1. Akintunde ME, Rose M, Krakowiak P, Heuer L, Ashwood P, Hansen R, Hertz-Picciotto I, Van de Water J. {{Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma}}. {Journal of neuroimmunology}. 2015 Sep 15;286:33-41.
Inflammation and asthma have both been reported in some children with autism spectrum disorder (ASD). To further assess this connection, peripheral immune cells isolated from young children with ASD and typically developing (TD) controls and the production of cytokines IL-17, -13, and -4 assessed following ex vivo mitogen stimulation. Notably, IL-17 production was significantly higher following stimulation in ASD children compared to controls. Moreover, IL-17 was increased in ASD children with co-morbid asthma compared to controls with the same condition. In conclusion, children with ASD exhibited a differential response to T cell stimulation with elevated IL-17 production compared to controls.
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2. Charman T, Baird G, Simonoff E, Chandler S, Davison-Jenkins A, Sharma A, O’Sullivan T, Pickles A. {{Testing two screening instruments for autism spectrum disorder in UK community child health services}}. {Developmental medicine and child neurology}. 2015 Aug 25.
AIM: The aim of this study was to test the accuracy of two screening instruments in UK Community health services: Modified Checklist for Autism in Toddlers (M-CHAT) and Social Communication Questionnaire (SCQ) for autism spectrum disorder (ASD). A two-stage screening and in-depth assessment procedure, combined with sampling stratification and statistical weighting, allowed the accuracy of the screens to be estimated in the entire population of referred children. METHOD: The study included all referrals of children aged 18 to 48 months to community paediatric and speech and language therapy services in two London districts over a 12-month period between September 2004 and September 2005. Parents of 808 children were approached; screen data were obtained on 543 children (67.2%). A stratified subsample of 120 children received an in-depth assessment for ASD as defined by the International Statistical Classification of Diseases and Related Health Problems, 10th edition. Community clinician judgement of likely ASD was available for 98 out of the 120 children. RESULTS: The sensitivity and specificity were 64% (95% confidence intervals; range 51-80%) and 75% (63-85%) for the SCQ, and 82% (72-92%) and 50% (33-64%) for M-CHAT. There was no evidence that the area under the curve differed between the two screening instruments. There was also no evidence that clinician judgement of likely ASD differed from either of the screening tests. The screening tests did not perform well to confirm preliminary clinical judgement to refer (in series), nor as an alternative indicator for referral (in parallel). INTERPRETATION: While screening tests may provide useful information, their accuracy is moderate. Screening information in isolation should not be used to make referral decisions regarding specialized ASD assessment.
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3. Frederikse PH, Nandanoor A, Kasinathan C. {{Fragile X Syndrome FMRP Co-localizes with Regulatory Targets PSD-95, GABA Receptors, CaMKIIalpha, and mGluR5 at Fiber Cell Membranes in the Eye Lens}}. {Neurochemical research}. 2015 Aug 23.
Fmr1 and FMRP underlie Fragile X Syndrome (FXS) and are linked with related autism spectrum disorders (ASD). Fmr1 also has an essential role in eye and lens development. Lenses express FMRP along with gamma-aminobutyric acid (GABA) receptors (GABARs), post-synaptic density protein 95 (PSD-95), Tyr-phosphatase STEP, CaMKIIalpha and Alzheimer’s disease Abeta precursor protein, which are verified targets of FMRP regulation in neurons and outline major topics in FXS/ASD research. PSD-95 as well as CaMKIIalpha transcripts undergo polypryimidine tract binding protein dependent alternative splicing in lens, consistent with PSD-95 translation in lens. At least 13 GABAR subunits and GAD25/65/67 GABA metabolism enzymes are expressed in lenses beginning in embryonic development, matching neural development. Interestingly, GABAergic drugs (e.g. baclofen) studied as FXS/ASD therapeutics are shown to resolve developmental vision defects in experimental myopia. Here, we demonstrated that FMRP co-localizes at fiber cell membranes with PSD-95, GABAAdelta, GABAAbeta3, GABBR1, STEP, CaMKIIalpha, and mGluR5 in young adult lenses. GAD65 and GABA detection was greatest at the peri-nuclear lens region where fiber cell terminal differentiation occurs. These findings add to an extensive list of detailed parallels between fiber cell and neuron morphology and their lateral membrane spine/protrusions, also reflected in the shared expression of genes involved in the morphogenesis and function of these membrane structures, and shared use of associated regulatory mechanisms first described as distinguishing the neuronal phenotype. Future studies can determine if GABA levels currently studied as a FXS/ASD biomarker in the brain, and generated by GAD25/65/67 in a comparable cell environment in the lens, may be similarly responsive to Fmr1 mutation in lens. The present demonstration of FMRP and key regulatory targets in the lens identifies a potential for the lens to provide a new research venue, in the same individual, to inform about Fmr1/FMRP pathobiology in brain as well as lens.
