1. Azad GF, Minton KE, Mandell DS, Landa RJ. {{Partners in School: An Implementation Strategy to Promote Alignment of Evidence-Based Practices Across Home and School for Children with Autism Spectrum Disorder}}. {Administration and policy in mental health}. 2020.
When parents and teachers align their practices across home and school, it may optimize services for children with autism spectrum disorder (ASD). Partners in School is a multi-faceted implementation strategy designed to improve ASD services in schools. The goal is to increase parents’ and teachers’ use of evidence-based practices (EBPs) and to align those EBPs across settings. We piloted Partners in School with 49 parent-teacher dyads to assess administration and the factors associated with reported fidelity to the model. Specifically, we measured the number of intervention steps both parents and teachers completed (reported alignment) and the characteristics associated with intervention alignment. Partners in School involves parent-teacher participation in a pre-consultation interview, an in-person consultation meeting, active implementation of the same EBPs in their respective settings, and a post-consultation interview. Parents and teachers also completed surveys pre- and post-consultation. On average, parents and teachers completed approximately five EBP steps on their own in their respective settings (i.e., at home or at school). Of these five steps, parents and teachers both completed three of the same EBPs steps, on average. Different factors were related to reported alignment for parents versus teachers; however, a similarity noted for both parents and teachers was that communication variables were associated with reported alignment. Our findings indicate the important role of communication in aligning stakeholders for ASD service delivery models.
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2. Berrigan P, Scott CWM, Zwicker JD. {{Employment, Education, and Income for Canadians with Developmental Disability: Analysis from the 2017 Canadian Survey on Disability}}. {J Autism Dev Disord}. 2020.
This study assessed needs and outcomes for people with developmental disability (DD) to understand the socioeconomic status of this group prior to implementation of the Accessible Canada Act in June 2019. The 2017 Canadian Survey on Disability (CSD) was used to analyze data for a sample of individuals with self-reported disability. Data related to employment, education, income, housing, caregivers, and use of government benefits is reported. Compared to the general Canadian public, persons with DD are less likely to: finish high-school or post-secondary education; participate in the labor force or be employed; and earn on average less/year in total income. To align with recent accessibility legislation, significant progress is needed to address disparities for people with DD.
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3. Boutain AR, Sheldon JB, Sherman JA. {{Evaluation of a telehealth parent training program in teaching self-care skills to children with autism}}. {Journal of applied behavior analysis}. 2020.
The present study used synchronous video conferencing to remotely deliver a behavioral skills training-based (BST) parent training program to 3 parents of children with autism in the family home. Parents were taught to implement graduated guidance to teach their children several important self-care skills. Parents did not correctly implement graduated guidance after receiving detailed written instructions only. After parents received the BST parent training package, however, all parents implemented graduated guidance with near-perfect levels of fidelity, and all children completed the targeted self-care skills with substantially higher levels of accuracy and independence. Furthermore, parents reported high levels of satisfaction with graduated guidance, the telehealth BST training package, and their children’s ability to complete self-care skills.
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4. Chan WK, Griffiths R, Price DJ, Mason JO. {{Cerebral organoids as tools to identify the developmental roots of autism}}. {Mol Autism}. 2020; 11(1): 58.
Some autism spectrum disorders (ASD) likely arise as a result of abnormalities during early embryonic development of the brain. Studying human embryonic brain development directly is challenging, mainly due to ethical and practical constraints. However, the recent development of cerebral organoids provides a powerful tool for studying both normal human embryonic brain development and, potentially, the origins of neurodevelopmental disorders including ASD. Substantial evidence now indicates that cerebral organoids can mimic normal embryonic brain development and neural cells found in organoids closely resemble their in vivo counterparts. However, with prolonged culture, significant differences begin to arise. We suggest that cerebral organoids, in their current form, are most suitable to model earlier neurodevelopmental events and processes such as neurogenesis and cortical lamination. Processes implicated in ASDs which occur at later stages of development, such as synaptogenesis and neural circuit formation, may also be modeled using organoids. The accuracy of such models will benefit from continuous improvements to protocols for organoid differentiation.
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5. Flower RL, Richdale AL, Lawson LP. {{Brief Report: What Happens After School? Exploring Post-school Outcomes for a Group of Autistic and Non-autistic Australian Youth}}. {J Autism Dev Disord}. 2020.
