1. Amaral DG, Anderson MP, Ansorge O, Chance S, Hare C, Hof PR, Miller M, Nagakura I, Pickett J, Schumann C, Tamminga C. {{Autism BrainNet: A network of postmortem brain banks established to facilitate autism research}}. {Handbook of clinical neurology}. 2018; 150: 31-9.
Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators.
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2. Constantino JN. {{Deconstructing autism: from unitary syndrome to contributory developmental endophenotypes}}. {International review of psychiatry (Abingdon, England)}. 2018: 1-7.
A recent generation of family studies has revealed that autism can be predicted from an array of neurobehavioural susceptibilities that are appreciable before the syndrome is diagnosed, and that each may be traceable to partially-independent sets of genetic variation. Some of these liabilities are not necessarily specific to ASD-those that are non-specific could account for a significant share of the ‘missing heritability’ of autism, would (by definition) contribute to pleiotropy, and relate to so-called ‘co-morbidities’, which are inappropriately named if they actually contribute to (or exacerbate) the severity of autism itself. Linking genetic variants to these underlying traits rather than to a diagnosis of ‘autism’ may be more productive in devising personalized approaches to developmental intervention, especially if autism represents an epiphenomenon of earlier-interacting susceptibilities. In this article, the implications of conceptualizing autism as a syndrome of neurobehavioural degeneration is considered, predicated on the notion that it can arise from a critical co-aggregation of earlier-interacting neuropsychiatric liabilities, the phenotypic expression of which-importantly-can be moderated by sex.
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3. El-Ansary A, Cannell JJ, Bjorklund G, Bhat RS, Al Dbass AM, Alfawaz HA, Chirumbolo S, Al-Ayadhi L. {{In the search for reliable biomarkers for the early diagnosis of autism spectrum disorder: the role of vitamin D}}. {Metabolic brain disease}. 2018.
Autism spectrum disorder (ASD) affects about 1% of the world’s population. Vitamin D is thought to be essential for normal brain development and modulation of the immune system. Worldwide about 1 billion people are affected by vitamin D deficiency. High-sensitivity C-reactive protein (hs-CRP), cytochrome P450 2E1 (CYP2E1) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) are biomarkers related to inflammation and oxidative stress. In the present study, these biomarkers were together with serum 25-hydroxyvitamin D (25(OH)D3) analyzed in 28 (mean age seven years) Saudi male patients with ASD. The study was conducted to determine if there is any relationship between vitamin D levels, the tested biomarkers and the presence and severity of ASD. The hope was to identify if these biomarkers may be useful for early ASD diagnosis. The Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS) were used to measure autism severity. The results of the ASD children were compared with 27 age and gender-matched neurotypical controls. The data indicated that Saudi patients with ASD have significantly lower plasma levels of 25(OH)D3 than neurotypical controls (38 ng/ml compared to 56 ng/ml, respectively; [P = 0.001]). Surprisingly, the levels of CYP2E1 were lower in the children with ASD than the neurotypical controls (0.48 +/- 0.08 vs. 69 +/- 0.07 ng/ml, respectively; P = 0.001). The ASD children also had significantly higher levels of hs-CRP (0.79 +/- 0.09 vs. 0.59 +/- 0.09 ng/ml, respectively; P = 0.001) and 8-OH-dG (8.17 +/- 1.04 vs. 4.13 +/- 1.01 ng/ml, respectively; P = 0.001, compared to neurotypical age and gender-matched controls. The values for hs-CRP and 8-OH-dG did not correlate [P < 0.001] with autism severity. There was found a relationship between autism severity on the CARS scale and the levels of 25(OH)D3 and CYP1B1. But this was not found for SRS. All four biomarkers seemed to have good sensitivity and specificity, but the sample size of the present study was too small to determine clinical usefulness. The findings also indicate that inadequate levels of vitamin D play a role in the etiology and severity of autism. Furthermore, the results of the present study suggest the possibility of using 25(OH)D3, CYP1B1, hs-CRP and 8-OH-dG, preferably in combination, as biomarkers for the early diagnosis of ASD. However, further research is needed to evaluate this hypothesis. Lien vers le texte intégral (Open Access ou abonnement)
4. Hirsch MM, Deckmann I, Fontes-Dutra M, Bauer-Negrini G, Della-Flora Nunes G, Nunes W, Rabelo B, Riesgo R, Margis R, Bambini-Junior V, Gottfried C. {{Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA}}. {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}. 2018.
