1. Bartkowski JP, Kohler J, Escude CL, Xu X, Bartkowski S. {{Evaluating the Impact of a Clinician Improvement Program for Treating Patients with Intellectual and Developmental Disabilities: The Challenging Case of Mississippi}}. {Healthcare (Basel, Switzerland)}. 2018; 6(1).
In recent years, people with intellectual and developmental disabilities (IDD) have moved from institutionalized settings to local community residences. While deinstitutionalization has yielded quality of life improvements for people with IDD, this transition presents significant health-related challenges. Community clinicians have typically not been trained to provide sound medical care to people with IDD, a subpopulation that exhibits unique medical needs and significant health disparities. This study reports the results of a comprehensive evaluation of an IDD-focused clinician improvement program implemented throughout Mississippi. DETECT (Developmental Evaluation, Training and Consultative Team) was formed to equip Mississippi’s physicians and nurses to offer competent medical care to people with IDD living in community residences. Given the state’s pronounced health disparities and its clinician shortage, Mississippi offers a stringent test of program effectiveness. Results of objective survey indicators and subjective rating barometers administered before and after clinician educational seminars reveal robust statistically significant differences in clinician knowledge and self-assessed competence related to treating people with IDD. These results withstand controls for various confounding factors. Positive post-only results were also evident in a related program designed specifically for medical students. The study concludes by specifying a number of implications, including potential avenues for the wider dissemination of this program and promising directions for future research.
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2. Bast N, Poustka L, Freitag CM. {{The locus coeruleus-norepinephrine system as pacemaker of attention – a developmental mechanism of derailed attentional function in autism spectrum disorder}}. {Eur J Neurosci}. 2018; 47(2): 115-25.
Children with autism spectrum disorder (ASD) exhibit diminished visual engagement to environmental stimuli. Aberrant attentional function provides an explanation by reduced phasic alerting and orienting to exogenous stimuli. We review aberrant attentional function (alerting, orienting and attentional control) in children with ASD as studied by neurocognitive and neurophysiological tasks as well as magnetic resonance imaging studies. The locus coeruleus-norepinephrine (LC-NE) system is outlined as a pacemaker of attentional function. The LC-NE system regulates adaptive gain in synaptic signal transmission, which moderates phasic alerting (‘promoting’) and the activation of the ventral frontoparietal attention network within orienting (‘permitting’). In children with ASD, atypical LC-NE activity is proposed as underlying mechanism of aberrant attentional function. It may manifest as (i) increased tonic activity with reduced phasic reactivity to exogenous stimuli, (ii) attenuated bottom-up signalling mitigating salience and predictive reward attribution during phasic alerting, and (iii) reduced activation of the ventral frontoparietal attention system attenuating orienting to exogenous stimuli. Increased tonic pupil dilation and aberrant pupil reactivity are discussed as indicators of atypical LC-NE activity. Pupillometry is outlined as feasible method to assess alerting, orienting and attentional control that can be dissected from the pupil dilation time course. In children with ASD, aberrant attentional function through atypical LC-NE activity is proposed as developmental mechanism leading to reduced social attention as well as social interaction and communication impairments.
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3. Caputo G, Ippolito G, Mazzotta M, Sentenza L, Muzio MR, Salzano S, Conson M. {{Effectiveness of a Multisystem Aquatic Therapy for Children with Autism Spectrum Disorders}}. {J Autism Dev Disord}. 2018.
Aquatic therapy improves motor skills of persons with Autism Spectrum Disorders (ASD), but its usefulness for treating functional difficulties needs to be verified yet. We tested effectiveness of a multisystem aquatic therapy on behavioural, emotional, social and swimming skills of children with ASD. Multisystem aquatic therapy was divided in three phases (emotional adaptation, swimming adaptation and social integration) implemented in a 10-months-programme. At post-treatment, the aquatic therapy group showed significant improvements relative to controls on functional adaptation (Vineland Adaptive Behavior Scales), emotional response, adaptation to change and on activity level (Childhood Autism Rating Scale). Swimming skills learning was also demonstrated. Multisystem aquatic therapy is useful for ameliorating functional impairments of children with ASD, going well beyond a swimming training.
