Transthyretin (TTR) is a serum biomarker for major depressive disorder (MDD). (a) Expression profiling of genes with significant changes and consistent trends in response to CMS treatment in at least three of the four brain areas. TTR exhibited significant downregulation in the amygdala, prefrontal cortex, and cerebral cortex after CMS treatments. (b) qPCR validation of TTR expression in the amygdala using three independent sets of primers. (c) Serum TTR concentrations in CMS-treated and control mice according to ELISA (n = 20 independent mouse serum samples from three independent CMS treatments per group). (d) Serum TTR concentrations in patients with diagnosed MDD and case-controls. (e) TTR concentrations in paired serum samples from patients at acute and remission phases of MDD. Statistical analysis was performed using an unpaired, two-tailed Student’s t-test (d) and a paired, two-tailed Student’s t-test (e). Amy, amygdala; hippo, hippocampus; PFC, prefrontal cortex; CC, cerebral cortex. * p < 0.05, and *** p < 0.001.