Precuneus neural synchronization and stress perception dimensions in first-episode, drug-naïve major depressive disorder.

Objective

First-episode, drug-naïve (FEDN) patients with major depressive disorder (MDD) frequently exhibit disturbances in stress perception and cognitive function, yet the neural correlates remain unclear. This study investigated associations of altered regional homogeneity (ReHo) in the right precuneus with subjective stress perception in FEDN MDD.

Methods

We enrolled 139 FEDN patients and 65 healthy controls. Propensity score matching (PSM) balanced age, sex, and head motion, yielding 63 pairs. Resting-state fMRI was acquired and preprocessed; whole-brain ReHo maps were computed. Voxel-wise group comparison with GRF correction identified decreased ReHo in the right precuneus, which was defined as the region of interest. Within patients, partial correlations between right precuneus ReHo and Perceived Stress Scale (PSS) total, helplessness, and self-efficacy scores were examined, controlling for age, sex, mean framewise displacement, HAMD-17, and HAMA.

Results

Compared to controls, FEDN patients showed significantly decreased right precuneus ReHo. In patients, after controlling for age, sex, mean framewise displacement, HAMD-17 score, and HAMA score, right precuneus ReHo was negatively associated with the self-efficacy dimension of the PSS (r = -0.497, p = 0.011). A nominal positive association was also observed between right precuneus ReHo and the PSS total score (r = 0.399, p = 0.048), whereas no significant association was found with helplessness.

Conclusion

Altered right precuneus spontaneous activity was associated with perceived stress-related cognitive appraisal, particularly stress-coping self-efficacy, in FEDN patients with MDD after controlling for depressive and anxiety symptom severity. These findings highlight a potential role of the right precuneus in stress-coping self-efficacy in FEDN MDD patients.