Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) in patients with major depressive disorder: rationale and design of a prospective multicentre cohort study.

Abstract

Major depressive disorder (MDD) represents a worldwide burden on healthcare and the response to antidepressants remains limited. Systems biology approaches have been used to explore the precision therapy. However, no reliable biomarker clinically exists for prognostic prediction at present. The objectives of the <b>I</b>ntegrated Module of <b>M</b>ultidimensional <b>O</b>mics for Pe<b>r</b>ipheral Biomark<b>e</b>rs (iMORE) study are to predict the efficacy of antidepressants by integrating multidimensional omics and performing validation in a real-world setting. As secondary aims, a series of potential biomarkers are explored for biological subtypes. iMore is an observational cohort study in patients with MDD with a multistage design in China. The study is performed by three mental health centres comprising an observation phase and a validation phase. A total of 200 patients with MDD and 100 healthy controls were enrolled. The protocol-specified antidepressants are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Clinical visits (baseline, 4 and 8 weeks) include psychiatric rating scales for symptom assessment and biospecimen collection for multiomics analysis. Participants are divided into responders and non-responders based on treatment response (>50% reduction in Montgomery-Asberg Depression Rating Scale). Antidepressants' responses are predicted and biomarkers are explored using supervised learning approach by integration of metabolites, cytokines, gut microbiomes and immunophenotypic cells. The accuracy of the prediction models constructed is verified in an independent validation phase. The study was approved by the ethics committee of Shanghai Mental Health Center (approval number 2020-87). All participants need to sign a written consent for the study entry. Study findings will be published in peer-reviewed journals. NCT04518592.