<p>This study employed the Self-Criticism Activation and Recall Task (SCART) to investigate the characteristics of self-criticism in first-episode, medication-naive patients with Major Depressive Disorder (MDD) and to explore the effects of 8-week antidepressant treatment on self-criticism and its longitudinal relationship with clinical symptom improvement. The findings revealed that MDD patients exhibited significantly higher self-criticism levels at baseline compared to healthy controls, with this characteristic manifesting in both cognitive and behavioral domains. Following eight weeks of pharmacotherapy, patients’ self-criticism levels significantly decreased, showing a positive correlation with depressive symptom remission. Further analyses revealed that the self-criticism improved group (defined by ≥ 50% self-criticism improvement) showed greater depression remission. The findings demonstrate that pharmacotherapy not only alleviate depression symptoms, but also self-criticism maladaptive cognition in MDD patients. Importantly, we suggest that self-criticism alleviated by pharmacotherapy is associated with depression improvement. These findings not only establish self-criticism as a core pathogenic mechanism in MDD but also provide a mechanistic framework for understanding antidepressant efficacy. Further exploration of the heterogeneity of medication-induced improvements in self-criticism is strongly warranted.</p>