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4. Forsberg SL, Ilieva M, Maria Michel T. {{Epigenetics and cerebral organoids: promising directions in autism spectrum disorders}}. {Translational psychiatry}. 2018; 8(1): 14.
Autism spectrum disorders (ASD) affect 1 in 68 children in the US according to the Centers for Disease Control and Prevention (CDC). It is characterized by impairments in social interactions and communication, restrictive and repetitive patterns of behaviors, and interests. Owing to disease complexity, only a limited number of treatment options are available mainly for children that alleviate but do not cure the debilitating symptoms. Studies confirm a genetic link, but environmental factors, such as medications, toxins, and maternal infection during pregnancy, as well as birth complications also play a role. Some studies indicate a set of candidate genes with different DNA methylation profiles in ASD compared to healthy individuals. Thus epigenetic alterations could help bridging the gene-environment gap in deciphering the underlying neurobiology of autism. However, epigenome-wide association studies (EWAS) have mainly included a very limited number of postmortem brain samples. Hence, cellular models mimicking brain development in vitro will be of great importance to study the critical epigenetic alterations and when they might happen. This review will give an overview of the state of the art concerning knowledge on epigenetic changes in autism and how new, cutting edge expertise based on three-dimensional (3D) stem cell technology models (brain organoids) can contribute in elucidating the multiple aspects of disease mechanisms.
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5. Frye RE, Nankova B, Bhattacharyya S, Rose S, Bennuri SC, MacFabe DF. {{Modulation of Immunological Pathways in Autistic and Neurotypical Lymphoblastoid Cell Lines by the Enteric Microbiome Metabolite Propionic Acid}}. {Frontiers in immunology}. 2017; 8: 1670.
Propionic acid (PPA) is a ubiquitous short-chain fatty acid which is a fermentation product of the enteric microbiome and present or added to many foods. While PPA has beneficial effects, it is also associated with human disorders, including autism spectrum disorders (ASDs). We previously demonstrated that PPA modulates mitochondrial dysfunction differentially in subsets of lymphoblastoid cell lines (LCLs) derived from patients with ASD. Specifically, PPA significantly increases mitochondrial function in LCLs that have mitochondrial dysfunction at baseline [individuals with autistic disorder with atypical mitochondrial function (AD-A) LCLs] as compared to ASD LCLs with normal mitochondrial function [individuals with autistic disorder with normal mitochondrial function (AD-N) LCLs] and control (CNT) LCLs. PPA at 1 mM was found to have a minimal effect on expression of immune genes in CNT and AD-N LCLs. However, as hypothesized, Panther analysis demonstrated that 1 mM PPA exposure at 24 or 48 h resulted in significant activation of the immune system genes in AD-A LCLs. When the effect of PPA on ASD LCLs were compared to the CNT LCLs, both ASD groups demonstrated immune pathway activation, although the AD-A LCLs demonstrate a wider activation of immune genes. Ingenuity Pathway Analysis identified several immune-related pathways as key Canonical Pathways that were differentially regulated, specifically human leukocyte antigen expression and immunoglobulin production genes were upregulated. These data demonstrate that the enteric microbiome metabolite PPA can evoke atypical immune activation in LCLs with an underlying abnormal metabolic state. As PPA, as well as enteric bacteria which produce PPA, have been implicated in a wide variety of diseases which have components of immune dysfunction, including ASD, diabetes, obesity, and inflammatory diseases, insight into this metabolic modulator may have wide applications for both health and disease.
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6. Grootscholten IAC, van Wijngaarden B, Kan CC. {{High Functioning Autism Spectrum Disorders in Adults: Consequences for Primary Caregivers Compared to Schizophrenia and Depression}}. {J Autism Dev Disord}. 2018.
