1. Carmo JC, Martins F, Pinho S, Barahona-Correa B, Ventura P, Filipe CN. {{We see the orange not the lemon: typicality effects in ultra-rapid categorization in adults with and without autism spectrum disorder}}. {Journal of neuropsychology}. 2018.
Semantic meaning can be extracted from pictures presented very briefly, in the order of tens of milliseconds. This ultra-rapid categorization processing appears to respect a coarse-to-fine path where lower level representations of concepts, or more detailed information, need additional time. We question whether variations in the levels of typicality of the target-item would implicate additional processing for correct classification, both in neurotypical (NT) individuals and with autism spectrum disorder (ASD). Previous research in ASD points out that atypical exemplars of a category might be abnormally processed (e.g., longer times in identifying a penguin as a bird), an observation that we further tested with a rapid serial visual presentation (RSVP) task. In this study, we applied a RSVP task, with four different presentation times (13, 27, 50, and 80 ms) and with typical and atypical exemplars to a group of NT individuals and a sample of individuals with ASD. We found, overall, a strong effect of typicality with a higher detection rate for typical items. In addition, we observed a group x typicality x duration interaction. We interpret these findings in the light of the competences of the feedforward sweep of information through our visual system.
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2. Chakrabarty B, Gulati S. {{Autism Spectrum Disorder: Sleep Morbidities and Sensory Impairment; Emerging Paradigm in Research and Management}}. {Indian journal of pediatrics}. 2018.
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3. Cohen IL, Flory MJ. {{Autism Spectrum Disorder Decision Tree Subgroups Predict Adaptive Behavior and Autism Severity Trajectories in Children with ASD}}. {Journal of autism and developmental disorders}. 2018.
A recent cross-sectional analysis of PDD Behavior Inventory (PDDBI) data, analyzed with a classification and regression tree algorithm, yielded a decision tree (the Autism Spectrum Disorder-Decision Tree or ASD-DT) that detected three behaviorally distinct ASD subgroups: minimally verbal, verbal, and atypical. These subgroups differed in PDDBI profiles and in factors previously reported to be predictors of autism severity and adaptive behavior trajectories. We retrospectively analyzed trajectories of adaptive skills and autism severity in these subgroups, defined by ASD-DTs calculated from initial evaluation PDDBIs. Results confirmed predictions that each subgroup had distinct trajectories that varied with the type of adaptive behavior assessed suggesting that the ASD-DT has prognostic value that could be helpful for both clinical and research applications.
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4. Fatima Z, Zahra A, Ghouse M, Wang X, Yuan Z. {{Maternal SSRIs experience and risk of ASD in offspring: a review}}. {Toxicology research}. 2018; 7(6): 1020-8.
Antidepressants are extensively used during pregnancy and associated with severe outcomes, including innate malformations, prematurity, and low birth weight, etc. A recent study suggested that prenatal exposure to antidepressants may impair child neurodevelopment process. Thus, the aim of this review is to investigate the potential association between prenatal use of selective 5-HT reuptake inhibitors (SSRIs) and the risk of autism spectrum disorders (ASDs). Twelve studies related to the linkage between SSRI exposure during pregnancy and ASD in children were explored and compiled. However, there is a knowledge gap concerning the potential link between gestational exposure to antidepressants and the risk of ASDs. Despite such limitations, the available data show that some signal exists and signifies that antenatal exposure to SSRIs may increase the risk of ASDs. Thus, there is a vital need for further, large and well-designed research to definitively evaluate the existence and the magnitude of this severe risk.
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5. Fujino J, Tei S, Itahashi T, Aoki Y, Ohta H, Kubota M, Isobe M, Hashimoto RI, Nakamura M, Kato N, Takahashi H. {{Need for closure and cognitive flexibility in individuals with autism spectrum disorder: A preliminary study}}. {Psychiatry research}. 2018; 271: 247-52.
