1. Andoh M, Ikegaya Y, Koyama R. {{Microglia as possible therapeutic targets for autism spectrum disorders}}. {Prog Mol Biol Transl Sci};2019;167:223-245.
Malfunctions of the nervous and immune systems are now recognized to be fundamental causes of autism spectrum disorders (ASDs). Studies have suggested that the brain’s resident immune cells, microglia are possible key players in ASDs. Specifically, deficits in synaptic pruning by microglia may underlie the pathogenesis of ASDs, in which excess synapses are occasionally reported. This idea has driven researchers to investigate causal links between microglial dysfunction and ASDs. In this review, we first introduce the characteristics of microglia in ASD brains and discuss their possible roles in the pathogenesis of ASDs. We also refer to immunomodulatory agents that could be potentially used as symptomatic therapies for ASDs in light of their ability to modify microglial functions. Finally, we will mention a possible strategy to radically cure some of the symptoms reported in ASDs through reorganizing neural circuits via microglia-dependent synaptic pruning.
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2. Bernstein U, Demuth S, Puk O, Eichhorn B, Schulz S. {{Novel MECP2 Mutation c.1162_1172del; p.Pro388* in Two Patients with Symptoms of Atypical Rett Syndrome}}. {Mol Syndromol};2019 (Jul);10(4):223-228.
We report 2 cases of girls with MECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in both patients.
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3. Bertelli MO, Del Furia C, Bonadiman M, Rondini E, Banks R, Lassi S. {{The Relationship Between Spiritual Life and Quality of Life in People with Intellectual Disability and/or Low-Functioning Autism Spectrum Disorders}}. {J Relig Health};2019 (Oct 10)
Spirituality seems to represent a relevant domain in the person-centred care planning and outcome assessment for persons with intellectual disability and low-functioning autism spectrum disorder. Despite this, the impact of spirituality on subjective well-being and quality of life (QoL) has been scarcely investigated. The aim of the present study was to map the international scientific literature in order to identify the reasons of such misconsideration and the key points for future research and practice implementation. The relationship between spirituality and QoL depends on a complexity of factors, ranging from QoL theoretical models to services’ organisation. Personal attitude, family members, health and social-care personnel, training, faith and life communities, and even different religions seem to deserve an in-depth analysis.
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4. Calderon J, Bellinger DC, Newburger JW. {{Autism and Congenital Heart Disease: Evidence and Unresolved Questions}}. {Pediatrics};2019 (Oct 10)
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5. Hegarty IJ, Lazzeroni LC, Raman MM, Hallmayer JF, Cleveland SC, Wolke ON, Phillips JM, Reiss AL, Hardan AY. {{Genetic and environmental influences on corticostriatal circuits in twins with autism}}. {J Psychiatry Neurosci};2019 (Oct 11);44(6):190030.
Background: Corticostriatal circuits (CSC) have been implicated in the presentation of some restricted and repetitive behaviours (RRBs) in children with autism-spectrum disorder (ASD), and preliminary evidence suggests that disruptions in these pathways may be associated with differences in genetic and environmental influences on brain development. The objective of this investigation was to examine the impact of genetic and environmental factors on CSC regions in twins with and without ASD and to evaluate their relationship with the severity of RRBs. Methods: We obtained T1-weighted MRIs from same-sex monozygotic and dizygotic twin pairs, aged 6-15 years. Good-quality data were available from 48 ASD pairs (n = 96 twins; 30 pairs concordant for ASD, 15 monozygotic and 15 dizygotic; 18 pairs discordant for ASD, 4 monozygotic and 14 dizygotic) and 34 typically developing control pairs (n = 68 twins; 20 monozygotic and 14 dizygotic pairs). We generated structural measures of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), caudate, putamen, pallidum and thalamus using FreeSurfer. Twin pair comparisons included intraclass correlation analyses and ACE modelling (a2 = additive genetics; c2 = common or shared environment; e2 = unique or nonshared environment). We also assessed correlations with RRB severity. Results: Structural variation in CSC regions was predominantly genetically mediated in typically developing twins (a2 = 0.56 to 0.87), except for ACC white matter volume (a2 = 0.42, 95% confidence interval [CI] 0.08 to 0.77). We also observed similar magnitudes of genetic influence in twins with ASD (a2 = 0.65 to 0.97), but the cortical thickness of the ACC (c2 = 0.44, 95% CI 0.22 to 0.66) and OFC (c2 = 0.60, 95% CI 0.25 to 0.95) was primarily associated with environmental factors in only twins with ASD. Twin pair differences in OFC grey matter volume were also correlated with RRB severity and were predominantly environmentally mediated. Limitations: We obtained MRIs on 2 scanners, and analytical approaches could not identify specific genetic and environmental factors. Conclusion: Genetic factors primarily contribute to structural variation in subcortical CSC regions, regardless of ASD, but environmental factors may exert a greater influence on the development of grey matter thickness in the OFC and ACC in children with ASD. The increased vulnerability of OFC grey matter to environmental influences may also mediate some heterogeneity in RRB severity in children with ASD.
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6. Jakubowski KP, Iverson JM. {{Look at Mommy: An Exploratory Study of Attention-Related Communication in Mothers of Toddlers at Risk for Autism}}. {Lang Learn Dev};2019;15(2):126-137.
