1. Abu-Akel A. {{Genetic variations in the SNP rs850807 reflect a trade-off between autism and paranoia symptom expressions: a comment on Crespi et al. 2018}}. {Biology letters}. 2018; 14(8).
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2. Aryal S, Klann E. {{Turning up translation in fragile X syndrome}}. {Science (New York, NY)}. 2018; 361(6403): 648-9.
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3. Baronio D, Bauer-Negrini G, Castro K, Della-Flora Nunes G, Riesgo R, Mendes-da-Cruz DA, Savino W, Gottfried C, Bambini-Junior V. {{Reduced CD4 T Lymphocytes in Lymph Nodes of the Mouse Model of Autism Induced by Valproic Acid}}. {Neuroimmunomodulation}. 2018: 1-5.
OBJECTIVE: Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal model of autism induced by valproic acid (VPA). Pregnant Swiss mice received a single intraperitoneal injection of 600 mg/kg of VPA (VPA group) or saline (control group) on day 11 of gestation. Male offspring were euthanized on postnatal day 60 for removal of thy-muses, spleens, and a pool of inguinal, axillary and brachial lymph nodes. Cellularity was evaluated, and flow cytometry analysis was performed on cell suspensions incubated with the mouse antibodies anti-CD3-FITC, anti-CD4-PE, and anti-CD8-PE-Cy7. We observed that the prenatal exposure to VPA induced a reduction in the numbers of CD3+CD4+ T cells in their lymph nodes when compared to the control animals. This was specific since it was not seen in the thymus or spleen. The consistent decrease in the number of CD4+ T cells in subcutaneous lymph nodes of mice from the animal model of autism may be related to the allergic symptoms frequently observed in ASD. Further research is necessary to characterize the immunological patterns in ASD and the connection with the pathophysiology of this disorder.
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4. Bazelmans T, Jones EJH, Ghods S, Corrigan S, Toth K, Charman T, Webb SJ. {{Heart rate mean and variability as a biomarker for phenotypic variation in preschoolers with autism spectrum disorder}}. {Autism Res}. 2018.
Interest in autonomic arousal in autism spectrum disorder (ASD) is increasing; however, reliability of these measures in ASD is unknown, and previously reported associations with social and cognitive abilities are inconsistent. This study assesses heart rate (HR) and HR variability (HRV) in preschoolers with ASD or typical development (TD) while they passively watched naturalistic videos. Measurement reliability, group differences, and the relationship with social and cognitive abilities were evaluated. Seventy one ASD and 66 TD children (2-4 years) provided cardiac data from two sessions. Test-retest intraclass correlations of HR and HRV over a 3-week period were moderate to good in both groups. Groups did not differ in mean level of HR or HRV. Intra-individual variability of HR between video segments within a session was higher in the ASD group, but intraclass correlations of this metric were low. Higher HR related to better language skills in TD children, but not after accounting for age and nonverbal ability. Higher HRV related to better expressive and receptive language in ASD children after controlling for age and nonverbal ability. HR/HRV were not related to social or executive functioning skills and did not explain any additional variance in abilities at a 12-month follow-up visit. In summary, variation in language abilities is associated with HR in the TD group and HRV in the ASD group. While preliminary, these results are promising for consideration of autonomic control as a biomarker for individual differences in ASD and may help us understand the mechanisms that contribute to communication skills. LAY SUMMARY: Cardiac activity, such as heart rate and heart rate variability, is linked to a wide range of psychological functions. This study shows that there is an association between heart rate and heart rate variability and language skills in young children with autism spectrum disorder (ASD). These results may help us understand what underlies individual differences in developmental abilities in young children with ASD.
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5. Brown AS, Cheslack-Postava K, Rantakokko P, Kiviranta H, Hinkka-Yli-Salomaki S, McKeague IW, Surcel HM, Sourander A. {{Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort}}. {Am J Psychiatry}. 2018: appiajp201817101129.