The need for closure (NFC), a desire for a firm answer and less ambiguity, has a key role in cognitive flexibility in typical development (TD) populations. This study investigated this motivational construct and its relation to cognitive inflexibility in autism spectrum disorder (ASD). Compared with individuals with TD, those with ASD reported higher levels in preference for predictability and closed-mindedness and lower levels in decisiveness. These NFC facets were significantly associated with cognitive flexibility in ASD as well as TD groups. The study findings provide further insights into the motivational underpinnings of flexible behavior in ASD.
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6. Hirosawa T, Kikuchi M, Fukai M, Hino S, Kitamura T, An KM, Sowman P, Takahashi T, Yoshimura Y, Miyagishi Y, Minabe Y. {{Association Between Magnetoencephalographic Interictal Epileptiform Discharge and Cognitive Function in Young Children With Typical Development and With Autism Spectrum Disorders}}. {Frontiers in psychiatry}. 2018; 9: 568.
Electroencephalograms of individuals with autism spectrum disorders (ASD) show higher rates of interictal epileptiform discharges (IEDs), which are known to have an inverse association with cognitive function in typically developed (TD) children. Nevertheless, that phenomenon has not been investigated adequately in children with ASD. From university and affiliated hospitals, 163 TD children (84 male, 79 female, aged 32-89 months) and 107 children (85 male, 22 female, aged 36-98 months) with ASD without clinical seizure were recruited. We assessed their cognitive function using the Kaufman Assessment Battery for Children (K-ABC) and recorded 10 min of MEG. Original waveforms were visually inspected. Then a linear regression model was applied to evaluate the association between the IED frequency and level of their cognitive function. Significantly higher rates of IEDs were found in the ASD group than in the TD group. In the TD group, we found significant negative correlation between mental processing scale scores (MPS) and the IED frequency. However, for the ASD group, we found significant positive correlation between MPS scores and the IED frequency. In terms of the achievement scale, correlation was not significant in either group. Although we found a correlative rather than a causal effect, typically developed children with higher IED frequency might better be followed up carefully. Furthermore, for children with ASD without clinical seizure, clinicians might consider IEDs as less harmful than those observed in TD children.
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7. Kozikowski A, Shen S, Pardo M, Tavares MT, Szarics D, Benoy V, Zimprich CA, Kutil Z, Zhang G, Barinka C, Robers MB, Van Den Bosch L, Eubanks JH, Jope RS. {{Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and Learning Impairments in a Mouse Model of Fragile X Syndrome}}. {ACS chemical neuroscience}. 2018.
Disease-modifying therapies are needed for Fragile X syndrome (FXS), as at present there are no effective treatments or cures. Herein, we report on a tetrahydroquinoline-based selective histone deacetylase 6 (HDAC6) inhibitor SW-100, its pharmacological and ADMET properties, and its ability to improve upon memory performance in a mouse model of FXS, Fmr1-/- mice. This small molecule demonstrates good brain penetrance, low-nanomolar potency for the inhibition of HDAC6 (IC50 = 2.3 nM), with at least a thousand-fold selectivity over all other class I, II, and IV HDAC isoforms. Moreover, through its inhibition of the alpha-tubulin deacetylase domain of HDAC6 (CD2), in cells SW-100 upregulates alpha-tubulin acetylation with no effect on histone acetylation and selectively restores the impaired acetylated alpha-tubulin levels in the hippocampus of Fmr1-/- mice. Lastly, SW-100 ameliorates several memory and learning impairments in Fmr1-/- mice, thus modeling the intellectual deficiencies associated with FXS, and hence providing a strong rationale for pursuing HDAC6-based therapies for the treatment of this rare disease.
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8. Kuehnel CA, Castro R, Furey WM. {{A comparison of WISC-IV and WISC-V verbal comprehension index scores for children with autism spectrum disorder}}. {The Clinical neuropsychologist}. 2018: 1-11.