Primary caregivers experience consequences from being in close contact to a person with autism spectrum disorder (ASD). This study used the Involvement Evaluation Questionnaire to explore the level of consequences of 104 caregivers involved with adults with High Functioning ASD (HF-ASD) and compared these with the consequences reported by caregivers of patients suffering from depression and schizophrenia. Caregivers involved with adults with an HF-ASD experience overall consequences comparable to those involved with patients with depression or schizophrenia. Worrying was the most reported consequence. More tension was experienced by the caregivers of ASD patients, especially by spouses. More care and attention for spouses of adults with an HF-ASD appears to be needed.
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7. Halstead E, Ekas N, Hastings RP, Griffith GM. {{Associations Between Resilience and the Well-Being of Mothers of Children with Autism Spectrum Disorder and Other Developmental Disabilities}}. {J Autism Dev Disord}. 2018.
There is variability in the extent to which mothers are affected by the behavior problems of their children with developmental disabilities (DD). We explore whether maternal resilience functions as a protective or compensatory factor. In Studies 1 and 2, using moderated multiple regression models, we found evidence that maternal resilience functioned as a compensatory factor-having a significant independent main effect relationship with well-being outcomes in mothers of children with DD and autism spectrum disorder. However, there was no longitudinal association between resilience and maternal well-being outcomes. There was little evidence of the role of resilience as a protective factor between child behavior problems and maternal well-being in both studies.
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8. Hiraide T, Nakashima M, Yamoto K, Fukuda T, Kato M, Ikeda H, Sugie Y, Aoto K, Kaname T, Nakabayashi K, Ogata T, Matsumoto N, Saitsu H. {{De novo variants in SETD1B are associated with intellectual disability, epilepsy and autism}}. {Human genetics}. 2018.
SETD1B (SET domain containing 1B) is a component of SET1 histone methyltransferase complex, which mediates the methylation of histone H3 on lysine 4 (H3K4). Here, we describe two unrelated individuals with de novo variants in SETD1B identified by trio-based whole exome sequencing: c.5524C>T, p.(Arg1842Trp) and c.5575C>T, p.(Arg1859Cy). The two missense variants occurred at evolutionarily conserved amino acids and are located within the SET domain, which plays a pivotal role in catalyzing histone methylation. Previous studies have suggested that de novo microdeletions in the 12q24.3 region encompassing SETD1B were associated with developmental delays, intellectual disabilities, autism/autistic behavior, large stature and craniofacial anomalies. Comparative mapping of 12q24.3 deletions refined the candidate locus, indicating KDM2B and SETD1B to be the most plausible candidate genes for the pathogenicity of 12q24.3 deletion syndrome. Our cases showed epilepsy, developmental delay, intellectual disabilities, autistic behavior and craniofacial dysmorphic features, which are consistent with those of individuals with de novo 12q24.31 deletions. Therefore, our study suggests that SETD1B aberration is likely to be the core defect in 12q24.3 deletion syndrome.
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9. Hirschberger RG, Kuban KCK, O’Shea TM, Joseph RM, Heeren T, Douglass L, Stafstrom CE, Jara H, Frazier JA, Hirtz D, Rollins J, Paneth N. {{Co-occurrence and Severity of Neurodevelopmental Burden (Cognitive Impairment, Cerebral Palsy, Autism Spectrum Disorder, and Epilepsy) at Age 10 Years in Children Born Extremely Preterm}}. {Pediatric neurology}. 2017.
