Abstract
OBJECTIVES: To better investigate neurobiological heterogeneity in fibromyalgia for its symptom diversity and individual differences. METHODS: We collected structural MRI data and clinical characteristics of Chinese female fibromyalgia patients and healthy controls matched by age and educational level, then invited qualified patients to undergo either Ba-Duan-Jin or pregabalin intervention for 12 weeks randomly. Structural MRI was analyzed by CAT12 software, and the regional volume of gray matter (GMV) was calculated according to the Brainnetome atlas. Fibromyalgia patients were clustered using the HYDRA algorithm to detect disease subtypes. RESULTS: Two distinct neuroanatomical subtypes were found among 75 patients. Compared to 93 healthy controls, patients in subtype 1 (n = 38, 50.7%) showed widespread GMV increase, especially in some pain-related brain regions, while no structural changes were observed in subtype 2 (n = 37, 49.3%). At the baseline before treatment, patients in subtype 1 showed a younger age (p = 0.037), longer illness duration (p = 0.042), and a severer psychological stress state evaluated by the Perceived Stress Scale (p = 0.008). After standardized treatment, subtype 1 patients showed less improvement in pain VAS score (p = 0.027) than subtype 2 patients. In addition, GMV of the bilateral dorsal caudate had negative correlations with stress level (Left r = -0.335, p = 0.040; Right r = -0.341, p = 0.036), and GMV of the left rostral temporal thalamus (r = 0.781, p = 0.038) and lateral amygdala (r = 0.761, p = 0.047) were positively related to the improvement of pain severity after treatment in subtype 1 patients. CONCLUSIONS: These two neuroanatomical subtypes in fibromyalgia emphasize different underlying neuropathological processes and need future studies to optimize individualized treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03890133.