OBJECTIVE: Autism is a complex neurodevelopmental disorder with a largely unknown etiology. To date, few studies have investigated prenatal exposure to toxins and risk of autism by using maternal biomarkers of exposure. Persistent organic pollutants are lipophilic halogenated organic compounds and include the insecticide dichlorodiphenyltrichloroethane (DDT), as well as its metabolite p,p’-dichlorodiphenyl dichloroethylene (p,p’-DDE), and polychlorinated biphenyls (PCBs). The objective of this study was to test whether elevated maternal levels of persistent organic pollutants are associated with autism among offspring. METHOD: The investigation was derived from the Finnish Prenatal Study of Autism, a national birth cohort study based on a nested case-control design. Cases of autism among children born between 1987 and 2005 were ascertained by national registry linkages. In cases of childhood autism and matched control subjects (778 matched case-control pairs), maternal serum specimens from early pregnancy were assayed for levels of p,p’-DDE and total levels of PCBs. RESULTS: The odds of autism among offspring were significantly increased with maternal p,p’-DDE levels that were in the highest 75th percentile, with adjustment for maternal age, parity, and history of psychiatric disorders (odds ratio=1.32, 95% CI=1.02, 1.71). The odds of autism with intellectual disability were increased by greater than twofold with maternal p,p’-DDE levels above this threshold (odds ratio=2.21, 95% CI=1.32, 3.69). There was no association between total levels of maternal PCBs and autism. CONCLUSIONS: These findings provide the first biomarker-based evidence that maternal exposure to insecticides is associated with autism among offspring. Although further research is necessary to replicate this finding, this study has implications for the prevention of autism and may provide a better understanding of its pathogenesis.
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6. Crespi BJ. {{Paranoia, autism and the architecture of genomic conflicts: a reply to Abu-Akel 2018}}. {Biology letters}. 2018; 14(8).
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7. Greenblatt EJ, Spradling AC. {{Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins}}. {Science (New York, NY)}. 2018; 361(6403): 709-12.
Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functional targets has been difficult. We analyzed quiescent Drosophila oocytes, which, like neural synapses, depend heavily on translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather than represses the translation of mRNAs that overlap previously identified FMR1 targets, and acts preferentially on large proteins. Human homologs of at least 20 targets are associated with dominant intellectual disability, and 30 others with recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually generate embryos with severe neural defects, unlike stored wild-type oocytes, which suggests that translation of multiple large proteins by stored mRNAs is defective in fragile X syndrome and possibly other autism spectrum disorders.
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8. Hassan WM, Al-Ayadhi L, Bjorklund G, Alabdali A, Chirumbolo S, El-Ansary A. {{The Use of Multi-parametric Biomarker Profiles May Increase the Accuracy of ASD Prediction}}. {Journal of molecular neuroscience : MN}. 2018.
Effective biomarkers are urgently needed to facilitate early diagnosis of autism spectrum disorder (ASD), permitting early intervention, and consequently improving prognosis. In this study, we evaluate the usefulness of nine biomarkers and their association (combination) in predicting ASD onset and development. Data were analyzed using multiple independent mathematical and statistical approaches to verify the suitability of obtained results as predictive parameters. All biomarkers tested appeared useful in predicting ASD, particularly vitamin E, glutathione-S-transferase, and dopamine. Combining biomarkers into profiles improved the accuracy of ASD prediction but still failed to distinguish between participants with severe versus mild or moderate ASD. Library-based identification was effective in predicting the occurrence of disease. Due to the small sample size and wide participant age variation in this study, we conclude that the use of multi-parametric biomarker profiles directly related to autism phenotype may help predict the disease occurrence more accurately, but studies using larger, more age-homogeneous populations are needed to corroborate our findings.
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9. Lucibello S, Verdolotti T, Giordano FM, Lapenta L, Infante A, Piludu F, Tartaglione T, Chieffo D, Colosimo C, Mercuri E, Battini R. {{Brain morphometry of preschool age children affected by autism spectrum disorder: correlation with clinical findings}}. {Clinical anatomy (New York, NY)}. 2018.
