1. Andreo-Martinez P, Garcia-Martinez N, Quesada-Medina J, Sanchez-Samper EP, Martinez-Gonzalez AE. {{[Candida spp. in the gut microbiota of people with autism: a systematic review]}}. {Rev Neurol};2019 (Jan 1);68(1):1-6.
INTRODUCTION: There is great interest in studies on the implications that gut microbiota exerts on the behavior of people with autism spectrum disorders (ASD), through the microbiota-gut-brain axis. Most studies on microbiota are focused on the possible involvement of bacteria on people with ASD, but few of them are focussed on the effect of microorganisms in the Fungi kingdom. SUBJECTS AND METHODS: The present study performs a systematic review of the presence of Candida spp. in people with ASD using the PRISMA method. RESULTS: A total of three articles were found after applying the exclusion and inclusion criteria of the systematic review. Two studies coincided in reporting significant differences in the increase in the frequency of the Candida spp. genus in people with ASD. while the third study did not report significant differences of Candida spp. genus between people with ASD. CONCLUSIONS: Although there is a clear lack of investigation of both the Candida ssp. genus and the whole Fungi kingdom in people with ASD, the studies point to an important presence of this genre in this group. Specifically, in the results found in this review, the highest prevalence of the C. albicans in children with ASD stands out. However, little is still known about the involvement of Candida spp., and other types of fungi, on gastrointestinal symptoms and ASD symptoms, in children with ASD.
2. Antezana L, Factor RS, Condy EE, Strege MV, Scarpa A, Richey JA. {{Gender differences in restricted and repetitive behaviors and interests in youth with autism}}. {Autism Res};2018 (Dec 17)
Previous work has found gender differences in restricted and repetitive behaviors and interests (RRBI) for autism spectrum disorder (ASD). Compared to girls, affected boys have increased stereotyped and restricted behaviors; however much less is known about gender differences in other areas of RRBI. This study aims to identify whether specific RRBI (i.e., stereotyped, self-injurious, compulsive, insistence on sameness, ritualistic, and restricted), as measured by item-level data on the Repetitive Behavior Scale-Revised (RBS-R), can distinguish girls from boys with ASD. Participants included 615 individuals with ASD (507 boys; 82.4%), ages 3-18 years of age (M = 10.26, SD = 4.20), who agreed to share data with the National Database for Autism Research (NDAR). Multivariate analysis of variance and discriminant function analysis (DFA) were used to determine whether item-level RBS-R data could correctly classify cases by gender. DFA results suggest that RBS-R items significantly differentiate gender. Strongly differentiating RBS-R items had greater success in correctly classifying affected boys (67.90%) than girls (61.00%). Items that best-discriminated gender were heightened stereotyped behaviors and restricted interests items in boys and compulsive, sameness, restricted, and self-injurious behavior items in girls. This study is the first to find that girls with ASD may have increased compulsive, sameness, and restricted RRBI compared to boys. Additionally, findings support heightened self-injurious behaviors in affected girls. Future research should disentangle whether elevated rates of RRBI in girls are central to the presentation of ASD in girls or an epiphenomenon of the high rates of co-occurring disorders (e.g., anxiety) noted in girls. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study is the first to examine a comprehensive measure of repetitive behavior in children with autism, with findings of increased compulsive, insistence on sameness, and self-injurious behavior characterizing girls and increased stereotyped and restricted behavior characterizing boys. Future research should determine whether these elevated behaviors in girls are directly part of the autism presentation in girls or symptoms of co-occurring psychopathology. It is important for autism diagnostic measures to best capture the types of repetitive behavior girls may demonstrate.
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3. Arastoo AA, Khojastehkia H, Rahimi Z, Khafaie MA, Hosseini SA, Mansoori SM, Yosefyshad S, Abshirini M, Karimimalekabadi N, Cheraghi M. {{Evaluation of serum 25-Hydroxy vitamin D levels in children with autism Spectrum disorder}}. {Ital J Pediatr};2018 (Dec 17);44(1):150.
BACKGROUND: Vitamin D plays an important role in etiology of Autism Spectrum Disorders (ASDs). We aimed to evaluate the serum 25 – hydroxyl vitamin D level among children with ASDs in Ahvaz city, Iran. METHODS: It was a cross-sectional study which had conducted on 62 subjects in two groups: a case group (n = 31) consisted of ASD children who study in especial schools; and a control group (n = 31) of healthy children who were selected by simple random sampling from regular schools in Ahvaz city, Iran during 2016. Maching between two groups has done regarding Socioeconomic status, type and amount of food intake, place of living and age. The levels of serum 25 – hydroxyl vitamin D were assessed in early morning means fasted state and also measured using ELISA method. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 20. The significant level was considered < 0.05. RESULTS: In ASD children, the average serum 25-hydroxyvitamine D level was 9.03 +/- 4.14 ng/mg. In ASD group, 96.8% (30 subjects) had vitamin D deficiency. In healthy children group, average serum 25-hydroxyvitamine D level was 15.25 +/- 7.89 ng/mg. Average serum 25-hydroxyvitamine D level in intervention group was significantly lower than the control group (P > 0.001). Although the parents of patients in control group reported longer exposure to sun (27.42 m per day against 33.06 m per day), no significant difference was observed between these groups in terms of exposure to sun (P < 0.05). CONCLUSIONS: A significant difference was observed between serum 25-hydroxyvitamine D levels between the healthy and ASD children. It is recommended to use vitamin D supplement in children with ASDs under medical care. Lien vers le texte intégral (Open Access ou abonnement)
4. Beroule DG. {{Offline encoding impaired by epigenetic regulations of monoamines in the guided propagation model of autism}}. {BMC Neurosci};2018 (Dec 17);19(1):80.
