1. Hedley D, Uljarevic M, Bury SM, Dissanayake C. {{Predictors of mental health and well-being in employed adults with autism spectrum disorder at 12-month follow-up}}. {Autism Res}. 2019.
People with Autism Spectrum Disorder (ASD) commonly experience poor outcomes in adulthood. Previous research on adult outcomes has focused on negative aspects of health and well-being, while positive well-being remains understudied. The current study charted 12-month change in daily living skills, job satisfaction, depression, anxiety, and positive well-being in 36 (32 male) newly employed adults with ASD aged 18 to 57 years who were participating in a supported employment program. There was a small increase in daily living skills, and a slight decrease in job satisfaction, with all other measures remaining stable over time. Regression analyses revealed that, controlling for baseline depression, positive well-being negatively predicted depression at follow-up. No significant predictors of anxiety were identified. Social support and depression at baseline were associated with positive well-being at follow-up; however, they were no longer significant predictors after the effects of baseline positive well-being were taken into account. The findings provide evidence that positive well-being may buffer against depression in people with ASD. Our finding of stability of mental health and well-being measures over time indicates more research is required to uncover the mechanisms underpinning mental health and well-being outcomes in employed adults with ASD. Autism Research 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience poor outcomes in adulthood. We studied mental health and well-being in newly employed adults with autism who were participating in a supported employment program. Apart from a slight increase in daily living skills and a slight decrease in job satisfaction, other measures of mental health and well-being remained stable over time. Our findings suggest that positive well-being may protect against symptoms of depression in people with autism.
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2. Horvath G, Otrokocsi L, Beko K, Baranyi M, Kittel A, Antonio Fritz-Ruenes P, Sperlagh B. {{P2X7 receptors drive poly(I:C) induced autism-like behavior in mice}}. {J Neurosci}. 2019.
Maternal immune activation (MIA) is a principal environmental risk factor contributing to autism spectrum disorder (ASD), which compromises fetal brain development at critical periods of pregnancy, and might be causally linked to ASD symptoms. We report that endogenous activation of the purinergic ion channel P2X7 (P2rx7) is necessary and sufficient to transduce MIA to autistic phenotype in male offspring. MIA induced by poly(I:C) injections to P2rx7 wild-type mouse dams elicited an autism-like phenotype in their offspring and these alterations were not observed in P2rx7 deficient mice, or following maternal treatment with a specific P2rx7 antagonist, JNJ7965567. Genetic deletion and pharmacological inhibition of maternal P2rx7s also counteracted the induction of IL-6 in the maternal plasma and fetal brain, and disrupted brain development, whilst postnatal P2rx7 inhibition alleviated behavioral and morphological alterations in the offspring. Administration of ATP to P2rx7 wild-type dams also evoked autistic phenotype, but not in knockout dams, implying that P2rx7 activation by ATP is sufficient to induce austim-like features in offspring. Our results point to maternal and offspring P2rx7s as potential therapeutic targets for the early prevention and treatment of ASD.SIGNIFICANCE STATEMENTAutism spectrum disorder (ASD) is a neurodevelopmental psychiatric disorder caused by genetic and environmental factors. Recent studies highlighted the importance of perinatal risks, in particular, maternal immune activation (MIA), showing strong association with the later emergence of ASD in the affected children. MIA could be mimicked in animal models via injection of a non-pathogenic agent poly(I:C) during pregnancy. This is the first report showing the key role of a ligand gated ion channel, the purinergic P2X7 receptor in MIA induced autism-like behavioral and biochemical features. We show that genetic or pharmacological inhibition of both maternal and offspring P2X7 receptors could reverse the compromised brain development and autistic phenotype pointing to new possibilities for prevention and treatment of ASD.
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3. Leblond CS, Cliquet F, Carton C, Huguet G, Mathieu A, Kergrohen T, Buratti J, Lemiere N, Cuisset L, Bienvenu T, Boland A, Deleuze JF, Stora T, Biskupstoe R, Halling J, Andorsdottir G, Billstedt E, Gillberg C, Bourgeron T. {{Both rare and common genetic variants contribute to autism in the Faroe Islands}}. {NPJ genomic medicine}. 2019; 4: 1.
The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism.
