1. Antshel KM, Russo N. {{Autism Spectrum Disorders and ADHD: Overlapping Phenomenology, Diagnostic Issues, and Treatment Considerations}}. {Curr Psychiatry Rep};2019 (Mar 22);21(5):34.
PURPOSE OF REVIEW: Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are both increasing in prevalence and commonly co-occur with each other. The goal of this review is to outline what has been published recently on the topics of ASD, ADHD, and the comorbid state (ASD+ADHD) with a particular focus on shared phenomenology, differential diagnosis, and treatment considerations. RECENT FINDINGS: ASD and ADHD have shared genetic heritability and are both associated with shared impairments in social functioning and executive functioning. Quantitative and qualitative differences exist, however, in the phenotypic presentations of the impairments which characterize ASD and ADHD. For ASD interventions to be maximally efficacious, comorbid ADHD needs to be considered (and vice versa). The research on ASD and ADHD suggests some overlap between the two disorders yet enough differences to indicate that these conditions are sufficiently distinct to warrant separate diagnostic categories.
Lien vers le texte intégral (Open Access ou abonnement)
2. Arroyo-Lopez C. {{Helminth therapy for autism under gut-brain axis- hypothesis}}. {Med Hypotheses};2019 (Apr);125:110-118.
Autism is a neurodevelopmental disease included within Autism Syndrome Disorder (ASD) spectrum. ASD has been linked to a series of genes that play a role in immune response function and patients with autism, commonly suffer from immune-related comorbidities. Despite the complex pathophysiology of autism, Gut-brain axis is gaining strength in the understanding of several neurological disorders. In addition, recent publications have shown the correlation between immune dysfunctions, gut microbiota and brain with the behavioral alterations and comorbid symptoms found in autism. Gut-brain axis acts as the « second brain », in a communication network established between neural, endocrine and the immunological systems. On the other hand, Hygiene Hypothesis suggests that the increase in the incidence of autoimmune diseases in the modern world can be attributed to the decrease of exposure to infectious agents, as parasitic nematodes. Helminths induce modulatory and protective effects against several inflammatory disorders, maintaining gastrointestinal homeostasis and modulating brain functions. Helminthic therapy has been previously performed in diseases such as ulcerative colitis, Crohn’s disease, diabetes, multiple sclerosis, asthma, rheumatoid arthritis, and food allergies. Considering gut-brain axis, Hygiene Hypothesis, and the modulatory effects of helminths I hypothesized that a treatment with Trichuris suis soluble products represents a feasible holistic treatment for autism, and the key for the development of novel treatments. Preclinical studies are required to test this hypothesis.
Lien vers le texte intégral (Open Access ou abonnement)
3. Borras-Ferris L, Perez-Ramirez U, Moratal D. {{Link-Level Functional Connectivity Neuroalterations in Autism Spectrum Disorder: A Developmental Resting-State fMRI Study}}. {Diagnostics (Basel)};2019 (Mar 21);9(1)
Autism spectrum disorder (ASD) is a neurological and developmental disorder whose late diagnosis is based on subjective tests. In seeking for earlier diagnosis, we aimed to find objective biomarkers via analysis of resting-state functional MRI (rs-fMRI) images obtained from the Autism Brain Image Data Exchange (ABIDE) database. Thus, we estimated brain functional connectivity (FC) between pairs of regions as the statistical dependence between their neural-related blood-oxygen-level-dependent (BOLD) signals. We compared FC of individuals with ASD and healthy controls, matched by age and intelligence quotient (IQ), and split into three age groups (50 children, 98 adolescents, and 32 adults), from a developmental perspective. After estimating the correlation, we observed hypoconnectivities in children and adolescents with ASD between regions belonging to the default mode network (DMN). Concretely, in children, FC decreased between the left middle temporal gyrus and right frontal pole (p = 0.0080), and between the left orbitofrontal cortex and right superior frontal gyrus (p = 0.0144). In adolescents, this decrease was observed between bilateral postcentral gyri (p = 0.0012), and between the right precuneus and right middle temporal gyrus (p = 0.0236). These results help to gain a better understanding of the involved regions on autism and its connection with the affected superior cognitive brain functions.