Autism spectrum disorder (ASD) is characterized by difficulties in social interaction, communication and language, and restricted repertoire of activities and interests. The etiology of ASD remains unknown and no clinical markers for diagnosis were identified. Environmental factors, including prenatal exposure to valproic acid (VPA), may contribute to increased risk of developing ASD. MicroRNA (miRNA) are small noncoding RNA that regulate gene expression and are frequently linked to biological processes affected in neurodevelopmental disorders. In this work, we analyzed the effects of resveratrol (an antioxidant and anti-inflammatory molecule) on behavioral alterations of the VPA model of autism, as well as the levels of circulating miRNA. We also evaluated the same set of miRNA in autistic patients. Rats of the VPA model of autism showed reduced total reciprocal social interaction, prevented by prenatal treatment with resveratrol (RSV). The levels of miR134-5p and miR138-5p increased in autistic patients. Interestingly, miR134-5p is also upregulated in animals of the VPA model, which is prevented by RSV. In conclusion, our findings revealed important preventive actions of RSV in the VPA model, ranging from behavior to molecular alterations. Further evaluation of preventive mechanisms of RSV can shed light in important biomarkers and etiological triggers of ASD.
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5. Hudson CC, Hall L, Harkness KL. {{Prevalence of Depressive Disorders in Individuals with Autism Spectrum Disorder: a Meta-Analysis}}. {Journal of abnormal child psychology}. 2018.
Substantial uncertainty exists about the prevalence of depressive disorders in individuals with autism spectrum disorder (ASD). This meta-analysis quantitatively summarized studies that assessed the lifetime and current prevalence of unipolar depressive disorders in children, adolescents, and adults with ASD. We also examined demographic, methodological, and study moderators. This meta-analysis adhered to PRISMA guidelines. A total of 7857 articles were identified through 5 databases (PubMed, Web of Science, PYSCInfo, CINAHL, ProQuest Dissertations and Theses), forward searches, and backward searches. Two reviewers independently screened articles and extracted data. Sixty-six articles met inclusion criteria. Results indicated that the pooled lifetime and current prevalence was 14.4% (95% CI 10.3-19.8) and 12.3% (95% CI 9.7-15.5), respectively. Rates of depressive disorders were highest among studies that used a standardized interview to assess depressive disorders (lifetime = 28.5%, 95% CI 20.1-38.8; current = 15.3%, 95% CI 11.0-20.9) and required participants to report on their own depressive symptoms (lifetime = 48.6%, 95% CI 33.3-64.2; current = 25.9%, 95% CI 17.0-37.3). Rates were also higher in studies that included participants with higher intelligence. Lifetime, but not current, prevalence was positively associated with age and the proportion of the sample that was White. In conclusion, we found that the rates of depressive disorders are high among individuals with ASD. Compared to typically developing individuals, individuals with ASD are 4-times more likely to experience depression in their lifetime. These results suggest that individuals with ASD should be regularly screened and offered treatment for depression.
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6. Kikkawa T, Casingal CR, Chun SH, Shinohara H, Hiraoka K, Osumi N. {{The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder}}. {Brain Res}. 2018.
Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
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7. Lawson LP, Joshi R, Barbaro J, Dissanayake C. {{Gender Differences During Toddlerhood in Autism Spectrum Disorder: A Prospective Community-Based Longitudinal Follow-Up Study}}. {J Autism Dev Disord}. 2018.
Relatively few studies have examined gender differences in infants and toddlers, and most focus on clinically referred samples or high-risk infant cohorts. The current study aimed to examine gender differences in early autism manifestations and cognitive development in a community-ascertained sample. In total, 46 males and 21 females with ASD were seen at approximately 24 and 48 months of age. No significant gender differences were observed on overall cognitive ability, verbal skills, non-verbal skills, overall autism severity, or restricted repetitive behaviours. However, females were found to exhibit more social communication impairments than males. These findings may indicate that female toddlers with less severe or different, social communication impairments may be more likely to be missed during routine surveillance during toddlerhood.