Young autistic Australians are less likely to attend higher education and have lower employment rates than non-autistic Australians (in: Australian Bureau of Statistics, Survey of disability, ageing and carers Australia: Summary of Findings 2018. Australian Bureau of Statistics, Canberra, 2019a). Few studies have examined post-school outcomes among this population. Using data from the first phase of a national longitudinal study including autistic (n = 79) and non-autistic (n = 107) 17-25-year olds, we found young autistic adults were (a) less likely to be employed, (b) more likely to attend technical and further education (TAFE) than university, (c) more likely to enrol in higher education on a part-time basis and (d) less likely to be engaged in both higher education and employment, than their non-autistic peers. Findings highlight a need to understand post-school trajectories of young autistic adults.
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6. Gao H, Zhong J, Huang Q, Wu X, Mo X, Lu L, Liang H. {{Integrated Systems Analysis Explores Dysfunctional Molecular Modules and Regulatory Factors in Children with Autism Spectrum Disorder}}. {Journal of molecular neuroscience : MN}. 2020.
Autism spectrum disorder (ASD) is a genetic neurodevelopmental disorder involving multiple genes that occurs in early childhood, and a number of risk genes have been reported in previous studies. However, the molecular mechanism of the polygenic regulation leading to pathological changes in ASD remains unclear. First, we identified 8 dysregulated gene coexpression modules by analyzing blood transcriptome data from 96 children with ASD and 42 controls. These modules are rich in ASD risk genes and function related to metabolism, immunity, neurodevelopment, and signaling. The regulatory factors of each module including microRNA (miRNA) and transcription factors (TFs) were subsequently predicted based on transcriptional and posttranscriptional regulation. We identified a set of miRNAs that regulate metabolic and immune modules, as well as transcription factors that cause dysregulation of the modules, and we constructed a coregulatory network between the regulatory factors and modules. Our work reveals dysfunctional modules in children with ASD, elucidates the role of miRNA and transcription factor dysregulation in the pathophysiology of ASD, and helps us to further understand the underlying molecular mechanism of ASD.
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7. Grigg I, Ivashko-Pachima Y, Hait TA, Korenková V, Touloumi O, Lagoudaki R, Van Dijck A, Marusic Z, Anicic M, Vukovic J, Kooy RF, Grigoriadis N, Gozes I. {{Tauopathy in the young autistic brain: novel biomarker and therapeutic target}}. {Translational psychiatry}. 2020; 10(1): 228.
Given our recent discovery of somatic mutations in autism spectrum disorder (ASD)/intellectual disability (ID) genes in postmortem aged Alzheimer’s disease brains correlating with increasing tauopathy, it is important to decipher if tauopathy is underlying brain imaging results of atrophy in ASD/ID children. We concentrated on activity-dependent neuroprotective protein (ADNP), a prevalent autism gene. The unique availability of multiple postmortem brain sections of a 7-year-old male, heterozygous for ADNP de novo mutation c.2244Adup/p.His559Glnfs*3 allowed exploration of tauopathy, reflecting on a general unexplored mechanism. The tested subject exhibited autism, fine motor delays, severe intellectual disability and seizures. The patient died after multiple organ failure following liver transplantation. To compare to other ADNP syndrome mutations, immortalized lymphoblastoid cell lines from three different patients (including ADNP p.Arg216*, p.Lys408Valfs*31, and p.Tyr719* heterozygous dominant mutations) and a control were subjected to RNA-seq. Immunohistochemistry, high-throughput gene expression profiles in numerous postmortem tissues followed. Comparisons to a control brain and to extensive datasets were used. Live cell imaging investigated Tau-microtubule interaction, protecting against tauopathy. Extensive child brain tauopathy paralleled by multiple gene expression changes was discovered. Tauopathy was explained by direct mutation effects on Tau-microtubule interaction and correction by the ADNP active snippet NAP. Significant pathway changes (empirical P value < 0.05) included over 100 genes encompassing neuroactive ligand-receptor and cytokine-cytokine receptor interaction, MAPK and calcium signaling, axon guidance and Wnt signaling pathways. Changes were also seen in steroid biosynthesis genes, suggesting sex differences. Selecting the most affected genes by the ADNP mutations for gene expression analysis, in multiple postmortem tissues, identified Tau (MAPT)-gene-related expression changes compared with extensive normal gene expression (RNA-seq) databases. ADNP showed relatively reduced expression in the ADNP syndrome cerebellum, which was also observed for 25 additional genes (representing >50% of the tested genes), including NLGN1, NLGN2, PAX6, SMARCA4, and SNAP25, converging on nervous system development and tauopathy. NAP provided protection against mutated ADNP disrupted Tau-microtubule association. In conclusion, tauopathy may explain brain-imaging findings in ADNP syndrome children and may provide a new direction for the development of tauopathy protecting drug candidates like NAP in ASD/ID.
