Abstract
Depression presents a significant challenge to global mental health, often intertwined with factors including oxidative stress. Although the precise relationship with mitochondrial pathways remains elusive, recent advances in machine learning present an avenue for further investigation. This study employed advanced machine learning techniques to classify major depressive disorders based on clinical indicators and mitochondrial oxidative stress markers. Six machine learning algorithms, including Random Forest, were applied and their performance was investigated in balanced and unbalanced data sets with respect to binary and multiclass classification scenarios. Results indicate promising accuracy and precision, particularly with Random Forest on balanced data. RF achieved an average accuracy of 92.7% and an F1 score of 83.95% for binary classification, 90.36% and 90.1%, respectively, for the classification of three classes of severity of depression and 89.76% and 88.26%, respectively, for the classification of five classes. Including only oxidative stress markers resulted in accuracy and an F1 score of 79.52% and 80.56%, respectively. Notably, including mitochondrial peptides alongside clinical factors significantly enhances predictive capability, shedding light on the interplay between depression severity and mitochondrial oxidative stress pathways. These findings underscore the potential for machine learning models to aid clinical assessment, particularly in individuals with comorbid conditions such as hypertension, diabetes mellitus, and cardiovascular disease.