Lien vers le texte intégral (Open Access ou abonnement)
4. Brookman-Frazee L, Chlebowski C, Suhrheinrich J, Finn N, Dickson KS, Aarons GA, Stahmer A. {{Characterizing Shared and Unique Implementation Influences in Two Community Services Systems for Autism: Applying the EPIS Framework to Two Large-Scale Autism Intervention Community Effectiveness Trials}}. {Adm Policy Ment Health};2019 (Mar 23)
The purpose of this study was to examine common and unique factors influencing implementation process for two evidence-based interventions for children with autism spectrum disorder (ASD) in mental health and education service contexts. This study prospectively collected qualitative data from intervention developers and research staff on the implementation process within the context of two separate ASD intervention effectiveness trials. Results reveal common and unique factors influencing implementation in both study contexts. Implementation leadership and provider attitudes and motivation emerge as key influences on implementation across systems. These findings provide promising targets for modular implementation interventions that can be leveraged within growing, large-scale translation efforts in usual care.
Lien vers le texte intégral (Open Access ou abonnement)
5. D’Annessa I, Cicconardi F, Di Marino D. {{Handling FMRP and its molecular partners: Structural insights into Fragile X Syndrome}}. {Prog Biophys Mol Biol};2019 (Jan);141:3-14.
Fragile X Mental Retardation Protein (FMRP) is a RNA-binding protein (RBP) known to control different steps of mRNA metabolism, even though its complete function is not fully understood yet. Lack or mutations of FMRP lead to Fragile X Syndrome (FXS), the most common form of inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). It is well established that FMRP has a multi-domain architecture, a feature that allows this RBP to be engaged in a large interaction network with numerous proteins and mRNAs or non-coding RNAs. Insights into the three-dimensional (3D) structure of parts of its three domains (N-terminus, central domain and C-terminus) were obtained using Nuclear Magnetic Resonance and X-ray diffraction, but the complete 3D arrangement of each domain with respect to the others is still missing. Here, we review the structural features of FMRP and of the network of its protein and RNA interactions. Understanding these aspects is the first necessary step towards the design of novel compounds for new therapeutic interventions in FXS.
Lien vers le texte intégral (Open Access ou abonnement)
6. Ehrhart F, Coort SL, Eijssen L, Cirillo E, Smeets EE, Bahram Sangani N, Evelo CT, Curfs LMG. {{Integrated analysis of human transcriptome data for Rett syndrome finds a network of involved genes}}. {World J Biol Psychiatry};2019 (Mar 25):1-23.
OBJECTIVES: Rett syndrome (RTT) is a rare disorder causing severe intellectual and physical disability. The cause is a mutation in the gene coding for the methyl-CpG binding protein 2 (MECP2), a multifunctional regulator protein. Purpose of the study was integration and investigation of multiple gene expression profiles in human cells with impaired MECP2 gene to obtain a robust, data-driven insight in molecular disease mechanisms. METHODS: Information about changed gene expression was extracted from five previously published studies, integrated and the resulting differentially expressed genes were analyzed using overrepresentation analysis of biological pathways and gene ontology, and network analysis. RESULTS: We identified a set of genes, which are significantly changed not in all but several transcriptomics datasets and were not mentioned in the context of RTT before. We found that these genes are involved in several processes and molecular pathways known to be affected in RTT. Integrating transcription factors we identified a possible link how MECP2 regulates cytoskeleton organization via MEF2C and CAPG. CONCLUSION: Integrative analysis of omics data and prior knowledge databases is a powerful approach to identify links between mutation and phenotype especially in rare disease research where little data is available.
Lien vers le texte intégral (Open Access ou abonnement)
7. Eilenberg JS, Paff M, Harrison AJ, Long KA. {{Disparities Based on Race, Ethnicity, and Socioeconomic Status Over the Transition to Adulthood Among Adolescents and Young Adults on the Autism Spectrum: a Systematic Review}}. {Curr Psychiatry Rep};2019 (Mar 22);21(5):32.