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8. Guinchat V, Vlamynck E, Diaz L, Chambon C, Pouzenc J, Cravero C, Baeza-Velasco C, Hamonet C, Xavier J, Cohen D. {{Compressive Garments in Individuals with Autism and Severe Proprioceptive Dysfunction: A Retrospective Exploratory Case Series}}. {Children (Basel, Switzerland)}. 2020; 7(7).
(1) Background: Compression garments (CGs) are an adjuvant treatment for generalized joint hypermobility (GJH), including the Ehlers-Danlos syndrome/hypermobility types. The effects of CGs are likely to be related to better proprioceptive control. We aimed to explore the use of CGs in individuals with autism and severe proprioceptive dysfunction (SPD), including individuals with GJH, to control posture and challenging behaviors. (2) Methods: We retrospectively described 14 patients with autism and SPD, including seven with comorbid GJH, who were hospitalized for major challenging behaviors with remaining behavioral symptomatology after the implementation of multidisciplinary approaches, including medication, treatment of organic comorbidities, and behavioral restructuring. Each patient received a CG to wear for at least 1 h (but most often longer) per day for six weeks. We assessed challenging behaviors in these participants with the Aberrant Behavior Checklist (ABC), sensory integration with the Dunn questionnaire, and postural sway and motor performance using a self-designed motricity path at baseline, two weeks, and six weeks. (3) Results: We observed a significant effect on most ABC rating scores at two weeks, which persisted at six weeks (total score, p = 0.004; irritability, p = 0.007; hyperactivity, p = 0.001; lethargy, p = 0.001). Postural control in dorsal and profile positions was significantly improved between before and after wearing the CGs (p = 0.006 and 0.007, respectively). Motor performance was also significantly improved. However, we did not observe a significant change in Dunn sensory scores. During the six-week duration, the treatment was generally well-tolerated. A comorbid GJH diagnosis was not associated with a better outcome. (4) Conclusions: CGs appear to be a promising adjuvant treatment for both behavioral and postural impairments in individuals with autism and SPD.
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9. Hashem S, Nisar S, Bhat AA, Yadav SK, Azeem MW, Bagga P, Fakhro K, Reddy R, Frenneaux MP, Haris M. {{Genetics of structural and functional brain changes in autism spectrum disorder}}. {Translational psychiatry}. 2020; 10(1): 229.
Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social impairment and restricted interactive and communicative behaviors. It may occur as an isolated disorder or in the context of other neurological, psychiatric, developmental, and genetic disorders. Due to rapid developments in genomics and imaging technologies, imaging genetics studies of ASD have evolved in the last few years. Increased risk for ASD diagnosis is found to be related to many specific single-nucleotide polymorphisms, and the study of genetic mechanisms and noninvasive imaging has opened various approaches that can help diagnose ASD at the nascent level. Identifying risk genes related to structural and functional changes in the brain of ASD patients provide a better understanding of the disease’s neuropsychiatry and can help identify targets for therapeutic intervention that could be useful for the clinical management of ASD patients.
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10. Hatch B, Iosif AM, Chuang A, de la Paz L, Ozonoff S, Miller M. {{Correction to: Longitudinal Differences in Response to Name Among Infants Developing ASD and Risk for ADHD}}. {J Autism Dev Disord}. 2020.
The original version of this article unfortunately contained a consistency mistake in Figure 1 legend. The legend for Figure 1 refers to « Non-ADHD/Non-ASD Concerns » instead of « Comparison, » which is the wording used in the text/tables, but that these terms are synonymous. The figure 1 with the correct legend is given below.
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11. Johnson NL, Krueger W, Jilek E, Haglund K. {{Conversations With Health Care Providers and Parents Before Autism Diagnosis: A Qualitative Study}}. {J Pediatr Health Care}. 2020.
INTRODUCTION: The purpose of this study was to explore communication with health care providers from the perceptions of parents before their child’s diagnosis of autism spectrum disorder and provide some examples of how communication may contribute to the autism diagnosis. METHOD: This study used a qualitative descriptive design with multiple individual structured in-person interviews. RESULTS: Three themes captured parents’ (n = 8) descriptions of the phases of communication during their children’s diagnoses including, (1) anguished questioning, (2) urgently seeking help, and (3) expecting a diagnosis. In addition, three themes characterized the communication style that parents needed, although not always received, in each of the periods of diagnosis including (1) compassionate curiosity, (2) acknowledgment and affirmation, and (3) engagement with parents. DISCUSSION: Results point to opportunities for pediatric providers to use a more empathic and engaging communication style during the diagnostic process with better identification of education and support needed by parents and families.
