1. Amal H, Barak B, Bhat V, Gong G, Joughin BA, Wishnok JS, Feng G, Tannenbaum SR. {{Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function}}. {Mol Psychiatry}. 2018.
Mutation in the SHANK3 human gene leads to different neuropsychiatric diseases including Autism Spectrum Disorder (ASD), intellectual disabilities and Phelan-McDermid syndrome. Shank3 disruption in mice leads to dysfunction of synaptic transmission, behavior, and development. Protein S-nitrosylation, the nitric oxide (NO(*))-mediated posttranslational modification (PTM) of cysteine thiols (SNO), modulates the activity of proteins that regulate key signaling pathways. We tested the hypothesis that Shank3 mutation would generate downstream effects on PTM of critical proteins that lead to modification of synaptic functions. SNO-proteins in two ASD-related brain regions, cortex and striatum of young and adult InsG3680(+/+) mice (a human mutation-based Shank3 mouse model), were identified by an innovative mass spectrometric method, SNOTRAP. We found changes of the SNO-proteome in the mutant compared to WT in both ages. Pathway analysis showed enrichment of processes affected in ASD. SNO-Calcineurin in mutant led to a significant increase of phosphorylated Synapsin1 and CREB, which affect synaptic vesicle mobilization and gene transcription, respectively. A significant increase of 3-nitrotyrosine was found in the cortical regions of the adult mutant, signaling both oxidative and nitrosative stress. Neuronal NO(*) Synthase (nNOS) was examined for levels and localization in neurons and no significant difference was found in WT vs. mutant. S-nitrosoglutathione concentrations were higher in mutant mice compared to WT. This is the first study on NO(*)-related molecular changes and SNO-signaling in the brain of an ASD mouse model that allows the characterization and identification of key proteins, cellular pathways, and neurobiological mechanisms that might be affected in ASD.
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2. Barahona-Correa JB, Velosa A, Chainho A, Lopes R, Oliveira-Maia AJ. {{Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis}}. {Frontiers in integrative neuroscience}. 2018; 12: 27.
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder manifesting as lifelong deficits in social communication and interaction, as well as restricted repetitive behaviors, interests and activities. While there are no specific pharmacological or other physical treatments for autism, in recent years repetitive Transcranial Magnetic Stimulation (rTMS), a technique for non-invasive neuromodulation, has attracted interest due to potential therapeutic value. Here we report the results of a systematic literature review and meta-analysis on the use of rTMS to treat ASD. Methods: We performed a systematic literature search on PubMed, Web of Science, Science Direct, Bielefeld Academic Search, and Educational Resources Information Clearinghouse. Search terms reflected diagnoses and treatment modalities of interest. Studies reporting use of rTMS to treat core ASD or cognitive symptoms in ASD were eligible. Two researchers performed article selection and data extraction independently, according to PRISMA guidelines. Changes in ASD clinical scores or in cognitive performance were the main outcomes. Random effects meta-analysis models were performed. Results: We found 23 eligible reports, comprising 4 case-reports, 7 non-controlled clinical trials, and 12 controlled clinical trials, comparing the effects of real TMS with waiting-list controls (n = 6) or sham-treatment (n = 6). Meta-analyses showed a significant, but moderate, effect on repetitive and stereotyped behaviors, social behavior, and number of errors in executive function tasks, but not other outcomes. Most studies had a moderate to high risk of bias, mostly due to lack of subject- and evaluator-blinding to treatment allocation. Only 5 studies reported stability of these gains for periods of up 6 months, with descriptions that improvements were sustained over time. Conclusions: Existing evidence supports that TMS could be useful to treat some dimensions of ASD. However, such evidence must be regarded with care, as most studies did not adequately control for placebo effects. Moreover, little is known regarding the most effective stimulation parameters, targets, and schedules. There is an urgent need for further randomized, double-blind, sham-controlled trials, with adequate follow-up periods, to test the efficacy of transcranial magnetic stimulation to treat these disorders. Available evidence must be regarded as preliminary and insufficient, at present, to support offering TMS to treat ASD.
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3. Cooper RA, Simons JS. {{Exploring the neurocognitive basis of episodic recollection in autism}}. {Psychonomic bulletin & review}. 2018.
Increasing evidence indicates that the subjective experience of recollection is diminished in autism spectrum disorder (ASD) compared to neurotypical individuals. The neurocognitive basis of this difference in how past events are re-experienced has been debated and various theoretical accounts have been proposed to date. Although each existing theory may capture particular features of memory in ASD, recent research questions whether any of these explanations are alone sufficient or indeed fully supported. This review first briefly considers the cognitive neuroscience of how episodic recollection operates in the neurotypical population, informing predictions about the encoding and retrieval mechanisms that might function atypically in ASD. We then review existing research on recollection in ASD, which has often not distinguished between different theoretical explanations. Recent evidence suggests a distinct difficulty engaging recollective retrieval processes, specifically the ability to consciously reconstruct and monitor a past experience, which is likely underpinned by altered functional interactions between neurocognitive systems rather than brain region-specific or process-specific dysfunction. This integrative approach serves to highlight how memory research in ASD may enhance our understanding of memory processes and networks in the typical brain. We make suggestions for future research that are important for further specifying the neurocognitive basis of episodic recollection in ASD and linking such difficulties to social developmental and educational outcomes.