BACKGROUND: Environmental factors can modify the expression of genes, including those involved in the metabolism of neurotransmitters. Accounting for a control role of monoamine neurotransmitters, the guided propagation (GP) memory model may contribute to investigate the consequences of neuromodulation impairments on development disorders such as autism. A prenatal transient excess of ‘monoamine oxidase A’ enzyme is assumed here to trigger persistent epigenetic regulations that would induce imbalanced metabolisms of synaptic monoamines. When imported into the ‘offline’ encoding cycles of a GP model, the consequent ‘serotoninergic noise’ leads to aberrant memory structures that can be linked with autism symptoms. RESULTS: In computer experiments, different levels of uncoupling between representations of monoamines correlate with the amount of impaired GP modules, the severity of irrelevant connections, as well as network overgrowth. Two types of faulty connections are respectively assumed to underlie autism traits, namely repetitive behavior and perceptual oversensitivity. Besides computational modelling, a genetic family-tree shows how the autism sex-ratio can result from combinations of pharmacological and epigenetic features. CONCLUSIONS: These results suggest that the current rise of autism is favored by three possible sources of biological masking: (1) during sleep, when cyclic variations of monoamines may undergo disrupted enzymatic activities; (2) across generations of ‘healthy carriers’ protected by the X-chromosome silencing and a specific genetic variant; (3) early in life, as long as the brain development draws on pools of neurons born when the transient enzymatic excess and its persistent epigenetic regulation overlapped, and as long as the B type of monoamine oxidase does not significantly impact dopamine. A disease-modifying therapy can be derived from this study, which involves relevant biomarkers to be first monitored over several months of clinical trial.
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5. Cai RY, Richdale AL, Dissanayake C, Uljarevic M. {{Cognitive reappraisal and psychological wellbeing but not autism spectrum disorder symptomatology is related to resting heart rate variability}}. {Int J Psychophysiol};2018 (Dec 19)
Heart rate variability (HRV) has been separately shown to be associated with ASD symptomatology, psychological wellbeing and emotion regulation (ER) in specific samples consisting of either individuals with ASD, those without ASD, or combined. However, no study has examined these constructs together or incorporated habitual ER strategy use. Hence, the aim of this study was to examine the relationships between resting HRV, ASD symptomatology, ER strategy use (reappraisal and suppression), and psychological wellbeing (anxiety, depression and positive wellbeing) in a combined sample of adults with and without ASD. Twenty-four adults with ASD (Mage=31.36; SDage=14.84) and twenty without ASD (Mage=35.45; SDage=12.19) completed the ER Questionnaire (ERQ), Diagnostic and Statistical Manual of Mental Disorders-5 Cross-cutting Dimensional Scale, Patient Health Questionnaire-9, Warwick-Edinburgh Mental Well-being Scale, and Autism-Spectrum Quotient-Short. Participants’ resting HRV data were also collected via short-term electrocardiogram. Self-reported use of reappraisal was associated with higher resting HRV. Additionally, reappraisal predicted variance in all three HRV indices above and beyond ASD symptomatology and medication use. These preliminary findings can inform the design of future studies to determine the extent to which reappraisal impacts autonomic flexibility.
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6. Cauvet E, Van’t Westeinde A, Toro R, Kuja-Halkola R, Neufeld J, Mevel K, Bolte S. {{Sex Differences Along the Autism Continuum: A Twin Study of Brain Structure}}. {Cereb Cortex};2018 (Dec 19)
Females might possess protective mechanisms regarding autism spectrum disorder (ASD) and require a higher detrimental load, including structural brain alterations, before developing clinically relevant levels of autistic traits. This study examines sex differences in structural brain morphology in autism and autistic traits using a within-twin pair approach. Twin design inherently controls for shared confounders and enables the study of gene-independent neuroanatomical variation. N = 148 twins (62 females) from 49 monozygotic and 25 dizygotic same-sex pairs were included. Participants were distributed along the whole continuum of autism including twin pairs discordant and concordant for clinical ASD. Regional brain volume, surface area, and cortical thickness were computed. Within-twin pair increases in autistic traits were related to decreases in cortical volume and surface area of temporal and frontal regions specifically in female twin pairs, in particular regions involved in social communication, while only two regions were associated with autistic traits in males. The same pattern was detected in the monozygotic twin pairs only. Thus, non-shared environmental factors seem to impact female more than male cerebral architecture associated with autistic traits. Our results are in line with the hypothesis of a female protective effect in autism and highlights the need to study ASD in females separately from males.
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7. Damiani S, Scalabrini A, Gomez-Pilar J, Brondino N, Northoff G. {{Increased scale-free dynamics in salience network in adult high-functioning autism}}. {Neuroimage Clin};2018 (Dec 10):101634.
