Altered function or presence of inhibitory neurons is documented in autism spectrum disorders (ASD), but the mechanism underlying this alternation is poorly understood. One major subtype of inhibitory neurons altered is the parvalbumin (PV)-containing neurons with reduced density and intensity in ASD patients and model mice. A subpopulation of PV+ neurons expresses perineuronal nets (PNN). To better understand whether the relationship between PV and PNN is altered in ASD, we measured quantitatively the intensities of PV and PNN in single PV+ neurons in the prelimbic prefrontal cortex (PrL-PFC) of a valproic acid (VPA) model of ASD at different ages. We found a decreased PV intensity but increased PNN intensity in VPA mice. The relationship between PV and PNN intensities is altered in VPA mice, likely due to an “abnormal” subpopulation of neurons with an altered PV-PNN relationship. Furthermore, reducing PNN level using in vivo injection of chondroitinase ABC corrects the PV expression in adult VPA mice. We suggest that the interaction between PV and PNN is disrupted in PV+ neurons in VPA mice which may contribute to the pathology in ASD.
Introduction Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy. Methods In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3–6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics. Ethics and dissemination Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy. Trial registration number ChiCTR2100043906; Pre-results.
Objective: This study investigates whether the dynamic functional connectivity (dFC) of the amygdala subregions is altered in children with attention-deficit/hyperactivity disorder (ADHD).Methods: The dFC of the amygdala subregions was systematically calculated using a sliding time window method, for 75 children with ADHD and 20 healthy control (HC) children.Results: Compared with the HC group, the right superficial amygdala exhibited significantly higher dFC with the right prefrontal cortex, the left precuneus, and the left post-central gyrus for children in the ADHD group. The dFC of the amygdala subregions showed a negative association with the cognitive functions of children in the ADHD group.Conclusion: Functional connectivity of the amygdala subregions is more unstable among children with ADHD. In demonstrating an association between the stability of functional connectivity of the amygdala and cognitive functions, this study may contribute by providing a new direction for investigating the internal mechanism of ADHD.
This study examined the mediating role of motor competence in the association between physical activity (PA) and quality of life (QoL) and the moderating role of age in the indirect relationship between PA and QoL in children with ADHD. Eighty‐six children aged 6‐12 years old (M age = 8.45, SD = 1.40, 17.4% girls) with the diagnosis of ADHD were recruited in this study. Participants wore a wGT3X‐BT accelerometer on their wrist for seven consecutive days to measure PA. Motor competence was measured by the Test of Gross Motor Development‐Third Edition (TGMD‐3). Quality of life (QoL) was assessed by the parent‐reported Chinese version of the Pediatric Quality of Life Inventory. MVPA was positively associated with object control skills but was not directly related to QoL. Using the bootstrapping method, the indirect effect of object control was found between MVPA and social functioning (0.10, 95%CI = [0.01, 0.21]), school functioning (0.09, 95%CI = [0.01, 0.18]), and overall QoL (0.07, 95%CI = [0.01, 0.16]), supporting the full mediation effect. Moderated mediation analysis further revealed that age strengthened the indirect effect from MVPA to social and school functioning via object control. Findings of this study indicated that MVPA is positively associated with object control skills, which in turn, is related to psychological aspects of QoL in children with ADHD. Age was found to moderate the indirect mediation paths. The findings may inform future expeditions on designing an effective intervention that helps to improve MC and QoL in children with ADHD.