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4. Grodberg D, Siper P, Jamison J, Buxbaum JD, Kolevzon A. {{A Simplified Diagnostic Observational Assessment of Autism Spectrum Disorder in Early Childhood}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Aug 25.
Subspecialty physicians who have expertise in the diagnosis of autism spectrum disorder typically do not have the resources to administer comprehensive diagnostic observational assessments for patients suspected of ASD. The autism mental status exam (AMSE) is a free and brief eight-item observation tool that addresses this practice gap. The AMSE, designed by Child and Adolescent Psychiatrists, Developmental Behavioral Pediatricians and Pediatric Neurologists structures the observation and documentation of signs and symptoms of ASD and yields a score. Excellent sensitivity and specificity was demonstrated in a population of high-risk adults. This protocol now investigates the AMSE’s test performance in a population of 45 young children age 18 months to 5 years with suspected ASD or social and communication concerns who are evaluated at an autism research center. Each subject received a developmental evaluation, including the AMSE, performed by a Child and Adolescent Psychiatrist, that was followed by independent standardized assessment using the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. A Best Estimate Diagnosis protocol used DSM-5 criteria to ascertain a diagnosis of ASD or non-ASD. Receiver operating characteristic curve analysis was used to determine the AMSE cut point with the highest sensitivity and specificity. Findings indicate an optimized sensitivity of 94% and a specificity of 100% for this high prevalence group. Because of its high classification accuracy in this sample of children the AMSE holds promise as a tool that can support both diagnostic decision making and standardize point of care observational assessment of ASD in high risk children. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Guyatt AL, Heron J, Knight Ble C, Golding J, Rai D. {{Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study}}. {BMJ open}. 2015;5(8):e007433.
OBJECTIVES: To investigate whether second-to-fourth digit ratio (2D:4D), a measure commonly used as a proxy for fetal testosterone exposure, is associated with autism spectrum disorders (ASDs), as predicted by the extreme male brain theory of autism. DESIGN: A birth cohort study. SETTING: The Avon Longitudinal Study of Parents and Children (ALSPAC). PARTICIPANTS: 6015 ALSPAC children with data on digit ratio, at least 1 outcome measure and information on potential confounding variables (parental occupational class, maternal education and age at digit ratio measurement). Digit ratio was measured by the photocopy and calliper method. OUTCOMES: ASD diagnosis (cases were identified previously by record linkage or maternal report) and 4 measures that combine optimally within ALSPAC to predict ASD: the Children’s Communication Checklist (coherence subscale), the Social and Communication Disorders Checklist, a repetitive behaviour measure, and the Emotionality, Activity and Sociability scale (sociability subscale). These measures were dichotomised, with approximately 10% defined as the ‘risk’ group. RESULTS: Using logistic regression, we examined the association of 2D:4D with ASDs and 4 dichotomised ASD traits. Covariates were occupational class, maternal education and age at 2D:4D measurement. 2D:4D was not associated with ASDs in males (adjusted OR per 1 SD increase in mean 2D:4D, 0.88 (95% CI 0.65 to 1.21), p=0.435) or females (adjusted OR=1.36 (95% CI 0.81 to 2.28), p=0.245). Similar results were observed after adjustment for IQ. There was 1 weak association between reduced coherence and increased left 2D:4D in males, in the opposite direction to that predicted by the extreme male brain theory (adjusted OR=1.15 (95% CI 1.02 to 1.29), p=0.023). Given multiple comparisons, this is consistent with chance. CONCLUSIONS: In this population-based study, there was no strong evidence of an association between 2D:4D and ASD diagnosis or traits, although the CIs were wide. These results are not consistent with the extreme male brain theory.