BACKGROUND: This study aims to determine the prevalence of neurodevelopmental impairments at age ten years among children born extremely preterm (less than 28 weeks gestational age) and to offer a framework for categorizing neurological limitations. METHODS: A multicenter, prospective cohort follow-up study recruited 889 ten-year-old children born from 2002 to 2004. We assessed prevalence of cognitive impairment, measured by intelligent quotient and tests of executive function, cerebral palsy (CP), autism spectrum disorder (ASD), and epilepsy singly and in combination. The three levels of impairment severity were: category I-no major neurodevelopmental impairment; category II-normal cognitive ability with CP, ASD, and/or epilepsy; and category III-children with cognitive impairment. RESULTS: A total 214 of 873 children (25%) had cognitive impairment, 93 of 849 children (11%) had CP, 61 of 857 children (7%) had ASD, and 66 of 888 children (7%) had epilepsy. Further, 19% of all children had one diagnosis, 10% had two diagnoses, and 3% had three diagnoses. Decreasing gestational age was associated with increasing number of impairments (P < 0.001). Half the children with cognitive impairment and one third of children with CP, ASD, or epilepsy had a single impairment. Six hundred one (68% [95% CI, 64.5%-70.7%]) children were in category I, 74 (8% [95% CI, 6.6%-10.3%]) were in category II, and 214 (24% [95% CI 21.7%-27.4%]) were in category III. CONCLUSIONS: Three quarters of children had normal intellect at age ten years; nearly 70% were free of neurodevelopmental impairment. Forty percent of children with impairments had multiple diagnoses. Lien vers le texte intégral (Open Access ou abonnement)
10. Khatri N, Gilbert JP, Huo Y, Sharaflari R, Nee M, Qiao H, Man HY. {{The Autism Protein Ube3A/E6AP Remodels Neuronal Dendritic Arborization via Caspase-Dependent Microtubule Destabilization}}. {J Neurosci}. 2018; 38(2): 363-78.
UBE3A gene copy number variation and the resulting overexpression of the protein E6AP is directly linked to autism spectrum disorders (ASDs). However, the underlying cellular and molecular neurobiology remains less clear. Here we report the role of ASD-related increased dosage of Ube3A/E6AP in dendritic arborization during brain development. We show that increased E6AP expression in primary cultured neurons leads to a reduction in dendritic branch number and length. The E6AP-dependent remodeling of dendritic arborization results from retraction of dendrites by thinning and fragmentation at the tips of dendrite branches, leading to shortening or removal of dendrites. This remodeling effect is mediated by the ubiquitination and degradation of XIAP (X-linked inhibitors of aptosis protein) by E6AP, which leads to activation of caspase-3 and cleavage of microtubules. In vivo, male and female Ube3A 2X ASD mice show decreased XIAP levels, increased caspase-3 activation, and elevated levels of tubulin cleavage. Consistently, dendritic branching and spine density are reduced in cortical neurons of Ube3A 2X ASD mice. In revealing an important role for Ube3A/E6AP in ASD-related developmental alteration in dendritic arborization and synapse formation, our findings provide new insights into the pathogenesis of Ube3A/E6AP-dependent ASD.SIGNIFICANCE STATEMENT Copy number variation of the UBE3A gene and aberrant overexpression of the gene product E6AP protein is a common cause of autism spectrum disorders (ASDs). During brain development, dendritic growth and remodeling play crucial roles in neuronal connectivity and information integration. We found that in primary neurons and in Ube3A transgenic autism mouse brain, overexpression of E6AP leads to significant loss of dendritic arborization. This effect is mediated by the ubiquitination of XIAP (X-linked inhibitor of aptosis protein) by E6AP, subsequent activation of caspases, and the eventual cleavage of microtubules, leading to local degeneration and retraction at the tips of dendritic branches. These findings demonstrate dysregulation in neuronal structural stability as a major cellular neuropathology in ASD.
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11. Lindsey RA, Barry TD. {{Protective Factors Against Distress for Caregivers of a Child with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2018.
Caregivers of a child with autism spectrum disorder (ASD) often experience elevated distress. The current study examined potential protective factors against caregiver distress when child externalizing and internalizing behaviors are present: family resources, perceived social support, parenting efficacy, knowledge of ASD, and the agreement between actual and perceived knowledge of ASD. Caregivers of a child with ASD completed an online questionnaire. Results demonstrated main effects for externalizing behavior, family resources, and perceived social support. Significant interactions were found among parenting efficacy and internalizing behavior, and the agreement between actual and perceived knowledge with both externalizing and internalizing behaviors. Results indicate important factors that should be emphasized when working with families of a child with ASD.
