Pubmed du 21/02/21
1. Maigoro AY, Lee S. Gut Microbiome-Based Analysis of Lipid A Biosynthesis in Individuals with Autism Spectrum Disorder : An In Silico Evaluation. Nutrients. 2021 ; 13(2).
The link between autism spectrum disorder (ASD) and the gut microbiome has received much attention, with special focus on gut-brain-axis immunological imbalances. Gastrointestinal problems are one of the major symptoms of ASD and are thought to be related to immune dysregulation. Therefore, in silico analysis was performed on mined data from 36 individuals with ASD and 21 control subjects, with an emphasis on lipid A endotoxin-producing bacteria and their lipopolysaccharide (LPS) metabolic pathways. Analysis of enzyme distribution among the 15 most abundant genera in both groups revealed that almost all these genera utilized five early-stage enzymes responsible for catalyzing the nine conserved lipid A synthesis steps. However, Haemophilus and Escherichia, which were significantly more abundant in individuals with ASD than in the control subjects, possess a complete set of essential lipid A synthesis enzymes. Furthermore, the 10 genera with the greatest increase in individuals with ASD showed high potential for producing late-stage lipid A products. Collectively, these results suggested that the synthesis rate of immunogenic LPS end products is likely to increase in individuals with ASD, which may be related to their gastrointestinal symptoms and elevated inflammatory conditions.
Lien vers le texte intégral (Open Access ou abonnement)
2. Pettit E. Transition to adulthood for individuals with autism : addressing the knowledge gap. Dev Med Child Neurol. 2021.
Lien vers le texte intégral (Open Access ou abonnement)
3. Richter JD, Zhao X. The molecular biology of FMRP : new insights into fragile X syndrome. Nat Rev Neurosci. 2021.
Fragile X mental retardation protein (FMRP) is the product of the fragile X mental retardation 1 gene (FMR1), a gene that – when epigenetically inactivated by a triplet nucleotide repeat expansion – causes the neurodevelopmental disorder fragile X syndrome (FXS). FMRP is a widely expressed RNA-binding protein with activity that is essential for proper synaptic plasticity and architecture, aspects of neural function that are known to go awry in FXS. Although the neurophysiology of FXS has been described in remarkable detail, research focusing on the molecular biology of FMRP has only scratched the surface. For more than two decades, FMRP has been well established as a translational repressor ; however, recent whole transcriptome and translatome analyses in mouse and human models of FXS have shown that FMRP is involved in the regulation of nearly all aspects of gene expression. The emerging mechanistic details of the mechanisms by which FMRP regulates gene expression may offer ways to design new therapies for FXS.
Lien vers le texte intégral (Open Access ou abonnement)
4. Simpraga S, Weiland RF, Mansvelder HD, Polderman TJ, Begeer S, Smit DJ, Linkenkaer-Hansen K. Adults with autism spectrum disorder show atypical patterns of thoughts and feelings during rest. Autism. 2021 : 1362361321990928.
Everyone knows the feeling of letting one’s mind wander freely in a quiet moment. The thoughts and feelings experienced in those moments have been shown to influence our well-being-and vice versa. In this study, we looked at which thoughts and feelings are being experienced by adults with autism spectrum disorder and compared them to adults without autism spectrum disorder. In total, 88 adults with autism spectrum disorder and 90 adults without autism spectrum disorder were asked to rest for 5 min with their eyes closed and let their mind wander. Directly after, they filled in the Amsterdam Resting-State Questionnaire, which probes what participants were feeling and thinking during the period of rest. We found that adults with autism spectrum disorder tend to think less about others, felt less comfortable, and had more disrupted thoughts during the rest compared to adults without autism spectrum disorder. Interestingly, autism spectrum disorder participants reporting lower levels of comfort during the rest also reported more autism spectrum disorder symptoms, specifically in social behaviors and skills, attention switching, and imagination. We propose to use the eyes-closed rest condition in combination with the Amsterdam Resting-State Questionnaire more widely to shed light on aberrant thoughts and feelings in brain disorders and to study the effect of therapeutic interventions.