INTRODUCTION: The aim of our study was to use a combined imaging and clinical approach to identify possible patterns of clinical and imaging findings in a cohort of preschool age Autism Spectrum Disorder (ASD) patients. MATERIAL AND METHODS: In order to identify imaging patterns that could be related to specific clinical features, a selected group of ASD patients (age range 3-6 years) without dysmorphic features, epilepsy or other major neurological signs, malformations or other lesions at MRI was subjected to brain volumetric analysis using semiautomatic brain segmentation. An age-matched group of typically developing children was subjected to the same analysis. RESULTS: Our results were consistent with previous literature: Total Gray Matter Volume, Total Cortical Gray Matter Volume and amygdalar volumes were significantly greater in the ASD group than the control group. When we divided the study group into subgroups on the basis of clinical findings such as high- or low-functioning, or verbal and non-verbal, the only significant difference between verbal and non-verbal subjects was in cerebellar hemispheric size. CONCLUSIONS: Our results confirm that newer brain MRI techniques using semiautomatic brain segmentation can provide information useful for defining the differences between ASD patients and controls, particularly if they form part of an integrated approach between MRI and cognitive-behavioral and genetic data. This article is protected by copyright. All rights reserved.
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10. Parras A, Anta H, Santos-Galindo M, Swarup V, Elorza A, Nieto-Gonzalez JL, Pico S, Hernandez IH, Diaz-Hernandez JI, Belloc E, Rodolosse A, Parikshak NN, Penagarikano O, Fernandez-Chacon R, Irimia M, Navarro P, Geschwind DH, Mendez R, Lucas JJ. {{Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing}}. {Nature}. 2018.
Common genetic contributions to autism spectrum disorder (ASD) reside in risk gene variants that individually have minimal effect sizes. As environmental factors that perturb neurodevelopment also underlie idiopathic ASD, it is crucial to identify altered regulators that can orchestrate multiple ASD risk genes during neurodevelopment. Cytoplasmic polyadenylation element binding proteins 1-4 (CPEB1-4) regulate the translation of specific mRNAs by modulating their poly(A)-tails and thereby participate in embryonic development and synaptic plasticity. Here we find that CPEB4 binds transcripts of most high-confidence ASD risk genes. The brains of individuals with idiopathic ASD show imbalances in CPEB4 transcript isoforms that result from decreased inclusion of a neuron-specific microexon. In addition, 9% of the transcriptome shows reduced poly(A)-tail length. Notably, this percentage is much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of ASD risk genes. An equivalent imbalance in CPEB4 transcript isoforms in mice mimics the changes in mRNA polyadenylation and protein expression of ASD risk genes and induces ASD-like neuroanatomical, electrophysiological and behavioural phenotypes. Together, these data identify CPEB4 as a regulator of ASD risk genes.
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11. Qian L, Wang Y, Chu K, Li Y, Xiao C, Xiao T, Xiao X, Qiu T, Xiao Y, Fang H, Ke X. {{Alterations in hub organization in the white matter structural network in toddlers with autism spectrum disorder: A 2-year follow-up study}}. {Autism Res}. 2018.
Little is currently known about the longitudinal developmental patterns of hubs in the whole-brain white matter (WM) structural networks among toddlers with autism spectrum disorder (ASD). This study utilized diffusion tensor imaging (DTI) and deterministic tractography to map the WM structural networks in 37 ASD toddlers and 27 age-, gender- and developmental quotient-matched controls with developmental delay (DD) toddlers aged 2-3 years old at baseline (Time 1) and at 2-year follow-up (Time 2). Furthermore, graph-theoretical methods were applied to investigate alterations in the network hubs in these patients at the two time points. The results showed that after 2 years, 17 hubs were identified in the ASD subjects compared to the controls, including 13 hubs that had not changed from baseline and 4 hubs that were newly identified. In addition, alterations in the properties of the hubs of the right middle frontal gyrus, right insula, left median cingulate gyri, and bilateral precuneus were significantly correlated with alterations in the behavioral data for ASD patients. These results indicated that at the stage of 2-5 years of age, ASD children showed distributions of network hubs that were relatively stable, with minor differences. Abnormal developmental patterns in the five areas mentioned above in ASD may contribute to abnormalities in the social and nonsocial characteristics of this disorder. LAY SUMMARY: This work studied the longitudinal developmental patterns of hubs in the whole-brain white matter (WM) structural network among toddlers with autism spectrum disorder (ASD). The findings of this study could have implications for understanding how the abnormalities in hub organization in ASD account for behavioral deficits in patients and may provide potential biomarkers for disease diagnosis and the subsequent monitoring of progression and treatment effects for patients with ASD.
