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INNOSC Theranostics and
Pharmacological Sciences MDD biomarkers: Clinical implications

Table 4. MiR expression for MDD treatment response
Tissue/Sample miR Expression Associated signaling pathways References
PBMCs (Human) Upregulated GO, KEGG and BioCarta 53
miR-4743, miR-4498, miR-4485 and miR-1972
Downregulated
miR-4485
Plasma and PFC Downregulated MAPK/Wnt 52
(human) miR-146a-5p, miR-146b-5p, miR-24-3p and miR-425-3p
Plasma (mouse)
Plasma, exosome Upregulated MAPK and Wnt 64
EDP, PNBCs miR-26a (in EDP – exosomes depleted plasma)
miR-494 (in exosomes and EDP)
Among MDD-treated patients
Plasma (human) Upregulated Morphogenesis, COPII vesicle coating, 65
miR-16-5p, miR-146a-5p and miR-21-5p IP3 metabolic process, apoptotic process,
cytoplasmic stress granule, NO metabolic
process, NO synthase, and virion assembly
PBMCs (human) Upregulated Prion diseases (TGFβ) and morphine 66
miR-27a-3p, miR-197-3p, miR-22-5p, miR-221-3p, addiction signaling pathways
miR-126-3p, miR-128-1-5p, miR-30b-5p, miR-339-3p,
miR-301a-3p, miR-345-5p, miR-505-3p, miR-1249,
miR-132-3p, miR-550a-5p, miR-589-5p, miR-769-5p,
miR-10b-5p, miR-210-3p, miR-628-3p, let-7d-3p,
miR-148a-5p, miR-155-5p, miR-140-3p, miR-150-3p,
miR-181a-5p, miR-24-3p, miR-629-5p, let-7a-3p,
miR-194-5p, miR-28-3p, miR-378a-3p, miR-6852-5p,
miR-7706
Plasma (human) Upregulated MAPK and Wnt 67
miR-135a-5p (the higher the miR-135a-5p expression, the
faster the remission.)
Abbreviations: EDP: Exosomes depleted plasma; lncRNA: Long non-coding RNAs; MDD: Major depressive disorder; miR: microRNA;
MAPK: Mitogen-activated protein kinase; NO: Nitric oxide; PBMC: Peripheral blood mononuclear cells; PFC: Prefrontal cortex; PNBC: Peripheral
nucleated blood cells; TGFβ: Transforming growth factor beta.

NONHSAG045500, ENST00000517573, NONHSAT034045, multiple regulatory roles in physiological and pathological
and NONHSAT142707) were found highly sensitive and processes at the nuclear and cellular levels. The mysterious
specific for the diagnosis of MDD (AUC = 0.719). Seki circRNAs are formed from pre-mRNA through back-
et al. discovered RMRP, a nuclear DNA-encoded lncRNA splicing of introns, exons, or both, while the canonical
and a component of nuclear RNase mitochondrial RNA splicing of the same pre-mRNA results in the formation of
processing (MRP) complex, as a potential biomarker for protein-coding mRNA. 74,75
the diagnosis and severity assessment of MDD in both
human and animal research models. Most recently, Liu Cui et al. were the first to recommend the expression
73
et al. conducted in vitro and in vivo studies on regulatory of circRNAs (circRNA_103636) in PBMCs as a biomarker
antisense lncRNAs of GSK3β, a serine-threonine kinase for MDD diagnosis and treatment response, with 73%
involved in synaptic plasticity, neurogenesis, and resilience sensitivity and 65% specificity as determined by receiver
40
to neuronal injury. The study identified gsk3βAS1 operating characteristic (ROC) curve analysis. Zhang et al.
39
[ENST00000482027], gsk3βAS2 [ENST00000491262], and conducted experiments to validate the ameliorative effects
gsk3βAS3 [BC035247] as novel diagnostic and therapeutic of circRNA DYM (circDYM) expression in depressive-
biomarkers for MDD. A summary of lncRNAs that play a like mice models. In vitro studies on BV-2 cells revealed
significant role in the diagnosis and treatment response of that circDYM inhibits miR-9 which increases target-
MDD is presented in Table 5. HECT domain E3 ubiquitin protein ligase 1 (HECTD1)
and depresses microglial activation. Following Zhang
61
4.1.4. circRNA expression as biomarkers for MDD et al., Song et al. sorted out the correlation between
Previously considered just a byproduct of genetic downregulated plasma circDYM and MDD up to 94%
malfunctioning, circRNAs have now been assigned sensitivity. 55

Volume 8 Issue 2 (2025) 38 doi: 10.36922/itps.4404