Autism spectrum disorder (ASD) is clinically characterized by extremely slow and inflexible behavior. The neuronal mechanisms of these symptoms remain unclear though. Using fMRI, we investigate the resting state’s temporal structure in the frequency domain (scale-free activity as measured with Power-Law Exponent, PLE, and Spectral Entropy, SE) and temporal variance (neural variability) in high-functioning, adult ASD comparing them with schizophrenic and neurotypical subjects. We show that ASD is characterized by high PLE in salience network, especially in dorsal anterior cingulate. This increase in PLE was 1) specific for salience network; 2) independent of other measures such as neuronal variability/SD and functional connectivity, which did not show any significant difference; 3) detected in two independent samples of ASD but not in the schizophrenia sample. Among salience network subregions, dorsal anterior cingulate cortex exhibited PLE differences between ASD and neurotypicals in both samples, showing high robustness in ROC curves values. Salience network abnormal temporal structure was confirmed by SE, which was strongly anticorrelated with PLE and thus decreased in ASD. Taken together, our findings show abnormal temporal structure (but normal temporal variance) in resting state salience network in adult high-functioning ASD. The abnormally high PLE indicates a relative predominance of slower over faster frequencies, which may underlie the slow adaptation to unexpected changes and the inflexible behavior observed in autistic individuals. The specificity of abnormal PLE in salience network suggests its potential utility as biomarker in ASD.
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8. Diaz-Caneja CM, Schnack H, Martinez K, Santonja J, Aleman-Gomez Y, Pina-Camacho L, Moreno C, Fraguas D, Arango C, Parellada M, Janssen J. {{Neuroanatomical deficits shared by youth with autism spectrum disorders and psychotic disorders}}. {Hum Brain Mapp};2018 (Dec 19)
Autism spectrum disorders (ASD) and early-onset psychosis (EOP) are neurodevelopmental disorders that share genetic, clinical and cognitive facets; it is unclear if these disorders also share spatially overlapping cortical thickness (CT) and surface area (SA) abnormalities. MRI scans of 30 ASD, 29 patients with early-onset first-episode psychosis (EO-FEP) and 26 typically developing controls (TD) (age range 10-18 years) were analyzed by the FreeSurfer suite to calculate vertex-wise estimates of CT, SA, and cortical volume. Two publicly available datasets of ASD and EOP (age range 7-18 years and 5-17 years, respectively) were used for replication analysis. ASD and EO-FEP had spatially overlapping areas of cortical thinning and reduced SA in the bilateral insula (all p’s < .00002); 37% of all left insular vertices presenting with significant cortical thinning and 20% (left insula) and 61% (right insula) of insular vertices displaying decreased SA overlapped across both disorders. In both disorders, SA deficits contributed more to cortical volume decreases than reductions in CT did. This finding, as well as the novel finding of an absence of spatial overlap (for ASD) or marginal overlap (for EOP) of deficits in CT and SA, was replicated in the two nonoverlapping independent samples. The insula appears to be a region with transdiagnostic vulnerability for deficits in CT and SA. The finding of nonexistent or small spatial overlap between CT and SA deficits in young people with ASD and psychosis may point to the involvement of common aberrant early neurodevelopmental mechanisms in their pathophysiology. Lien vers le texte intégral (Open Access ou abonnement)
9. Erickson CA, Kaufmann WE, Budimirovic DB, Lachiewicz A, Haas-Givler B, Miller RM, Weber JD, Abbeduto L, Hessl D, Hagerman RJ, Berry-Kravis E. {{Best Practices in Fragile X Syndrome Treatment Development}}. {Brain Sci};2018 (Dec 15);8(12)
Preclinical studies using animal models of fragile X syndrome have yielded several agents that rescue a wide variety of phenotypes. However, translation of these treatments to humans with the disorder has not yet been successful, shedding light on a variety of limitations with both animal models and human trial design. As members of the Clinical Trials Committee of the National Fragile X Foundation, we have discussed a variety of recommendations at the level of preclinical development, transition from preclinical to human projects, family involvement, and multi-site trial planning. Our recommendations are made with the vision that effective new treatment will lie at the intersection of innovation, rigorous and reproducible research, and stakeholder involvement.
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10. Gooskens B, Bos DJ, Mensen VT, Shook DA, Bruchhage MMK, Naaijen J, Wolf I, Brandeis D, Williams SCR, Buitelaar JK, Oranje B, Durston S. {{No evidence of differences in cognitive control in children with autism spectrum disorder or obsessive-compulsive disorder: An fMRI study}}. {Dev Cogn Neurosci};2018 (Nov 29)
Repetitive behaviors are among the core symptoms of both Autism Spectrum Disorder (ASD) and Obsessive-Compulsive Disorder (OCD) and are thought to be associated with impairments in cognitive control. However, it is still unknown how deficits in cognitive control and associated neural circuitry relate to the quality or severity of repetitive behavior in children with these disorders. Therefore, we investigated the behavioral and neural correlates of cognitive control using a modified stop-signal task in a multicenter study of children (aged 8-12 years) with ASD, OCD and typically developing (TD) children (N = 95). As both ASD and OCD have high levels of comorbidity with Attention Deficit/Hyperactivity Disorder (ADHD), we did an exploratory analysis addressing ADHD-symptoms. We found that children with ASD and OCD did not show deficits in cognitive control or changes in brain activity in task-relevant neural networks when compared to TD children. However, increased activity in prefrontal brain areas was associated with increased symptoms of comorbid ADHD. As such, this study does not support differences in cognitive control or associated neural circuitry in children with ASD and OCD, but rather suggests that changes in cognitive control in these disorders may be related to symptoms of comorbid ADHD.