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6. Hall T, Kriz D, Duvall S, Nguyen-Driver M, Duffield T. {{Healthcare transition challenges faced by young adults with autism spectrum disorder}}. {Clinical pharmacology and therapeutics}. 2015 Aug 24.
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7. Hobson JA, Tarver L, Beurkens N, Peter Hobson R. {{The Relation between Severity of Autism and Caregiver-Child Interaction: a Study in the Context of Relationship Development Intervention}}. {Journal of abnormal child psychology}. 2015 Aug 23.
The aim of this study was to examine the relations between severity of children’s autism and qualities of parent-child interaction. We studied these variables at two points of time in children receiving a treatment that has a focus on social engagement, Relationship Development Intervention (RDI; Gutstein 2009). Participants were 18 parent-child dyads where the child (16 boys, 2 girls) had a diagnosis of autism and was between the ages of 2 and 12 years. The severity of the children’s autism was assessed at baseline and later in treatment using the autism severity metric of the Autism Diagnostic Observation Schedule (ADOS; Gotham et al. Journal of Autism and Developmental Disorders, 39, 693-705 2009). Although the ADOS was designed as a diagnostic measure, ADOS calibrated severity scores (CSS) are increasingly used as one index of change (e.g., Locke et al. Autism, 18, 370-375 2014). Videotapes of parent-child interaction at baseline and later in treatment were rated by independent coders, for a) overall qualities of interpersonal relatedness using the Dyadic Coding Scales (DCS; Humber and Moss The American Journal of Orthopsychiatry, 75, 128-141 2005), and b) second-by-second parent-child Co-Regulation and Intersubjective Engagement (processes targeted by the treatment approach of RDI). Severity of autism was correlated with lower quality of parent-child interaction. Ratings on each of these variables changed over the course of treatment, and there was evidence that improvement was specifically related to the quality of parent-child interaction at baseline.
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8. Izuwah DN, Okoh BA, Alikor EA. {{Clinical Pattern of Autism in Nigeria}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Aug 25.
Autism, a global disorder has been widely studied in the Western world. However, there are limited studies on its occurrence, risk factors, and presentation in developing countries such as Nigeria. This retrospective study highlights the pattern of presentation of autism and presence of some risk factors in 75 Nigerian cases referred to a private autism center. The diagnosis of autism was made using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV), International Classification of Diseases Fourth edition, the Modified Checklist for Autism in Toddlers, Autism Treatment Evaluation Checklist, and Childhood Autism Rating Scale. There were 60 males and 15 females with a male to female ratio of 4:1. The mean age at presentation to the center was 6.87 +/- 4.20 years and majority (91.9%) belonged to a high socioeconomic class. Already established risk factors, clinical features, and comorbidities of autism present among the study group were similar to findings in individuals with autism in other parts of the world. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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9. Khowaja K, Salim SS. {{Correction: Heuristics to Evaluate Interactive Systems for Children with Autism Spectrum Disorder (ASD)}}. {PloS one}. 2015;10(8):e0136977.
[This corrects the article DOI: 10.1371/journal.pone.0132187.].
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10. Meyza K, Nikolaev T, Kondrakiewicz K, Blanchard DC, Blanchard RJ, Knapska E. {{Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model of autism}}. {Frontiers in behavioral neuroscience}. 2015;9:199.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized, in part, by an inability to adequately respond to social cues. Patients diagnosed with ASD are often devoid of empathy and impaired in understanding other people’s emotional perspective. The neuronal correlates of this impairment are not fully understood. Replicating such a behavioral phenotype in a mouse model of autism would allow us insight into the neuronal background of the problem. Here we tested BTBR T(+)Itpr3(tf)/J (BTBR) and c57BL/6J (B6) mice in two behavioral paradigms: the Transfer of Emotional Information test and the Social Proximity test. In both tests BTBR mice displayed asocial behavior. We analyzed c-Fos protein expression in several brain regions after each of these tests, and found that, unlike B6 mice, BTBR mice react to a stressed cagemate exposure in the Transfer of Emotional Information test with no increase of c-Fos expression in either the prefrontal cortex or the amygdala. However, after Social Proximity exposure we observed a strong increase in c-Fos expression in the CA3 field of the hippocampus and two hypothalamic regions of BTBR brains. This response was accompanied by a strong activation of periaqueductal regions related to defensiveness, which suggests that BTBR mice find unavoidable social interaction highly aversive.
