1. Angell AM, Solomon O. {{‘If I was a different ethnicity, would she treat me the same?’: Latino parents’ experiences obtaining autism services}}. {Disabil Soc}. 2017; 32(8): 1142-64.
This article reports on an ethnographic study with 12 Latino families of children on the autism spectrum related to obtaining autism services in Los Angeles County. Using critical discourse analysis of interviews, observations, and records, we consider the experiences of the Latino families in relation to: 1) A discursively constructed ‘autism parent’ subject position that mandates ‘fighting’ service systems to ‘win’ autism services for children, originating from White middle-class parents’ socio-economic resources and social capital; 2) A neoliberal social services climate that assumes scarcity of available resources and prioritizes austerity in their authorization; and 3) A media and institutional ‘cultural deficit’ discourse that attributes disparities in autism services for Latino children to their parents’ presumed culturally-based ‘passivity.’ We argue that parental discourse about fighting, or not fighting, for autism services is engendered by a tension between a parental logic of care, and the logic of competition of the economic market.
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2. Garcia-Medina JJ, Garcia-Pinero M, Del-Rio-Vellosillo M, Fares-Valdivia J, Ragel-Hernandez AB, Martinez-Saura S, Carcel-Lopez MD, Zanon-Moreno V, Pinazo-Duran MD, Villegas-Perez MP. {{Comparison of Foveal, Macular, and Peripapillary Intraretinal Thicknesses Between Autism Spectrum Disorder and Neurotypical Subjects}}. {Invest Ophthalmol Vis Sci}. 2017; 58(13): 5819-26.
Purpose: To compare thicknesses of intraretinal layers segmented by spectral-domain optical coherence tomography (SD-OCT) between autism spectrum disorder (ASD) and neurotypical (NT) individuals. Methods: We performed 2 scans on 108 eyes from 54 participants (27 high-functioning ASD and 27 age- and sex-matched NT subjects): macular fast volume and peripapillary retinal nerve fiber layer (pRNFL). Macula was automatically segmented. The mean foveal and macular thickness of nine different layers and the thickness of nine pRNFL sectors were considered. Data from the right and left eyes were averaged for each participant. The results were compared between the ASD and NT groups. Associations between the Kaufman brief intelligence test (K-BIT), head circumference and SD-OCT results were also investigated in ASD individuals. Results: ASD subjects showed greater foveal thickness at total retina, total inner retina, inner plexiform and inner nuclear layers, and greater macular thickness at total retina and total inner retina. Inferior, nasal inferior and temporal inferior sectors of pRNFL were also thicker in the ASD participants than in the controls (P < 0.05, unpaired t-test). Significant correlations were found between some K-BIT results and temporal inferior and inferior pRNFL thicknesses in the ASD group (P < 0.05, Spearman's rank correlation). No associations were seen between head circumference and OCT parameters. Conclusions: There are intraretinal thickenings at different locations in ASD subjects when compared to NT controls. This fact should be taken into account when interpreting SD-OCT examinations in ASD individuals. Plus, some pRNFL thicknesses present positive correlations with scores of cognitive status in ASD. Lien vers le texte intégral (Open Access ou abonnement)
3. Lemay JF, Eastabrook G, MacKenzie H. {{The Little Prince: a glimpse into the world of autism?}}. {Arch Dis Child}. 2017.
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4. Mazzucchelli TG, Hodges J, Kane RT, Sofronoff K, Sanders MR, Einfeld S, Tonge B, Gray KM. {{Parenting and family adjustment scales (PAFAS): validation of a brief parent-report measure for use with families who have a child with a developmental disability}}. {Res Dev Disabil}. 2017; 72: 140-51.
BACKGROUND: Children with a developmental disability are three to four times more likely than their typically developing peers of developing significant emotional and behavioural problems. There is strong evidence to suggest that individual biological and psychological factors interact with family functioning to precipitate and perpetuate these problems. AIMS: This study examined the psychometric properties of a brief measure, the Parent and Family Adjustment Scales (PAFAS) for use with parents of children with a developmental disability. METHODS: A sample of 914 parents of children (M=6.27years) with a developmental disability participated in the study. Disabilities included Autism Spectrum Disorder and Intellectual Disability RESULTS: A confirmatory factor analysis supported a 16-item, four factor model of PAFAS Parenting, and an 11-item, three factor model of PAFAS Family Adjustment. The Parenting Scale measures parental consistency, coercive practices, use of encouragement and the quality of parent-child relationship. The Family Adjustment Scale measures parental emotional adjustment and partner and family support in parenting. CONCLUSIONS: The current study indicated that the PAFAS demonstrates promise as a brief measure of multiple domains of family functioning important for families who have a child with a developmental disability.
