Functional and Structural Abnormalities in the Pain Network of Generalized Anxiety Disorder Patients with Pain Symptoms

Abstract

Pain symptoms significantly impact the well-being and work capacity of individuals with generalized anxiety disorder (GAD), and hinder treatment and recovery. Despite existing literature focusing on the neural substrate of pain and anxiety separately, further exploration is needed to understand the possible neuroimaging mechanisms of the pain symptoms in GAD patients. We recruited 73 GAD patients and 75 matched healthy controls (HC) for clinical assessments, as well as resting-state functional and structural magnetic resonance imaging scans. We defined a pain-related network through a published meta-analysis, including the insula, thalamus, periaqueductal gray, prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus. Subsequently, we conducted the regional homogeneity (ReHo) and the gray matter volume (GMV) within the pain-related network. Correlation analysis was then employed to explore associations between abnormal regions and self-reported outcomes, assessed using the Patient Health Questionnaire-15 (PHQ-15) and pain scores. We observed significantly increased ReHo in the bilateral insula but decreased GMV in the bilateral thalamus of GAD compared to HC. Further correlation analysis revealed a positive correlation between ReHo of the left anterior insula and pain scores in GAD patients, while a respective negative correlation between GMV of the bilateral thalamus and PHQ-15 scores. In summary, GAD patients exhibit structural and functional abnormalities in pain-related networks. The enhanced ReHo in the left anterior insula is correlated with pain symptoms, which might be a crucial brain region of pain symptoms in GAD.