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11. Murray AL, Booth T, McKenzie K, Kuenssberg R. {{What Range of Trait Levels Can the Autism-Spectrum Quotient (AQ) Measure Reliably? An Item Response Theory Analysis}}. {Psychological assessment}. 2015 Aug 24.
It has previously been noted that inventories measuring traits that originated in a psychopathological paradigm can often reliably measure only a very narrow range of trait levels that are near and above clinical cutoffs. Much recent work has, however, suggested that autism spectrum disorder traits are on a continuum of severity that extends well into the nonclinical range. This implies a need for inventories that can capture individual differences in autistic traits from very high levels all the way to the opposite end of the continuum. The Autism-Spectrum Quotient (AQ) was developed based on a closely related rationale, but there has, to date, been no direct test of the range of trait levels that the AQ can reliably measure. To assess this, we fit a bifactor item response theory model to the AQ. Results suggested that AQ measures moderately low to moderately high levels of a general autistic trait with good measurement precision. The reliable range of measurement was significantly improved by scoring the instrument using its 4-point response scale, rather than dichotomizing responses. These results support the use of the AQ in nonclinical samples, but suggest that items measuring very low and very high levels of autistic traits would be beneficial additions to the inventory. (PsycINFO Database Record
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12. Neuhaus E, Bernier RA, Beauchaine TP. {{Children with Autism Show Altered Autonomic Adaptation to Novel and Familiar Social Partners}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Aug 25.
Social deficits are fundamental to autism spectrum disorder (ASD), and a growing body of research implicates altered functioning of the autonomic nervous system (ANS), including both sympathetic and parasympathetic branches. However, few studies have explored both branches concurrently in ASD, particularly within the context of social interaction. The current study investigates patterns of change in indices of sympathetic (pre-ejection period; PEP) and parasympathetic (respiratory sinus arrhythmia; RSA) cardiac influence as boys (ages 8-11 years) with (N = 18) and without (N = 18) ASD engage in dyadic social interaction with novel and familiar social partners. Groups showed similar patterns of autonomic change during interaction with the novel partner, but differed in heart rate, PEP, and RSA reactivity while interacting with a familiar partner. Boys without ASD evinced decreasing sympathetic and increasing parasympathetic influence, whereas boys with ASD increased in sympathetic influence. Boys without ASD also demonstrated more consistent ANS responses across partners than those with ASD, with parasympathetic responding differentiating familiar and novel interaction partners. Finally, PEP slopes with a familiar partner correlated with boys’ social skills. Implications include the importance of considering autonomic state during clinical assessment and treatment, and the potential value of regulation strategies as a complement to intervention programs aiming to support social cognition and behavior. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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13. O’Keefe JA, Robertson-Dick EE, Hall DA, Berry-Kravis E. {{Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia Syndrome}}. {Cerebellum (London, England)}. 2015 Aug 23.
Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a « premutation » (PM) size CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Cerebellar gait ataxia is the primary feature in some FXTAS patients causing progressive disability. However, no studies have quantitatively characterized gait and mobility deficits in FXTAS. We performed quantitative gait and mobility analysis in seven FMR1 PM carriers with FXTAS and ataxia, six PM carriers without FXTAS, and 18 age-matched controls. We studied four independent gait domains, trunk range of motion (ROM), and movement transitions using an instrumented Timed Up and Go (i-TUG). We correlated these outcome measures with FMR1 molecular variables and clinical severity scales. PM carriers with FXTAS were globally impaired in every gait performance domain except trunk ROM compared to controls. These included total i-TUG duration, stride velocity, gait cycle time, cadence, double-limb support and swing phase times, turn duration, step time before turn, and turn-to-sit duration, and increased gait variability on several measures. Carriers without FXTAS did not differ from controls on any parameters, but double-limb support time was close to significance. Balance and disability scales correlated with multiple gait and movement transition parameters, while the FXTAS Rating Scale did not. This is the first study to quantitatively examine gait and movement transitions in FXTAS patients. Gait characteristics were consistent with those from previous cohorts with cerebellar ataxia. Sensitive measures like the i-TUG may help determine efficacy of interventions, characterize disease progression, and provide early markers of disease in FXTAS.