PURPOSE OF REVIEW: Few studies have examined disparities in autism services and functional outcomes over the life course. Transition to adulthood is an especially important developmental period, as it sets up trajectories of adult functioning. This systematic review summarizes patterns of service use and transition outcomes according to race, ethnicity, and socioeconomic characteristics over the transition to adulthood. RECENT FINDINGS: Forty studies were included. Low-income and racial/ethnic minority youth on the autism spectrum were less likely to participate in transition planning meetings, enroll in postsecondary education, find competitive employment after high school, live independently, participate in social activities, and receive health care transition services than their White and higher income peers on the autism spectrum. Racial/ethnic minority and low-income youth on the autism spectrum were more likely to be disconnected from educational, occupational, and social activities upon entering adulthood. Future research should explore the mechanisms underlying these disparities as a first step to addressing them.
Lien vers le texte intégral (Open Access ou abonnement)
8. Endo N, Makinodan M, Somayama N, Komori T, Kishimoto T, Nishi M. {{Characterization of behavioral phenotypes in the BTBR T(+) Itpr3(tf)/J mouse model of Autism Spectrum Disorder under social housing conditions using the Multiple Animal Positioning System}}. {Exp Anim};2019 (Mar 22)
The BTBR T(+) Itpr3(tf)/J (BTBR) mouse strain is a widely used model of Autism spectrum disorder (ASD). The BTBR mice display behavior consistent with the three diagnostic categories of ASD. However, the behavioral phenotypes of the BTBR mice in a long-term group housing setting are largely unknown because conventional behavioral tests for ASD model mice are designed for use under simplified artificial conditions over a short observation period. In this study, we applied a newly developed assay system, the Multiple Animal Positioning System (MAPS), to quantify behaviors under group housing conditions over four days of continuous observation. Using MAPS, we showed that in a group housing condition, the BTBR mice exhibited lower activity levels in the dark phase and alteration of social behavior in comparison with the C57BL/6J mice. The phenotypes of the BTBR mice were affected by co-housing with the C57BL/6J mice for four days, but the influence was weak and limited. Our results by MAPS differ from those obtained using conventional behavioral tests. The present study demonstrated that MAPS would be useful for evaluating the usual/natural behaviors of various animal models in detail and under more ethological conditions.
Lien vers le texte intégral (Open Access ou abonnement)
9. Gogliotti RG, Niswender CM. {{A Coordinated Attack: Rett Syndrome Therapeutic Development}}. {Trends Pharmacol Sci};2019 (Apr);40(4):233-236.
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MeCP2) gene. This Science & Society article focuses on pharmacological strategies that attack RTT treatment from multiple angles, including drug repurposing and de novo discovery efforts, and discusses the impacts of preclinical study design and translationally relevant outcome measures.
Lien vers le texte intégral (Open Access ou abonnement)
10. Hoffman BL, Felter EM, Chu KH, Shensa A, Hermann C, Wolynn T, Williams D, Primack BA. {{It’s not all about autism: The emerging landscape of anti-vaccination sentiment on Facebook}}. {Vaccine};2019 (Mar 14)
BACKGROUND: Due in part to declining vaccination rates, in 2018 over 20 states reported at least one case of measles, and over 40,000 cases were confirmed in Europe. Anti-vaccine posts on social media may be facilitating anti-vaccination behaviour. This study aimed to systematically characterize (1) individuals known to publicly post anti-vaccination content on Facebook, (2) the information they convey, and (3) the spread of this content. METHODS: Our data set consisted of 197 individuals who posted anti-vaccination comments in response to a message promoting vaccination. We systematically analysed publicly-available content using quantitative coding, descriptive analysis, social network analysis, and an in-depth qualitative assessment. The final codebook consisted of 26 codes; Cohen’s kappa ranged 0.71-1.0 after double-coding. RESULTS: The majority (89%) of individuals identified as female. Among 136 individuals who divulged their location, 36 states and 8 other countries were represented. In a 2-mode network of individuals and topics, modularity analysis revealed 4 distinct sub-groups labelled as « trust, » « alternatives, » « safety, » and « conspiracy. » For example, a comment representative of « conspiracy » is that poliovirus does not exist and that pesticides caused clinical symptoms of polio. An example from the « alternatives » sub-group is that eating yogurt cures human papillomavirus. Deeper qualitative analysis of all 197 individuals’ profiles found that these individuals also tended to post material against other health-related practices such as water fluoridation and circumcision. CONCLUSIONS: Social media outlets may facilitate anti-vaccination connections and organization by facilitating the diffusion of centuries old arguments and techniques. Arguments against vaccination are diverse but remain consistent within sub-groups of individuals. It would be valuable for health professionals to leverage social networks to deliver more effective, targeted messages to different constituencies.