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8. Nordahl-Hansen A, Hart L, Oien RA. {{The Scientific Study of Parents and Caregivers of Children with ASD: A Flourishing Field but Still Work to be Done}}. {J Autism Dev Disord}. 2018.
There is a long history of research on parents and caregivers of individuals within autism. Parents and other primary caregivers typically play the most important part in the lives of persons with ASD although the need for support as the child becomes of age varies widely. This special issue includes 30 articles on central areas related to parenting and caregiving for people with ASD. Some of the key themes include intervention and training, mental health issues related to parent and family stress, measurement and assessment, and parent-child transactional processes. Other articles in this issue consider different but equally important topics such as sibling as potential future caregivers and parent support of preschool peer relationships.
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9. Rodgers J, Ofield A. {{Understanding, Recognising and Treating Co-occurring Anxiety in Autism}}. {Current developmental disorders reports}. 2018; 5(1): 58-64.
Purpose of Review: Autistic people are at increased risk of anxiety, with around 50% of autistic adults and children experiencing this debilitating mental health condition. The purpose of this review is to consider some contemporary ideas about underlying mechanisms for anxiety in autism, explore issues in the identification and assessment of anxiety and discuss emerging trends in anxiety interventions for autistic people, before identifying some important next steps in the field. Recent Findings: Emerging evidence suggests that anxiety may present differently in autism compared to the general population and that whilst CBT holds promise, there may be important differences in neurobiological, affective and cognitive responses to stressors for autistic people, which warrant tailored anxiety models, assessments and interventions. Summary: We conclude that research is needed to develop and evaluate theoretical frameworks, assessment methods and interventions for anxiety in autism, particularly for autistic adults and those with co-occurring intellectual disability.
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10. Rutherford M, Forsyth K, McKenzie K, McClure I, Murray A, McCartney D, Irvine L, O’Hare A. {{Implementation of a Practice Development Model to Reduce the Wait for Autism Spectrum Diagnosis in Adults}}. {J Autism Dev Disord}. 2018.
This study examined waiting times for diagnostic assessment of Autism Spectrum Disorder in 11 adult services, prior to and following the implementation of a 12 month change program. Methods to support change are reported and a multi-level modelling approach determined the effect of the change program on overall wait times. Results were statistically significant (b = – 0.25, t(136) = – 2.88, p = 0.005). The average time individuals waited for diagnosis across all services reduced from 149.4 days prior to the change program and 119.5 days after it, with an average reduction of 29.9 days overall. This innovative intervention provides a promising framework for service improvement to reduce the wait for diagnostic assessment of ASD in adults across the range of spectrum presentations.
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11. Woodman AC, Breviglia E, Mori Y, Golden R, Maina J, Wisniewski H. {{The Effect of Music on Exercise Intensity among Children with Autism Spectrum Disorder: A Pilot Study}}. {J Clin Med}. 2018; 7(3).
Children with autism spectrum disorder (ASD) are at risk for obesity, commonly have sleep disorders, and exhibit stereotypic behaviors that disrupt their learning. Vigorous levels of exercise have been shown to ameliorate these issues in children with ASD, but little research exists to provide techniques for motivating children with ASD to engage in exercise. The present study examined the effect of music on exercise intensity in a group of 13 elementary school students with ASD. Data were collected across six days during structured (e.g., verbal and physical prompts) and unstructured (e.g., minimal prompting) exercise periods. During these exercise periods, three music conditions were randomized: no music, slow-tempo music, and fast-tempo music. Exercise intensity, measured in Metabolic Equivalent of Tasks by triaxial accelerometers, was greatest during the structured exercise periods and during the slow music condition. Student characteristics moderated the impact of music condition on exercise intensity, such that students with high levels of adaptive behavior or lower levels of maladaptive behavior displayed greater exercise intensity during the fast music condition.
