to examine the recurrence risk for autism spectrum disorders (ASDs), including time trends, and the first study to consider the ASDs recurrence risk for full- and half-siblings. OBJECTIVES To estimate the relative recurrence risk for ASDs in a Danish population, including recurrence in full- and half-siblings, and to examine time trends in ASDs relative to the recurrence risk. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study in Denmark. All children (about 1.5 million) born in Denmark between January 1, 1980, and December 31, 2004, were identified and followed up to December 31, 2010. We identified a maternal sibling subcohort derived from mothers with at least 2 children and a paternal sibling subcohort derived from fathers with at least 2 children. EXPOSURES Children having an older sibling with ASDs are compared with children not having an older sibling with ASDs. MAIN OUTCOMES AND MEASURES The adjusted hazard ratio for ASDs among children having an older sibling with ASDs compared with children not having an older sibling with ASDs. RESULTS The overall relative recurrence risk for ASDs was 6.9 (95% CI, 6.1-7.8), and it did not change significantly over time; similar risks were observed in maternal and paternal full-siblings. The relative recurrence risks were 2.4 (95% CI, 1.4-4.1) for maternal half-siblings and 1.5 (95% CI, 0.7-3.4) for paternal half-siblings. CONCLUSIONS AND RELEVANCE Our population-based recurrence risk estimate is lower than the recently reported estimates from clinical samples. Our results demonstrate no time trend in the ASDs recurrence risk as seen in the ASDs prevalence. The difference in the recurrence risk between full- and half-siblings supports the role of genetics in ASDs, while the significant recurrence risk in maternal half-siblings may support the role of factors associated with pregnancy and the maternal intrauterine environment in ASDs.
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16. Heller T, Sorensen A. {{Promoting healthy aging in adults with developmental disabilities}}. {Dev Disabil Res Rev}. 2013; 18(1): 22-30.
This article reviews the research on health promotion for adults aging with developmental disabilities. First, it examines barriers to healthy aging, including health behaviors and access to health screenings and services. Second, it reviews the research on health promotion interventions, including physical activity interventions, health education interventions, and health care and screening preventive services. This review found evidence that the three types of health promotion interventions, physical activity and exercise, health education and mixed approaches, and health care and screening services can play a role in reducing health disparities for adults with developmental disabilities. Studies focusing primarily on physical activity and exercise tended to show improved fitness and some success in reducing obesity, reducing maladaptive behaviors, and improving alertness, though none of these studies showed longer term health benefits. The studies that took a more holistic approach by also including exercise and nutrition health education tended to show some evidence not only for changes in weight reduction but also for changes in health behavior attitudes (exercise self-efficacy, outcomes expectations, and barriers) and behaviors (e.g., dietary intake) and to a limited extent for improved life satisfaction. The literature on health screenings and services demonstrated the important role of health checks in identifying previously undetected conditions. These conditions include life threatening ones such as cancer and cardio-vascular disease, as well as less serious conditions that are often more common among adults with developmental disabilities and could be treated if caught early. (c) 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2013;18:22-30.
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17. Hoffman K, Vieira VM, Daniels JL. {{Brief Report: Diminishing Geographic Variability in Autism Spectrum Disorders Over Time?}}. {J Autism Dev Disord}. 2013.
We investigated differences in the geographic distribution of autism spectrum disorders (ASD) over time in central North Carolina with data from the Autism and Developmental Disabilities Monitoring Network. Using generalized additive models and geographic information systems we produced maps of ASD risk in 2002-2004 and 2006-2008. Overall the risk of ASD increased 52.9 % from 2002-2004 to 2006-2008. However, the magnitude of change in risk was not uniform across the study area; while some areas experienced dramatic increases in ASD risk (>400 %), others experienced slight decreases. Generally, areas with the lowest risk in 2002-2004 experienced the greatest increases over time. Education and outreach efforts in North Carolina expanded during this period, possibly contributing to the observed leveling of risk over time.