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4. Dieleman LM, Moyson T, De Pauw SSW, Prinzie P, Soenens B. {{Parents’ Need-related Experiences and Behaviors When Raising a Child With Autism Spectrum Disorder}}. {Journal of pediatric nursing}. 2018.
PURPOSE: Research suggests that parenting a child with autism spectrum disorder (ASD) brings about major challenges to parents’ own psychological resources. Considered through the lens of Self-Determination Theory (Ryan & Deci, 2017), parents rearing a child with ASD particularly face challenges to their psychological needs for autonomy, competence, and relatedness. In turn, these challenges potentially jeopardize parents’ capacity to attune to their child. This qualitative study aims to advance insight into (the interplay between) parents’ experiences and parenting behaviors when raising a child with ASD, thereby using SDT as a framework to understand how these experiences and behaviors relate to the psychological needs for autonomy, relatedness and competence. DESIGN AND METHODS: Fifteen parents of children with ASD, aged 6 to 17, participated in an interview concerning their behaviors and experiences in raisin their child with ASD. RESULTS: Four sets of parental behaviors and five sets of parental experiences were identified, with the majority being relevant to the psychological needs postulated by SDT. CONCLUSIONS: The findings of this study provide (1) a deeper understanding of the threats and opportunities for the well-being of parents of children with ASD, (2) an in-depth insight into how these parents adjust their parenting behaviors to their child, and (3) an understanding of how parents’ need-related experiences and parenting behaviors are dynamically intertwined. PRACTICAL IMPLICATIONS: By structuring how parents perceive threats and opportunities when raising a child with ASD within the SDT-framework, important targets for parent-support are identified.
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5. Lu ZA, Mu W, Osborne LM, Cordner ZA. {{Eighteen-year-old man with autism, obsessive compulsive disorder and a SHANK2 variant presents with severe anorexia that responds to high-dose fluoxetine}}. {BMJ case reports}. 2018; 2018.
The SHANK2 gene codes for a protein involved in organising the postsynaptic density and disruptions have been associated with autism spectrum disorders (ASDs). ASDs are frequently comorbid with intellectual disability and anxiety disorders and emerging evidence suggests potentially common aetiologies. Here, we report the case of an 18-year-old man with ASD who presented with severe anorexia due to fear of food contamination, food avoidance and stereotypies attributable to underlying obsessive compulsive disorder (OCD). The patient was found to be heterozygous for c.2518C>T (p.Pro840Ser), a likely damaging coding variant in the proline rich region of SHANK2 Interestingly, the patient’s disordered eating behaviour began to improve only after high-dose fluoxetine was initiated to target OCD symptoms. Overall, this case highlights the utility of molecular genetic testing in clinical psychiatry and provides an example of how genetic information can inform clinicians in the treatment of complex neuropsychiatric syndromes.
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6. Maier S, Tebartz van Elst L, Perlov E, Duppers AL, Nickel K, Fangmeier T, Endres D, Riedel A. {{Cortical properties of adults with autism spectrum disorder and an IQ>100}}. {Psychiatry research Neuroimaging}. 2018; 279: 8-13.
Previous studies on cortical volume and thickness measures in autism spectrum disorders (ASD) show inconsistent results. We acquired structural magnetic resonance images of 30 individuals with ASD and individually matched controls and extracted surface-based and deformation-based morphometry measures. All participants had an IQ>100. Neither surface-based cortical thickness nor deformation based gyrification measures differed significantly across groups. Significant decreases but no increases of the gyrification index and sulcus depth could only be observed in the ASD group before correcting for multiple comparisons. This finding suggests that possible cortical anomalies in ASD are either weak or, given the heterogeneity of findings in earlier studies, might only apply to small ASD-subgroups.
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7. Tipton-Fisler LA, Rodriguez G, Zeedyk SM, Blacher J. {{Stability of bullying and internalizing problems among adolescents with ASD, ID, or typical development}}. {Res Dev Disabil}. 2018; 80: 131-41.
BACKGROUND: It is known that children with disabilities, especially adolescents with autism spectrum disorder (ASD), are at increased risk for victimization. However, little is known about the impact of victimization over time. AIMS: Primary aims included identifying to what extent risk factors (i.e., internalizing behavior problems and conflict in friendship) related to bullying victimization over time. METHODS AND PROCEDURES: In-depth interviews conducted separately with 15-year-olds with autism spectrum disorder (ASD), intellectual disability (ID), or typical development (TD) and their mothers investigated the experiences of victimization in a two-year follow up to an earlier study at adolescent age 13. OUTCOMES AND RESULTS: Findings at age 15 demonstrated that the highest rates of bullying continued to be endorsed by youth with ASD. However, youth with ID were found to experience and report the most severe bullying. Longitudinal examination revealed that internalizing behaviors at age 13 predicted victimization experiences at age 15. CONCLUSIONS AND IMPLICATIONS: During middle adolescence, youth with ASD continue to experience more frequent victimization. Thus, shifting the focus of interventions that not only target the salient social deficits of ASD, but also address comorbid conditions such as internalizing symptoms, may further contribute to reduction of social isolation and peer difficulties.