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12. Sadouk L, Gadi T, Essoufi EH. {{A Novel Deep Learning Approach for Recognizing Stereotypical Motor Movements within and across Subjects on the Autism Spectrum Disorder}}. {Computational intelligence and neuroscience}. 2018; 2018: 7186762.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties including repetitive patterns of behavior known as stereotypical motor movements (SMM). So far, several techniques have been implemented to track and identify SMMs. In this context, we propose a deep learning approach for SMM recognition, namely, convolutional neural networks (CNN) in time and frequency-domains. To solve the intrasubject SMM variability, we propose a robust CNN model for SMM detection within subjects, whose parameters are set according to a proper analysis of SMM signals, thereby outperforming state-of-the-art SMM classification works. And, to solve the intersubject variability, we propose a global, fast, and light-weight framework for SMM detection across subjects which combines a knowledge transfer technique with an SVM classifier, therefore resolving the « real-life » medical issue associated with the lack of supervised SMMs per testing subject in particular. We further show that applying transfer learning across domains instead of transfer learning within the same domain also generalizes to the SMM target domain, thus alleviating the problem of the lack of supervised SMMs in general.
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13. Santoro AF, Shear SM, Haber A. {{Childhood adversity, health and quality of life in adults with intellectual and developmental disabilities}}. {J Intellect Disabil Res}. 2018.
BACKGROUND: Associations between childhood adversity and negative health outcomes are well documented within the general population; however, this relationship has yet to be confirmed in adults with intellectual and developmental disabilities (I/DD). Bridging the gap between public health and I/DD research is critical in order to better understand the ways in which the health of people with I/DD are compromised by adversity and social disadvantage and to develop preventative care frameworks and health-promoting practices specifically for adults with I/DD. The aim of this exploratory study was to examine the relationships among adversity, physical health and quality of life in a sample of adults with I/DD. METHOD: Participants were adults with I/DD currently residing within campus-based residences. Demographic data, psychiatric and medical diagnoses, adverse childhood experiences scores and quality of life scores were aggregated from participants’ electronic medical records. A health history form was completed for each participant based on a review of participants’ medical records. RESULTS: Results indicated childhood adversity was significantly associated with number of chronic medical conditions (r = .35, P < .001, 95% BCa CI [.13, .53]). Childhood adversity was not significantly related to quality of life. After controlling for demographic variables, childhood adversity remained a significant predictor of health history (B = .32, P < .005, 95% BCa CI [.10, .52]), with greater adversity predicting greater medical illness. CONCLUSION: Participants demonstrated higher rates of childhood adversity compared with the general population, suggesting that individuals with I/DD may be particularly vulnerable to experiencing adversity during development. Childhood adversity was a significant predictor of physical illness in adults with I/DD. These findings emphasise the importance of screening for childhood adversity histories in adults with I/DD. Additionally, results demonstrate the importance of offering preventative interventions geared at preventing physical illness and promoting health in adults with I/DD with adversity and trauma backgrounds. Lien vers le texte intégral (Open Access ou abonnement)
14. Stainbrook JA, Weitlauf AS, Juarez AP, Taylor JL, Hine J, Broderick N, Nicholson A, Warren Z. {{Measuring the service system impact of a novel telediagnostic service program for young children with autism spectrum disorder}}. {Autism}. 2018: 1362361318787797.