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18. Iuculano T, Rosenberg-Lee M, Supekar K, Lynch CJ, Khouzam A, Phillips J, Uddin LQ, Menon V. {{Brain Organization Underlying Superior Mathematical Abilities in Children with Autism}}. {Biol Psychiatry}. 2013.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits. While such deficits have been the focus of most research, recent evidence suggests that individuals with ASD may exhibit cognitive strengths in domains such as mathematics. METHODS: Cognitive assessments and functional brain imaging were used to investigate mathematical abilities in 18 children with ASD and 18 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate classification and regression analyses were used to investigate whether brain activity patterns during numerical problem solving were significantly different between the groups and predictive of individual mathematical abilities. RESULTS: Children with ASD showed better numerical problem solving abilities and relied on sophisticated decomposition strategies for single-digit addition problems more frequently than TD peers. Although children with ASD engaged similar brain areas as TD children, they showed different multivariate activation patterns related to arithmetic problem complexity in ventral temporal-occipital cortex, posterior parietal cortex, and medial temporal lobe. Furthermore, multivariate activation patterns in ventral temporal-occipital cortical areas typically associated with face processing predicted individual numerical problem solving abilities in children with ASD but not in TD children. CONCLUSIONS: Our study suggests that superior mathematical information processing in children with ASD is characterized by a unique pattern of brain organization and that cortical regions typically involved in perceptual expertise may be utilized in novel ways in ASD. Our findings of enhanced cognitive and neural resources for mathematics have critical implications for educational, professional, and social outcomes for individuals with this lifelong disorder.
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19. Khanna R, Jariwala K, Bentley JP. {{Health Utility Assessment Using EQ-5D among Caregivers of Children with Autism}}. {Value Health}. 2013; 16(5): 778-88.
OBJECTIVES: Health utility of caregivers of children with autism was assessed by using the EuroQol five-dimensional (EQ-5D) questionnaire. Utility scores of autism caregivers were compared with norms for the general adult US population. Predictors of health utility were identified. METHODS: A cross-sectional online survey design was used. Caregivers registered with the Interactive Autism Network were approached for participation in the online survey. Three hundred and sixteen usable responses were received. Health utility among caregivers was calculated and compared with the US population norms by using Student’s t test. Problems in EQ-5D questionnaire domains and utility scores were analyzed by study characteristics by using Kruskal-Wallis analysis of variance. Factors predicting health utility were identified by using ordinary least square regression. RESULTS: Roughly 94% of the caregivers who participated in the study were females. As compared to their counterparts in the general US population, caregivers who were aged 18 to 44 years and were females had lower utility scores (P < 0.001). Significant differences in utility scores were observed among caregivers. When compared to males, females had lower health utility. Caregivers of lower socioeconomic status had lower utility scores and reported more problems in EQ-5D questionnaire domains than did those from higher socioeconomic status. Caregiver burden was inversely correlated with health utility. Caregiver physical and mental health status, objective strain, education, and relationship with the care recipient were found to significantly predict health utility (adjusted R(2) ~57%). CONCLUSIONS: Autism caregivers had lower health utility than did the general adult US population. There is an immediate need to address health concerns among this growing population.
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20. Kitazoe N, Inoue S, Izumoto Y, Kumagai N, Iwasaki Y. {{The Autism-Spectrum Quotient in university students: Pattern of changes in its scores and associated factors}}. {Asia Pac Psychiatry}. 2013.
INTRODUCTION: Support to university students with autism spectrum disorders (ASD) is becoming increasingly important. To determine the validity of the Autism-Spectrum Quotient (AQ) for ASD screening of university students, we conducted longitudinal measurements of the AQ in a large sample of university students and investigated the possibility of changes in the AQ and associated factors. METHODS: The AQ, University Personality Inventory (UPI), and the willingness of the students to be interviewed were determined at admission in students from four departments of Kochi University; the AQ was determined again in the second year. Changes in the AQ and associated factors were analyzed statistically. RESULTS: The number of valid responses in the initial survey was 3427 (87.2%). The AQ was significantly higher in the group with high UPI scores (F = 156.08, P < 0.001). Of the 486 students interviewed at admission, 22 had suspected ASD. The sensitivity/specificity of the AQ for ASD was 81.8%/92.0%. A total of 319 (11.0%) students responded to the second-year survey, which revealed significant decrease of the AQ in the group with high AQ values at admission. DISCUSSION: The AQ measured at admission was correlated with the UPI score, regardless of the sex or department; in the second survey, the scores decreased significantly in those with high AQ values at admission, suggesting that an unstable mental state can produce a temporary increase of the AQ scores.
