Mineralocorticoid receptor stimulation effects on stress-induced cortisol and alpha-amylase in female patients with borderline personality disorder and healthy controls: A randomized placebo-controlled experimental study.

Borderline personality disorder (BPD) has been associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis, such as a blunted cortisol response to acute psychosocial stress. The mineralocorticoid receptor (MR) is involved in HPA-axis feedback regulation and plays a key role in stress regulation. In response to stress, pharmacological blockade of the MR leads to exaggerated cortisol release, but MR stimulation has not been investigated in BPD. This is of special interest as altered hippocampal feedback regulation, possibly due to MR dysfunction, has been suggested in BPD. In a double-blind, randomized design, 120 female patients with BPD and 120 healthy controls (HC) received 0.4 mg fludrocortisone or placebo. Two hours later, participants were exposed to the Trier Social Stress Test (TSST) or a placebo version (pTSST). Salivary cortisol and alpha-amylase (sAA) were collected at baseline (T0), +120 min (T1, pre-(p)TSST), +135 min (T2) and + 195 min (T3) after drug intake. Despite reporting higher subjective affective response to stress, patients with BPD exhibited a blunted cortisol response to the TSST compared to HC after placebo. After fludrocortisone, cortisol values were diminished in both conditions and across groups. sAA increased in response to stress across groups and was not affected by MR stimulation. These findings demonstrate that BPD show a blunted cortisol response to stress. Because negative feedback through exogenous MR stimulation leads to comparable cortisol values in BPD and HC, these findings make it less likely that increased MR-mediated feedback is the primary mechanism underlying the blunted cortisol response to stress in BPD. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov ID: NCT05310253.