Emerging biomarkers in major depressive disorder: Diagnostic, prognostic, and therapeutic implications

Recent advancements in biomarker research for the diagnosis, prognosis, and treatment strategies of major depressive disorder (MDD) have yielded significant findings that warrant documentation. The clinical demand for biomarkers persists due to the limited accuracy and efficiency of subjective diagnostic approaches. This review scrutinized research papers related to MDD biomarkers published between January 2011 and till July 2024, focusing exclusively on human studies with statistically significant results. The compiled biomarkers encompass cellular membrane receptors, cytoplasmic organelles, and genomic and epigenomic intranuclear markers. Cell surface molecular receptors implicated in MDD pathogenesis include brain-derived neurotrophic factor (BDNF) receptors, N-methyl D-aspartate receptors (NMDAR), and interleukin (IL) receptors. Endogenous compounds with diagnostic and prognostic potential, such as L-carnitine and alpha-L-carnitine, have also been identified. Transcriptomic biomarkers, including mRNA expression levels of the BDNF, IL-1β, macrophage migration inhibitory factor, and tumor necrosis factor-alpha (TNF-α), have demonstrated utility in MDD management. MicroRNAs (miRNAs), the endogenous molecules that alter the structure of mRNA, show potential for diagnosis and treatment outcome prediction, with miR-221-3p, miR-129-5p, miR-134, and miR-184 emerging as key candidates for MDD monitoring. Long non-coding RNAs (lncRNAs), such as GSK3βAS1, GSK3βAS2, and GSK3βAS3 have been investigated for the evaluation of disease severity and treatment response. Most recently, the pathological role of circular (circRNA) and DNA methylation in MDD has also been documented. The rs155979 polymorphism in the lncRNA NOTHSAT102891 was significantly associated with depression and risk of suicide. The data compiled in this review aim to guide further research in the quest for biomarkers that will improve the management of MDD.