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21. Latta A, Rampton T, Rosemann J, Peterson M, Mandleco B, Dyches T, Roper S. {{Snapshots reflecting the lives of siblings of children with autism spectrum disorders}}. {Child Care Health Dev}. 2013.
BACKGROUND: Past research focused on the effects of raising a child with autism spectrum disorder on families. However, most research examined parents’ perspectives rather than siblings’ perspectives. Therefore, the purpose of this qualitative descriptive design was to use photo elicitation to capture perspectives of siblings living with a child with autism spectrum disorder. METHODS: Fourteen siblings (nine male) of 13 children with autism spectrum disorder received disposable cameras with 24-27 colour exposures, and were asked to photograph what was important to them within 2 weeks. After developing snapshots, investigators interviewed siblings about their photographs, and used open, axial and selective coding to determine photograph categories and subcategories. RESULTS: Two major categories were found: people (family members, non-family members) and non-people (personal items/objects, animals, buildings, scenery). Interviews about photographs reflected experiences siblings had with people/non-people in the snapshots and their normal everyday activities. Most photographs revealed family life and activities any sibling would experience whether or not they lived in a family raising a child with autism spectrum disorder. CONCLUSIONS: Photo elicitation facilitates communication between children and health-care professionals, and provides information about living with a child with autism spectrum disorder from the sibling’s perspective. This information contributes to our knowledge base and allows development of specific intervention plans for siblings of these children.
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22. Levin-Decanini T, Maltman N, Francis SM, Guter S, Anderson GM, Cook EH, Jacob S. {{Parental Broader Autism Subphenotypes in ASD Affected Families: Relationship to Gender, Child’s Symptoms, SSRI Treatment, and Platelet Serotonin}}. {Autism Res}. 2013.
Relationships between parental broader autism phenotype (BAP) scores, gender, selective serotonin reuptake inhibitor (SSRI) treatment, serotonin (5HT) levels, and the child’s symptoms were investigated in a family study of autism spectrum disorder (ASD). The Broader Autism Phenotype Questionnaire (BAPQ) was used to measure the BAP of 275 parents. Fathers not taking SSRIs (F-SSRI; n = 115) scored significantly higher on BAP Total and Aloof subscales compared to mothers not receiving treatment (M-SSRI; n = 136.) However, mothers taking SSRIs (M + SSRI; n = 19) scored higher than those not taking medication on BAP Total and Rigid subscales, and they were more likely to be BAPQ Total, Aloof, and Rigid positive. Significant correlations were noted between proband autism symptoms and parental BAPQ scores such that Total, Aloof, and Rigid subscale scores of F-SSRI correlated with proband restricted repetitive behavior (RRB) measures on the ADOS, CRI, and RBS-R. However, only the Aloof subscale score of M + SSRI correlated with proband RRB on the ADOS. The correlation between the BAPQ scores of mothers taking SSRIs and child scores, as well as the increase in BAPQ scores of this group of mothers, requires careful interpretation and further study because correlations would not withstand multiple corrections. As expected by previous research, significant parent-child correlations were observed for 5HT levels. However, 5HT levels were not correlated with behavioral measures. Study results suggest that the expression of the BAP varies not only across parental gender, but also across individuals using psychotropic medication and those who do not. Autism Res 2013, : -. (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.
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23. Mavel S, Nadal-Desbarats L, Blasco H, Bonnet-Brilhault F, Barthelemy C, Montigny F, Sarda P, Laumonnier F, Vourc HP, Andres CR, Emond P. {{(1)H-(13)C NMR-based urine metabolic profiling in autism spectrum disorders}}. {Talanta}. 2013; 114: 95-102.