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11. Hanabusa K, Oi M, Tsukidate N, Yoshimura Y. {{Association between maternal Autism Spectrum Quotient scores and the tendency to see pragmatic impairments as a problem}}. {PLoS One};2018;13(12):e0209412.
The aim of the present study was to test the hypothesis that individuals with higher Autism Spectrum Quotient (AQ) scores would be more permissive of pragmatic impairments than those with lower AQ scores. We investigated the presence of a correlation between the AQ scores of mothers with children in grades 1 to 6 and their evaluation of assumed pragmatic impairments in children using the Maternal Evaluation of Pragmatic Impairments in Children (MEPC) measure. Mothers were asked to rate how they would feel if their child showed the communication behaviors listed in scales D (coherence), E (inappropriate initiation), F (stereotyped language), G (use of context), and H (nonverbal communication) of the Children’s Communication Checklist-2, which measures pragmatic impairments. All responses were given on a five-point Likert scale. The results indicated that the higher the maternal AQ score, the less the mother tended to evaluate pragmatic impairments as a problem. We also examined whether the age and gender of assumed children influenced the correlation between AQ and MEPC scores, but found no significant correlation. The partial correlation coefficients were calculated for each subscale, none of which was significant. A negative correlation was found between AQ and MEPC scores as a whole.
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12. Hong SJ, Hyung B, Paquola C, Bernhardt BC. {{The Superficial White Matter in Autism and Its Role in Connectivity Anomalies and Symptom Severity}}. {Cereb Cortex};2018 (Dec 19)
In autism spectrum disorders (ASDs), the majority of neuroimaging studies have focused on the analysis of cortical morphology. White matter changes remain less understood, particularly their association to cortical structure and function. Here, we focused on region that has gained only little attention in ASD neuroimaging: the superficial white matter (SWM) immediately beneath the cortical interface, a compartment playing a prominent role in corticogenesis that incorporates long- and short-range fibers implicated in corticocortical connectivity. Studying a multicentric dataset of ASD and neurotypical controls, we harnessed surface-based techniques to aggregate microstructural SWM diffusion features. Multivariate analysis revealed SWM anomalies in ASD compared with controls in medial parietal and temporoparietal regions. Effects were similar in children and adolescents/adults and consistent across sites. Although SWM anomalies were more confined when correcting for cortical thickness and surface area, findings were overall robust. Diffusion anomalies modulated functional connectivity reductions in ASD and related to symptom severity. Furthermore, mediation models indicated a link between SWM changes, functional connectivity, and symptom load. Analyses targeting the SWM offer a novel perspective on the interplay between structural and functional network perturbations in ASD, highlighting a potentially important neurobiological substrate contributing to its diverse behavioral phenotype.
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13. Huang H, Cheng S, Ding M, Wen Y, Ma M, Zhang L, Li P, Cheng B, Liang X, Liu L, Du Y, Zhao Y, Kafle OP, Han B, Zhang F. {{Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identifies Candidate Genes Associated With Autism Spectrum Disorders}}. {Autism Res};2018 (Dec 18)
Autism spectrum disorders (ASD) are a group of highly heritable psychiatric syndromes with high prevalence. The genetic mechanism of ASD remains elusive now. Here we conducted a transcriptome-wide association study (TWAS) of ASD. The GWAS summary data of ASD was driven from the Psychiatric Genomics Consortium (PGC) portal, totally involving 5,305 ASD cases and 5,305 controls. FUSION software was applied to the GWAS summary data for tissue-related TWAS of ASD considering brain and blood. The ASD associated genes identified by TWAS were further validated by mRNA expression profiling of ASD and the Simons Foundation for Autism Research (SFARI) Gene tool. DAVID 6.8 was used to perform gene ontology (GO) enrichment analysis of ASD associated genes identified by TWAS. TWAS identified 85 genes with TWAS P value <0.05 for ASD. Further comparing the 85 genes with the differentially expressed genes identified by mRNA expression profiling of ASD patients found 5 overlapped genes, including MUTYH (PTWAS = 0.0460, PmRNA = 0.0040), ARHGAP27 (PTWAS = 0.0100, PmRNA = 0.0016), GCA (PTWAS = 0.0480, PmRNA = 0.0063), CCDC14 (PTWAS = 0.0067, PmRNA = 0.0035), and MED15 (PTWAS = 0.0324, PmRNA = 0.0092). Gene Ontology (GO) enrichment analysis of the genes identified by TWAS detected 10 significant GO terms, such as mitochondrion (P = 0.0051), NAD or NADH binding (P = 0.0169), mitochondrial part (P = 0.0386) and 2-oxoglutarate metabolic process (P = 0.0399). In conclusion, this study identified multiple ASD associated genes and gene sets, providing novel clues for revealing the pathogenesis of ASD. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Recent genetic studies of autism spectrum disorders (ASD) have found multiple ASD related genes. However, the results of these studies were hardly replicated with each other, providing limited clues for exploring the genetic mechanism of ASD. This study detected a group of candidate genes showing transcriptome-wide associations with ASD. These results may provide novel clues for revealing the pathogenesis of ASD. Lien vers le texte intégral (Open Access ou abonnement)