Lien vers le texte intégral (Open Access ou abonnement)
11. Kilroy E, Aziz-Zadeh L, Cermak S. {{Ayres Theories of Autism and Sensory Integration Revisited: What Contemporary Neuroscience Has to Say}}. {Brain Sci};2019 (Mar 21);9(3)
Abnormal sensory-based behaviors are a defining feature of autism spectrum disorders (ASD). Dr. A. Jean Ayres was the first occupational therapist to conceptualize Sensory Integration (SI) theories and therapies to address these deficits. Her work was based on neurological knowledge of the 1970’s. Since then, advancements in neuroimaging techniques make it possible to better understand the brain areas that may underlie sensory processing deficits in ASD. In this article, we explore the postulates proposed by Ayres (i.e., registration, modulation, motivation) through current neuroimaging literature. To this end, we review the neural underpinnings of sensory processing and integration in ASD by examining the literature on neurophysiological responses to sensory stimuli in individuals with ASD as well as structural and network organization using a variety of neuroimaging techniques. Many aspects of Ayres’ hypotheses about the nature of the disorder were found to be highly consistent with current literature on sensory processing in children with ASD but there are some discrepancies across various methodological techniques and ASD development. With additional characterization, neurophysiological profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions, such as SI therapy.
Lien vers le texte intégral (Open Access ou abonnement)
12. Kurz EM, Conzelmann A, Barth GM, Hepp L, Schenk D, Renner TJ, Born J, Zinke K. {{Signs of enhanced formation of gist memory in children with autism spectrum disorder – a study of memory functions of sleep}}. {J Child Psychol Psychiatry};2019 (Mar 25)
BACKGROUND: Autism spectrum disorder (ASD) is characterized by impaired cognitive and social skills, including emotional dysregulation, and symptoms have been suspected to partly arise from impaired formation of memory representations regulating these behaviours. Sleep, which is subjectively impaired in ASD, is critical for forming long-term memories and abstracted gist-based representations. We expected a generally reduced memory benefit from sleep in children with ASD, and a diminished enhancement of gist representations, in particular. METHODS: We compared effects of sleep on memory consolidation between boys (9-12 years) with ASD (n = 21) and typically developing (TD, n = 20) boys, matched for age and IQ, in a within-subjects crossover design. We employed an emotional picture recognition task and the Deese-Roediger-McDermott (DRM) word list task for assessing gist memory formation in the emotional and nonemotional domain, respectively. Learning took place before retention intervals of nocturnal sleep and daytime wakefulness, and retrieval was tested afterwards. RESULTS: Surprisingly, on the DRM task, children with ASD showed an enhanced sleep-dependent formation of gist-based memory (i.e. more recall of ‘critical lure words’ after sleep compared to wakefulness) than TD children, with this effect occurring on top of a diminished veridical word memory. On the picture recognition task, children with ASD also showed a stronger emotional enhancement in memory (i.e. relatively better memory for negative than neutral pictures) than TD children, with this enhancement occurring independent of sleep. Sleep polysomnography was remarkably comparable between groups. CONCLUSIONS: Children with ASD show well-preserved sleep-dependent memory consolidation. Enhanced gist memory formation in these children might reflect a compensatory response for impairments at earlier stages of memory processing, that is during encoding.
