Metabolomics as A Strategic Tool for Addressing Heterogeneity in Major Depressive Disorder Clinical Management

The Lancet-World Psychiatric Association Commission emphasises the critical need for a multidimensional approach in MDD research to tackle the challenges of its heterogeneity in research and clinical contexts. This proposed three-year collaborative project between Sweden and the UK is highly relevant.

Building on the hypothesis that metabolic alternations may play a crucial role in MDD heterogeneity, the project aims to examine this hypothesis and leverage insights gained into metabolomic-informed biomarkers for clinical application.

Specifically, I will (i) conduct a metabolome-wide analysis using UK biobank data with causal mechanism investigation to determine the metabolic underpinnings of MDD heterogeneity, (ii) develop metabolomic scores for MDD manifestations and validate their applicability in seven independent cohorts, and (iii) construct DNA-methylation-based epigenetic scores for metabolomics and a multiple omics-based integrated model for MDD manifestations and health outcomes prognosis.

Achieving this project will deepen the current understanding of the biological mechanisms of MDD heterogeneity and deliver vigorously validated biomarkers to inform clinical decision-making processes.

The anticipated advancements will accelerate the shift towards patient-centred, mechanism-directed precision medicine for MDD, ultimately benefiting patients with tailored treatment and improved overall well-being.