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12. Manzano-Garcia G, Ayala JC. {{Relationship between Psychological Capital and Psychological Well-Being of Direct Support Staff of Specialist Autism Services. The Mediator Role of Burnout}}. {Front Psychol}. 2017; 8: 2277.
This study investigates the specific role of burnout as a mediator in the relationship between psychological capital and psychological well-being (PWB) in direct support staff of specialist autism services. A time lagged design with three data-collection points was conducted to survey 56 professionals (direct support staff) who work at a Spanish center specialized in autism. Participants completed measures of psychological capital, burnout and PWB. The hypothesized model was tested using structural equation modeling. Our findings show that psychological capital has a significant main effect on PWB. The results also show that psychological capital in the work environment should result in lower burnout which in turn, should lead to higher degrees of PWB in the direct support staff of autism services. Our results support that psychological capital is a key variable in the working life of the direct support staff of autism services. The findings suggest the need of implementing programmes which strengthen each individual’s psychological capital in order to prevent burnout and achieve a greater PWB.
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13. Ncube BL, Perry A, Weiss JA. {{The quality of life of children with severe developmental disabilities}}. {J Intellect Disabil Res}. 2018.
BACKGROUND: Research examining the quality of life (QoL) of children with severe developmental disabilities (SDD) is limited. The present study examines parent perceptions of child QoL in children with SDD compared with typically developing (TD) children and then examines predictors of QoL for the SDD group. METHOD: Parents of 246 children with SDD (aged 4 to 19 years) and 210 TD children (aged 4 to 18 years) responded to an online survey. QoL was measured using a composite variable composed of the child’s happiness, achievement of potential and friendship quality. RESULTS: Children with DD had lower QoL ratings than TD children. In children with DD, higher QoL was related to younger age, higher adaptive skills, lower maladaptive behaviour, lower parent psychological distress and higher satisfaction with the child’s education. CONCLUSIONS: Interventions to promote positive outcomes for children with SDD should target both characteristics of the individual and the environment.
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14. Petrelli F, Bezzi P. {{mGlu5-mediated signalling in developing astrocyte and the pathogenesis of autism spectrum disorders}}. {Current opinion in neurobiology}. 2018; 48: 139-45.
Astrocytes, the largest glial population in human and murine brains, are crucial to the regulation of synaptic connectivity. During the first three weeks of postnatal development, immature astrocytes express mGlu5 and expands several fold while undergoing a transition towards their mature phase. Although mGlu5-mediated signalling in astrocyte functions has been extensively studied in the last decades, whether this signalling is implicated in the mechanisms governing their development, as well as the effects of dysregulated astrocytic development on neurodevelopmental disorders, are still unclear. The aim of this review is to examine what is known about the mGlu5-mediated signalling in the developing astrocytes and its possible contribution to the pathophysiology of autism spectrum disorders.
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15. Ptomey LT, Steger FL, Lee J, Sullivan DK, Goetz JR, Honas JJ, Washburn RA, Gibson CA, Donnelly JE. {{Changes in Energy Intake and Diet Quality during an 18-Month Weight-Management Randomized Controlled Trial in Adults with Intellectual and Developmental Disabilities}}. {Journal of the Academy of Nutrition and Dietetics}. 2018.
