Gut Microbial Profile Is Associated With the Severity of Social Impairment and IQ Performance in Children With Autism Spectrum Disorder

Background and Objective: Autism spectrum disorder (ASD) refers to a heterogeneous set of neurodevelopmental disorders with diverse symptom severity and comorbidities. Although alterations in gut microbiota have been reported in individuals with ASD, it remains unclear whether certain microbial pattern is linked to specific symptom or comorbidity in ASD. We aimed to investigate the associations between gut microbiota and the severity of social impairment and cognitive functioning in children with ASD.Methods: A total of 261 age-matched children, including 138 children diagnosed with ASD, 63 with developmental delay or intellectual disability (DD/ID), and 60 typically developing (TD) children, were enrolled from the Shanghai Xinhua Registry. The children with ASD were further classified into two subgroups: 76 children diagnosed with ASD and developmental disorder (ASD+DD) and 62 with ASD only (ASD-only). The gut microbiome of all children was profiled and evaluated by 16S ribosomal RNA sequencing.Results: The gut microbial analyses demonstrated an altered microbial community structure in children with ASD. The alpha diversity indices of the ASD+DD and ASD-only subgroups were significantly lower than the DD/ID or TD groups. At the genus level, we observed a decrease in the relative abundance of Prevotella. Simultaneously, Bacteroides and Faecalibacterium were significantly increased in ASD compared with DD/ID and TD participants. There was a clear correlation between alpha diversity and the Childhood Autism Rating Scale (CARS) total score for all participants, and this correlation was independent of IQ performance. Similar correlations with the CARS total score were observed for genera Bacteroides, Faecalibacterium, and Oscillospira. However, there was no single genus significantly associated with IQ in all participants.Conclusions: Specific alterations in bacterial taxonomic composition and associations with the severity of social impairment and IQ performance were observed in children with ASD or ASD subgroups, when compared with DD/ID or TD groups. These results illustrate that gut microbiota may serve as a promising biomarker for ASD symptoms. Nevertheless, further investigations are warranted.

Mindfulness predicts less depression, anxiety, and social impairment in emergency care personnel: A longitudinal study

Medical personnel working in emergency rooms (ER) are at increased risk of mental health problems and suicidality. There is increasing evidence that mindfulness-based interventions can improve burnout and other mental health outcomes in health care providers. In contrast, few longitudinal prospective studies have examined protective functions of dispositional mindfulness in this population. The objective of this study was to examine whether mindfulness prospectively predicts anxiety, depression, and social impairment in a sample of emergency care professionals. The authors administered online surveys to ER personnel prior to work in ER, and at 3 and 6 months follow up. Participants were 190 ER personnel (73% residents, 16% medical students, 11% nurses). Linear mixed effects regression was used to model longitudinal 3-month and 6-month follow up of depression, anxiety, and social impairment. Predictors included time-varying contemporaneous work stressors, perceived social support at work and life events, and baseline dispositional mindfulness, demographics, and workplace characteristics. Mindfulness indexed when starting ER work predicted less depression, anxiety, and social impairment 6 months later. Mindfulness remained a strong predictor of mental health outcomes after controlling for time-varying stressful events in emergency care, negative life events, and social support at work. Mindfulness moderated the adverse impact of poor social support at work on depression. To our knowledge, this is the first longitudinal study to show that mindfulness prospectively and robustly predicts anxiety, depression, and social impairment. Results support the role of mindfulness as a potential resilience factor in at-risk health care providers.

Atypical Resting State Functional Neural Network in Children With Autism Spectrum Disorder: Graph Theory Approach

Measuring whole brain networks is a promising approach to extract features of autism spectrum disorder (ASD), a brain disorder of widespread regions. Objectives of this study were to evaluate properties of resting-state functional brain networks in children with and without ASD and to evaluate their relation with social impairment severity. Magnetoencephalographic (MEG) data were recorded for 21 children with ASD (7 girls, 60–89 months old) and for 25 typically developing (TD) control children (10 girls, 60–91 months old) in a resting state while gazing at a fixation cross. After signal sources were localized onto the Desikan–Killiany brain atlas, statistical relations between localized activities were found and evaluated in terms of the phase lag index. After brain networks were constructed and after matching with intelligence using a coarsened exact matching algorithm, ASD and TD graph theoretical measures were compared. We measured autism symptoms severity using the Social Responsiveness Scale and investigated its relation with altered small-worldness using linear regression models. Children with ASD were found to have significantly lower small-worldness in the beta band (p = 0.007) than TD children had. Lower small-worldness in the beta band of children with ASD was associated with higher Social Responsiveness Scale total t-scores (p = 0.047). Significant relations were also inferred for the Social Awareness (p = 0.008) and Social Cognition (p = 0.015) sub-scales. Results obtained using graph theory demonstrate a difference between children with and without ASD in MEG-derived resting-state functional brain networks, and the relation of that difference with social impairment. Combining graph theory and MEG might be a promising approach to establish a biological marker for ASD.

Early Life Stress Alters Gene Expression and Cytoarchitecture in the Prefrontal Cortex Leading to Social Impairment and Increased Anxiety

Early life stress (ELS), such as abuse, neglect, and maltreatment, exhibits a strong impact on the brain and mental development of children. However, it is not fully understood how ELS affects social behaviors and social-associated behaviors as well as developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice until adolescence and investigated these behaviors and PFC characteristics in adolescent mice. We found the ELS induced social impairments in social novelty, social interaction, and social preference in adolescent mice. We also observed increases of anxiety-like behaviors in ELS mice. In histological analysis, we found a reduced number of neurons and an increased number of microglia in the PFC of ELS mice. To identify the gene associated with behavioral and histological features, we analyzed transcriptome in the PFC of ELS mice and identified 15 differentially expressed genes involved in transcriptional regulation, stress, and synaptic signaling. Our study demonstrates that ELS influences social behaviors, anxiety-like behaviors through cytoarchitectural and transcriptomic alterations in the PFC of adolescent mice.