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5. Ni HC, Lin HY, Tseng WI, Chiu YN, Wu YY, Tsai WC, Gau SS. {{Neural correlates of impaired self-regulation in male youths with autism spectrum disorder: A voxel-based morphometry study}}. {Prog Neuropsychopharmacol Biol Psychiatry}. 2017.
Although recent studies revealed impaired self-regulation (dysregulation) in autism spectrum disorder (ASD), neural correlates of dysregulation and its impacts on autistic neuroanatomy remain unclear. Voxel-based morphometry was applied on structural MRI images in 81 ASD and 61 typically developing (TD) boys aged 7-17years. Dysregulation was defined by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales in the Child Behavior Checklist>180. There were 53 and 28 boys in the ASD+Dysregulation and ASD-Dysregulation groups, respectively. First, we compared regional gray matter (GM) volume for ASD and TD. Second, we investigated regional GM volumetric differences among the ASD+Dysregulation, ASD-Dysregulation and TD groups. Lastly, shared and distinct neurostructural correlates of dysregulation were investigated in the ASD and TD groups. The ASD-TD difference on neuroanatomy no longer existed after controlling the dysregulation severity. ASD+Dysregulation had larger regional GM volumes in the right fusiform gyrus, and smaller GM volumes in the anterior prefrontal cortex than ASD-Dysregulation and TD, respectively. ASD+Dysregulation had smaller GM volumes in the left lateral occipital/superior parietal cortex than TD boys. No GM difference was identified between ASD-Dysregulation and TD. ASD and TD had a shared association between GM volumes in the orbitofrontal cortex and dysregulation levels. Our findings suggest that atypical neuroanatomy associated with ASD might partially reflect a disproportionate level of impaired self-regulation. Categorical and dimensional considerations of dysregulation should be implemented in future ASD studies.
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6. Russo FB, Freitas BC, Pignatari GC, Fernandes IR, Sebat J, Muotri AR, Beltrao-Braga PCB. {{Modeling the Interplay Between Neurons and Astrocytes in Autism Using Human Induced Pluripotent Stem Cells}}. {Biol Psychiatry}. 2017.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unclear etiology and imprecise genetic causes. The main goal of this work was to investigate neuronal connectivity and the interplay between neurons and astrocytes from individuals with nonsyndromic ASD using induced pluripotent stem cells. METHODS: Induced pluripotent stem cells were derived from a clinically well-characterized cohort of three individuals with nonsyndromic ASD sharing common behaviors and three control subjects, two clones each. We generated mixed neural cultures analyzing synaptogenesis and neuronal activity using a multielectrode array platform. Furthermore, using an enriched astrocyte population, we investigated their role in neuronal maintenance. RESULTS: ASD-derived neurons had a significant decrease in synaptic gene expression and protein levels, glutamate neurotransmitter release, and, consequently, reduced spontaneous firing rate. Based on co-culture experiments, we observed that ASD-derived astrocytes interfered with proper neuronal development. In contrast, control-derived astrocytes rescued the morphological neuronal phenotype and synaptogenesis defects from ASD neuronal co-cultures. Furthermore, after identifying interleukin-6 secretion from astrocytes in individuals with ASD as a possible culprit for neural defects, we were able to increase synaptogenesis by blocking interleukin-6 levels. CONCLUSIONS: Our findings reveal the contribution of astrocytes to neuronal phenotype and confirm previous studies linking interleukin-6 and autism, suggesting potential novel therapeutic pathways for a subtype of individuals with ASD. This is the first report demonstrating that glial dysfunctions could contribute to nonsyndromic autism pathophysiology using induced pluripotent stem cells modeling disease technology.
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7. Tu S, Akhtar MW, Escorihuela RM, Amador-Arjona A, Swarup V, Parker J, Zaremba JD, Holland T, Bansal N, Holohan DR, Lopez K, Ryan SD, Chan SF, Yan L, Zhang X, Huang X, Sultan A, McKercher SR, Ambasudhan R, Xu H, Wang Y, Geschwind DH, Roberts AJ, Terskikh AV, Rissman RA, Masliah E, Lipton SA, Nakanishi N. {{NitroSynapsin therapy for a mouse MEF2C haploinsufficiency model of human autism}}. {Nat Commun}. 2017; 8(1): 1488.