BACKGROUND: Previous research indicates that individuals with intellectual and developmental disabilities (IDDs) are at risk for poor diet quality. OBJECTIVE: The purpose of this secondary analysis was to determine whether two different weight-loss diets affect energy intake, macronutrient intake, and diet quality as measured by the Healthy Eating Index-2010 (HEI-2010) during a 6-month weight-loss period and 12-month weight-management period, and to examine differences in energy intake, macronutrient intake, and HEI-2010 between groups. DESIGN: Overweight/obese adults with IDDs took part in an 18-month randomized controlled trial and were assigned to either an enhanced Stop Light Diet utilizing portion-controlled meals or a conventional diet consisting of reducing energy intake and following the 2010 Dietary Guidelines for Americans. Proxy-assisted 3-day food records were collected at baseline, 6 months, and 18 months, and were analyzed using Nutrition Data System for Research software. HEI-2010 was calculated using the data from Nutrition Data System for Research. PARTICIPANTS/SETTING: The study took place from June 2011 through May 2014 in the greater Kansas City metropolitan area. MAIN OUTCOME MEASURES: This was a secondary analysis of a weight-management intervention for adults with IDDs randomized to an enhanced Stop Light Diet or conventional diet, to examine differences in energy intake, macronutrient intake, and HEI-2010 across time and between groups. STATISTICAL ANALYSES PERFORMED: Independent- and paired-samples t tests and general mixed modeling for repeated measures were performed to examine group differences and changes at baseline, 6 months, and 18 months between the enhanced Stop Light Diet and conventional diet groups. RESULTS: One hundred and forty six participants (57% female, mean+/-standard deviation age=36.2+/-12.0 years) were randomized to either the enhanced Stop Light Diet or conventional diet group (77 enhanced Stop Light Diet, 69 conventional diet) and provided data for analysis at baseline, 124 completed the 6-month weight-loss period, and 101 completed the 18-month study. Participants on the enhanced Stop Light Diet diet significantly reduced energy intake at 6 and 18 months (both P<0.001), but those on the conventional diet did not (both P=0.13). However, when accounting for age, sex, race, education level, and support level (mild vs moderate IDD), there was a significant decrease during the 18-month intervention in energy intake for the enhanced Stop Light Diet and conventional diet groups combined (P<0.01 for time effect), but no significant group difference in this change (P=0.39 for group-by-time interaction). There was no significant change in total HEI-2010 score at 6 and 18 months (P=0.05 and P=0.38 for the enhanced Stop Light Diet group; P=0.22 and P=0.17 for the conventional diet group), and no significant group difference at 6 and 18 months (P=0.08 and P=0.42). However, when participants' age, sex, race, education level, and support level were accounted for, mixed modeling indicated a significant increase in total HEI-2010 scores for the enhanced Stop Light Diet and conventional diet groups combined during the 18-month intervention (P=0.01 for time effect). CONCLUSIONS: The results of this study found that after controlling for demographic factors, individuals with IDDs can decrease their energy intake and increase their diet quality, with no significant differences between the enhanced Stop Light Diet and conventional diet groups. Lien vers le texte intégral (Open Access ou abonnement)
16. Subramanian D, Pralong E, Daniel RT, Chacko AG, Stoop R, Babu KS. {{Gamma oscillatory activity in vitro: a model system to assess pathophysiological mechanisms of comorbidity between autism and epilepsy}}. {Translational psychiatry}. 2018; 8(1): 16.
Autism spectrum disorder (ASD) and temporal lobe epilepsy exhibit remarkable comorbidity, but for reasons not clearly understood. To reveal a common pathophysiological mechanism, we here describe and characterize an in vitro epileptiform activity in the rat hippocampus that exhibits common features with in vivo activity in rodent ASD models. We discovered the development of this activity in the CA1 region of horizontal slices after prolonged interictal-like epileptiform activity in the CA3 region that was provoked by incubation in high potassium artificial cerebrospinal fluid. The CA1 epileptiform bursts were insensitive to blockers of glutamatergic transmission, and were carried by synaptic as well as extrasynaptic, tonically activated gamma-aminobutyric acid type A (GABA(A)) receptors. The bursts bear resemblance to in vivo gamma-oscillatory activity found in rat ASD models with respect to their gamma frequency spectrum, their origin (in the CA1), and their sensitivity to blockers of cation-chloride pumps (NKCC1 and KCC2), as well as to oxytocin. Considering this bursting activity as an in vitro model for studying comorbidity between epilepsy and ASD may help to disentangle the intricate interactions that underlie the comorbidity between both diseases and suggests that extrasynaptic tonic GABAergic transmission could represent a potential target for ASD.
