Associations between psychotropic drugs and rsEEG connectivity and network characteristics: a cross-sectional study in hospital-admitted psychiatric patients

INTRODUCTION: Resting-state EEG (rsEEG) characteristics, such as functional connectivity and network topology, are studied as potential biomarkers in psychiatric research. However, the presence of psychopharmacological treatment in study participants poses a potential confounding factor in biomarker research. To address this concern, our study aims to explore the impact of both single and multi-class psychotropic treatments on aforementioned rsEEG characteristics in a psychiatric population. METHODS: RsEEG was analyzed in a real-world cross-sectional sample of 900 hospital-admitted psychiatric patients. Patients were clustered into eight psychopharmacological groups: unmedicated, single-class treatment with antipsychotics (AP), antidepressants (AD) or benzodiazepines (BDZ), and multi-class combinations of these treatments. To assess the associations between psychotropic treatments and the macroscale rsEEG characteristics mentioned above, we employed a general linear model with post-hoc tests. Additionally, Spearman's rank correlation analyses were performed to explore potential dosage effects. RESULTS: Compared to unmedicated patients, single-class use of AD was associated with lower functional connectivity in the delta band, while AP was associated with lower functional connectivity in both the delta and alpha bands. Single-class use of BDZ was associated with widespread rsEEG differences, including lower functional connectivity across frequency bands and a different network topology within the beta band relative to unmedicated patients. All of the multi-class groups showed associations with functional connectivity or topology measures, but effects were most pronounced for concomitant use of all three classes of psychotropics. Differences were not only observed in comparison with unmedicated patients, but were also evident in comparisons between single-class, multi-class, and single/multi-class groups. Importantly, multi-class associations with rsEEG characteristics were found even in the absence of single-class associations, suggesting potential cumulative or interaction effects of different classes of psychotropics. Dosage correlations were only found for antipsychotics. CONCLUSION: Our exploratory, cross-sectional study suggests small but significant associations between single and multi-class use of antidepressants, antipsychotics and benzodiazepines and macroscale rsEEG functional connectivity and network topology characteristics. These findings highlight the importance of considering the effects of specific psychotropics, as well as their interactions, when investigating rsEEG biomarkers in a medicated psychiatric population

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Associations between psychotropic drugs and rsEEG connectivity and network characteristics:a cross-sectional study in hospital-admitted psychiatric patients

Introduction: Resting-state EEG (rsEEG) characteristics, such as functional connectivity and network topology, are studied as potential biomarkers in psychiatric research. However, the presence of psychopharmacological treatment in study participants poses a potential confounding factor in biomarker research. To address this concern, our study aims to explore the impact of both single and multi-class psychotropic treatments on aforementioned rsEEG characteristics in a psychiatric population. Methods: RsEEG was analyzed in a real-world cross-sectional sample of 900 hospital-admitted psychiatric patients. Patients were clustered into eight psychopharmacological groups: unmedicated, single-class treatment with antipsychotics (AP), antidepressants (AD) or benzodiazepines (BDZ), and multi-class combinations of these treatments. To assess the associations between psychotropic treatments and the macroscale rsEEG characteristics mentioned above, we employed a general linear model with post-hoc tests. Additionally, Spearman's rank correlation analyses were performed to explore potential dosage effects. Results: Compared to unmedicated patients, single-class use of AD was associated with lower functional connectivity in the delta band, while AP was associated with lower functional connectivity in both the delta and alpha bands. Single-class use of BDZ was associated with widespread rsEEG differences, including lower functional connectivity across frequency bands and a different network topology within the beta band relative to unmedicated patients. All of the multi-class groups showed associations with functional connectivity or topology measures, but effects were most pronounced for concomitant use of all three classes of psychotropics. Differences were not only observed in comparison with unmedicated patients, but were also evident in comparisons between single-class, multi-class, and single/multi-class groups. Importantly, multi-class associations with rsEEG characteristics were found even in the absence of single-class associations, suggesting potential cumulative or interaction effects of different classes of psychotropics. Dosage correlations were only found for antipsychotics. Conclusion: Our exploratory, cross-sectional study suggests small but significant associations between single and multi-class use of antidepressants, antipsychotics and benzodiazepines and macroscale rsEEG functional connectivity and network topology characteristics. These findings highlight the importance of considering the effects of specific psychotropics, as well as their interactions, when investigating rsEEG biomarkers in a medicated psychiatric population