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4. Li Y, Mache MA, Todd TA. {{Complexity of Center of Pressure in Postural Control for Children With Autism Spectrum Disorders Was Partially Compromised}}. {Journal of applied biomechanics}. 2019: 1-20.
The purpose of this study was to compare the complexity of postural control between children with autism spectrum disorder (ASD) and typical developing children during altered visual and somatosensory conditions using the multiscale entropy. Eleven children with ASD and 11 typical developing children were tested during quiet standing under four conditions: (1) eyes open and standing on a stable surface; (2) eyes open and standing on a compliant surface; (3) eyes closed and standing on a stable surface and (4) eyes closed and standing on a compliant surface. The COP data were collected and multiscale entropy and sway area of COP were calculated. The ASD group exhibited lower complexity in mediolateral sway compared to typical developing children with a large effect size (partial eta(2) = 0.21). However, based on the different postural control modes, the anteroposterior sway complexity did not demonstrate a similar decrease for children with ASD. The altered visual or somatosensory conditions alone did not significantly affect the postural sway complexity. We concluded that the complexity of postural control for children with ASD was partially compromised. Reduced mediolateral sway complexity could potentially increase the risks of fall.
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5. Mash LE, Linke AC, Olson LA, Fishman I, Liu TT, Muller RA. {{Transient states of network connectivity are atypical in autism: A dynamic functional connectivity study}}. {Hum Brain Mapp}. 2019.
There is ample evidence of atypical functional connectivity (FC) in autism spectrum disorders (ASDs). However, transient relationships between neural networks cannot be captured by conventional static FC analyses. Dynamic FC (dFC) approaches have been used to identify repeating, transient connectivity patterns (« states »), revealing spatiotemporal network properties not observable in static FC. Recent studies have found atypical dFC in ASDs, but questions remain about the nature of group differences in transient connectivity, and the degree to which states persist or change over time. This study aimed to: (a) describe and relate static and dynamic FC in typical development and ASDs, (b) describe group differences in transient states and compare them with static FC patterns, and (c) examine temporal stability and flexibility between identified states. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 62 ASD and 57 typically developing (TD) children and adolescents. Whole-brain, data-driven regions of interest were derived from group independent component analysis. Sliding window analysis and k-means clustering were used to explore dFC and identify transient states. Across all regions, static overconnnectivity and increased variability over time in ASDs predominated. Furthermore, significant patterns of group differences emerged in two transient states that were not observed in the static FC matrix, with group differences in one state primarily involving sensory and motor networks, and in the other involving higher-order cognition networks. Default mode network segregation was significantly reduced in ASDs in both states. Results highlight that dynamic approaches may reveal more nuanced transient patterns of atypical FC in ASDs.
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6. Mazurek MO, Dovgan K, Neumeyer AM, Malow BA. {{Course and Predictors of Sleep and Co-occurring Problems in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2019.
The chronicity of sleep disturbance and its relation to co-occurring symptoms in children with autism spectrum disorder (ASD) are not well understood. The current study examined longitudinal relations among sleep and co-occurring symptoms in a large well-characterized sample of 437 children with ASD assessed at baseline and follow-up (M = 3.8 years later). Twenty-three percent experienced worsening sleep problems over time, while 31.5% showed improvement. Path analysis indicated that sleep problems at baseline predicted later development of ADHD symptoms in younger children and somatic complaints in older children. For younger children, sensory over-responsivity predicted future sleep problems. Findings suggest that sensory over-reactivity may contribute to sleep problems in some children with ASD, and that sleep problems may result in poor daytime functioning.
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7. Pacheva I, Ivanov I, Yordanova R, Gaberova K, Galabova F, Panova M, Petkova A, Timova E, Sotkova I. {{Epilepsy in Children with Autistic Spectrum Disorder}}. {Children (Basel, Switzerland)}. 2019; 6(2).