OBJECTIVES: This study aimed to explore changes in verbal comprehension subtest and index scores from Wechsler Intelligence Scale for Children, fourth edition (WISC)-IV to WISC-V for individuals with autism spectrum disorder (ASD), as the test revision dropped the subtest that has proven to be most challenging for those with ASD (i.e. Comprehension). METHODS: In all, 48 children with ASD who had been assessed with WISC-IV and re-evaluated with WISC-V were included in this study. Paired samples t-tests were used to examine changes in scores between administrations. RESULTS: Results indicated that changes in subtest scores were minimal although a statistically significant index score change occurred. DISCUSSION: These data suggest that administering additional measures of verbal intellect to individuals with ASD (i.e. beyond the two core verbal comprehension subtests of WISC-V) is critical for capturing the totality of their strengths and weaknesses, to effectively inform treatment planning.
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9. Kumazaki H, Warren Z, Swanson A, Yoshikawa Y, Matsumoto Y, Yoshimura Y, Shimaya J, Ishiguro H, Sarkar N, Wade J, Mimura M, Minabe Y, Kikuchi M. {{Brief Report: Evaluating the Utility of Varied Technological Agents to Elicit Social Attention from Children with Autism Spectrum Disorders}}. {Journal of autism and developmental disorders}. 2018.
Technological agents could be effective tools to be used in interventions for enhancing social orienting for some young children with ASD. We examined response to social bids in preschool children with ASD and typical development (TD) at a very early age (i.e., around 3 years) using social prompts presented by technological agents of various forms and human comparisons. Children with ASD demonstrated less response overall to social bids compared to TD controls, across agents or human. They responded more often to a simple humanoid robot and the simple avatar compared to the human. These results support the potential utilization of specific robotic and technological agents for harnessing and potentially increasing motivation to socially-relevant behaviors in some young children with ASD.
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10. Laidi C, Boisgontier J, de Pierrefeu A, Duchesnay E, Hotier S, d’Albis MA, Delorme R, Bolognani F, Czech C, Bouquet C, Amestoy A, Petit J, Holiga S, Dukart J, Gaman A, Toledano E, Ly-Le Moal M, Scheid I, Leboyer M, Houenou J. {{Decreased Cortical Thickness in the Anterior Cingulate Cortex in Adults with Autism}}. {Journal of autism and developmental disorders}. 2018.
Autism spectrum disorder (ASD) is a developmental disorder underdiagnosed in adults. To date, no consistent evidence of alterations in brain structure has been reported in adults with ASD and few studies were conducted at that age. We analyzed structural magnetic resonance imaging data from 167 high functioning adults with ASD and 195 controls. We ran our analyses on a discovery (n = 301) and a replication sample (n = 61). The right caudal anterior cingulate cortical thickness was significantly thinner in adults with ASD compared to controls in both the discovery and the replication sample. Our work underlines the relevance of studying the brain anatomy of an adult ASD population.
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11. Li L, Li M, Lu J, Ge X, Xie W, Wang Z, Li X, Li C, Wang X, Han Y, Wang Y, Zhong L, Xiang W, Huang X, Chen H, Yao P. {{Prenatal Progestin Exposure Is Associated With Autism Spectrum Disorders}}. {Frontiers in psychiatry}. 2018; 9: 611.
We have previously reported that prenatal progestin exposure induces autism-like behavior in offspring through ERbeta (estrogen receptor beta) suppression in the brain, indicating that progestin may induce autism spectrum disorders (ASD). In this study, we aim to investigate whether prenatal progestin exposure is associated with ASD. A population-based case-control epidemiology study was conducted in Hainan province of China. The ASD children were first screened with the Autism Behavior Checklist (ABC) questionnaire, and then diagnosed by clinical professionals using the ASD diagnosis criteria found in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). Eventually, 235 cases were identified as ASD from 37863 children aged 0-6 years old, and 682 matched control subjects with typically developing children were selected for the analysis of potential impact factors on ASD prevalence using multivariate logistic regression. Our data show that the ASD prevalence rate in Hainan was 0.62% with a boy:girl ratio of 5.4:1. Interestingly, we found that the following factors were strongly associated with ASD prevalence: use of progestin to prevent threatened abortion, use of progestin contraceptives at the time of conception, and prenatal consumption of progestin-contaminated seafood during the first trimester of pregnancy. All the above factors were directly or indirectly involved with prenatal progestin exposure. Additionally, we conducted in vivo experiments in rats to further confirm our findings. Either endogenous (progesterone) or synthetic progestin (norethindrone)-treated seafood zebrafish were used to feed pregnant dams, and the subsequent offspring showed autism-like behavior, which further demonstrated that prenatal progestin exposure may induce ASD. We conclude that prenatal progestin exposure may be associated with ASD development.
