ObjectiveThis study aimed to investigate the association of altered cortical thickness and functional connectivity (FC) with depression in Parkinson's disease (PD). Materials and methodsA total of 26 non-depressed PD patients (PD-ND), 30 PD patients with minor depression (PD-MnD), 32 PD patients with major depression (PD-MDD), and 30 healthy controls (HC) were enrolled. Differences in cortical thickness among the four groups were assessed, and the results were used to analyze FC differences in regions of cortical atrophy. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were also performed to identify clinical features and neuroimaging biomarkers that might help in the prediction of PD-MDD. ResultsPatients with PD-MDD showed decreased cortical thickness compared to patients with PD-ND in the left superior temporal and right rostral middle frontal gyri (RMFG), as well as weak FC between the left superior temporal gyrus and right cerebellum posterior lobe and between right RMFG and right inferior frontal gyrus and insula. The combination of cortical thickness, FC, and basic clinical features showed strong potential for predicting PD-MDD based on the area under the ROC curve (0.927, 95% CI 0.854-0.999, p < 0.001). ConclusionPatients with PD-MDD show extensive cortical atrophy and FC alterations, suggesting that cortical thickness and FC may be neuroimaging-based diagnostic biomarkers for PD-MDD.