14. McKenna B, Koomar T, Vervier K, Kremsreiter J, Michaelson JJ. {{Whole-genome sequencing in a family with twin boys with autism and intellectual disability suggests multimodal polygenic risk}}. {Cold Spring Harb Mol Case Stud};2018 (Dec);4(6)
Over the past decade, a focus on de novo mutations has rapidly accelerated gene discovery in autism spectrum disorder (ASD), intellectual disability (ID), and other neurodevelopmental disorders (NDDs). However, recent studies suggest that only a minority of cases are attributable to de novo mutations, and instead these disorders often result from an accumulation of various forms of genetic risk. Consequently, we adopted an inclusive approach to investigate the genetic risk contributing to a case of male monozygotic twins with ASD and ID. At the time of the study, the probands were 7 yr old and largely nonverbal. Medical records indicated a history of motor delays, sleep difficulties, and significant cognitive deficits. Through whole-genome sequencing of the probands and their parents, we uncovered elevated common polygenic risk, a coding de novo point mutation in CENPE, an ultra-rare homozygous regulatory variant in ANK3, inherited rare variants in NRXN3, and a maternally inherited X-linked deletion situated in a noncoding regulatory region between ZNF81 and ZNF182 Although each of these genes has been directly or indirectly associated with NDDs, evidence suggests that no single variant adequately explains the probands’ phenotype. Instead, we propose that the probands’ condition is due to the confluence of multiple rare variants in the context of a high-risk genetic background. This case emphasizes the multifactorial nature of genetic risk underlying most instances of NDDs and aligns with the « female protective model » of ASD.
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15. Motegi M, Inagaki A, Minakata T, Sekiya S, Takahashi M, Sekiya Y, Murakami S. {{Developmental delays assessed using the Enjoji Scale in children with cochlear implants who have intellectual disability with or without autism spectrum disorder}}. {Auris Nasus Larynx};2018 (Dec 19)
OBJECTIVE: Intellectual disability (ID) and autism spectrum disorder (ASD) are common among children who are candidates for cochlear implants. However, the implications of these comorbidities for cochlear implant placement have been not fully established. This study sought to identify these implications by comparing developmental delays among children with these conditions. METHODS: Participants were children who were followed up at least every 6 months for 24 months after cochlear implant surgery. Developmental delays were assessed using the Enjoji Scale of Infant Analytical Development (Enjoji Scale) and compared in three groups with hearing loss: those with ID (ID group, n=4); those with ASD and ID (ASD+ID group, n=4); and those with typical development (control group, n=5). Developmental delay was evaluated longitudinally before and after cochlear implant placement for 18 months. RESULTS: Among the six subscales that make up the Enjoji Scale, language development and intelligence development were significantly delayed in all three groups and were exacerbated over time except for language development in the control group. Emotional development and social behavior were significantly delayed only in the ASD+ID group. Comparison of intergroup differences revealed delays in language development in the ID and ASD+ID groups compared with the control group. CONCLUSION: The Enjoji Scale successfully demonstrated developmental delays characteristic to the underlying comorbidities of ID with or without ASD in children with cochlear implants. The Enjoji Scale can be a useful diagnostic tool for screening children with cochlear implants for ID with or without ASD.
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16. Papadopoulos C, Lodder A, Constantinou G, Randhawa G. {{Systematic Review of the Relationship Between Autism Stigma and Informal Caregiver Mental Health}}. {J Autism Dev Disord};2018 (Dec 19)
Families play a crucial role in determining the mental health of the autistic individual(s) they are caring for. However, the stigma associated with autism can impair caregiver health. To investigate this, empirical evidence pertaining to stigma’s impact on informal caregivers’ mental health was systematically reviewed. All twelve included studies (n = 1442 informal caregivers) consistently reported the impact of autism related stigma upon caregiver mental health to be significant, meaningful and complex. A new theoretical framework describing the relationship between stigma and caregiver mental health is constructed. Moderating variables include those both changeable through intervention (e.g. hopelessness, self-esteem, self-compassion) and not changeable (gender, culture, financial burden and time since diagnosis). Implications and recommendations for professionals, interventions and future research are proposed.
