Effective connectivity signatures in major depressive disorder: fMRI study using a multi-site dataset

Diagnosis of major depressive disorder (MDD) primarily relies on the patient's self-reported symptoms and a clinical evaluation. Effective connectivity (EC) from resting-state functional magnetic resonance imaging (rs-fMRI) analysis can reflect the directionality of connections between brain regions, making it a candidate method to classify MDD. This study used Granger causality analysis to extract EC features from a large multi-site MDD dataset. The ComBat algorithm and multivariate linear regression were used to harmonize site difference and to remove age and sex covariates, respectively. Two-sample t-tests and model-based feature selection methods were used to screen for highly discriminative EC features for MDD, and LightGBM was used to classify MDD. In this large-scale multi-site rs-fMRI dataset, 97 EC features deemed highly discriminative for MDD were screened. In the nested five-fold cross-validation, the best classification model with the 97 EC features achieved accuracy, sensitivity, and specificity of 94.35%, 93.52%, and 95.25%, respectively. In another independent large dataset, which tested the generalization performance of the 97 EC features, the best classification models achieved 94.74%, 90.59%, and 96.75% for accuracy, sensitivity, and specificity, respectively. This work demonstrated that EC had a reasonable discriminative ability and supported the notion for using EC to potentially assist clinical diagnosis of MDD.