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12. Myers SM, Voigt RG, Colligan RC, Weaver AL, Storlie CB, Stoeckel RE, Port JD, Katusic SK. {{Autism Spectrum Disorder: Incidence and Time Trends Over Two Decades in a Population-Based Birth Cohort}}. {Journal of autism and developmental disorders}. 2018.
We retrospectively identified autism spectrum disorder (ASD) incident cases among 31,220 individuals in a population-based birth cohort based on signs and symptoms uniformly abstracted from medical and educational records. Inclusive and narrow research definitions of ASD (ASD-RI and ASD-RN, respectively) were explored, along with clinical diagnoses of ASD (ASD-C) obtained from the records. The incidence of ASD-RI, ASD-RN, and ASD-C increased significantly from 1985 to 1998, then ASD-RI and ASD-RN plateaued while the rate of ASD-C continued to increase during 1998-2004. The rising incidence of research-defined ASD may reflect improved recognition and documentation of ASD signs and symptoms. Although the frequency of threshold ASD symptoms stabilized, the rate of ASD-C continued to increase, narrowing the gap between clinical ascertainment and symptom documentation.
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13. Sener EF, Taheri S, Sahin MC, Bayramov KK, Marasli MK, Zararsiz G, Mehmetbeyoglu E, Oztop DB, Canpolat M, Canatan H, Ozkul Y. {{Altered Global mRNA Expressions of Pain and Aggression Related Genes in the Blood of Children with Autism Spectrum Disorders}}. {Journal of molecular neuroscience : MN}. 2018.
Autism spectrum disorder (ASD) is characterized by repetitive stereotypic behaviors, restricted interests, social withdrawal, and communication deficits. Aggression and insensitivity to pain are largely unexplained in these cases. We analyzed nine mRNA expressions of the candidate genes related to aggression and insensitivity to pain in the peripheral blood of patients with ASD. Whole blood samples were obtained from 40 autistic patients (33 boys, 7 girls) and 50 age- and sex-matched controls (37 boys and 13 girls) to isolate RNA. Gene expression was assessed by quantitative Real-Time PCR (qRT-PCR) in the Erciyes University Genome and Stem Cell Center (GENKOK). All of the gene expressions except CRHR1 and SLC6A4 were found to be statistically different between the ASD patients and controls. Gene expression also differed according to gender. Alterations in the mRNA expression patterns of the HTR1E, OPRL1, OPRM1, TACR1, PRKG1, SCN9A and DRD4 genes provide further evidence for a relevant effect of the respective candidate genes on the pathophysiology of ASD. Future studies may determine the sensitivity of these candidate markers in larger samples including further neuropsychiatric diagnosis.
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14. Shin HM, Schmidt RJ, Tancredi D, Barkoski J, Ozonoff S, Bennett DH, Hertz-Picciotto I. {{Prenatal exposure to phthalates and autism spectrum disorder in the MARBLES study}}. {Environmental health : a global access science source}. 2018; 17(1): 85.
BACKGROUND: Evidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD. METHODS: We quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a high-risk ASD longitudinal cohort. At 3 years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n = 46), non-typical development (Non-TD, n = 55), and typical development (TD, n = 100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD. RESULTS: Most associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR) = 1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR = 0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR = 0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR = 0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR = 5.09; 95% CI: 2.05, 12.6), MCOP (RRR = 1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR = 3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (SigmaDEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null. CONCLUSIONS: Our study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings.
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15. Soto-Acosta R, Xie X, Shan C, Baker CK, Shi PY, Rossi SL, Garcia-Blanco MA, Bradrick S. {{Fragile X mental retardation protein is a Zika virus restriction factor that is antagonized by subgenomic flaviviral RNA}}. {eLife}. 2018; 7.
