Potential Mitochondria-Related Key Genes in Post-Traumatic Stress Disorder Analyzed by Machine Learning Methods

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Post-traumatic stress disorder (PTSD) is a significant psychiatric condition linked to traumatic events.
• Mitochondrial dysfunction is increasingly recognized as a potential contributor to PTSD pathogenesis, affecting cellular energy, oxidative stress, and neuroplasticity.

Purpose of the Study:

• To identify and validate mitochondrial dysfunction-associated biomarkers for post-traumatic stress disorder (PTSD).
• To explore potential diagnostic and therapeutic targets for PTSD by investigating mitochondrial gene expression.

Main Methods:

• Differential gene expression analysis was performed on peripheral blood samples from PTSD patients and healthy controls.
• Machine learning algorithms (LASSO, SVM-RFE, Random Forest) and ROC analysis were used to identify and validate potential PTSD biomarkers.
• Mitochondrial gene expression was examined in mouse models of PTSD, and correlations with immune cell infiltration were investigated.

Main Results:

• Differentially expressed genes in PTSD were significantly enriched in mitochondrial pathways.
• Four key mitochondrial genes (UCP2, CISD1, NADK2, IDE) were identified as potential diagnostic biomarkers for PTSD with good performance in discovery and validation cohorts.
• These identified genes demonstrated conserved dysregulation in murine models and correlated with specific immune cell proportions, suggesting neuroimmune links.

Conclusions:

• The mitochondrial genes UCP2, CISD1, NADK2, and IDE show promise as cross-species diagnostic biomarkers for PTSD.
• These biomarkers may be associated with neuroimmune mechanisms underlying PTSD pathogenesis.
• Further research into these mitochondrial genes could lead to novel therapeutic strategies for PTSD.