1. 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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2. 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)
3. 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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4. Geetha B, Sukumar C, Dhivyadeepa E, Reddy JK, Balachandar V. {{Autism in India: a case-control study to understand the association between socio-economic and environmental risk factors}}. {Acta Neurol Belg};2018 (Dec 15)
Autism spectrum disorder is a neurodevelopmental disorder and the cause of autism is still unclear. The aim of this study was to investigate the association of socioeconomic, environmental, pregnancy and newborn-related risk factors among children with autism spectrum disorders. This was a population-based case-control study. The study included 55 children with autism spectrum disorder and 55 age and sex matched typically developing normal children (TD) between 3 and 12 years. Several socio-economic factors, environmental factors, pregnancy related, natal, post-natal factors and the first noticed signs by the parents were analyzed. Chi-square test was used to compare nominal variables. For multivariate analysis, forward stepwise logistic regression model was employed to examine the association between autism and the chances that the child develops ASD to assess the odds ratios. Male predominance was observed in the study. Logistic regression model showed statistical significance of the following factors: paternal age greater than 40 years, family history of autism, nutrition during pregnancy, mode of labor, fetal hypoxia, NICU stay and history of breast feeding. In this epidemiological study of autism in Coimbatore city, we found correlation between several environmental factors during fetal development and can be transmitted to succeeding generations, causing atypical behavior phenotypes. The exact exposure magnitude, exposure time in relation to vital developmental periods need to be studied to understand the influence of socioeconomic and environmental factors, which can be improved to prevent ASD-related challenges.
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5. Goodrich M, Armour AC, Panchapakesan K, You X, Devaney J, Knoblach S, Sullivan CAW, Herrero MJ, Gupta AR, Vaidya CJ, Kenworthy L, Corbin JG. {{PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder}}. {Autism Res};2018 (Dec 17)
Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala. We reveal that Pac1r/PAC1R is expressed in both mouse and human amygdala from mid-neurogenesis through early postnatal stages, critical time points when altered brain trajectories are hypothesized to unfold in ASD. We further find that parents of autistic children carrying a previously identified PTSD-risk genotype (CC) report greater reciprocal social deficits compared to those carrying the non-risk GC genotype. Additionally, by exploring resting-state functional connectivity differences in a subsample of the larger behavioral sample, we find higher functional connectivity between the amygdala and right middle temporal gyrus in individuals with the CC risk genotype. Thus, using multimodal approaches, our data reveal that the amygdala-expressed PAC1R gene may be linked to severity of ASD social phenotype and possible alterations in brain connectivity, therefore potentially acting as a modifier of amygdala-related phenotypes. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this multimodal study across mouse and human, we examined expression patterns of Pac1r/PAC1R, a gene implicated in social behavior, and further explored whether a previously identified human PTSD-linked mutation in PAC1R can predict brain connectivity and social deficits in ASD. We find that PAC1R is highly expressed in the both the mouse and human amygdala. Furthermore, our human data suggest that PAC1R genotype is linked to severity of social deficits and functional amygdala connectivity in ASD.
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6. 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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7. Roberts MY, Stern Y, Hampton LH, Grauzer JM, Miller A, Levin A, Kornfeld B, Davis MM, Kaat A, Estabrook R. {{Beyond pass-fail: Examining the potential utility of two thresholds in the autism screening process}}. {Autism Res};2018 (Dec 17)
Access to early intervention as early in development as possible is critical to maximizing long-term outcomes for children with autism spectrum disorders (ASD). However, despite the fact that ASD can be reliably diagnosed by 24 months, the average age of diagnosis is 2 years later. Waitlists for specialized developmental evaluations are one barrier to early diagnosis. The purpose of this study was to examine one potential approach to reducing wait time for an ASD diagnostic evaluation by examining the utility of using more than one threshold for an autism screening tool, the Screening Tool for Autism in Toddlers and Young Children (STAT). Participants included 171 children between 24 and 36 months of age who received a medical diagnostic evaluation through Illinois’ Early Intervention Program. This study directly compared the performance of the STAT when scored: (a) using the original single threshold, (b) using seven equally weighted items using a single threshold, and (c) using all items differentially weighted based on how strongly that item predicts a later ASD diagnosis. In addition, this study explored the potential utility of using two thresholds rather than a single threshold for each scoring method. Results of this study suggest that using a two-threshold logistic regression method has potential psychometric advantages over a single threshold and categorical scoring. Using this approach may reduce the wait time for specialty ASD diagnostic evaluations by maximizing true negatives and true positives, such that specialty evaluations may be reserved for those cases that are more ambiguous or more complex. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study examined the benefits of using two versus one cutoff score when screening for autism. Results indicate that having two scores and weighting test items based on predictive association with an autism diagnosis is better than using a single score and weighting each item equally. Using such an approach may reduce the wait time for specialty autism diagnostic evaluations, such that specialty evaluations may be reserved for those cases that are more ambiguous or more complex.
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8. Siddiqi S, Urooj A, D’Souza MJ. {{Dietary Patterns and Anthropometric Measures of Indian Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2018 (Dec 15)
Research literature on dietary patterns & eating habits of children with Autism Spectrum Disorder (ASD) in India is limited. To explore this, a pilot study (n = 53) which included 45 boys and 8 girls (age group of 2-13 years) was conducted. Three day food records, Food Frequency Questionnaire and Children Eating Behavior Inventory were used to assess the dietary intakes and mealtime behavior problems respectively. Findings revealed lower intake of fruits and vegetables which reflected on their micronutrient status which was significantly (p Lien vers le texte intégral (Open Access ou abonnement)
9. 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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10. Wiedemann A, Renard E, Hernandez M, Dousset B, Brezin F, Lambert L, Weryha G, Feillet F. {{Annual Injection of Zoledronic Acid Improves Bone Status in Children with Cerebral Palsy and Rett Syndrome}}. {Calcif Tissue Int};2018 (Dec 15)
Osteoporosis is a common complication of cerebral palsy and Rett’s syndrome. It is responsible for multiple fractures, bone pain, and impaired quality of life. In case of Rett’s syndrome, a specific dysfunction of osteoblasts causes bone fragility. We observed the effects of annual zoledronic acid (ZA) infusion in a cohort of children with cerebral palsy and Rett’s syndrome. 27 children under 18 years (19 with cerebral palsy and 8 girls with Rett syndrome confirmed by MCEP2 mutation) were treated with an annual injection of 0.1 mg/kg (max 4 mg) of ZA. Calcium and vitamin D were combined in all patients from the first injection of ZA. Dental examination was performed before treatment. Data were analyzed retrospectively. Bone mineral density was measured at diagnosis and yearly thereafter. Bone mass density (BMD) is decreased in patient with cerebral palsy and RS. One year after injection of ZA, we observe an increase of Lumbar spine BMD from – 2.99 to – 2.14 SD (p < 0.0001) and femoral BMD from - 4.26 to - 3.32 SD (p < 0.001) In the subgroup of patient with Rett syndrome, we also observe an increase from - 3.27 to 2.50 SD (p = 0.018) of Lumbar spine BMD. No fractures have been observed in our cohort since the first infusion. Side effects (flu-like syndrome and hypocalcemia) were more common in younger patients and after the first infusion. No serious complications were noticed. This study confirms the efficacy and the safety of an annual injection of ZA to improve bone status in children with cerebral palsy and Rett syndrome. No severe adverse effects were observed. Lien vers le texte intégral (Open Access ou abonnement)