Lien vers le texte intégral (Open Access ou abonnement)
13. Marchezan J. {{Editorial: Autism Spectrum Disorder and Autoimmune Diseases: A Pathway in Common?}}. {J Am Acad Child Adolesc Psychiatry};2019 (Mar 19)
Lien vers le texte intégral (Open Access ou abonnement)
14. Martins N, King A, Beights R. {{Audiovisual Media Content Preferences of Children with Autism Spectrum Disorders: Insights from Parental Interviews}}. {J Autism Dev Disord};2019 (Mar 23)
Most research on the media use of children with autism spectrum disorder (ASD) focuses on media device use and less on content preferences of these children. We interviewed parents (N = 31) of children with ASD to examine parental observations of their children’s audiovisual media content preferences. Thematic analysis of the in-depth interviews found children with ASD preferred media content with features aimed at younger audiences. Parents also reported that content that fostered imitation was appealing to their children, occasionally with observable benefits (e.g., verbalizing words of favorite characters). Additionally, parents indicated that ease of control (e.g., content repetition) and ease of use (e.g., accessibility) made mainstream appealing to their children. Parents reported limited awareness of apps designed specifically for children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
15. Miranda A, Mira A, Berenguer C, Rosello B, Baixauli I. {{Parenting Stress in Mothers of Children With Autism Without Intellectual Disability. Mediation of Behavioral Problems and Coping Strategies}}. {Front Psychol};2019;10:464.
The present study investigated the mediating role of behavioral difficulties, coping strategies, and social functional support in the relationship between symptoms severity and parenting stress in mothers of children with ASD (autism spectrum disorder). The parenting stress questionnaire, coping orientation to problems experienced scale, strengths and difficulties questionnaire, and Duke-UNC social support questionnaire were administered to 52 mothers, who also estimated the ASD severity symptoms of their children. Correlation analyses revealed that parenting stress was positively correlated with the children’s ASD symptoms and behavioral problems. On the other hand, parenting stress was negatively correlated with the engagement coping and social functional support reported by the mothers. Multiple mediation analysis indicated that engagement coping and behavioral difficulties were significant mediators in the relationship between ASD symptoms and parenting stress, with the engagement variable having a larger effect. The findings illustrate the need to promote the mothers’ engagement coping orientation and the application of behavioral strategies with their children to help them to buffer the impact of stress.
Lien vers le texte intégral (Open Access ou abonnement)
16. Spiga O, Gardini S, Rossi N, Cicaloni V, Pettini F, Niccolai N, Santucci A. {{Structural investigation of Rett-inducing MeCP2 mutations}}. {Genes Dis};2019 (Mar);6(1):31-34.
X-ray structure of methyl-CpG binding domain (MBD) of MeCP2, an intrinsically disordered protein (IDP) involved in Rett syndrome, offers a rational basis for defining the spatial distribution for most of the sites where mutations responsible of Rett syndrome, RTT, occur. We have ascribed pathogenicity for mutations of amino acids bearing positively charged side chains, all located at the protein-DNA interface, as positive charge removal cause reduction of the MeCP2-DNA adduct lifetime. Pathogenicity of the frequent proline replacements, outside the DNA contact moiety of MBD, can be attributed to the role of this amino acid for maintaining both unfolded states for unbound MeCP2 and, at the same time, to favor some higher conformational order for stabilizing structural determinants required by protein activity. These hypotheses can be extended to transcription repressor domain, TRD, the other MeCP2-DNA interaction site and, in general, to all the IDP that interact with nucleic acids.