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17. Sumner E, Leonard HC, Hill EL. {{Comparing Attention to Socially-Relevant Stimuli in Autism Spectrum Disorder and Developmental Coordination Disorder}}. {Journal of abnormal child psychology}. 2018.
Difficulties with social interaction have been reported in both children with an autism spectrum disorder (ASD) and children with developmental coordination disorder (DCD), although these disorders have very different diagnostic characteristics. To date, assessment of social skills in a DCD population has been limited to paper-based assessment or parent report. The present study employed eye tracking methodology to examine how children attend to socially-relevant stimuli, comparing 28 children with DCD, 28 children with ASD and 26 typically-developing (TD) age-matched controls (aged 7-10). Eye movements were recorded while children viewed 30 images, half of which were classed as ‘Individual’ (one person in the scene, direct gaze) and the other half were ‘Social’ (more naturalistic scenes showing an interaction). Children with ASD spent significantly less time looking at the face/eye regions in the images than TD children, but children with DCD performed between the ASD and TD groups in this respect. Children with DCD demonstrated a reduced tendency to follow gaze, in comparison to the ASD group. Our findings confirm that social atypicalities are present in both ASD and to a lesser extent DCD, but follow a different pattern. Future research would benefit from considering the developmental nature of the observed findings and their implications for support.
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18. Vasa RA, Kreiser NL, Keefer A, Singh V, Mostofsky SH. {{Relationships between autism spectrum disorder and intolerance of uncertainty}}. {Autism Res}. 2018.
Intolerance of uncertainty (IU) is a dispositional risk factor involving maladaptive responding under conditions of uncertainty. Recent data indicate that IU is likely elevated in youth with autism spectrum disorder (ASD) and is positively correlated with anxiety. This study examined whether IU may be associated with ASD independent of anxiety. Relationships between anxiety, ASD, and IU were examined in 57 children with ASD without co-occurring intellectual disability and 32 control participants, ages 7-16 years. Hierarchal linear regressions were run to examine whether ASD variables, including emotion dysregulation, were predictive of IU when controlling for anxiety. Severity of social communication deficits, repetitive behaviors, and emotion dysregulation were each related to IU when controlling for the effects of anxiety. When these variables were entered into the regression model together, emotion dysregulation was the only significant predictor of IU. These findings suggest that IU is directly related to features of ASD possibly due to shared genetic, neurological, or psychological underpinnings. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Youth with ASD without co-occurring intellectual disability experience high levels of intolerance of uncertainty (IU), which is related to anxiety. This study found that IU may also have a relationship with certain aspects of ASD, particularly emotion dysregulation.
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19. Wang P, Zhao D, Lachman HM, Zheng D. {{Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons}}. {Translational psychiatry}. 2018; 8(1): 13.
Autism spectrum disorder (ASD) is highly heritable but genetically heterogeneous. The affected neural circuits and cell types remain unclear and may vary at different developmental stages. By analyzing multiple sets of human single cell transcriptome profiles, we found that ASD candidates showed relatively enriched gene expression in neurons, especially in inhibitory neurons. ASD candidates were also more likely to be the hubs of the co-expression gene module that is highly expressed in inhibitory neurons, a feature not detected for excitatory neurons. In addition, we found that upregulated genes in multiple ASD cortex samples were enriched with genes highly expressed in inhibitory neurons, suggesting a potential increase of inhibitory neurons and an imbalance in the ratio between excitatory and inhibitory neurons in ASD brains. Furthermore, the downstream targets of several ASD candidates, such as CHD8, EHMT1 and SATB2, also displayed enriched expression in inhibitory neurons. Taken together, our analyses of single cell transcriptomic data suggest that inhibitory neurons may be a major neuron subtype affected by the disruption of ASD gene networks, providing single cell functional evidence to support the excitatory/inhibitory (E/I) imbalance hypothesis.