The comorbidity of autistic spectrum disorder (ASD) and epilepsy has been widely discussed but many questions still remain unanswered. The aim of this study was to establish the occurrence of epilepsy among children with ASD to define the type of epileptic seizures and syndromes, the age of onset of epilepsy, EEG abnormalities, the used antiepileptic drugs and the therapeutic responses for seizures and autistic behavior, as well as to find some correlations between epilepsy and gender, etiology and intellectual disability (ID). A retrospective study of medical files of 59 patients (aged 1(-)18 years) with ASD during a 5-year period was performed. ASD diagnosis was based on the DSM-5 diagnostic criteria. The patients were examined with a detailed medical history, physical and neurological examination, as well as some additional functional, imaging, laboratory and genetic investigations ASD etiology was syndromic in 9, probable syndromic in 9, and idiopathic in 41 children. ID was established in 90% of ASD children, and epilepsy in 44.4%. The onset of epilepsy prevailed before 7 years of age. The most common seizure types were focal with or without secondary generalization (53.4%). Focal epileptiform EEG abnormalities prevailed. Therapeutic response to seizures was good: 58% were seizure-free, while 27% had >50% seizure reduction but no improvement in autistic behavior. There was no correlation between epilepsy and either occurrence or degree of ID. There was a correlation between the frequency of epileptic seizures and the degree of ID. There was no significant difference among epilepsy rates in different etiologic, gender, and ID groups, probably because of the high percentage of ID and because this was a hospital-based study. Our study showed a significant percentage of epilepsy in ASD population and more than 1/4 were of symptomatic etiology. Those could be managed with specific treatments based on the pathophysiology of the gene defect.
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8. Saha S, Saha T, Sinha S, Rajamma U, Mukhopadhyay K. {{Autistic traits and components of the folate metabolic system: an explorative analysis in the eastern Indian ASD subjects (dagger)}}. {Nutr Neurosci}. 2019: 1-8.
OBJECTIVES: Proper metabolism of the folate is crucial for maintaining DNA integrity, chromosome structure, methylation, as well as gene expression, and thus, folate is speculated to contribute to the etiology of different disorders. Since the etiology of autism spectrum disorder (ASD) is believed to be influenced by both genetic and environmental factors, we hypothesized that functional single nucleotide polymorphisms (SNPs) affecting folate metabolic pathway may have a causal role in the etiology of ASD. METHODS: We analyzed three SNPs, rs2071010, rs2298444 and rs1801198 (in the folate receptor 1, folate receptor 2 and transcobalamin 2, respectively), in 867 ethnically matched subjects including 206 ASD probands and 286 controls. Plasma vitamin B6 and folate were measured in age-matched probands and controls. RESULTS: ASD probands showed a higher frequency of rs2298444 ‘A’ allele (P = 0.01) and genotypes with ‘A’ allele (P = 0.03) when compared with the controls. rs1801198 ‘C’ allele and ‘CG’ genotype also showed higher occurrence in the probands (P = 0.009 and 0.005, respectively). Gender-based stratified analysis revealed a significant higher frequency of rs2298444 ‘A’ allele (P = 0.003), genotypes with rs2298444 ‘A’ allele (P = 0.003) and rs1801198 CG (P = 0.001) in the male probands. Studied variants also showed statistically significant associations with ASD-associated traits measured by the Childhood Autism Rating Scale. ASD subjects exhibited gross deficiency in vitamin B6 level when compared with age-matched controls (P < 0.001), which correlated with risk genetic variants. DISCUSSION: We infer from this pioneering study on eastern Indian subjects that vitamin B6 deficiency, along with risk gene variants, may affect ASD-associated symptoms, warranting further investigation in large cohorts. Lien vers le texte intégral (Open Access ou abonnement)
9. Shiohama T, Levman J, Takahashi E. {{Surface- and voxel-based brain morphologic study in Rett and Rett-like syndrome with MECP2 mutation}}. {Int J Dev Neurosci}. 2019.