Attentional difficulties are evident in children with autism spectrum disorder (ASD). Accordingly, mothers of children with ASD may modify communication to direct their child’s attention, and this pattern may generalize to later-born children. This study examined patterns of child-directed communication in eleven mothers of 18-month-old toddlers at heightened risk (HR) for ASD and compared them to eleven low-risk (LR; no first- or second-degree relative with ASD) dyads. Naturalistic interactions at home were coded for communication that captured, directed, or maintained children’s attention and/or actions. Results provide preliminary evidence that LR mothers produce more utterances that involve labeling objects and gestures, while HR mothers use more suggestions. Thus, having an older child with ASD may influence maternal behavior with later-born children, even when those children do not themselves manifest obvious ASD symptomatology. Results highlight the need for further research on dyadic interactions between mothers and HR toddlers in larger samples.
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7. Leung C, Lai C, Lau D, Leung S, Pin TW. {{Effectiveness of a multidisciplinary parent training program for children with developmental disabilities: A single-blind randomized waitlist controlled trial}}. {J Child Health Care};2019 (Oct 10):1367493519880447.
This study aimed to evaluate the effectiveness of a multidisciplinary parent training program, Promoting Holistic Development of Young Kids (Poly Kids), using a single-blind randomized waitlist controlled design. The participants included 218 parents of children with developmental disabilities (DD) (intervention group = 107 and waitlist control group = 111). The primary outcomes were child learning, expressive language, fine and gross motor skills (based on individual assessment by respective blinded professionals), and parental reports of child behavior problems. The parents in the intervention group reported significantly lower child behavior problems (d = .34), higher child task motivation (d = .63), and lower parenting stress post-intervention (d = .25), while the children in the intervention group produced significantly more words post-intervention (d = .82). McNemar test results were significant for movement out of the clinical range in child behavior problems and cognitive skills in the intervention group, but not the control group. The results provided initial evidence on the effectiveness of this train-the-trainer program in supporting families with preschool children with DD in terms of child behavior problems, expressive language, cognitive skills, task motivation, and parenting stress.
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8. Rein B, Yan Z, Wang ZJ. {{Diminished Social Interaction Incentive Contributes to Social Deficits in Mouse Models of Autism Spectrum Disorder}}. {Genes Brain Behav};2019 (Oct 10):e12610.
One of the core symptoms of Autism spectrum disorder (ASD) is impaired social interaction. Currently, no pharmacotherapies exist for this symptom due to complex biological underpinnings and distinct genetic models which fail to represent the broad disease spectrum. One convincing hypothesis explaining social deficits in human ASD patients is amotivation, however it is unknown whether mouse models of ASD represent this condition. Here we used two highly trusted ASD mouse models (male Shank3 deficient [Shank3(+/DeltaC) ] mice modeling the monogenic etiology of ASD, and inbred BTBR mice [both male and female] modeling the idiopathic and highly polygenic pathology for ASD) to evaluate the level of motivation to engage in a social interaction. In the behavioral paradigms utilized, a social stimulus was placed in the open arm of the elevated plus maze (EPM), or the light compartment of the light-dark box (LDB). To engage in a social interaction, mice were thus required to endure innately aversive conditions (open areas, height, and/or light). In the modified EPM paradigm, both Shank3(+/DeltaC) and BTBR mice demonstrated decreased open-arm engagement with a social stimulus but not a novel object, suggesting reduced incentive to engage in a social interaction in these models. However, these deficits were not expressed under the less severe aversive pressures of the light-dark box. Collectively, we show that ASD mouse models exhibit diminished social interaction incentive, and provide a new investigation strategy facilitating the study of the neurobiological mechanisms underlying social reward and motivation deficits in neuropsychiatric disorders.
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9. Sigmon ER, Kelleman M, Susi A, Nylund CM, Oster ME. {{Congenital Heart Disease and Autism: A Case-Control Study}}. {Pediatrics};2019 (Oct 10)
OBJECTIVES: There has long been an association between congenital heart disease (CHD) and general neurodevelopmental delays. However, the association between CHD and autism spectrum disorders (AuSDs) is less well understood. Using administrative data, we sought to determine the association between CHD and AuSD and identify specific CHD lesions with higher odds of developing AuSD. METHODS: We performed a 1:3 case-control study of children enrolled in the US Military Health System from 2001 to 2013. Children with International Classification of Disease, Ninth Revision, Clinical Modification codes for AuSD were identified as cases and matched with controls on the basis of date of birth, sex, and enrollment time frame. Each child’s records were reviewed for CHD lesions and associated procedures. Conditional logistic regression determined odds ratios (ORs) and 95% confidence intervals (CIs) for comparative associations. RESULTS: There were 8760 cases with AuSD and 26 280 controls included in the study. After adjustment for genetic syndrome, maternal age, gestational diabetes, short gestation, newborn epilepsy, birth asphyxia, and low birth weight, there were increased odds of AuSD in patients with CHD (OR 1.32; 95% CI 1.10-1.59). Specific lesions with significant OR included atrial septal defects (n = 82; OR 1.72; 95% CI 1.07-2.74) and ventricular septal defects (n = 193; OR 1.65; 95% CI 1.21-2.25). CONCLUSIONS: Children with CHD have increased odds of developing AuSD. Specific lesions associated with increased risk include atrial septal defects and ventricular septal defects. These findings will be useful for counseling parents of children with CHD.