Lien vers le texte intégral (Open Access ou abonnement)
17. Voss C, Schwartz J, Daniels J, Kline A, Haber N, Washington P, Tariq Q, Robinson TN, Desai M, Phillips JM, Feinstein C, Winograd T, Wall DP. {{Effect of Wearable Digital Intervention for Improving Socialization in Children With Autism Spectrum Disorder: A Randomized Clinical Trial}}. {JAMA Pediatr};2019 (Mar 25)
Importance: Autism behavioral therapy is effective but expensive and difficult to access. While mobile technology-based therapy can alleviate wait-lists and scale for increasing demand, few clinical trials exist to support its use for autism spectrum disorder (ASD) care. Objective: To evaluate the efficacy of Superpower Glass, an artificial intelligence-driven wearable behavioral intervention for improving social outcomes of children with ASD. Design, Setting, and Participants: A randomized clinical trial in which participants received the Superpower Glass intervention plus standard of care applied behavioral analysis therapy and control participants received only applied behavioral analysis therapy. Assessments were completed at the Stanford University Medical School, and enrolled participants used the Superpower Glass intervention in their homes. Children aged 6 to 12 years with a formal ASD diagnosis who were currently receiving applied behavioral analysis therapy were included. Families were recruited between June 2016 and December 2017. The first participant was enrolled on November 1, 2016, and the last appointment was completed on April 11, 2018. Data analysis was conducted between April and October 2018. Interventions: The Superpower Glass intervention, deployed via Google Glass (worn by the child) and a smartphone app, promotes facial engagement and emotion recognition by detecting facial expressions and providing reinforcing social cues. Families were asked to conduct 20-minute sessions at home 4 times per week for 6 weeks. Main Outcomes and Measures: Four socialization measures were assessed using an intention-to-treat analysis with a Bonferroni test correction. Results: Overall, 71 children (63 boys [89%]; mean [SD] age, 8.38 [2.46] years) diagnosed with ASD were enrolled (40 [56.3%] were randomized to treatment, and 31 (43.7%) were randomized to control). Children receiving the intervention showed significant improvements on the Vineland Adaptive Behaviors Scale socialization subscale compared with treatment as usual controls (mean [SD] treatment impact, 4.58 [1.62]; P = .005). Positive mean treatment effects were also found for the other 3 primary measures but not to a significance threshold of P = .0125. Conclusions and Relevance: The observed 4.58-point average gain on the Vineland Adaptive Behaviors Scale socialization subscale is comparable with gains observed with standard of care therapy. To our knowledge, this is the first randomized clinical trial to demonstrate efficacy of a wearable digital intervention to improve social behavior of children with ASD. The intervention reinforces facial engagement and emotion recognition, suggesting either or both could be a mechanism of action driving the observed improvement. This study underscores the potential of digital home therapy to augment the standard of care. Trial Registration: ClinicalTrials.gov identifier: NCT03569176.
Lien vers le texte intégral (Open Access ou abonnement)
18. Wagner KE, McCormick JB, Barns S, Carney M, Middleton FA, Hicks SD. {{Parent Perspectives Towards Genetic and Epigenetic Testing for Autism Spectrum Disorder}}. {J Autism Dev Disord};2019 (Mar 22)
Examining community views on genetic/epigenetic research allows collaborative technology development. Parent perspectives toward genetic/epigenetic testing for autism spectrum disorder (ASD) are not well-studied. Parents of children with ASD (n = 131), non-ASD developmental delay (n = 39), and typical development (n = 74) completed surveys assessing genetic/epigenetic knowledge, genetic/epigenetic concerns, motives for research participation, and attitudes/preferences toward ASD testing. Most parents (96%) were interested in saliva-based molecular testing for ASD. Some had concerns about privacy (14%) and insurance-status (10%). None (0%) doubted scientific evidence behind genetic/epigenetic testing. Most reported familiarity with genetics (88%), but few understood differences from epigenetics (19%). Child developmental status impacted insurance concerns (p = 0.01). There is broad parent interest in a genetic/epigenetic test for ASD. It will be crucial to carefully consider and address bioethical issues surrounding this sensitive topic while developing such technology.
