Molecular Signatures of Blood Biomarkers in Depression: Gene Expression Analysis of GAR1, PER3, MTPAP, SLC25A26, and CD19, a Case–Control Study

TL;DR

This study identifies blood-based gene markers for depression, which could help in diagnosis and treatment.

Contribution

The study identifies CD19, MTPAP, and PER3 as novel peripheral biomarkers for major depressive disorder.

Findings

CD19, MTPAP, and PER3 were significantly upregulated in MDD patients compared to controls.

Combined biomarkers achieved a high diagnostic accuracy (AUC = 0.885).

Gene expression levels correlated with depression severity measures.

Abstract

Background/Objective: Major depressive disorder (MDD) is a common mental illness that lacks objective diagnostic biomarkers and has a complicated pathogenesis. Peripheral blood-based gene expression profiling provides a potential, non-invasive method to identify the molecular markers associated with risk stratification and depression severity.This study aimed to investigate the gene expression of five candidate genes—CD19, MTPAP, PER3, GAR1, and SLC25A26—in the peripheral blood of drug-naïve patients with MDD and to evaluate their potential as diagnostic biomarkers. Methods: Peripheral blood samples were collected from 100 newly diagnosed, drug-naïve MDD patients and 100 age- and sex-matched healthy controls. The total RNA was extracted and reverse-transcribed for quantitative real-time PCR analysis. Fold change and ∆∆Ct values were calculated for each gene, followed by statistical analysis using t-tests and ANOVA. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance. Gene co-expression and pathway enrichment analyses were conducted to explore functional relevance. Results: Significant upregulation was observed for CD19 (fold change = 6.15, p = 6.17 × 10−10), MTPAP (fold change = 3.99, p = 1.74 × 10−8), and PER3 (fold change = 2.42, p = 5.33 × 10−6) in MDD. GAR1 showed modest upregulation (fold change = 1.26, p = 0.47), while SLC25A26 (fold change = 1.24, p = 0.47) was not significantly altered. Combined ROC analysis yielded an AUC of 0.885, indicating a strong discriminative ability. Gene expression correlated with depression severity (HAM-D and PHQ-9). Conclusions: This study identifies CD19, MTPAP, and PER3 as promising peripheral blood biomarkers for MDD, with potential implications for early diagnosis, severity assessment, and personalized treatment strategies.

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