Rett syndrome (RTT) is a rare congenital disorder which in most cases (95%) is caused by methyl-CpG binding protein 2 (MECP2) mutations. RTT is characterized by regression in global development, epilepsy, autistic features, acquired microcephaly, habitual hand clapping, loss of purposeful hand skills, and autonomic dysfunctions. Although the literature has demonstrated decreased volumes of the cerebrum, cerebellum, and the caudate nucleus in RTT patients, surface-based brain morphology including cortical thickness and cortical gyrification analyses are lacking in RTT. We present quantitative surface- and voxel-based morphological measurements in young children with RTT and Rett-like syndrome (RTT-l) with MECP2 mutations. The 8 structural T1-weighted MR images were obtained from 7 female patients with MECP2 mutations (3 classic RTT, 2 variant RTT, and 2 RTT-l) (mean age 5.2 [standard deviation 3.3] years old). Our analyses demonstrated decreased total volumes of the cerebellum in RTT/RTT-l compared to gender- and age-matched controls (t (22)=-2.93, p = .008, Cohen’s d = 1.27). In contrast, global cerebral cortical surface areas, global/regional cortical thicknesses, the degree of global gyrification, and global/regional gray and white matter volumes were not statistically significantly different between the two groups. Our findings, as well as literature findings, suggest that early brain abnormalities associated with RTT/RTT-l (with MECP2 mutations) can be detected as regionally decreased cerebellar volumes. Decreased cerebellar volume may be helpful for understanding the etiology of RTT/RTT-l.
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10. So WC, Wong MK, Lam WY, Cheng CH, Ku SY, Lam KY, Huang Y, Wong WL. {{Who is a better teacher for children with autism? Comparison of learning outcomes between robot-based and human-based interventions in gestural production and recognition}}. {Res Dev Disabil}. 2019; 86: 62-75.
BACKGROUND: Individuals with autism spectrum disorder (ASD) tend to show deficits in engaging with humans. Previous findings have shown that robot-based training improves the gestural recognition and production of children with ASD. It is not known whether social robots perform better than human therapists in teaching children with ASD. AIMS: The present study aims to compare the learning outcomes in children with ASD and intellectual disabilities from robot-based intervention on gestural use to those from human-based intervention. METHODS AND PROCEDURES: Children aged six to 12 with low-functioning autism were randomly assigned to the robot group (N = 12) and human group (N = 11). In both groups, human experimenters or social robots engaged in daily life conversations and demonstrated to children 14 intransitive gestures in a highly-structured and standardized intervention protocol. OUTCOMES AND RESULTS: Children with ASD in the human group were as likely to recognize gestures and produce them accurately as those in the robot group in both training and new conversations. Their learning outcomes maintained for at least two weeks. CONCLUSIONS AND IMPLICATIONS: The social cues found in the human-based intervention might not influence gestural learning. It does not matter who serves as teaching agents when the lessons are highly structured.
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11. Soto-Icaza P, Vargas L, Aboitiz F, Billeke P. {{Beta oscillations precede joint attention and correlate with mentalization in typical development and autism}}. {Cortex}. 2019; 113: 210-28.
A precursor of adult social functioning is joint attention (JA), which is the capacity to share attention on an object with another person. JA precedes the development of the capacity to attribute mental states to others (i.e., mentalization or theory of mind). The neural mechanisms involved in the development of mentalization are not fully understood. Electroencephalographic recordings were made of children while they watched stimuli on a screen and their interaction with the experimenter was assessed. We tested whether neuronal activity preceding JA correlates with mentalization in typically developing (TD) children and whether this activity is impaired in children with autistic spectrum disorder (ASD) who evidence deficits in JA and mentalization skills. Both groups exhibited JA behavior with comparable frequency. TD children displayed a higher amplitude of negative central (Nc) event-related potential preceding JA behavior ( approximately 500 msec after stimuli presentation), than did the ASD group. Previous to JA behavior, TD children demonstrated beta oscillatory activity in the temporoparietal region, while ASD children did not show an increase in beta activity. In both groups, the beta power correlated with mentalization, suggesting that this specific neuronal mechanism is involved in mentalization, which used during social interaction.
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12. Trembath D, Westerveld MF, Teppala S, Thirumanickam A, Sulek R, Rose V, Tucker M, Paynter J, Hetzroni O, Keen D, Vivanti G. {{Profiles of vocalization change in children with autism receiving early intervention}}. {Autism Res}. 2019.
Children with autism spectrum disorder (ASD) commonly present with comorbid language impairment, negatively impacting their learning and participation across settings. Addressing these needs requires a detailed understanding of their communication trajectories. In this study, we used the language environment and analysis (LENA) system to examine possible changes in children’s (a) vocalizations and (b) ratio of speech to nonspeech vocalizations over a 10-month period. Data for 23 children with ASD (17M, 6F; ages 32-67 months) were analyzed, including monthly 3-hr in-class recordings and standardized measures of language, cognition, and ASD characteristics. Using hierarchical generalized linear models, we found significant time-trends for child vocalizations (P Lien vers le texte intégral (Open Access ou abonnement)
13. Wang X, Yang J, Zhang H, Yu J, Yao Z. {{Oral probiotic administration during pregnancy prevents autism-related behaviors in offspring induced by maternal immune activation via anti-inflammation in mice}}. {Autism Res}. 2019.