Lien vers le texte intégral (Open Access ou abonnement)
5. Soda T, Pereira S, Small BJ, Torgerson LN, Muñoz KA, Austin J, Storch EA, Lázaro-Muñoz G. Child and Adolescent Psychiatrists’ Perceptions of Utility and Self-rated Knowledge of Genetic Testing Predict Usage for Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry. 2021.
Lien vers le texte intégral (Open Access ou abonnement)
6. Vita DJ, Meier CJ, Broadie K. Neuronal fragile X mental retardation protein activates glial insulin receptor mediated PDF-Tri neuron developmental clearance. Nat Commun. 2021 ; 12(1) : 1160.
Glia engulf and phagocytose neurons during neural circuit developmental remodeling. Disrupting this pruning process contributes to Fragile X syndrome (FXS), a leading cause of intellectual disability and autism spectrum disorder in mammals. Utilizing a Drosophila FXS model central brain circuit, we identify two glial classes responsible for Draper-dependent elimination of developmentally transient PDF-Tri neurons. We find that neuronal Fragile X Mental Retardation Protein (FMRP) drives insulin receptor activation in glia, promotes glial Draper engulfment receptor expression, and negatively regulates membrane-molding ESCRT-III Shrub function during PDF-Tri neuron clearance during neurodevelopment in Drosophila. In this context, we demonstrate genetic interactions between FMRP and insulin receptor signaling, FMRP and Draper, and FMRP and Shrub in PDF-Tri neuron elimination. We show that FMRP is required within neurons, not glia, for glial engulfment, indicating FMRP-dependent neuron-to-glia signaling mediates neuronal clearance. We conclude neuronal FMRP drives glial insulin receptor activation to facilitate Draper- and Shrub-dependent neuronal clearance during neurodevelopment in Drosophila.
Lien vers le texte intégral (Open Access ou abonnement)
7. Wichers RH, Findon JL, Jelsma A, Giampietro V, Stoencheva V, Robertson DM, Murphy CM, Blainey S, McAlonan G, Ecker C, Rubia K, Murphy DGM, Daly EM. Modulation of atypical brain activation during executive functioning in autism : a pharmacological MRI study of tianeptine. Mol Autism. 2021 ; 12(1) : 14.
BACKGROUND : Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD : We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males : 19 with ASD and 19 matched controls. RESULTS : Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS : We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS : Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms.
Lien vers le texte intégral (Open Access ou abonnement)
8. Wiggins LD, Rubenstein E, Windham G, Barger B, Croen L, Dowling N, Giarelli E, Levy S, Moody E, Soke G, Fields V, Schieve L. Evaluation of sex differences in preschool children with and without autism spectrum disorder enrolled in the study to explore early development. Res Dev Disabil. 2021 ; 112 : 103897.
BACKGROUND AND AIMS : Research in school-aged children, adolescents, and adults with autism spectrum disorder (ASD) has found sex-based differences in behavioral, developmental, and diagnostic outcomes. These findings have not been consistently replicated in preschool-aged children. We examined sex-based differences in a large sample of 2-5-year-old children with ASD symptoms in a multi-site community-based study. METHODS AND PROCEDURES : Based on a comprehensive evaluation, children were classified as having ASD (n = 1480, 81.55 % male) or subthreshold ASD characteristics (n = 593, 70.15 % male). Outcomes were behavior problems, developmental abilities, performance on ASD screening and diagnostic tests, and parent-reported developmental conditions diagnosed before study enrollment. OUTCOMES AND RESULTS : We found no statistically significant sex differences in behavioral functioning, developmental functioning, performance on an ASD screening test, and developmental conditions diagnosed before study enrollment among children with ASD or subthreshold ASD characteristics. Males in both study groups had more parent reported restricted interests and repetitive behaviors than females, but these differences were small in magnitude and not clinically meaningful. CONCLUSIONS AND IMPLICATIONS : Preschool males and females who showed risk for ASD were more similar than different in the outcomes assessed in our study. Future research could examine sex-based differences in ASD phenotypes as children age.