Transcription factor MEF2C regulates multiple genes linked to autism spectrum disorder (ASD), and human MEF2C haploinsufficiency results in ASD, intellectual disability, and epilepsy. However, molecular mechanisms underlying MEF2C haploinsufficiency syndrome remain poorly understood. Here we report that Mef2c (+/-)(Mef2c-het) mice exhibit behavioral deficits resembling those of human patients. Gene expression analyses on brains from these mice show changes in genes associated with neurogenesis, synapse formation, and neuronal cell death. Accordingly, Mef2c-het mice exhibit decreased neurogenesis, enhanced neuronal apoptosis, and an increased ratio of excitatory to inhibitory (E/I) neurotransmission. Importantly, neurobehavioral deficits, E/I imbalance, and histological damage are all ameliorated by treatment with NitroSynapsin, a new dual-action compound related to the FDA-approved drug memantine, representing an uncompetitive/fast off-rate antagonist of NMDA-type glutamate receptors. These results suggest that MEF2C haploinsufficiency leads to abnormal brain development, E/I imbalance, and neurobehavioral dysfunction, which may be mitigated by pharmacological intervention.
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8. Vogel Ciernia A, Careaga M, LaSalle JM, Ashwood P. {{Microglia from offspring of dams with allergic asthma exhibit epigenomic alterations in genes dysregulated in autism}}. {Glia}. 2017.
Dysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain’s resident immune cells. We therefore tested the hypothesis that epigenomic alterations to microglia may be involved in behavioral abnormalities observed in MAA offspring. We used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation and RNA sequencing to examine gene expression in microglia from juvenile MAA offspring. Differentially methylated regions were enriched for immune signaling pathways and important microglial developmental transcription factor binding motifs. Differential expression analysis identified genes involved in controlling microglial sensitivity to the environment and shaping neuronal connections in the developing brain. Differentially expressed genes significantly overlapped genes with altered expression in human ASD cortex, supporting a role for microglia in the pathogenesis of ASD.
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9. Wang W, Cox BM, Jia Y, Le AA, Cox CD, Jung KM, Hou B, Piomelli D, Gall CM, Lynch G. {{Treating a novel plasticity defect rescues episodic memory in Fragile X model mice}}. {Mol Psychiatry}. 2017.
Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and use of episodes, with semantic (cue identity) information relayed to the structure via the lateral perforant path (LPP). The unusual form of synaptic plasticity expressed by the LPP (lppLTP) was profoundly impaired in Fmr1-KOs relative to wild-type mice. Two factors contributed to this defect: (i) reduced GluN1 subunit levels in synaptic NMDA receptors and related currents, and (ii) impaired retrograde synaptic signaling by the endocannabinoid 2-arachidonoylglycerol (2-AG). Studies using a novel serial cue paradigm showed that episodic encoding is dependent on both the LPP and the endocannabinoid receptor CB1, and is strikingly impaired in Fmr1-KOs. Enhancing 2-AG signaling rescued both lppLTP and learning in the mutants. Thus, two consequences of the Fragile-X mutation converge on plasticity at one site in hippocampus to prevent encoding of a basic element of cognitive memory. Collectively, the results suggest a clinically plausible approach to treatment.Molecular Psychiatry advance online publication, 14 November 2017; doi:10.1038/mp.2017.221.
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10. Wong MK, So WC. {{Absence of delay in spontaneous use of gestures in spoken narratives among children with Autism Spectrum Disorders}}. {Res Dev Disabil}. 2017; 72: 128-39.
BACKGROUND: Gestures are spontaneous hand movements produced when speaking. Despite gestures being of communicative significance, little is known about the gestural production in spoken narratives in six- to 12-year-old children with Autism Spectrum Disorders (ASD). AIMS: The present study examined whether six- to 12-year-old children with ASD have a delay in gestural production in a spoken narrative task, in comparison to their typically-developing (TD) peers. METHODS AND PROCEDURES: Six- to-12-year-old children with ASD (N=14) and their age- and IQ-matched TD peers (N=12) narrated a story, which could elicit spontaneous speech and gestures. Their speech and gestures were then transcribed and coded. OUTCOMES AND RESULTS: Both groups of children had comparable expressive language skills. Children with ASD produced a similar number of pointing and marker gestures to TD children and significantly more iconic gestures in their spoken narratives. While children with ASD produced more reinforcing gestures than their TD counterparts, both groups of children produced comparable numbers of disambiguating and supplementary gestures. CONCLUSIONS: Our findings indicate that children with ASD may be as capable as TD children in gestural production when they engage in spoken narratives, which gives them spontaneity in producing gestures.
