SAT-045 Exploring the Relationship Between ACTH and Cortisol Response to CRH Stimulation and Anxiety and Depressive Symptoms

Abstract Disclosure: A.P. Lopez Lopez: None. Q. Asla: None. E. Urgell: None. S. Terzan: None. M. Garrido: None. A. Santos: None. E.A. Lawson: Merck, EAL and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, Merck and West Pharmaceutical Services.. A. Aulinas Maso: None. Hypercortisolemia (e.g., due to glucocorticoid administration or endogenous Cushing’s syndrome) can result in increased anxiety and depressive symptoms that improve with normalization of cortisol levels. Further, anxiety and depressive disorders are associated with endogenous hypercortisolemia, leading to the hypothesis that hypothalamic-pituitary-adrenal (HPA) axis dysregulation may drive psychological symptoms. However, the link between HPA reactivity and anxiety and depressive symptoms in healthy individuals without a psychiatric disorder is less understood. We aimed to explore the relationship between HPA axis response to stimulation [by corticotrophin (CRH) test] and anxiety and depressive symptoms in healthy adults. We hypothesized that greater ACTH and cortisol response to CRH stimulation would be associated with higher anxiety and depressive symptoms, providing evidence of interindividual variability in HPA sensitivity that might precede and contribute to clinical anxiety and depression. 21 healthy individuals mean age 48 ± 3 years (52% female) were enrolled in a randomized, placebo-controlled crossover study with two main visits. One female participant discontinued the study after the first visit. Participants completed self-report questionnaires to assess anxiety (State Trait Anxiety Inventory State, STAI-S; and Trait, STAI-T) and depressive (Beck Depression Inventory-II, BDI-II) symptoms; higher scores indicate greater symptom severity. STAI scores >45 and BDI-II scores >14 suggest clinically significant anxiety or depressive symptoms respectively. Blood samples for ACTH and cortisol were obtained before and 15, 30, 45, 60, 90, and 120 minutes, following administration of CRH or placebo (P). Wilcoxon test was used to compare cortisol and ACTH dynamics between CRH vs P conditions (P). For correlations, Spearman’s test was used. Participant’s STAI-S, STAI-T, and BDI-II scores were in the non-clinical range (13.0 ± 1.3; 16.2 ±1.6; 4.5±1.0). As expected, ACTH and cortisol area under the curve (AUC), peak and percent change from baseline to peak were higher in the CRH vs P (p<0.002). In the CRH condition, cortisol AUC and peak were positively associated with STAI-S scores (ρ≥0.48, p≤0.034) Additionally, there was a trend-level positive correlation between cortisol peak and STAI-T score (ρ= 3.9, p=0.09). In the P, there were no associations between hormone levels and STAI or BDI-II scores. Further, there were no associations between cortisol levels and BDI-II scores, nor ACTH levels and STAI or BDI-II scores in either condition. In healthy individuals, greater cortisol but not ACTH response to CRH stimulation was associated with increased anxiety symptoms. Further research is warranted to determine whether increased HPA reactivity results from anxiety symptoms and/or contributes to development of clinically significant anxiety and depressive symptoms. Presentation: Saturday, July 12, 2025