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INNOSC Theranostics and
Pharmacological Sciences MDD biomarkers: Clinical implications

Table 2. Intranuclear biomarkers and their clinical relevance in MDD
Biomarker Type Role in MDD Clinical utility References
mRNA of IL-1β Transcriptomic Inflammation Predicts treatment response 37
miR-221-3p Epitranscriptomic Post-transcriptional Diagnostic and prognostic marker 38
modification
gsk3βAS1 lncRNA Epitranscriptomic Synaptic plasticity Diagnostic and therapeutic marker 39
circRNA_103636 Epitranscriptomic Development Diagnostic marker with 73% sensitivity 40
stage-specific and 65% specificity
expression
DNA methylation of GSK3β gene Epigenetic Gene regulation Diagnostic marker with 100% 41
sensitivity and specificity
Abbreviations: circRNA: Circular RNA; IL: Interleukin; lncRNA: Long non-coding RNAs; MDD: Major depressive disorder;
mRNA: Messenger RNA; miR: microRNA.

8A (PDE-8A) mRNA editing profile have been observed in of significant miR expression patterns for MDD diagnosis
brain areas, including the dorsolateral prefrontal cortex and and treatment response is given in Table 3 and Table 4.
anterior cingulate gyrus, between depressed suicidal victims Torres-Berrio et al. documented that miR-218
and healthy controls. They further suggested that suicidal expression in the prefrontal cortex significantly correlates
ideation results from immune response-mediated brain with susceptibility to depression and its expression can
damage due to the involvement of PDE-8A, and that in the be detected in the blood as well. Feng et al. identified
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future, this may act as a predictive biomarker for suicide. miR-221-3p expression in human serum and suggested
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In the same year, Salvetat et al. invented an application that it can predict depressed mood. Their work revealed
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for estimating the mRNA editing profile of PDE8A that IFN-α-induced activation of nuclear factor kappa
from blood, saliva, and urine samples, demonstrating B (NF-κB) in astrocytes, mediated by miR-221-3p
its potential for identifying mood disorders, including targeting of IRF2, may be one of the potential mechanisms
suicidal behavior. Rotter et al. discovered a positive underlying MDD.
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correlation between the RNA expression level of alpha-
synuclein (SNCA) and the severity of MDD – characterized 4.1.3. lncRNA expression as biomarkers for MDD
by the Hamilton Depression Rating Scale (HAM-D 17)
and Beck’s Depression Inventory (BDI-II) score. The Non-coding RNAs are pivotal for many cellular functions,
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study showed that mRNA expression levels of SNCA, a such as splicing, gene regulation, chromosome structure
presynaptic membrane protein, could serve as a potential regulation, and hormone-like activity. lncRNAs, which
biomarker for both diagnosis and grading MDD. Most range from 200 to several hundred nucleotides, have
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recently, it has been documented that mRNA expression of recently been explored as genetic biomarkers for various
serotonin transporter (SERT) on the surface of peripheral diseases. While protein and DNA constitute the majority of
blood mononuclear cells (PBMCs) is significantly reduced chromatin, an increasing number of studies have revealed
in subjects with MDD. 49 that lncRNAs occupy a large portion of chromatin and act
as regulators of nuclear architecture and the expression of
4.1.2. miRs expression as biomarkers for MDD nuclear chromatin as coding RNA (genomic role) or non-
coding RNA (epigenomic role). 69
miRs are small endogenous molecules consisting
of approximately 20 nucleotides that play a role in Liu et al. were the first to link co-expression of lncRNA
post-transcriptional modification of mRNA. Several and mRNA with MDD pathogenesis. Chromosomal
neurobiological processes including neurogenesis, regions chr10:874695-874794, chr10:75873456-75873642,
neuronal proliferation, and synaptic plasticity have been and chr3:47048304-47048512 were identified as major
linked to this epitranscriptome. As miR expression in the sites co-expressions associated with MDD. Gene ontology
peripheral circulating cells changes both during MDD (GO) and pathway analyses revealed metabolic pathway
progression and remission, their levels could serve as and neurodevelopment disease (Alzheimer’s disease and
potential biomarkers and may facilitate the management Parkinson’s disease) pathways. Two studies examined
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of intricate MDD. Differential expression (DE) of the DE of lncRNAs in PBMCs among patients of
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miR can be determined through tissues (e.g., brain), schizophrenia (SZ), MDD, and generalized anxiety disorder
cells (e.g., lymphocytes and monocytes), and body fluid (GAD). 71,72 After cross-validation, six downregulated
exosomes (e.g., blood, urine, and saliva). 51,52 A summary lncRNAs (TCONS_00019174, ENST00000566208,

Volume 8 Issue 2 (2025) 36 doi: 10.36922/itps.4404