Subgenomic flaviviral RNA (sfRNA) accumulates during infection due to incomplete degradation of viral genomes and interacts with cellular proteins to promote infection. Here we identify host proteins that bind the Zika virus (ZIKV) sfRNA. We identified fragile X mental retardation protein (FMRP) as a ZIKV sfRNA-binding protein and confirmed this interaction in cultured cells and mouse testes. Depletion of FMRP elevated viral translation and enhanced ZIKV infection, indicating that FMRP is a ZIKV restriction factor. We further observed that an attenuated ZIKV strain compromised for sfRNA production was disproportionately stimulated by FMRP knockdown, suggesting that ZIKV sfRNA antagonizes FMRP activity. Importantly, ZIKV infection and expression of ZIKV sfRNA upregulated endogenous FMRP target genes in cell culture and ZIKV-infected mice. Together, our observations identify FMRP as a ZIKV restriction factor whose activity is antagonized by the sfRNA. Interaction between ZIKV and FMRP has significant implications for the pathogenesis of ZIKV infections.
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16. Srinivasan SM, Bhat AN. {{Differences in means-end exploration between infants at risk for autism and typically developing infants in the first 15 months of life}}. {Developmental psychobiology}. 2018.
Our study compared means-end exploration in infants at risk (AR) for autism and typically developing (TD) infants using a nested box paradigm. Sixteen AR and 16 TD infants were observed at 9, 12, and 15 months with follow-up at 18 and 24 months. We collected video data on three tasks involving retrieval of a small toy by opening (a) an opaque box, (b) a transparent box, and (c) two nested boxes. Dependent variables included hand bias, time to completion, bilateral hand use, problem-solving strategies used, and tester assistance required. There were no group differences in terms of hand biases. Compared to TD infants, AR infants had lower bilateral hand use, poor problem solving skills, and required greater assistance. Both groups demonstrated age-related improvements in motor and cognitive skills. Means-end exploration provides a window into the bilateral coordination and motor planning/problem-solving abilities of young infants at risk for autism. Lastly, object retrieval tasks could serve as important learning contexts for at-risk infants.
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17. Yu D, Jiao X, Cao T, Huang F. {{Serum miRNA expression profiling reveals miR-486-3p may play a significant role in the development of autism by targeting ARID1B}}. {Neuroreport}. 2018; 29(17): 1431-6.
Recent studies have implicated microRNAs (miRNAs) in autism and have supported changes in serum miRNA expression profile. We proposed to analyze miRNA expression and its target genes related to regulatory networks in autism within a cohort of Chinese patients. The aim of this study was to explore the dysregulation of miRNAs in autism and investigate the potential mechanistic implications in the pathogenesis of autism. MiRNA was isolated from the serum samples of 20 patients with autism and 23 controls. Dysfunctional miRNAs were identified using miRNA microarray analyses. We used quantitative reverse transcription-PCR to examine the four differentially expressed miRNAs. The target gene of miR-486-3p was confirmed by luciferase assay and miRNA transfection in SH-SY5Y cell lines. A total of 77 differentially expressed miRNAs were found in the miRNA microarray analysis of two patients with autism compared with three controls. On the basis of the microarray results, quantitative reverse transcription-PCR analysis indicated that miR-557 and miR-486-3p expression levels were significantly increased (P<0.05) in 18 patients with autism compared with 20 controls. Overexpression of miR-486-3p decreased ARID1B mRNA and protein levels (P<0.05), whereas inhibition of miR-486-3p increased the mRNA and protein levels of ARID1B in SH-SY5Y cell lines. Luciferase activity was significantly decreased compared with the control group (P<0.05) after cells were co-transfected with miR-486-3p mimics and ARID1B 3'-untranslated region. Our study has highlighted that miR-486-3p expression is increased in serum of patients with autism and supports that miR-486-3p inhibits the expression of ARID1B. Lien vers le texte intégral (Open Access ou abonnement)
