Towards Objective Major Depressive Disorder Detection: a Systematic Review and Meta-Analysis of Diagnostic Biomarkers

Despite extensive research, identifying reliable diagnostic biomarkers for MDD remains an open question. This systematic review quantifies the most promising diagnostic biomarkers for major depressive disorder (MDD) that can be utilized in clinical settings. We performed a comprehensive electronic search across PubMed, PsycINFO, ScienceDirect, and Google Scholar, covering the literature from January 2013 to December 2023. Inclusion criteria consisted of studies with human participants ages 18 and above, focusing on diagnostic biomarkers in bodily fluids and comparing patients with MDD with healthy controls. Exclusion criteria included comorbid physical or psychological illnesses, animal studies, and neuroimaging studies. We quantified 312 diagnostic biomarkers of MDD from 175 selected studies and found that interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), cortisol, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) were the most frequently appearing biomarkers in the selected studies. Meta-analyses of these top five biomarkers indicated that IL-6, BDNF, cortisol, and TNF-α were significantly associated with MDD, but further validation in different populations needs more work. Future research may focus on developing panels of diagnostic biomarkers and standardizing methodologies for diverse populations to enhance the diagnostic accuracy for MDD.