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14. Simut RE, Vanderfaeillie J, Peca A, Van de Perre G, Vanderborght B. {{Children with Autism Spectrum Disorders Make a Fruit Salad with Probo, the Social Robot: An Interaction Study}}. {Journal of autism and developmental disorders}. 2015 Aug 25.
Social robots are thought to be motivating tools in play tasks with children with autism spectrum disorders. Thirty children with autism were included using a repeated measurements design. It was investigated if the children’s interaction with a human differed from the interaction with a social robot during a play task. Also, it was examined if the two conditions differed in their ability to elicit interaction with a human accompanying the child during the task. Interaction of the children with both partners did not differ apart from the eye-contact. Participants had more eye-contact with the social robot compared to the eye-contact with the human. The conditions did not differ regarding the interaction elicited with the human accompanying the child.
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15. Solso S, Xu R, Proudfoot J, Hagler DJ, Jr., Campbell K, Venkatraman V, Carter Barnes C, Ahrens-Barbeau C, Pierce K, Dale A, Eyler L, Courchesne E. {{Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers}}. {Biological psychiatry}. 2015 Jul 4.
BACKGROUND: Theories of brain abnormality in autism spectrum disorder (ASD) have focused on underconnectivity as an explanation for social, language, and behavioral deficits but are based mainly on studies of older autistic children and adults. METHODS: In 94 ASD and typical toddlers ages 1 to 4 years, we examined the microstructure (indexed by fractional anisotropy) and volume of axon pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto-temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as posterior contrast tracts. Differences between ASD and typical toddlers in the nature of the relationship of age to these measures were tested. RESULTS: Frontal tracts in ASD toddlers displayed abnormal age-related changes with greater fractional anisotropy and volume than normal at younger ages but an overall slower than typical apparent rate of continued development across the span of years. Posterior cortical contrast tracts had few significant abnormalities. CONCLUSIONS: Frontal fiber tracts displayed deviant early development and age-related changes that could underlie impaired brain functioning and impact social and communication behaviors in ASD.
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16. Vijayashankar S, Arumugam G, Sridharan S. {{Urine proteome analysis to evaluate protein biomarkers in children with autism}}. {Clinica chimica acta; international journal of clinical chemistry}. 2015 Aug 19.
BACKGROUND: Autism is a complex developmental disability for which no specific diagnostic markers have been identified so far. The present study aimed to evaluate whether there is any abnormal protein(s) excreted in the urine of autistic children by proteome analysis which may act as diagnostic marker. METHODS: Urine proteome analysis was carried out in first void urine samples of autistic and normal children (n=30) in the age group of 4-12years by 2D-PAGE followed by MALDI-TOF-MS analysis. RESULTS: Comparison of 2D-PAGE gels revealed that many urinary proteins are expressed differentially in autistic children. Total numbers of spots observed were 250 and 159 in autism and normal samples respectively, out of which 95 matches were observed. In addition, 3 spots of abnormally expressed peptides were selected, excised and analyzed. Peptide sequence with significant match score was for kininogen-1 (KNG-1)-50 (spot-1), IgG1 heavy chain variable region-35(spot-2) and mannan-binding lectin serine protease-2 isoform-2 precursor-45(spot-3). All the autistic children showed significant increase (p<0.001) in urinary kininogen level measured quantitatively by ELISA, when compared to normal children. CONCLUSION: Increased urinary kininogen-1 level in all the autistic children and the possibility of this protein as a diagnostic marker need further investigation.
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17. Zeidan-Chulia F, Salmina AB, Noda M, Verkhratsky A. {{Rho GTPase RAC1 at the Molecular Interface Between Genetic and Environmental Factors of Autism Spectrum Disorders}}. {Neuromolecular medicine}. 2015 Aug 25.