Lien vers le texte intégral (Open Access ou abonnement)
19. Wittman S, Abdala AP, Rubin JE. {{Reduced computational modeling of Kolliker-Fuse contributions to breathing patterns in Rett syndrome}}. {J Physiol};2019 (Mar 25)
KEY POINTS: Reduced computational models are used to test effects of loss of inhibition to the Kolliker-Fuse nucleus (KFn). Three reduced computational models that simulate eupneic and vagotomized respiratory rhythms are considered. All models exhibit the emergence of respiratory perturbations associated with Rett syndrome as inhibition to the KFn is diminished. Simulations suggest that application of 5-HT1A agonists can mitigate the respiratory pathology. The three models can be distinguished and tested based on their predictions about connections and dynamics within the respiratory circuit and about effects of perturbations on certain respiratory neuron populations. This article is protected by copyright. All rights reserved ABSTRACT: Rett syndrome (RTT) is a developmental disorder that can lead to respiratory disturbances featuring prolonged apneas of variable durations. Determining the mechanisms underlying these effects at the level of respiratory neural circuits would have significant implications for treatment efforts and would also enhance our understanding of respiratory rhythm generation and control. While experimental studies have suggested possible factors contributing to the respiratory patterns of RTT, we take a novel computational approach to the investigation of RTT, which allows for direct manipulation of selected system parameters and testing of specific hypotheses. Specifically, we present three reduced computational models, developed using an established framework, all of which successfully simulate respiratory outputs across eupneic and vagotomized conditions. All three models show that loss of inhibition to the Kolliker-Fuse nucleus reproduces the key respiratory alterations associated with RTT and, as suggested experimentally, that effects of 5-HT1A agonists on the respiratory neural circuit suffice to alleviate this respiratory pathology. Each of the models makes distinct predictions regarding the neuronal populations and interactions underlying these effects, suggesting natural directions for future experimental testing.
Lien vers le texte intégral (Open Access ou abonnement)
20. Zwaigenbaum L, Duku E, Fombonne E, Szatmari P, Smith IM, Bryson SE, Mirenda P, Vaillancourt T, Volden J, Georgiades S, Roberts W, Bennett T, Elsabbagh M, Waddell C, Steiman M, Simon R, Bruno R. {{Developmental functioning and symptom severity influence age of diagnosis in Canadian preschool children with autism}}. {Paediatr Child Health};2019 (Feb);24(1):e57-e65.
Background: Early diagnosis of autism spectrum disorder (ASD) is essential in most Canadian jurisdictions to access interventions that improve long-term child outcomes. Our main objective was to identify factors associated with timing of ASD diagnosis in five provinces across Canada. Methods: Factors influencing age of diagnosis were assessed in the analyses of an inception cohort of children diagnosed with ASD between ages 2 and 5 years. We examined bivariate associations and using a series of multiple variable regression models, evaluated the unique contributions of developmental functioning, ASD symptoms and demographic variables. Children with known genetic abnormalities, or severe sensory or motor impairments interfering with assessment were excluded. Results: Participants were 421 children (84.6% boys). The mean age of diagnosis was 38.2 months (SD=8.7), an average of 19 months after parents identified initial concerns. Factors associated with later diagnosis included more advanced language and cognitive skills, and higher levels of restricted repetitive behaviour symptoms. Child sex and family demographics were not associated with age of diagnosis. In regression analyses, language and cognitive skills accounted for 6.8% of variance in age of diagnosis and ASD symptoms contributed an additional 5.5%. Provincial site accounted for 4.0% of variance in age of diagnosis, independent of developmental skills and ASD symptoms. Interpretation: Diagnosis of ASD occurred, on average, 19 months after parents’ initial concerns. Language and cognitive skills, symptom severity and provincial site accounted for variation in age of ASD diagnosis in this Canadian cohort. Variable presentation across the developmental continuum must be considered in planning assessment services to ensure timely ASD diagnosis so that outcomes can be improved. Policy and practice leadership is also needed to reduce interprovincial variability.