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12. Kelly E, Meng F, Fujita H, Morgado F, Kazemi Y, Rice LC, Ren C, Escamilla CO, Gibson JM, Sajadi S, Pendry RJ, Tan T, Ellegood J, Albert Basson M, Blakely RD, Dindot SV, Golzio C, Hahn MK, Katsanis N, Robins DM, Silverman JL, Singh KK, Wevrick R, Taylor MJ, Hammill C, Anagnostou E, Pfeiffer BE, Stoodley CJ, Lerch JP, du Lac S, Tsai PT. {{Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits}}. {Nat Neurosci}. 2020.
Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.
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13. Langlois PH, Canfield MA, Rutenberg GW, Mandell DJ, Hua F, Reilly B, Ruktanonchai DJ, Jackson JF, Hunt P, Freedenberg D, Lee R, Villanacci JF. {{The association between newborn screening analytes as measured on a second screen and childhood autism in a Texas Medicaid population}}. {Am J Med Genet B Neuropsychiatr Genet}. 2020.
Autism (or autism spectrum disorder [ASD]) is an often disabling childhood neurologic condition of mostly unknown cause. We previously explored whether there was an association of ASD with any analyte measured in the first newborn screening blood test. Here we explore the second screen. Our matched case-control study examined data on 3-5 year-old patients with any ASD diagnosis in the Texas Medicaid system in 2010-2012. Subjects were linked to their 2007-2009 newborn screening blood test data, which included values for 36 analytes or analyte ratios. Data were available for 3,005 cases and 6,212 controls. The most compelling associations were evident for fatty acid oxidation analytes octanoylcarnitine (C8) and octanoylcarnitine/acetylcarnitine (C8/C2). Their adjusted odds ratios comparing 10th versus first analyte deciles were between 1.42 and 1.54 in total births, term births, and males. C8 was consistent with first screen results. Adipylcarnitine (C6DC), an organic acid analyte, showed opposite results in the two screens. Several other analytes exhibiting significant associations in the first screen did not in the second. Our results provide evidence that abnormal newborn blood levels of some carnitines may be associated with risk of later ASD, possibly related to their involvement with mitochondrial function in the developing brain.
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14. Lin Y, Xue J, Deng J, He H, Luo S, Chen J, Li J, Yu L, Zhao J, Chen J, Allen EG, Jin P, Duan R. {{Neddylation activity modulates the neurodegeneration associated with fragile X associated tremor/ataxia syndrome (FXTAS) through regulating Sima}}. {Neurobiology of disease}. 2020: 105013.
Fragile X associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by expansion of CGG repeats in the 5′ UTR of the fragile X mental retardation 1 (FMR1) gene. Using the well-established FXTAS Drosophila model, we performed a high-throughput chemical screen using 3200 small molecules. NSC363998 was identified to suppress the neurodegeneration caused by riboCGG (rCGG) repeats. Three predicted targets of a NSC363998 derivative are isopeptidases in the neddylation pathway and could modulate the neurotoxicity caused by the rCGG repeats. Decreasing levels of neddylation resulted in enhancing neurodegeneration phenotypes, while up-regulation could rescue the phenotypes. Furthermore, known neddylation substrates, Cul3 and Vhl, and their downstream target, Sima, were found to modulate rCGG(90)-dependent neurotoxicity. Our results suggest that altered neddylation activity can modulate the rCGG repeat-mediated toxicity by regulating Sima protein levels, which could serve as a potential therapeutic target for FXTAS.
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15. Malecki C, Hambly BD, Jeremy RW, Robertson EN. {{The RNA-binding fragile-X mental retardation protein and its role beyond the brain}}. {Biophysical reviews}. 2020.
It is well-established that variations of a CGG repeat expansion in the gene FMR1, which encodes the fragile-X mental retardation protein (FMRP), cause the neurocognitive disorder, fragile-X syndrome (FXS). However, multiple observations suggest a general and complex regulatory role of FMRP in processes outside the brain: (1) FMRP is ubiquitously expressed in the body, suggesting it functions in multiple organ systems; (2) patients with FXS can exhibit a physical phenotype that is consistent with an underlying abnormality in connective tissue; (3) different CGG repeat expansion lengths in FMR1 result in different clinical outcomes due to different pathogenic mechanisms; (4) the function of FMRP as an RNA-binding protein suggests it has a general regulatory role. This review details the complex nature of FMRP and the different CGG repeat expansion lengths and the evidence supporting the essential role of the protein in a variety of biological and pathological processes.