Autism Spectrum Disorders (ASD) are a group of developmental disorders caused by environmental and genetic factors. Diagnosis is based on behavioral and developmental signs detected before 3 years of age with no reliable biological marker. The purpose of this study was to evaluate the potential use of a 2D NMR-based approach to express the global biochemical signature of autistic individuals compared to normal controls. This technique has greater spectral resolution than to 1D (1)H NMR spectroscopy, which is limited by overlapping signals. The urinary metabolic profiles of 30 autistic and 28 matched healthy children were obtained using a (1)H-(13)C NMR-based approach. The data acquired were processed by multivariate orthogonal partial least-squares discriminant analysis (OPLS-DA). Some discriminating metabolites were identified: beta-alanine, glycine, taurine and succinate concentrations were significatively higher, and creatine and 3-methylhistidine concentrations were lower in autistic children than in controls. We also noted differences in several other metabolites that were unidentified but characterized by a cross peak correlation in (1)H-(13)C HSQC. Statistical models of (1)H and (1)H-(13)C analyses were compared and only 2D spectra allowed the characterization of statistically relevant changes [R(2)Y(cum)=0.78 and Q(2)(cum)=0.60] in the low abundance metabolites. This method has the potential to contribute to the diagnosis of neurodevelopment disorders but needs to be validated on larger cohorts and on other developmental disorders to define its specificity.
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24. McMahon CM, Lerner MD, Britton N. {{Group-based social skills interventions for adolescents with higher-functioning autism spectrum disorder: a review and looking to the future}}. {Adolesc Health Med Ther}. 2013; 2013(4): 23-8.
In this paper, we synthesize the current literature on group-based social skills interventions (GSSIs) for adolescents (ages 10-20 years) with higher-functioning autism spectrum disorder and identify key concepts that should be addressed in future research on GSSIs. We consider the research participants, the intervention, the assessment of the intervention, and the research methodology and results to be integral and interconnected components of the GSSI literature, and we review each of these components respectively. Participant characteristics (eg, age, IQ, sex) and intervention characteristics (eg, targeted social skills, teaching strategies, duration and intensity) vary considerably across GSSIs; future research should evaluate whether participant and intervention characteristics mediate/moderate intervention efficacy. Multiple assessments (eg, parent-report, child-report, social cognitive assessments) are used to evaluate the efficacy of GSSIs; future research should be aware of the limitations of current measurement approaches and employ more accurate, sensitive, and comprehensive measurement approaches. Results of GSSIs are largely inconclusive, with few consistent findings across studies (eg, high parent and child satisfaction with the intervention); future research should employ more rigorous methodological standards for evaluating efficacy. A better understanding of these components in the current GSSI literature and a more sophisticated and rigorous analysis of these components in future research will lend clarity to key questions regarding the efficacy of GSSIs for individuals with autism spectrum disorder.
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25. Poslawsky IE, Naber FB, Van Daalen E, Van Engeland H. {{Parental Reaction to Early Diagnosis of Their Children’s Autism Spectrum Disorder: An Exploratory Study}}. {Child Psychiatry Hum Dev}. 2013.
This study explores parental reactions subsequent to receiving their child’s autism spectrum disorder (ASD)-diagnosis. Seventy seven parents of recently diagnosed children participated in the Reaction to Diagnosis Interview. Within this group, associations between parental reaction to diagnosis, parental and child characteristics and prediagnostic circumstances were analysed. In a sub-sample, the stability of reaction to diagnosis was examined. The majority of parents were classified as ‘resolved’ regarding their child’s diagnosis. Conversely, parents of children with more severe ASD symptoms or non-Dutch parents were more likely to be classified as ‘unresolved’. Sub-sample analysis revealed stability of reaction to ASD-diagnosis. The majority of parents adapted well to the circumstances and the care for their child. Autism severity and parental nationality were significant factors affecting parental reactions. Thus, early identification of parental reaction to children’s ASD-diagnosis may aid in providing more tailored parental support programs.
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26. Pugliese CE, White SW. {{Brief Report: Problem Solving Therapy in College Students with Autism Spectrum Disorders: Feasibility and Preliminary Efficacy}}. {J Autism Dev Disord}. 2013.
Students with autism spectrum disorder (ASD), though academically capable, can have difficulty succeeding in college. Evidence-based intervention to promote effective problem solving may improve quality of life, as well as success and satisfaction in college. This study adapted and piloted a group-based cognitive-behavioral intervention program, Problem Solving Skills: 101 (PSS: 101), to teach effective problem solving ability in college students with ASD. Therapists met all treatment integrity objectives across sessions, four of the five participants completed at least eight of the nine sessions, and between-session assignments were generally completed (83 % completion rate), indicating a high level of treatment adherence. Two participants demonstrated reliable improvement post-intervention in problem solving ability and subjective distress. Further evaluation to assess efficacy of the intervention is warranted.
