Early Treatment-related Changes in Dorsolateral Prefrontal Cortex Activity and Functional Connectivity as Potential Biomarkers for Antidepressant Response in Major Depressive Disorder

Previous research has demonstrated that patients with major depressive disorder (MDD) exhibit cognitive deficits. As a crucial region within the executive control network, the dorsolateral prefrontal cortex (DLPFC) activity and its functional connectivity (FC) may serve as potential indicators of antidepressant response. This prospective cohort study recruited 115 MDD patients and 43 healthy controls. Psychological assessments, electroencephalogram and event-related potential recordings were performed at baseline and 1 week after venlafaxine treatment, with a 12-week follow-up. Group differences were analyzed using independent sample t-tests and Mann-Whitney U tests, while linear mixed-effects models and logistic regression evaluated associations between DLPFC activity/FC changes and clinical outcomes. The MDD group showed significantly reduced right DLPFC current density during the N2 time window evoked by oddball stimuli ( p  = 0.028), which negatively correlated with 21-item Hamilton Depression Rating Scale (HAMD-21) scores ( p  = 0.041) (n = 46). Furthermore, an early increase predicted remission at week 12 ( p  = 0.005). Decreased beta-band FC between the left DLPFC and both the left posterior cingulate cortex (PCC) ( p  = 0.003) and right PCC ( p  = 0.004) predicted lower HAMD-21 scores (n = 71). Moreover, an early reduction in these connectivity measures (left: odds ratio (OR) = 0.534, 95% confidence interval (CI): 0.297–0.972, p  = 0.036; right: OR = 0.533, 95% CI: 0.299–0.950, p  = 0.033) predicted remission at week 12. Early changes in DLPFC activity and FC may serve as biomarkers for monitoring treatment efficacy and predicting clinical outcomes, informing personalized treatment approaches.