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16. Mayhew E, Stuttard L, Beresford B. {{An Assessment of the Psychometric Properties of the GHQ-12 in an English Population of Autistic Adults Without Learning Difficulties}}. {J Autism Dev Disord}. 2020.
Valid and reliable tools to measure mental health are a key requirement to developing a robust evidence base on mental health difficulties and autism. There are several reasons why mental health measures developed for the neurotypical population may not be valid and reliable when used with autistic adults. Using data collected from a national evaluation of community-based, specialist autism provision in England, this study assessed the psychometric properties of the General Health Questionnaire (GHQ-12) in a population of autistic adults without learning difficulties. We examined the measure’s acceptability, reliability and internal construct validity. The GHQ-12 was found to have good psychometric properties in this population. This provides first evidence that this measure can be used with autistic adults without LD.
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17. Meyyazhagan A, Balasubramanian B, Kathannan S, Alagamuthu KK, Easwaran M, Shanmugam S, Pappusamy M, Bhotla HK, Mustaqahamed S, Arumugam VA, Kaul T, Keshavarao S. {{Scrutinizing the molecular, biochemical, and cytogenetic attributes in subjects with Rett syndrome (RTT) and their mothers}}. {Epilepsy Behav}. 2020; 111: 107277.
Rett syndrome (RTT) is a stern dominant progressive neurological development disorder linked with X chromosome ranking second for mental slowdown, exclusively in females after few months of birth with normal development and growth period. Genetically any defects in universally expressed methyl-CpG binding protein 2 (MeCP2) transcription regulator gene are considered as radix for RTT in almost all the previous studies. Our study mainly focuses in unraveling the genetic alterations like identifying MeCP2 gene polymorphisms, chromosomal abnormalities, or X-chromosome inactivation (XCI) as underlying cause of RTT in prototypes sorted through Diagnostic and Statistical Manual of Mental Disorders-Text Revised (DSM IV). In addition, we have examined the probable surrogates of brain function disabilities like serotonin, homocysteine (Hcy), calcium, potassium, and lead from blood in both RTT porotypes and their mothers. In our investigation, we have observed varied amino acid substitution of MeCP2 and varied frequency of skewed XCI in RTT prototype. Our study validates that the demonstration of chromosomal analysis, biochemical analysis, and genomic observations helps in concluding RTT condition and can be helpful in providing appropriate treatment and counseling as well as improve the currently available protocol of diagnosis.
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18. Nah YH, Tan JW. {{The effect of diagnostic labels on teachers’ perceptions of behaviours of students with autism spectrum disorder}}. {The British journal of educational psychology}. 2020.
BACKGROUND: In Singapore, despite the availability of specialized services and resources in mainstream schools for students with special educational needs, parents can still be hesitant to disclose their child’s diagnosis of autism spectrum disorder (ASD), for fear of stigma or negative attitudes from teachers and peers. AIM: This study aims to understand how diagnostic labels affect teachers’ perceptions of behaviours in students with ASD in mainstream primary schools, particularly behaviours which are difficult for educators to manage in the classroom setting. Based on research suggesting that a diagnostic label can provide an alternative explanation for atypical behaviours and reduce negative impressions, we hypothesize that teachers would perceive these behaviours of children with ASD less negatively as compared to children without any diagnostic labels. SAMPLE: The sample consisted of 120 mainstream primary school teachers who reported a mean of 9.97 years (SD = 7.96) of teaching experience. Majority of participants (65%) indicated that they had direct experience of teaching students with ASD in mainstream schools (mean years = 3.58, SD = 4.77). METHOD: Participants read a total of 20 vignettes depicting a range of behaviours typically observed in primary school-aged students with ASD. Participants were asked to rate the featured student’s behaviour on a 5-point Likert scale (i.e., 1 = strongly negative, 2 = negative, 3 = neutral, 4 = positive, and 5 = strongly positive). The survey vignettes were presented in a randomized order, and participants were randomly assigned to either the experimental group (awareness of diagnostic label) or the control group (non-awareness of label). RESULTS: Results indicated that the experimental group rated the behaviours less negatively than the control group. Qualitative feedback from participants also indicated that knowledge of the diagnostic label helped them to perceive the behaviours more positively. CONCLUSION: Findings from this study have implications for parents regarding diagnosis disclosure and may serve as an encouragement to parents to consider disclosing their child’s ASD diagnosis to the school.