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27. Rosania K. {{Cholesterol key in Rett syndrome}}. {Lab Anim (NY)}. 2013; 42(9): 309.
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28. Schneider A, Ligsay A, Hagerman RJ. {{Fragile X syndrome: An aging perspective}}. {Dev Disabil Res Rev}. 2013; 18(1): 68-74.
Cognitive and behavioral correlates of molecular variations related to the FMR1 gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical manifestations of aging in fragile X syndrome, and the FMR1 premutation. (c) 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2013;18:68-74.
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29. Shic F, Macari S, Chawarska K. {{Speech Disturbs Face Scanning in 6-Month-Old Infants Who Develop Autism Spectrum Disorder}}. {Biol Psychiatry}. 2013.
BACKGROUND: From birth, infants show a preference for the faces, gaze, and voices of others. In individuals with autism spectrum disorders (ASDs) these biases seem to be disturbed. The source of these disturbances is not well-understood, but recent efforts have shown that the spontaneous deployment of attention to social targets might be atypical as early as 6 months of age. The nature of this atypical behavior and the conditions under which it arises are currently unknown. METHODS: We used eye-tracking to examine the gaze patterns of 6-month-old infants (n = 99) at high risk (n = 68) and low risk (n = 54) for developing ASD as they viewed faces that were: 1) still; 2) moving and expressing positive affect; or 3) speaking. Clinical outcomes were determined through a comprehensive assessment at the age of 3 years. The scanning patterns of infants later diagnosed with ASD were compared with infants without an ASD outcome. RESULTS: Infants who later developed ASD spent less time looking at the presented scenes in general than other infants. When these infants looked at faces, their looking toward the inner features of faces decreased compared with the other groups only when the presented face was speaking. CONCLUSIONS: Our study suggests that infants later diagnosed with ASD have difficulties regulating attention to complex social scenes. It also suggests that the presence of speech might uniquely disturb the attention of infants who later develop ASD at a critical developmental point when other infants are acquiring language and learning about their social world.
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30. Sprenger L, Buhler E, Poustka L, Bach C, Heinzel-Gutenbrunner M, Kamp-Becker I, Bachmann C. {{Impact of ADHD symptoms on autism spectrum disorder symptom severity}}. {Res Dev Disabil}. 2013; 34(10): 3545-52.
Despite the official exclusion criteria for autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) in the DSM-IV and ICD-10, patients with ASD often show ADHD symptoms. We aimed to examine the potential influence of ADHD symptoms on autistic psychopathology in a large sample of patients with ASD. We tested the hypothesis that patients with ASD and an additional ADHD (ASD+) would show a higher severity of autistic symptoms than those with ASD only (ASD-). We measured autistic symptoms using the autism diagnostic observation schedule (ADOS-G), the autism diagnostic interview (ADI-R), and the social responsiveness scale (SRS). To measure overall psychopathology and ADHD symptoms, we used the child behavior checklist (CBCL) and the ADHD rating scale (FBB-ADHS), respectively. Group differences between the ASD+ and the ASD- group (group division was conducted according to the results of the FBB-ADHS) were calculated using a univariate analysis of variance (ANOVA). The ASD+ group showed a greater severity of autistic symptoms than the ASD- group, measured by the SRS and the ADI-R. Especially in the social interaction subscale (ADI-R), a significantly higher symptom severity was found in the ASD+ group. No significant group differences were found regarding autistic symptoms measured by the ADOS-G. Patients with ASD and an additional ADHD expressed a stronger severity of autistic symptoms than patients with ASD only. According to our results, the possibility of a co-diagnosis of ADS and ADHD, as is being planned in the DSM-5, is in line with earlier studies, is highly reasonable, will simplify research, and have therapeutic implications.
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31. Theoharides TC. {{Extracellular Mitochondrial ATP, Suramin, and Autism?}}. {Clin Ther}. 2013.
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32. Tian Y, Yabuki Y, Moriguchi S, Fukunaga K, Mao PJ, Hong LJ, Lu YM, Wang R, Ahmed MM, Liao MH, Huang JY, Zhang RT, Zhou TY, Long S, Han F. {{Melatonin reverses the decreases in hippocampal protein serine/threonine kinases observed in an animal model of autism}}. {J Pineal Res}. 2013.
Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)-induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho-CaMKII (Thr286) in the hippocampus of VPA-treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin-treated rat, long-term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 +/- 3.9% of the baseline, P < 0.01 versus VPA-treated rats) following high-frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in VPA-treated rats. Taken together, the increased phosphorylation of CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin on autism symptoms.
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33. Visser E, Zwiers MP, Kan CC, Hoekstra L, van Opstal AJ, Buitelaar JK. {{Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders}}. {J Psychiatry Neurosci}. 2013; 38(5): 120177.
BACKGROUND: Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. METHODS: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). RESULTS: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. LIMITATIONS: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. CONCLUSION: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.
34. White SW, Smith LA, Schry AR. {{Assessment of global functioning in adolescents with autism spectrum disorders: Utility of the Developmental Disability-Child Global Assessment Scale}}. {Autism}. 2013.
Assessment of global functioning is an important consideration in treatment outcome research; yet, there is little guidance on its evidence-based assessment for children with autism spectrum disorders. This study investigated the utility and validity of clinician-rated global functioning using the Developmental Disability-Child Global Assessment Scale in a sample of higher functioning adolescents with autism spectrum disorders and comorbid anxiety disorders enrolled in a randomized controlled trial (n = 30). Pretreatment Developmental Disability-Child Global Assessment Scale scores correlated with severity of autism spectrum disorders core symptoms (r = -.388, p = .034), pragmatic communication (r = .407, p = .032), and verbal ability (r = .449, p = .013) and did not correlate with severity of anxiety symptoms or with parent-reported adaptive behavior. Change in Developmental Disability-Child Global Assessment Scale scores during treatment was associated with autism spectrum disorders symptomatic improvement (r = .414, p = .040) and with improved general communication (r = .499, p = .013). Results support the importance of assessing global functioning in addition to symptom change and treatment response in clinical trials.
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35. Williams K, Brignell A, Randall M, Silove N, Hazell P. {{Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)}}. {Cochrane Database Syst Rev}. 2013; 8: CD004677.
BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To determine if treatment with an SSRI:1. improves the core features of autism (social interaction, communication and behavioural problems);2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;3. improves the quality of life of adults or children and their carers;4. has short- and long-term effects on outcome;5. causes harm. SEARCH METHODS: We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and appraised each study’s risk of bias. MAIN RESULTS: Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety. AUTHORS’ CONCLUSIONS: There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.
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36. Zuckerman KE, Mattox K, Donelan K, Batbayar O, Baghaee A, Bethell C. {{Pediatrician Identification of Latino Children at Risk for Autism Spectrum Disorder}}. {Pediatrics}. 2013.
BACKGROUND AND OBJECTIVES:Latino-white disparities in age at autism spectrum disorder (ASD) diagnosis may be modified by primary care pediatrician (PCP) practices and beliefs. The objectives of this study were to assess ASD and developmental screening practices, attitudes toward ASD identification in Latino children, and barriers to ASD identification for Latino children, in a sample of 267 California PCPs.METHODS:In mail-based PCP survey, we assessed rates of bilingual general developmental and ASD screening, perceptions of parent ASD knowledge in Latino and white families, reports of difficulty assessing for ASDs in Latino and white children, and perceptions of barriers to early ASD identification for Latinos.RESULTS:Although 81% of PCPs offered some form of developmental screening, 29% of PCPs offered Spanish ASD screening per American Academy of Pediatrics guidelines, and only 10% offered both Spanish general developmental and Spanish ASD screening per American Academy of Pediatrics guidelines. Most PCPs thought that Latino (English and Spanish primary family language) parents were less knowledgeable about ASDs than white parents. PCPs had more difficulty assessing ASD risk for Latino children with Spanish primary family language than for white children, even when the PCP conducted recommended ASD screening or had >25% Latino patients. The most frequent barrier to ASD identification in Latinos was access to developmental specialists.CONCLUSIONS:Multiple factors in the primary care setting may contribute to delayed ASD identification for Latinos. Promoting language-appropriate screening, disseminating culturally appropriate ASD materials to Latino families, improving the specialist workforce, and providing PCP support in screening and referral of Latino children may be important ways to reduce racial and ethnic differences in care.
