<p>This study examined how serum interleukin-1 beta (sIL-1β) interacts with the Big Five personality trait of Neuroticism to influence 12-week antidepressant treatment outcomes in patients with depressive disorders. Baseline measurements of sIL-1β and Neuroticism were obtained from 1086 participants enrolled in a naturalistic, stepwise antidepressant treatment program. Remission was defined as a Hamilton depression rating scale score of 7 or below after 12&#xa0;weeks of treatment. Using logistic regression models that accounted for sociodemographic and clinical variables, we assessed the independent and interactive effects of these factors on treatment response. Elevated sIL-1β levels were significantly associated with non-remission in participants with high Neuroticism, whereas this relationship was not evident among those with lower Neuroticism levels. Notably, the interaction between sIL-1β and Neuroticism was a significant predictor of remission status, even after adjusting for confounders. Our findings reveal that the dynamic modulation of antidepressant response through the interaction of sIL-1β and Neuroticism could inform more personalized treatment strategies, enhancing clinical outcomes for patients with depression. Future research should continue to explore these biomarker-psychological trait interactions to fully understand their role in treatment efficacy.</p>