Comparison of Salivary Cortisol Levels in Patients with Bipolar I Disorder and General Population: A Case-Control Study

Abstract

Background: Bipolar I disorder is associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels. This study aimed to compare salivary cortisol as a non-invasive biomarker in euthymic patients with bipolar I disorder and healthy controls. Methods: In this case-control study conducted in Isfahan in 2024, 30 euthymic patients with bipolar I disorder (confirmed by DSM-5-TR, YMRS≤2, HDRS≤7) and 30 age-, sex-, and education-matched healthy individuals were selected via purposive sampling. Morning salivary cortisol (6–8 AM) was measured using Diametra ELISA kit (Diametra, Italy, 2024). Data were analyzed using independent t-test in SPSS version 27. Findings: Mean salivary cortisol level in the patient group (12.84 ± 8.11 ng/mL) was significantly higher than in the healthy group (7.30 ± 4.33 ng/mL). Conclusion: Elevated salivary cortisol even during euthymia indicates persistent HPA axis hyperactivity. This finding is consistent with previous studies in acute phases and suggests that cortisol dysregulation is a trait marker in bipolar disorder. Salivary cortisol can serve as a cost-effective, non-invasive biomarker for screening and monitoring of patients. © 2026, Isfahan University of Medical Sciences(IUMS). All rights reserved.