Integration of transcriptome profiling to identify key genes involved in the interplay between oxidative stress and mitophagy in major depressive disorder, followed by multidimensional phenotypic validation.

Background: Major depressive disorder (MDD) is recognized as a pressing global public health burden. However, its molecular mechanisms remain incompletely understood. Methods: In this study, an integrative analysis of transcriptome datasets from the GEO database was conducted. GEO2R and the R programming language were used to identify differentially expressed genes (DEGs) related to oxidative stress and mitophagy. Key hub genes, such as Results: This study combined bioinformatics screening and multidimensional phenotypic validation to construct an MDD-specific molecular regulatory network focused on carbon metabolism, thereby elucidating the interplay between four genes and oxidative stress and mitophagy. Although Conclusion: Although this study did not experimentally validate the regulatory functions of the target genes or identify highly specific diagnostic biomarkers, it offers a novel molecular perspective for deciphering the complex pathology of MDD. Notably, this highlights the synergistic interaction between translational regulation and metabolic homeostasis. Further validation in larger independent cohorts is warranted to assess the viability of these genes as mechanistic therapeutic targets.