Maternal immune activation (MIA) is associated with an increased risk for autism spectrum disorders (ASD) in offspring. Animal experiments have found that interleukin 6 (IL-6) and IL-17a are key cytokines in the induction of ASD by MIA. Moreover, probiotics were verified to inhibit the production of proinflammatory cytokines. Therefore, we investigated whether the administration of oral probiotics during pregnancy might protect the offspring that have suffered MIA from developing ASD. Probiotics were orally administered to pregnant mice with/without the simultaneous administration of Poly(I:C). We found that oral probiotics prevented the ASD-like behaviors induced by MIA in offspring. Furthermore, oral probiotics prevented the MIA-induced increases in the IL-6 and IL-17a levels in both maternal serum and fetal brains, parvalbumin positive (PV(+) ) neuron loss, and the decrease in the gamma-aminobutyric acid levels in the prefrontal cortex of adult offspring. This work suggests that administering oral probiotics during pregnancy may help decrease the risk of ASD following MIA during pregnancy. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Interleukin 6 (IL-6) and IL-17a are key cytokines in the maternal immune activation (MIA)-induced autism spectrum disorders (ASD). Based on emerging evidence that probiotics can inhibit the production of proinflammatory cytokines, we found that oral probiotics prevented MIA-induced ASD-like behaviors in offspring. This work suggested that oral probiotics during pregnancy may be an effective means for decreasing the incidence of ASD in offspring.
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14. Wei SH, Cao J, Mi T, Feng JR, Liao J. {{[Development of social skills in children with autism spectrum disorder and related influencing factors]}}. {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics}. 2019; 21(1): 77-81.
OBJECTIVE: To investigate the development of social skills in children with autism spectrum disorder (ASD) and related influencing factors. METHODS: A total of 889 children with ASD in 10 cities of China were enrolled as subjects. The Autism Social Skills Scale was used to assess their social skills. RESULTS: The children with ASD had a lower score of each factor than the theoretical median, with the lowest score for social communication and the highest score for self-regulation. There were significant differences in the total score of social skills and the scores of social cognition and social participation between the children with ASD in different age groups (P<0.05). There were also significant differences in the total score of social skills and the scores of social orientation, social communication, social participation, and self-regulation between the ASD children with different language levels (P<0.01). CONCLUSIONS: Children with ASD have low social skills, and their social skills are associated with age and language level. Lien vers Pubmed
15. Zhang T, Zhang J, Wang Z, Jia M, Lu T, Wang H, Yue W, Zhang D, Li J, Wang L. {{Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium}}. {Autism Res}. 2019.
Autism is a childhood neuropsychiatric disorder with evidence of a strong genetic component in the complex etiologies. Contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, plays an essential role in neural development. CNTNAP2 was considered as one of the most susceptible genes for autism spectrum disorder (ASD). Some studies indicated the association of CNTNAP2 with ASD, while others reported no association. Given the inconsistent results of the previous studies, we performed a family-based association study between 9 single-nucleotide polymorphisms (SNPs) of CNTNAP2 and autism in 640 autistic trios in the Chinese Han population. Then, an updated meta-analysis, combined with the data from Psychiatric Genomics Consortium (iPSYCH-PGC ASD, 2017) and available association studies, was conducted. No SNPs were significantly associated with autism in the Chinese Han population. In the meta-analysis, the two frequently reported SNPs (rs2710102 and rs7794745) showed no significant association with ASD. Therefore, CNTNAP2 polymorphisms might not be associated with autism. Autism Research 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In present family-based association study, no single-nucleotide polymorphisms (SNPs) were significantly associated with autism in the Chinese Han population. In the updated meta-analysis, the association between the two frequently reported SNPs (rs2710102 and rs7794745) in CNTNAP2 and the risk of ASD was explored. However, the results showed no significant association. Therefore, our study suggested that CNTNAP2 polymorphisms might not be associated with autism.
