Decreased serum cortisol levels in women with major depressive disorder and suicidal ideation in the antenatal period

INTRODUCTION: Pregnancy is associated with physiological changes in endocrine production and immune activity. However, the role of hypothalamus-pituitary-gonadal and hypothalamus-pituitary-adrenal axes, alongside the immune system, in women with antenatal major depressive disorder (MDD) is complex, with conflicting findings, particularly in the context of suicidal ideation. AIM: We aimed to investigate the role of sex hormones, cortisol and immune-related biomarkers in women in the antenatal period by comparing 1) controls, women with history of MDD, and women with current antenatal MDD, and 2) women with suicidal ideation and without suicidal ideation within the current MDD group from the Psychiatry Research and Motherhood - Depression (PRAM-D) study, a longitudinal, observational study investigating perinatal MDD. METHODS: We included 60 women with a current diagnosis of MDD (cases) or history of MDD and 43 women without psychiatric conditions (controls), recruited in the late second trimester of pregnancy. We measured serum testosterone (T, nmol/L), 17-β-estradiol (E2, pmol/L), and cortisol (C, nmol/L) levels as well as a panel of immune-related biomarkers. We calculated the total testosterone-to-E2 (T/E2) and testosterone-to-cortisol (T/C) ratios. We leveraged item 3 of the Hamilton rating scale for depression to categorise cases into those with suicidal ideation and those without suicidal ideation. Non-parametric and parametric statistical analyses were performed (Kruskal-Wallis test, Mann-Whitney U test, independent samples t-test and ANOVA) to investigate differences in endocrine parameters between controls, participants with a history-only of MDD and participants with current MDD. The analyses focused on suicidal ideation were limited to participants with current MDD diagnosis and investigated both endocrine and immune-related biomarkers. RESULTS: We found a significant difference in T levels between the three study groups (p = 0.032), but this association was no longer significant after adjusting for education levels. Furthermore, in the group of women with current MDD, those with suicidal ideation showed significantly higher levels of testosterone (p = 0.045), T/E2 ratio (p = 0.023), T/C ratio (p = 0.001), and significantly lower cortisol levels (p = 0.007) compared with cases without suicidal ideation. However, in adjusted analyses, only the difference in cortisol levels remained significant (p = 0.034). Additionally, those with suicidal ideation showed significantly lower IL-1β (p = 0.025) and IL-10 (p = 0.018), while the difference in MCP-1 concentrations disappeared after adjusting for race. CONCLUSION: In conclusion, we found decreased levels of cortisol in pregnant women with current MDD and suicidal ideation, highlighting cortisol as a potential biomarker for screening, early identification and therapeutic intervention.