Abstract
BACKGROUND: Adolescents with moderate depression and suicidal ideation constitute a high-risk psychiatric population. Major depressive disorder with suicidal ideation in this age group is a disabling psychiatric disorder. Current selective serotonin reuptake inhibitor treatments are limited by their low efficacy rates (approximately 50%-60%) and delayed onset of action. Informed by the gut-brain axis theory, this study aimed to evaluate the synergistic efficacy and anti-inflammatory mechanisms of sertraline combined with a Bacillus subtilis probiotic preparation in this high-risk population. METHODS: This retrospective cohort study included 160 adolescents meeting International Classification of Diseases 10th Revision diagnostic criteria were identified and categorised into either monotherapy (sertraline) or combination therapy (sertraline + probiotics) groups. Over a 12-week treatment period, clinical symptoms were assessed using the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale and Beck Scale for Suicide Ideation-Chinese Version, and serum inflammatory factors, namely, interleukin-6 (IL-6), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and C-reactive protein (CRP) and peripheral blood inflammatory ratios, namely, platelet-to-lymphocyte, neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios, were measured. RESULTS: The proportion of patients with severe depression was significantly reduced in the combination group (1.25% vs. 7.5%, p = 0.004), and anxiety symptoms showed significant improvement (severe anxiety proportion: 1.25% vs. 11.25%, p = 0.008). Biomarker analysis revealed significantly reduced levels of IL-6 (p = 0.007), IL-1β (p = 0.002), TNF-α (p = 0.005) and CRP (p = 0.001) in the combination group, and IL-6 and CRP showed strong positive correlations with depression scores (r = 0.35-0.39). CONCLUSIONS: This study confirms that modulating the intestinal smicroecology can enhance antidepressant efficacy by reducing neuroinflammation.