As prevalence of autism spectrum disorder continues to increase, so too does the need for timely, accessible diagnostic consultation. The present work extends from a previous study which provided preliminary evidence for the feasibility of expert clinicians to utilize telemedicine to triage autism spectrum disorder risk in young children. However, it did not examine whether a telediagnostic model had a demonstrable impact on tertiary care center referrals and usage. We therefore examined whether the introduction of telemedicine-based diagnostic consultation for families served by a rural medical facility affected referrals overall as well as to a metropolitan tertiary care diagnostic center. Results suggest that telemedicine diagnostic consultation in partnership with a referring early intervention system may positively impact referrals for diagnostic evaluation as well as the ability of families to schedule and attend appointments.
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15. Vaccaro TDS, Sorrentino JM, Salvador S, Veit T, Souza DO, de Almeida RF. {{Alterations in the MicroRNA of the Blood of Autism Spectrum Disorder Patients: Effects on Epigenetic Regulation and Potential Biomarkers}}. {Behav Sci (Basel)}. 2018; 8(8).
Aims: Autism spectrum disorder (ASD) refers to a group of heterogeneous brain-based neurodevelopmental disorders with different levels of symptom severity. Given the challenges, the clinical diagnosis of ASD is based on information gained from interviews with patients’ parents. The heterogeneous pathogenesis of this disorder appears to be driven by genetic and environmental interactions, which also plays a vital role in predisposing individuals to ASD with different commitment levels. In recent years, it has been proposed that epigenetic modifications directly contribute to the pathogenesis of several neurodevelopmental disorders, such as ASD. The microRNAs (miRNAs) comprises a species of short noncoding RNA that regulate gene expression post-transcriptionally and have an essential functional role in the brain, particularly in neuronal plasticity and neuronal development, and could be involved in ASD pathophysiology. The aim of this study is to evaluate the expression of blood miRNA in correlation with clinical findings in patients with ASD, and to find possible biomarkers for the disorder. Results: From a total of 26 miRNA studied, seven were significantly altered in ASD patients, when compared to the control group: miR34c-5p, miR92a-2-5p, miR-145-5p and miR199a-5p were up-regulated and miR27a-3p, miR19-b-1-5p and miR193a-5p were down-regulated in ASD patients. Discussion: The main targets of these miRNAs are involved in immunological developmental, immune response and protein synthesis at transcriptional and translational levels. The up-regulation of both miR-199a-5p and miR92a-2a and down-regulation of miR-193a and miR-27a was observed in AD patients, and may in turn affect the SIRT1, HDAC2, and PI3K/Akt-TSC:mTOR signaling pathways. Furthermore, MeCP2 is a target of miR-199a-5p, and is involved in Rett Syndrome (RTT), which possibly explains the autistic phenotype in male patients with this syndrome.
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16. Yingling ME, Bell BA. {{Racial-ethnic and neighborhood inequities in age of treatment receipt among a national sample of children with autism spectrum disorder}}. {Autism}. 2018: 1362361318791816.
The aim of this study is to examine the impact of child race-ethnicity and neighborhood characteristics on age of treatment receipt among children with autism spectrum disorder. Here, we included 1309 children diagnosed with autism spectrum disorder in the National Survey of Children’s Health, 2011-2012. Controlling for key covariates, we used a weighted generalized logit model to analyze differences in age of treatment receipt (<2 years, 2 years, 3 years, and 4 years). Compared to non-Hispanic White children, the relative probability (odds) of entering treatment at 3 years and 4 years rather than <2 years was 326% and 367% higher, respectively, for non-Hispanic Black children. Compared to children whose parents perceived their neighborhood to be cohesive, the relative probability of entering treatment at 2 years and 3 years rather than <2 years was 59% and 61% lower, respectively, for children whose parents did not. Significant racial-ethnic and neighborhood inequities exist in age of treatment receipt, suggesting a need for research that explores the underlying causal mechanisms of inequities. Lien vers le texte intégral (Open Access ou abonnement)
