Identification and experimental validation of biomarkers related to mitochondrial and programmed cell death in obsessive-compulsive disorder

Abstract Background Obsessive-compulsive disorder (OCD) poses a substantial global challenge in identifying biomarkers linked to mitochondrial-related genes (MRGs) and programmed cell death-related genes (PCD-RGs), offering new insights into the disorder's pathogenesis. Methods Differentially expressed genes (DEGs) between OCD and control samples were identified from the GSE78104 dataset. Differentially expressed MRGs (DE MRG-MRGs) and PCD-RGs (DE-PCD-RGs) were derived by intersecting with MRG and PCD-RG gene sets, respectively, yielding DE mitochondrial-related PCD (DE-MPCD) genes. Key OCD-related genes were identified using weighted gene co-expression network analysis (WGCNA), and candidate genes for OCD were selected by intersecting these with DE-MPCD-RGs. Machine learning algorithms were applied to further screen potential biomarkers from the GSE78104, and GSE60190 datasets. The expression levels of selected biomarkers were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in samples from patients with OCD and healthy individuals to validate the mRNA expression of the biomarkers.controls. Gene Set Enrichment Analysis (GSEA) was conducted to analyze the pathways enriched in these biomarkers. Immune cell infiltration patterns in OCD and potential therapeutic agents for OCD were also investigated. Results A total of 13 DE-MPCD-RGs were intersected with 374 key module genes, resulting in 12 candidate genes. Among these, eight potential biomarkers for OCD were identified. Notably, NDUFA1 and COX7C were significantly downregulated in OCD in both the datasets and clinical samples, making them reliable biomarkers for OCD. GSEA revealed that NDUFA1 and COX7C were significantly co-enriched in pathways such as ‘ribosome’, ‘oxidative phosphorylation’, ‘phosphorylation’, ‘Parkinson's disease’. Furthermore, activated CD8 T cells and neutrophils were identified as the differential immune cells between the OCD and control samples. Additionally, 73 potential therapeutic agents were predicted through drug-target interaction analysis. Conclusion This study identifies two mitochondrial-related biomarkers in OCD, offering novel perspectives on the disorder’s pathogenesis. These findings hold potential for advancing early diagnosis and developing targeted therapeutic strategies for OCD.