HPA axis in depression — MRCPsych Paper A MCQ

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ModerateNeurophysiology and neurochemistryHPA axis in depressionMRCPsych Paper A

A 46-year-old woman has severe depression with anhedonia, loss of mood reactivity, early-morning waking, reduced appetite and weight loss. Her evening cortisol concentration is persistently raised, with no evidence of corticosteroid use or a primary endocrine disorder. Which neuroendocrine change best explains this finding?

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Correct answer: E — Impaired glucocorticoid feedback sensitivity

The correct answer is E. Melancholic depression, particularly when severe, is classically associated with HPA-axis overactivity and hypercortisolism. Reduced glucocorticoid-receptor sensitivity weakens cortisol-mediated negative feedback at the hypothalamus and pituitary, permitting continued CRH and ACTH drive and an abnormally sustained cortisol concentration. Reduced CRH secretion, enhanced glucocorticoid feedback and accelerated ACTH clearance would instead tend to decrease cortisol output. Melatonin contributes to circadian and sleep regulation, but increased pineal secretion does not explain persistent hypercortisolism. The association is not present in every patient and is not a diagnostic test for depression, but it is the characteristic neuroendocrine model tested here.

Reference: Juruena MF, Bocharova M, Agustini B, Young AH. Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review. Journal of Affective Disorders 2018;233:45-67. https://pubmed.ncbi.nlm.nih.gov/29150144/