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

<b>Background/Objective:</b> 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-<i>CD19</i>, <i>MTPAP</i>, <i>PER3</i>, <i>GAR1</i>, and <i>SLC25A26</i>-in the peripheral blood of drug-naïve patients with MDD and to evaluate their potential as diagnostic biomarkers. <b>Methods:</b> 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 <i>t</i>-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. <b>Results:</b> Significant upregulation was observed for CD19 (fold change = 6.15, <i>p</i> = 6.17 × 10^-10), MTPAP (fold change = 3.99, <i>p</i> = 1.74 × 10^-8), and PER3 (fold change = 2.42, <i>p</i> = 5.33 × 10^-6) in MDD. GAR1 showed modest upregulation (fold change = 1.26, <i>p</i> = 0.47), while SLC25A26 (fold change = 1.24, <i>p</i> = 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). <b>Conclusions:</b> This study identifies <i>CD19</i>, <i>MTPAP</i>, and <i>PER3</i> as promising peripheral blood biomarkers for MDD, with potential implications for early diagnosis, severity assessment, and personalized treatment strategies.