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17. Rabin SJ, Bamberger E, Mor-Snir I, Feldman R, Golan O. {{Parent-Adolescent Reciprocity in a Conflictual Situation Predicts Peer Interaction in Adolescents With ASD}}. {Autism Res};2018 (Dec 18)
Parent-child reciprocity plays a signicant role in shaping children’s social interaction skills. The development of conflict management skills throughout childhood and adolescence impacts the individual’s social adjustment. The increase in conflictual interaction with one’s parents during adolescence affects the transformation of parent-adolescent interaction into a more mutual, equal relationship. Adolescents with ASD and their parents may struggle in this type of interaction due to the adolescents’ social and regulatory impairments, in addition to their dependence on their parents’ involvement and guidance. The current study aimed to evaluate differences in the way adolescents with and without ASD interact with their parents in a conflictual situation. In addition, the association between parent-adolescent reciprocity and the adolescent’s social interaction with an unfamiliar peer was examined in the ASD group. Thirty adolescents with ASD and their parents and 30 typically developing (TD) controls were assessed during a standardized conflict interaction. In addition, adolescents with ASD took part in a conversation with an unfamiliar peer. Interactions were videotaped and coded. Results revealed that during the conflictual interaction, compared to their TD peers, adolescents with ASD were more involved in the conversation and less withdrawn from the parent, while their parents were more sensitive and less intrusive toward them. Parent-adolescent reciprocity was poorer in the ASD (compared to the TD) dyad and was positively associated with the adolescents’ social-conversational skills with a peer. These findings emphasize the different developmental trajectory parent-adolescent relationship takes in adolescents with ASD, and its impact on the adolescent’s social skills. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The development of conflict management skills throughout childhood and adolescence impacts the individual’s social adjustment. The ability of parents to engage in reciprocal social interaction with the children plays a significant role in shaping children’s social interaction skills with peers and with other adults. The transition to adolescence is characterized by an increase in conflictual interaction with one’s parents, which transforms the interaction between adolescents and their parents into a more mutual, equal relationship. Adolescents with ASD and their parents may struggle in this type of interaction due to the adolescents’ social and emotional difficulties, and their dependence on their parents’ involvement and guidance. However, the nature of parent-adolescent interaction, and particularly conflict management has rarely been studied. This study evaluated the way parents and their adolescents with ASD interact in a conflictual conversation, compared to parents and their typically developing adolescents. In addition, we examined how this type of interaction associated with adolescents’ social conversation skills with a peer, in the ASD group. A videotaped interaction between adolescents and their parents indicated that parents and their adolescents with ASD engaged more positively in the conflict, but were less reciprocal with each other. In addition, higher reciprocity among parents and their adolescents with ASD was associated with better conversation skills with an unfamiliar peer. These findings demonstrate the different ways parent-adolescent relationships evolve in families affected by ASD, and the important role parents have in shaping the adolescent’s social communication skills.
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18. Remington A, Hanley M, O’Brien S, Riby DM, Swettenham J. {{Implications of capacity in the classroom: Simplifying tasks for autistic children may not be the answer}}. {Res Dev Disabil};2018 (Dec 19);85:197-204.
BACKGROUND: Research has demonstrated evidence for increased perceptual capacity in autism: autistic people can process more information at any given time than neurotypical individuals. The implications of this for educating autistic pupils have not been investigated. For example, this ability to process more information at any given time may explain why autistic children sometimes process more peripheral task-irrelevant information than neurotypical individuals (e.g. in background classroom wall-displays). AIMS: The current study assessed the impact of different types of background information on autistic and non-autistic children’s ability to perform a learning task. METHODS AND PROCEDURES: Autistic (N = 23) and non-autistic (N = 50) children took part in a computer-based task designed to simulate a lesson. They watched three videos of a teacher telling a story, each with a different background condition: blank, relevant images, or irrelevant images. OUTCOMES AND RESULTS: When the visual display contained story-relevant information, both groups recalled background information in addition to the central story. When the background displays were irrelevant to the story, autistic children recalled more background information than their neurotypical peers, yet maintained their ability to recall information from the central story. CONCLUSION AND IMPLICATIONS: The current study suggests that pupils’ perceptual capacity- including those on the autistic spectrum – can indeed be capitalised on to support learning in the classroom. To do so, however, we must ensure that the child can use their capacity for task-relevant processing, rather than irrelevant distractions.
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19. Sui YV, Donaldson J, Miles L, Babb JS, Castellanos FX, Lazar M. {{Diffusional kurtosis imaging of the corpus callosum in autism}}. {Mol Autism};2018;9:62.
Background: The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined. Methods: We employed diffusional kurtosis imaging (DKI) metrics to characterize white matter properties within five discrete segments of the corpus callosum in 17 typically developing (TD) adults and 16 age-matched participants with ASD without co-occurring intellectual disability (ID). The DKI metrics included axonal water fraction (f axon) and intra-axonal diffusivity (D axon), which reflect axonal density and caliber, and extra-axonal radial (RDextra) and axial (ADextra) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined. Results: ASD group had significantly decreased callosal f axon and D axon (p = .01 and p = .045), particularly in the midbody, isthmus, and splenium. Regression analysis showed that variation in DKI metrics, primarily in the mid and posterior callosal regions explained up to 70.7% of the variance in processing speed scores for TD (p = .001) but not for ASD (p > .05). Conclusion: Decreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants.
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20. Tran SS, Jun HI, Bahn JH, Azghadi A, Ramaswami G, Van Nostrand EL, Nguyen TB, Hsiao YE, Lee C, Pratt GA, Martinez-Cerdeno V, Hagerman RJ, Yeo GW, Geschwind DH, Xiao X. {{Widespread RNA editing dysregulation in brains from autistic individuals}}. {Nat Neurosci};2019 (Jan);22(1):25-36.
Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of postmortem brains of people with ASD. We observed a global bias for hypoediting in ASD brains, which was shared across brain regions and involved many synaptic genes. We show that the Fragile X proteins FMRP and FXR1P interact with RNA-editing enzymes (ADAR proteins) and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA-editing alterations in ASD and Fragile X syndrome, establishing this as a molecular link between these related diseases. Our findings, which are corroborated across multiple data sets, including dup15q (genomic duplication of 15q11.2-13.1) cases associated with intellectual disability, highlight RNA-editing dysregulation in ASD and reveal new mechanisms underlying this disorder.
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21. Tsai JM, Lu L, Jeng SF, Cheong PL, Gau SS, Huang YH, Wu YT. {{Validation of the modified checklist for autism in toddlers, revised with follow-up in Taiwanese toddlers}}. {Res Dev Disabil};2018 (Dec 19);85:205-216.
BACKGROUND: The Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F) is a two-stage screening scale for determining the risk of autism spectrum disorder (ASD) in toddlers. However, the validity of the M-CHAT-R/F for Asian populations has not yet been established. AIMS: This study investigated the psychometric properties of the M-CHAT-R/F, Taiwan version (M-CHAT-R/F-T), among low- and high-risk Taiwanese toddlers aged 16-30 months. The associations among M-CHAT-R/F-T scores, developmental performance at 24 and 30 months, and ASD diagnosis prediction at 36 months were examined. METHODS AND PROCEDURES: A two-stage screening of the M-CHAT-R/F-T was applied to a study sample comprising 25 toddlers with ASD and 71 atypically developing (ATD) and 221 typically developing (TD) toddlers. OUTCOMES AND RESULTS: The M-CHAT-R/F-T exhibited acceptable internal consistency and test-retest reliability. The M-CHAT-R/F-T scores were significantly correlated with several syndrome scores of the Child Behavior Checklist for Ages 1.5-5 and were significantly higher among toddlers with ASD than among ATD or TD toddlers. Furthermore, M-CHAT-R/F-T scores were negatively correlated with developmental scores in the Mullen Scales of Early Learning at 24 and 30 months. Moreover, the screening exhibited acceptable predictive validity (sensitivity = 0.86; specificity = 0.96) for ASD diagnosis at 36 months. CONCLUSIONS AND IMPLICATIONS: The findings indicate that the M-CHAT-R/F-T is a valid and reliable tool for the developmental screening of low- and high-risk Taiwanese toddlers in community and clinical settings.
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22. Wegiel J, Kaczmarski W, Flory M, Martinez-Cerdeno V, Wisniewski T, Nowicki K, Kuchna I, Wegiel J. {{Deficit of corpus callosum axons, reduced axon diameter and decreased area are markers of abnormal development of interhemispheric connections in autistic subjects}}. {Acta Neuropathol Commun};2018 (Dec 19);6(1):143.
INTRODUCTION: In autism spectrum disorder, lack of coherence and of complex information processing, and narrowly focused interests and repetitive behaviors are considered a sign of long-range underconnectivity and short-range overconnectivity. The goal of this morphometric study of five anatomically and functionally different segments of the corpus callosum (CC) was to establish patterns of differences between long-range interhemispheric connections in nine neurotypical and nine autistic subjects. RESULTS: Electron microscopy revealed a significant reduction in average axon diameter and axon cross-sectional area in autistic subjects, and reduction in CC segment-specific diversification of connections of functionally different cortical regions. The study shows an increase in the percentage of small diameter axons (< 0.651 mum) and a decrease in the percentage of axons with large diameter (> 1.051 mum). The total number of small-diameter axons is reduced in segment I and III by 43% on average. The number of medium- and large-diameter axons is reduced in all five CC segments by an average of 49 and 72%, respectively. CONCLUSIONS: The detected pattern of pathology suggests a failure of mechanisms controlling guidance of axons during development leading to axonal deficit, and failure of mechanisms controlling axon structure. A reduction in axon diameter may affect the velocity and volume of signal transmission, and distort functional specialization of CC segments. Significant deficits in axon number and reduction in axon size in all five CC segments appear to be substantial components of brain connectome integrity distortion which may contribute to the autism phenotype.
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23. Wichnick-Gillis AM, Vener SM, Poulson CL. {{Script fading for children with autism: generalization of social initiation skills from school to home}}. {J Appl Behav Anal};2018 (Dec 19)
We used a script-fading package to teach children with autism to initiate social interactions across various activities in the school setting, and we programmed for generalization in the untrained home setting with a sibling. The three participants, ages 8 to 10 years, demonstrated deficits in social initiations with their peers. During baseline, the participants emitted initiations to one another, although this behavior was variable and did not endure over time. With the introduction of the script-fading package, however, social initiations systematically increased. Moreover, the effects of the script-fading package generalized to the untrained home setting with a sibling. This study expands upon previous research by demonstrating the generalization of social initiations from school with peers to the home setting with siblings.
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24. Xu Q, Liu YY, Wang X, Tan GH, Li HP, Hulbert SW, Li CY, Hu CC, Xiong ZQ, Xu X, Jiang YH. {{Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons}}. {Mol Autism};2018;9:65.
