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REVIEW ARTICLE

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

Muhammad Kamran Ameer1,2† ,  Muhammad Ikram3 ,  Muhammad Imran Khan4 ,  Fazal Wahab4 ,  Muhammad Imran Naseer5 ,  Najeeb Ullah2†*
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1 Department of Anatomy, Company Multan Medical and Dental College, Multan, Pakistan
2 Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
3 Institute of Pharmaceutical Sciences, Khyber Medical College, Peshawar, Pakistan
4 Pak Austria Fachhochschule: Institute of Applied Sciences and Technology, Mang, Haripur, Pakistan
5 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Institute of Genomic Medicine Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
INNOSC Theranostics and Pharmacological Sciences, 4404 https://doi.org/10.36922/itps.4404
Submitted: 1 August 2024 | Revised: 19 November 2024 | Accepted: 16 December 2024 | Published: 10 January 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

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.

Keywords
Biomarkers
Cell signaling markers
Intranuclear markers
Major depressive disorder
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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