Shared and distinctive neural substrates of generalized anxiety disorder with or without depressive symptoms and their roles in prognostic prediction

Background: The neurophysiological mechanisms underlying generalized anxiety disorder (GAD) with or without depressive symptoms are obscure. This study aimed to uncover them and assess their predictive value for treatment response. Methods: We enrolled 98 GAD patients [58 (age: 33.22 +/- 10.23 years old, males/females: 25/33) with and 40 (age: 33.65 +/- 10.49 years old, males/females: 14/26) without depressive symptoms] and 54 healthy controls (HCs, age: 32.28 +/- 10.56 years old, males/females: 21/33). Patients underwent clinical assessments and resting -state functional MRI (rs-fMRI) at baseline and after 4-week treatment with paroxetine, while HCs underwent rs-fMRI at baseline only. Regional homogeneity (ReHo) was employed to measure intrinsic brain activity. We compared ReHo in patients to HCs and examined changes in ReHo within the patient groups after treatment. Support vector regression (SVR) analyses were conducted separately for each patient group to predict the patients' treatment response. Results: Both patient groups exhibited higher ReHo in the middle/superior frontal gyrus decreased ReHo in different brain regions compared to HCs. Furthermore, differences in ReHo were detected between the two patient groups. After treatment, the patient groups displayed distinct ReHo change patterns. By utilizing SVR based on baseline abnormal ReHo, we effectively predicted treatment response of patients (p-value for corre-lation < 0.05). Limitations: The dropout rate was relatively high. Conclusions: This study identified shared and unique neural substrates in GAD patients with or without depressive symptoms, potentially serving as biomarkers for treatment response prediction. Comorbid depressive symptoms were associated with differences in disease manifestation and treatment response compared to pure GAD cases.