Background: Mutations in CHD8, chromodomain helicase DNA-binding protein 8, are among the most replicated and common findings in genetic studies of autism spectrum disorder (ASD). The CHD8 protein is believed to act as a transcriptional regulator by remodeling chromatin structure and recruiting histone H1 to target genes. The mechanism by which deficiency of CHD8 causes ASD has not been fully elucidated. Methods: We examined the expression of CHD8 in human and mouse brains using both immunohistochemistry and RNA in situ hybridization. We performed in utero electroporation, neuronal culture, and biochemical analysis using RNAi to examine the functional consequences of CHD8 deficiency. Results: We discovered that CHD8 is expressed highly in neurons and at low levels in glia cells in both humans and mice. Specifically, CHD8 is localized predominately in the nucleus of both MAP2 and parvalbumin-positive neurons. In the developing mouse brain, expression of Chd8 peaks from E16 to E18 and then decreases significantly at P14 to adulthood. Knockdown of Chd8 results in reduced axon and dendritic growth, disruption of axon projections to the contralateral cortex, and delayed neuronal migration at E18.5 which recovers by P3 and P7. Conclusion: Our findings indicate an important role for CHD8 in dendritic and axon development and neuronal migration and thus offer novel insights to further dissect the underlying molecular and circuit mechanisms of ASD caused by CHD8 deficiency.
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25. Yamashiro A, Sorcinelli A, Rahman T, Elbogen R, Curtin S, Vouloumanos A. {{Shifting Preferences for Primate Faces in Neurotypical Infants and Infants Later Diagnosed With ASD}}. {Autism Res};2018 (Dec 18)
Infants look at others’ faces to gather social information. Newborns look equally at human and monkey faces but prefer human faces by 1 month, helping them learn to communicate and interact with others. Infants later diagnosed with autism spectrum disorder (ASD) look at human faces less than neurotypical infants, which may underlie some deficits in social-communication later in life. Here, we asked whether infants later diagnosed with ASD differ in their preferences for both human and nonhuman primate faces compared to neurotypical infants over their first 2 years of life. We compare infants’ relative looking times to human or monkey faces paired with nonface controls (Experiment 1) and infants’ total looking times to pairs of human and monkey faces (Experiment 2). Across two experiments, we find that between 6 and 18 months, infants later diagnosed with ASD show a greater downturn (decrease after an initial increase) in looking at both primate faces than neurotypical infants. A decrease in attention to primate faces may partly underlie the social-communicative difficulties in children with ASD and could reveal how early perceptual experiences with faces affect development. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Looking at faces helps infants learn to interact with others. Infants look equally at human and monkey faces at birth but prefer human faces by 1 month. Infants later diagnosed with ASD who show deficits in social-communication look at human faces less than neurotypical infants. We find that a downturn (decline after an initial increase) in attention to both human and monkey faces between 6 and 18 months may partly underlie the social-communicative difficulties in children with ASD.
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26. Yerys BE, Bertollo JR, Kenworthy L, Dawson G, Marco EJ, Schultz RT, Sikich L. {{Brief Report: Pilot Study of a Novel Interactive Digital Treatment to Improve Cognitive Control in Children with Autism Spectrum Disorder and Co-occurring ADHD Symptoms}}. {J Autism Dev Disord};2018 (Dec 19)
The presence of attention deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD) is associated with worse cognitive control. Children with ASD and ADHD often respond poorly to medications, thus we need alternative treatments. We examined the feasibility, acceptability, and preliminary efficacy of Project Evo-a digital treatment. Nineteen children with ASD and co-occurring ADHD symptoms completed this app-based treatment that targets multi-tasking through gameplay versus a comparison educational treatment. Children had a high engagement with both treatments, and parents and children reported high acceptability. Within-group analyses suggest the multi-tasking but not the educational treatment may improve cognitive control. This multi-tasking treatment is feasible, acceptable, and possibly efficacious for cognitive control impairments in children with ASD and ADHD.
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27. Yoon JA, Yoo Y, Lee JS, Kim YM, Shin YB. {{An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation}}. {Mol Genet Genomic Med};2018 (Dec 19)
BACKGROUND: The clinical spectrum of Rett syndrome (RTT; Mendelian Inheritance in Man [MIM] #312750) in males is considered to be wider than previously expected. Therefore, the existence of RTT with a normal male karyotype is still controversial. Here, we report the first case of a male patient presenting with an early seizure type of Rett-like phenotypes with a missense variant of MECP2. METHOD: An 8-month-old male was admitted to the pediatric department due to an initial seizure event following aspiration pneumonia and was referred to our clinic for the evaluation of unexplained neuroregression. Genomic DNA was prepared from venous blood by standard procedures and was processed at the Yale Center for Genome Analysis (YCGA) for whole exome sequencing (WES). Processing of sequence data, variant calling, and the identification of de novo mutations were then performed. Direct Sanger sequencing was performed following PCR amplification. RESULT: In this patient with a normal karyotype, WES analysis led to the identification of a novel, de novo missense variant of MECP2 (p.Arg133His) that is not observed in the normal population. CONCLUSION: This rare case of an p.Arg133His hemizygous MECP2 missense mutation could guide future treatment and follow-up plans for RETT-like phenotypes.