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19. O’Neal S, Foster TP, Bhatt A, Lossius MN, Dayton K. {{Hypercalcemia from hypervitaminosis A in a child with autism}}. {Journal of pediatric endocrinology & metabolism : JPEM}. 2020.
Objectives Vitamin A is essential for normal cellular physiology and is often taken as a dietary supplement. Hypervitaminosis A can lead to hypercalcemia by increasing osteoclasts and subsequent bone resporption. Dietary supplements including vitamin A are new popular treatment stategies for autism. Case presentation We report a five-year old boy with autism spectrum disorder presenting with severe abdominal pain and bilateral lower extremity pain, who was found to have persistent hypercalcemia due to hypervitaminosis A. The patient ingested over 700 times the recommended intake of Vitamin A per day for age. Retention of vitamin A in the liver and adipose tissue causes toxic levels of retinoids and hypercalcemia. Conclusions Acute treatment included intravenous rehydration, furosemide, and calcitonin. Pamidronate was the definitive treatment for hypercalcemia from hypervitaminosis A due to its osteoclast inhibition and long biologic half-life. Parents should be counseled on risks of toxicity and absence of evidence showing benefits of vitamin A therapy for autism.
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20. Ouellette J, Toussay X, Comin CH, Costa LDF, Ho M, Lacalle-Aurioles M, Freitas-Andrade M, Liu QY, Leclerc S, Pan Y, Liu Z, Thibodeau JF, Yin M, Carrier M, Morse CJ, Dyken PV, Bergin CJ, Baillet S, Kennedy CR, Tremblay M, Benoit YD, Stanford WL, Burger D, Stewart DJ, Lacoste B. {{Vascular contributions to 16p11.2 deletion autism syndrome modeled in mice}}. {Nat Neurosci}. 2020.
While the neuronal underpinnings of autism spectrum disorder (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2(df/+) mouse model of 16p11.2 deletion ASD syndrome. We discover that 16p11.2 hemizygosity leads to male-specific, endothelium-dependent structural and functional neurovascular abnormalities. In 16p11.2(df/+) mice, endothelial dysfunction results in impaired cerebral angiogenesis at postnatal day 14, and in altered neurovascular coupling and cerebrovascular reactivity at postnatal day 50. Moreover, we show that there is defective angiogenesis in primary 16p11.2(df/+) mouse brain endothelial cells and in induced-pluripotent-stem-cell-derived endothelial cells from human carriers of the 16p11.2 deletion. Finally, we find that mice with an endothelium-specific 16p11.2 deletion (16p11.2(ΔEC)) partially recapitulate some of the behavioral changes seen in 16p11.2 syndrome, specifically hyperactivity and impaired motor learning. By showing that developmental 16p11.2 haploinsufficiency from endothelial cells results in neurovascular and behavioral changes in adults, our results point to a potential role for endothelial impairment in ASD.
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21. Pattison E, Papadopoulos N, Marks D, McGillivray J, Rinehart N. {{Behavioural Treatments for Sleep Problems in Children with Autism Spectrum Disorder: a Review of the Recent Literature}}. {Curr Psychiatry Rep}. 2020; 22(9): 46.
PURPOSE OF REVIEW: Behavioural sleep problems in children with autism spectrum disorder (ASD) are common and burdensome for both the child and their family. We provide an up-to-date review on behavioural sleep interventions and their core features and conclude with expert recommendations regarding the modification of interventions for children with ASD. RECENT FINDINGS: In the past 3 years, four original research studies (n ≥ 10) have evaluated behavioural sleep interventions for children with ASD (one RCT, three pre-post studies). All four studies reported significant improvements across various sleep outcomes and daytime behaviours. The interventions varied, however, in assessment comprehensiveness, nature of implementation support, length and delivery of intervention, outcome measurements, and follow-up periods. Clinically, behavioural sleep interventions are regarded as the first-line of treatment for sleep problems experienced by children with ASD. However, there is still much to be learnt regarding their clinical effectiveness.
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22. Pecora LA, Hancock GI, Hooley M, Demmer DH, Attwood T, Mesibov GB, Stokes MA. {{Gender identity, sexual orientation and adverse sexual experiences in autistic females}}. {Mol Autism}. 2020; 11(1): 57.
