HPA Axis Dysfunction In Treatment Resistant Affective Disorders
Background: TRD (Treatment Resistant Depression) patients have been shown to have hypercortisolemia and a hyperactive HP A (hypothalamo-pituitary-adrenal) axis. The Cortisol Awakening Response (CAR) is a naturalistic measure of the HP A axis activity. Although found to be elevated in depression, it has never been explicitly studied in TRD; furthermore, results have never been compared between Treatment Resistant Unipolar Depression (TRUD) and Treatment Resistant Bipolar Depression (TRBD). In addition, dehydroepiandrosterone (DHEA), the other main adrenal steroid, and which may counteract the effects of cortisol on the brain, has never been measured in TRUD or TRBD. Aims and Methods: To assess the state and relevance of HP A axis changes in treatment-resistant depression using the following methods: (a) salivary cortisol, DHEA and the ratio of Cortisol/DHEA, measured at several points of the day over 2 days; and (b) the CAR (AUCg and AUCi), measured over 2 days. These parameters were compared: between TRUD and TRBD; between patients in episode and in remission; and with matched healthy controls. Results: TRUD patients in episode had a higher CAR (AUCg) compared to controls, remitted patients and TRBD. They also exhibited hypercortisolemia throughout the day (AUCg), and on some measures an elevated Cortisol/DHEA ratio. TRBD patients in episode exhibited a lower CAR (AUCg and AUCi) than controls, remitted patients and TRUD, particularly on Day 1. The Cortisol/DHEA ratio was also lower than controls on some measures. However, patients with remitted TRBD had higher Cortisol/DHEA ratios (but not CAR) than controls.
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