Transthyretin as a biomarker to predict and monitor major depressive disorder identified by whole‐genome transcriptomic analysis in mouse models

Abstract

Background: Accumulations of stressful life events result in the onset of major depressive disorder (MDD). Comprehensive genomic analysis is required to elucidate pathophysiological changes and identify applicable biomarkers. Methods: Transcriptomic analysis was performed on different brain parts of a chronic mild stress (CMS)‐induced MDD mouse model followed by systemic analysis. QPCR and ELISA were utilized for validation in mice and patients. Results: The highest numbers of genes with significant changes induced by CMS were 505 in the amygdala followed by 272 in the hippocampus (twofold changes; FDR, p < 0.05). Enrichment analysis indicated that the core‐enriched genes in CMS‐treated mice were positively enriched for IFN‐γ response genes in the amygdala, and hedgehog signaling in the hippocampus. Transthyretin (TTR) was severely reduced in CMS‐treated mice. In patients with diagnosed MDD, serum concentrations of TTR were reduced by 48.7% compared to controls (p = 0.0102). Paired samples from patients with MDD demonstrated a further 66.3% increase in TTR at remission compared to the acute phase (p = 0.0339). Conclusions: This study provides comprehensive information on molecular networks related to MDD as a basis for further investigation and identifies TTR for MDD monitoring and management. A clinical trial with bigger patient cohort should be conducted to validate this translational study.