BACKGROUND: There is growing recognition that autistic females present with more diverse gender and sexual identities than their non-autistic counterparts. Likewise, autistic females are also at an increased risk of adverse sexual experiences. As higher rates of sexual victimisation are observed in individuals with diverse sexual identities in the broader population, rates of negative sexual experiences among autistic females remain unclear. This study aimed to investigate the representation of gender and sexual diversity within autistic females and examine their rates of regretted, and unwanted, sexual encounters among females with a transgender gender identity and non-heterosexual sexual orientation. METHODS: Two hundred and ninety-five females completed the Sexual Behaviour Scale-III (SBS-III) online. Self-reported gender identity and sexual orientation were compared between 134 autistic (M(age)= 26.2 years, SD = 8.7) and 161 non-autistic females (M(age) = 22.0 years, SD = 4.6). Differences in the prevalence of negative sexual experiences were compared across diagnosis and each gender identity and sexual orientation label. RESULTS: Autistic females were more likely to identify with a transgender gender identity (p < .05) and non-heterosexual sexual orientation (p < .007) compared to non-autistic females. Autistic homosexual females were more likely to have experienced a range of negative sexual experiences than autistic heterosexual females (OR ≥ 3.29; p < .01) and were more likely to have experienced unwanted sexual experiences than non-autistic females regardless of sexual orientation (OR ≥ 2.38; p < .05). There were no differences in rates of negative sexual experiences between autistic bisexual and both autistic heterosexual and non-autistic bisexual females. Non-autistic bisexual females (OR = 0.24; p = .018) presented with a reduced risk of regretted sexual experiences than non-autistic heterosexual peers. There were no differences in negative sexual experiences across gender identity in the autistic sample. LIMITATIONS: The use of fixed format response items may have restricted participants' abilities to provide rich responses pertaining to their sexual identities and nature of negative sexual experiences. The small number of participants who identified as transgender (n = 40) limits the reliability of results pertaining to sexual experiences across gender identity. Moreover, although multiple recruitment methods were used in this study, non-representative may bias estimates of prevalence rates. Thus, the data may not be representative of the broader population. CONCLUSIONS: Results indicate that autistic females present with greater diversity in their sexual identities than individuals without autism, with those with a homosexual sexual orientation being at greater risk of experiencing adverse sexual encounters. Findings suggest the importance of increased clinical attention to this diversity and the need to provide support to facilitate the development of a healthy sexual identity and reduce the risks identified in this study. Lien vers le texte intégral (Open Access ou abonnement)
23. Shalev I, Uzefovsky F. {{Empathic disequilibrium in two different measures of empathy predicts autism traits in neurotypical population}}. {Mol Autism}. 2020; 11(1): 59.
BACKGROUND: Features of autism spectrum conditions (ASC) are normally distributed within the population, giving rise to the notion of the autism spectrum. One of the hallmark features of ASC is difficulties in social communication, which relies heavily on our ability to empathize with others. Empathy comprises of both cognitive (CE) and emotional (EE) components that, together, allow us to understand another’s emotions and be affected by them appropriately, while maintaining a self-other distinction. Although CE and EE depend on distinct neural and developmental trajectories, it was suggested that the two empathic capacities can influence, balance, and regulate each other. Previous findings regarding the role of emotional and cognitive empathy in ASC have been mixed. Therefore, our study aimed to investigate whether the intra-personal empathy imbalance between the cognitive and emotional components, a measure we termed empathic disequilibrium (ED), can be associated with autism traits at the neurotypical range. METHODS: Participants were 671 young-adults at the neurotypical range who self-reported their empathy, assessed using two highly validated questionnaires-the Interpersonal Reactivity Index and the Empathy Quotient, autism traits using the Autism-Spectrum Quotient, and the related traits, alexithymia, and systemizing. RESULTS: Controlling for the total empathy score, greater ED was found to be positively correlated with autism traits. Specifically, autism traits were found to be elevated in groups of individuals with relatively higher EE than CE, underscoring their imbalance. CONCLUSIONS: Our study offers a novel perspective on the understanding of the social difficulties associated with autism tendencies in the general population and has potentially important clinical implications for understanding of ASC. We also propose a novel characterization of autism tendencies based on the imbalance between EE and CE, which we term ED, as opposed to examining EE and CE separately.
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24. Tang JSY, Falkmer M, Chen NTM, Bӧlte S, Girdler S. {{Development and Feasibility of MindChip™: A Social Emotional Telehealth Intervention for Autistic Adults}}. {J Autism Dev Disord}. 2020.
