Objective To explore the effect of physical exercise intervention on mild-to-moderate depression in college students, and to provide empirical evidence for informing treatment.

Methods A total of 108 college students with mild-to-moderate depression receiving care at the outpatient department and inpatient department of the Second Affiliated Hospital, Xinxiang Medical University between January 2022 and March 2024 were enrolled. The participants were divided into a control group (n = 54) and a physical exercise group (n = 54) according to the time of consultation. The control group received conventional drug therapy, whereas the physical exercise group was an aerobic exercise intervention regimen in addition to the routine drug therapy. Both groups were treated for 8 weeks. The primary outcome indicator (clinical efficacy) and secondary outcome indicators, including the 24-Item Hamilton Depression Rating Scale (HAMD-24) score, the Pittsburgh Sleep Quality Index (PSQI) score, the P300 component of the event-related potential (latency and amplitude), the serum levels of hypothalamic-pituitary-adrenal (HPA) axis-related indicators (adrenocorticotropic hormone ACTH and cortisol Cor), and the World Health Organization Quality of Life-Brief scale (WHOQOL-BREF) score, before and after intervention were measured and compared between the two groups.

Results Comparison of the primary outcome indicator revealed that, after treatment, the efficacy grading in the physical exercise group was better than that in the control group (Z = 2.546, P = 0.011). Regarding secondary outcomes, both groups showed significant reductions in HAMD-24 and PSQI scores after treatment (P < 0.05), with the physical exercise group demonstrating lower scores than the control group (P < 0.05). Event-related potential P300 latency was shortened in both groups, and the reduction was greater in the physical exercise group (P < 0.05). P300 amplitude increased in both groups, with a larger increase observed in the physical exercise group (P < 0.05). Levels of ACTH and cortisol decreased across groups, with lower values in the physical exercise group compared with controls (P < 0.05). Quality-of-life scores improved in both groups, with the physical exercise group reporting higher scores than the control group (P < 0.05).

Conclusion Physical exercise can regulate the function of the HPA axis of college students with mild-to-moderate depression, alleviate their depressive symptoms, promote the recovery of cognitive function, and improve the sleep quality and quality of life of patients.