Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an innovative approach that integrates structural connectome analysis with machine learning models to discern individuals with MDD from individuals with BD. High-resolution MRI images were obtained from individuals diagnosed with MDD or BD and from HCs. Structural connectomes were constructed to represent the complex interplay of brain regions using advanced graph theory techniques. Machine learning models were employed to discern unique connectivity patterns associated with MDD and BD. At the global level, both BD and MDD patients exhibited increased small-worldness compared to the HC group. At the nodal level, patients with BD and MDD showed common differences in nodal parameters primarily in the right amygdala and the right parahippocampal gyrus when compared with HCs. Distinctive differences were found mainly in prefrontal regions for BD, whereas MDD was characterized by abnormalities in the left thalamus and default mode network. Additionally, the BD group demonstrated altered nodal parameters predominantly in the fronto-limbic network when compared with the MDD group. Moreover, the application of machine learning models utilizing structural brain parameters demonstrated an impressive 90.3% accuracy in distinguishing individuals with BD from individuals with MDD. These findings demonstrate that combined structural connectome and machine learning enhance diagnostic accuracy and may contribute valuable insights to the understanding of the distinctive neurobiological signatures of these psychiatric disorders.
Keywords: bipolar disorder; graph theory; gray matter; machine learning; major depressive disorder.