Correlation between hypothalamic-pituitary-adrenal function and clinical characteristics in the acute phase of first-episode drug-naive major depressive disorder

Abstract

Background First-episode drug-naïve depressive disorders have high heterogeneity in clinical features, and there is still room for in-depth exploration of the correlation with serum cortisol levels. This study aimed to explore the correlation between hypothalamic-pituitary-adrenal (HPA) function in the acute phase of first-episode drug-naïve major depressive disorder (MDD) and clinical features evaluated by the Hamilton Depression Rating Scale (HAMD-24) and the Zung Self-Rating Depression Scale (SDS). Methods Patients with first-episode drug-naïve MDD in the acute phase meeting the DSM-V diagnostic criteria were selected as the study group, and healthy individuals matched for gender and age were recruited as the control group. Serum cortisol levels were measured in both groups, and patients in the MDD group were evaluated using HAMD-24 and SDS. Results The serum cortisol level in the MDD group(307.03 ± 77.80 nmol/L) was significantly higher than that in the healthy control group(261.13 ± 58.15 nmol/L) (Z-Value = -3.539, P < 0.05). The serum cortisol level showed a positive correlation trend (ρ > 0) with the anxiety factor, cognitive impairment factor, retardation factor, despair factor, total HAMD score, and SDS score, with statistical significance (p < 0.05). It showed a negative correlation trend (ρ < 0) with the sleep factor, without statistical significance (p > 0.05). It also showed a positive correlation trend (ρ > 0) with the weight factor and diurnal variation factor, without statistical significance (p > 0.05). Conclusion A significant increase in serum cortisol level can serve as one of the biological indicators for predicting the core symptom clusters and disease severity of MDD. Regulation of The HPA axis cortisol pathway may have potential value in alleviating MDD symptoms.

The authors' abstract, as published at the source. Frontiers in Psychiatry, 2026 · DOI ↗