Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression

Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study

\ua9 The Author(s) 2024.Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD

Current status of molecular classification of the phytoplasmas

Phytoplasmas for which 16S rDNA sequences are available have been classified into 20 major phylogenetic groups or subclades. Further phytoplasmas have been assigned to these groups, according to other molecular data such as RFLP analysis of PCR-amplified ribosomal DNA, nucleic acid hybridization, and serological comparison. A total of 75 phytoplasmas were distinguishable among the molecularly characterized phytopathogenic mollicutes