Functional connectivity markers of depression in advanced Parkinson's disease

Abstract Background Depression is a common comorbid condition in Parkinson's disease and a major contributor to poor quality of life. Despite this, depression in PD is under-diagnosed due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired old patients. Objectives This study is to explore functional connectivity markers of depression in PD patients using resting-state fMRI and help diagnose whether patients have depression or not. Methods We reviewed 156 advanced PD patients (duration > 5 years; 59 depressed ones) and 45 healthy control subjects who underwent a resting-state fMRI scanning. Functional connectivity analysis was employed to characterize intrinsic connectivity networks using group independent component analysis and extract connectivity features. Features were put into an all-relevant feature selection procedure within cross-validation loops, to identify features with significant discriminative power for classification. Random forest classifiers were built for depression diagnosis, on the basis of identified features. Results 42 intrinsic connectivity networks were identified and arranged into subcortical, auditory, somatomotor, visual, cognitive control, default-mode and cerebellar networks. Six features were significantly relevant to classification. They were connectivity within posterior cingulate cortex, within insula, between posterior cingulate cortex and insula/hippocampus+amygdala, between insula and precuneus, and between superior parietal lobule and medial prefrontal cortex. The mean accuracy achieved with classifiers to discriminate depressed patients from the non-depressed was 82.4%. Conclusions Our findings provide preliminary evidence that resting-state functional connectivity can characterize depressed PD patients and help distinguish them from non-depressed ones.