Gut microbiota profiles of autism spectrum disorder and attention deficit/hyperactivity disorder:A systematic literature review

Accumulating evidence has implicated an involvement of the gut-brain axis in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), however with highly diverse results. This systematic review aims to describe and evaluate studies investigating the gut microbiota composition in individuals with ASD or ADHD and to evaluate if variations in gut microbiota are associated with these disorders. Twenty-four articles were identified in a systematic literature search of PubMed and Embase up to July 22, 2019. They consisted of 20 studies investigating ASD and four studies investigating ADHD. For ASD, several studies agreed on an overall difference in β-diversity, although no consistent bacterial variation between all studies was reported. For ADHD, the results were more diverse, with no clear differences observed. Several common characteristics in gut microbiota function were identified for ASD compared to controls. In contrast, highly heterogeneous results were reported for ADHD, and thus the association between gut microbiota composition and ADHD remains unclear. For both disorders, methodological differences hampered the comparison of studies

Urbanicity and Autism Spectrum Disorders

The etiology of autism spectrum disorders (ASD) is for the majority of cases unknown and more studies of risk factors are needed. Geographic variation in ASD occurrence has been observed, and urban residence has been suggested to serve as a proxy for etiologic and identification factors in ASD. We examined the association between urbanicity level and ASD at birth and during childhood. The study used a Danish register-based cohort of more than 800,000 children of which nearly 4,000 children were diagnosed with ASD. We found a dose–response association with greater level of urbanicity and risk of ASD. This association was found for residence at birth as well as residence during childhood. Further, we found an increased risk of ASD in children who moved to a higher level of urbanicity after birth. Also, earlier age of ASD diagnosis in urban areas was observed. While we could not directly examine the specific reasons behind these associations, our results demonstrating particularly strong associations between ASD diagnosis and post-birth migration suggest the influence of identification-related factors such as access to services might have a substantive role on the ASD differentials we observed

Early development in Rett syndrome – the benefits and difficulties of a birth cohort approach

© 2017 Taylor & Francis Purposes: Typically, early (pre-diagnostic) development in individuals later diagnosed with Rett syndrome (RTT) has been investigated retrospectively using parent reports, medical records and analysis of home videos. In recent years, prospective research designs have been increasingly applied to the investigation of early development in individuals with late phenotypical onset disorders, for example, autism spectrum disorder. Methods: In this study, data collected by the Danish National Birth Cohort lent itself to prospective exploration of the early development of RTT, in particular early motor-, speech-language, and socio-communicative behaviors, mood, and sleep. Results and Conclusions: Despite limitations, this quasi prospective methodology proved promising. In order to add substantially to the body of knowledge, however, specific questions relating to peculiarites in early development could usefully be added to future cohort studies. As this involves considerable work, it may be more realistic to consider a set of indicators which point to a number of developmental disorders rather than to one

The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria

Classic drug development strategies have failed to meet the urgent clinical needs in treating infections with Gram-negative bacteria. Repurposing drugs can lead to timely availability of new antibiotics, accelerated by existing safety profiles. Glatiramer acetate (GA) is a widely used and safe formulation for treatment of multiple sclerosis. It contains a large diversity of essentially isomeric polypeptides with the cationic and amphiphilic character of many antimicrobial peptides (AMP). Here, we report that GA is antibacterial, targeting Gram-negative organisms with higher activity towards Pseudomonas aeruginosa than the naturally-occurring AMP LL-37 in human plasma. As judged from flow cytometric assays, bacterial killing by GA occurred within minutes. Laboratory strains of Escherichia coli and P. aeruginosa were killed by a process of condensing intracellular contents. Efficient killing by GA was also demonstrated in Acinetobacter baumannii clinical isolates and approximately 50% of clinical isolates of P. aeruginosa from chronic airway infection in CF patients. By contrast, the Gram-positive Staphylococcus aureus cells appeared to be protected from GA by an increased formation of nm-scale particulates. Our data identify GA as an attractive drug repurposing candidate to treat infections with Gram-negative bacteria

Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

BACKGROUND: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. METHODS/DESIGN: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12 weeks after randomisation. The primary outcome is change in the positive symptom score of the Positive and Negative Syndrome Scale. The recruitment period is 2010-2014. DISCUSSION: Antipsychotics are currently the only available pharmacologic treatments for psychotic disorders. However, information about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable population. Here, we account for the trial design, address methodological challenges, and discuss the estimation of sample size. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0111901