The study aims to develop and pilot a telehealth social emotional program, MindChip™ delivered with a computer based interventions (CBI) (Mind Reading(©)) for autistic adults. MindChip™ combined four theoretical perspectives and community feedback underpinning the essential mechanisms for targeting the social emotional understanding of autistic adults. A randomised pragmatic pilot trial (N = 25) was conducted to explore the feasibility of MindChip™ (n = 11) and to understand the preliminary efficacy of combining it with CBI compared to CBI only (n = 14). The use of MindChip™ and CBI combined demonstrated partial feasibility, with preliminary efficacy findings revealing increased emotion recognition generalisation outcomes compared to CBI only. Further research is required to improve the engagement and personalisation of the intervention for autistic adults.
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25. Utami KH, Skotte NH, Colaço AR, Yusof N, Sim B, Yeo XY, Bae HG, Garcia-Miralles M, Radulescu CI, Chen Q, Chaldaiopoulou G, Liany H, Nama S, Peteri UA, Sampath P, Castrén ML, Jung S, Mann M, Pouladi MA. {{Integrative Analysis Identifies Key Molecular Signatures Underlying Neurodevelopmental Deficits in Fragile X Syndrome}}. {Biol Psychiatry}. 2020.
BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by epigenetic silencing of FMR1 and loss of FMRP expression. Efforts to understand the molecular underpinnings of the disease have been largely performed in rodent or nonisogenic settings. A detailed examination of the impact of FMRP loss on cellular processes and neuronal properties in the context of isogenic human neurons remains lacking. METHODS: Using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to introduce indels in exon 3 of FMR1, we generated an isogenic human pluripotent stem cell model of FXS that shows complete loss of FMRP expression. We generated neuronal cultures and performed genome-wide transcriptome and proteome profiling followed by functional validation of key dysregulated processes. We further analyzed neurodevelopmental and neuronal properties, including neurite length and neuronal activity, using multielectrode arrays and patch clamp electrophysiology. RESULTS: We showed that the transcriptome and proteome profiles of isogenic FMRP-deficient neurons demonstrate perturbations in synaptic transmission, neuron differentiation, cell proliferation and ion transmembrane transporter activity pathways, and autism spectrum disorder-associated gene sets. We uncovered key deficits in FMRP-deficient cells demonstrating abnormal neural rosette formation and neural progenitor cell proliferation. We further showed that FMRP-deficient neurons exhibit a number of additional phenotypic abnormalities, including neurite outgrowth and branching deficits and impaired electrophysiological network activity. These FMRP-deficient related impairments have also been validated in additional FXS patient-derived human-induced pluripotent stem cell neural cells. CONCLUSIONS: Using isogenic human pluripotent stem cells as a model to investigate the pathophysiology of FXS in human neurons, we reveal key neural abnormalities arising from the loss of FMRP.
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26. Wang Y, Wang J, Wu FX, Hayrat R, Liu J. {{AIMAFE: Autism spectrum disorder identification with multi-atlas deep feature representation and ensemble learning}}. {Journal of neuroscience methods}. 2020; 343: 108840.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that could cause problems in social communications. Clinically, diagnosing ASD mainly relies on behavioral criteria while this approach is not objective enough and could cause delayed diagnosis. Since functional magnetic resonance imaging (fMRI) can measure brain activity, it provides data for the study of brain dysfunction disorders and has been widely used in ASD identification. However, satisfactory accuracy for ASD identification has not been achieved. NEW METHOD: To improve the performance of ASD identification, we propose an ASD identification method based on multi-atlas deep feature representation and ensemble learning. We first calculate multiple functional connectivity based on different brain atlases from fMRI data of each subject. Then, to get the more discriminative features for ASD identification, we propose a multi-atlas deep feature representation method based on stacked denoising autoencoder (SDA). Finally, we propose multilayer perceptron (MLP) and an ensemble learning method to perform the final ASD identification task. RESULTS: Our proposed method is evaluated on 949 subjects (including 419 ASDs and 530 typical control (TCs)) from the Autism Brain Imaging Data Exchange (ABIDE) and achieves accuracy of 74.52% (sensitivity of 80.69%, specificity of 66.71%, AUC of 0.8026) for ASD identification. COMPARISON WITH EXISTING METHODS: Compared with some previously published methods, our proposed method obtains the better performance for ASD identification. CONCLUSION: The results suggest that our proposed method is efficient to improve the performance of ASD identification, and is promising for ASD clinical diagnosis.