Shielding Effect of Ryanodine Receptor Modulator in Rat Model of Autism

Introduction: A neurodevelopmental disorder, autism typically identified with three primary behavioral consequences, such as social impairment, communication problems and limited or stereotypical behavior. Because of its co-morbidity and lack of therapeutic options, autism is a global economic burden. A short chain of fatty acid, propionic acid formed biologically by gut microbiome. Propionic acid levels that are too high can cause leaky intestines, which can lead to autism-like symptoms. Methods: To induce autism, male Albino Wistar rats were given propionic acid (250 mg/kg / po on the 21st, 22nd, and 23rd postnatal days). Rats were also received a ryanodine receptor antagonist (Ruthenium red: 3 mg/kg/po; postnatal 21st to 50th day) to see what influence it had on the propionic acid-induced autism. Anxiety, social behavior, and repeated behaviors were all assessed, as well as oxidative stress, inflammatory indicators, neuro signaling proteins, and blood brain barrier permeability. Results: Ruthenium red was found to counter the propionic acid induced increases in anxiety, repetitive behavior prefrontal cortex levels of IL-6, TNF-α, TBARS, Evans blue leakage and water content along with decreases in social behavior, IL-10, and GSH followed by hippocampus CREB and BDNF levels. Conclusion: Ryanodine receptor antagonist presented neuroprotective effect in propionic acid induced conditions like autism by modulatory effects on social and repetitive behavior, oxidative stress, neuroinflammation, and neuroprotein changes. Ryanodine receptors can be further explored in depth to manage autism as a condition.

Avoidance Behavior in Adults with Developmental Coordination Disorder is Related to Quality of Life

Although it is now widely accepted that developmental co-ordination disorder (DCD) persists into adolescence and adulthood, few studies have assessed the concept of Quality of Life (QOL) within the adult DCD population. This is despite a growing recognition that children and adolescents with DCD experience poorer QOL than their typically developed peers. The small body of literature which has examined QOL in adults with DCD has reported that they also report lower levels of QOL as a result of motor coordination deficits. Little research has investigated the factors that result in adults with DCD reporting lower QOL than their typically developed counterparts. The current study explored the relationships between QOL and motor coordination, and QOL and three individual subtypes of avoidance within an adult DCD sample. Eighty-five adults (27 males; 58 females) who reported a diagnosis of, or believe that they have DCD, completed an online questionnaire that consisted of three already established questionnaires in order to measure the concepts of QOL, motor coordination and avoidance, respectively. A hierarchal multiple regression revealed that all three types of avoidance behaviors were significant predictors of QOL scores, while levels of motor coordination did not significantly predict scores of QOL. These results highlight the need for clinicians to develop interventions to help reduce avoidance behavior and social impairment, in order to improve QOL within the DCD adult population.

A pilot study of dialectical behaviour therapy skills training for autistic adults

Background: Autism spectrum disorder (ASD) is a common and lifelong neurodevelopmental disorder with the hallmark features of social impairment and restricted and repetitive patterns of behaviour. Individuals with ASD often experience co-occurring mental health difficulties, some of which may obfuscate the ASD features themselves. Although there is a high need for mental health services for autistic adults, there are surprisingly few evidence-based treatments (EBTs) available; moreover, many mental health practitioners who are well-trained in EBTs shy away from treating autistic individuals due to lack of training in ASD. Aims: The aim of the current study was to evaluate the feasibility and acceptability of dialectical behaviour therapy skills training (DBT-ST) in a sample of autistic adults without intellectual disability. Method: Sixteen adults with ASD were recruited from a treatment waiting list to enrol in this study, which included 24 weeks of DBT-ST delivered in a group setting. Feasibility and acceptability were assessed using retention and attendance data and a participant satisfaction questionnaire. Results: Retention (81.3%) and attendance data (mean 87.5%) provided support for the feasibility of this intervention. Overall satisfaction ratings were high (mean 4.5 out of 5), and participants reported that they felt that DBT-ST would probably be helpful for others with ASD (mean 4.5 out of 5). Conclusions: The study findings provide preliminary evidence of (1) the feasibility of providing DBT-ST for autistic adults in community-based clinics, and (2) the perceived benefit of DBT-ST for this under-served population. Recommended modifications to the standard DBT-ST materials are discussed.

Thriving in adversity: Do life skills programs work for developing world children? A pragmatic randomized controlled trial

The severe adversity experienced by millions of children in the developing world leads to failure to thrive associated with cognitive deficits, emotional management problems, and social impairment. In this pragmatic randomized controlled trial, 909 children (aged 8–15 years) in India with disadvantaged backgrounds took part in a semistructured program involving sports or creative arts activities. The Life Skills Assessment Scale was used to assess the children's life skills before and after taking part in the program. Children who took part in the program showed significant increases in life skills following participation, compared to a control group. This study demonstrates the impact of simple, low-budget programs on cognitive, emotional, and social life skills that are typically delayed by severe adversity. The findings have clear implications for children in other adverse environments, such as conflict zones and settlements for displaced children resulting from war, natural disasters, and emergency events.

Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism

Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut–brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.