The effects of panic disorder (PD) and pharmacotherapy on brain functional hubs in drug-free patients, and the utility of their degree centrality (DC) in diagnosing and predicting treatment response (TR) for PD, remained unclear. This study aimed to assess the effects of PD and paroxetine on brain functional hubs in drug-free patients and to identify neuroimaging biomarkers for diagnosing and predicting TR in patients with PD. Imaging data from 54 medication-free PD patients and 54 matched healthy controls (HCs) underwent DC and functional connectivity (FC) analyses before and after a 4-week paroxetine treatment. Diagnosis and prediction of TR models for PD were constructed using support vector machine (SVM) and support vector regression (SVR), with DC as features. Patients with PD showed aberrant DC and FC in the anterior cingulum, temporal, and occipital areas compared with HCs at baseline. After treatment, DC of the patients increased in the calcarine cortex, lingual gyrus, and cerebellum IV/V, along with improved clinical symptoms. Utilizing voxel-wise DC values at baseline, the SVM effectively distinguished patients with PD from HCs with an accuracy of 83.33%. In SVR, the predicted TR significantly correlated with the observed TR (correlation coefficient (r) = 0.893, Mean Squared Error = 0.009). Patients with PD exhibited abnormal DC and FC, notably in the limbic network, temporal, and occipital regions. Paroxetine ameliorated patients' symptoms while altering their brain FC. SVM and SVR models, utilizing baseline DC, effectively distinguished the patients from HCs and accurately predicted TR.
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