Depression etiology: Hypothalamic-Pituitary-Adrenal Axis Dysregulation

Elevated cortisol levels over 24 hours have been observed in patients with MDD. Cortisol is a steroid hormone in the glucocorticoid class of hormones. It’s released in response to stress and low-blood glucose. It functions to increase blood sugar, suppresses the immune response, and aids in the metabolism of fat, protein, and carbohydrates. 

In studies a test called the dexamethasone suppression test (DST) has been used to assess cortisol release in depressed patients. Nelson and Davis used this test in patients with depression. They found that 41% of those with MDD with melancholia and 64% of those with MDD with psychotic features either had decreased suppression or were non-suppressors of serum cortisol. They determined that the utility of this test in routine clinical practice is limitted due to low sensitivity and specificity. 

There is a theory that may explain HPA axis dysregulation in depressed patients. Patients who are depressed, may have a dysfunction in the ability of cortisol-glucocorticoid receptor complex to enter the cell. This will disrupt the negative feedback mechanism which tells the body to stop producing cortisol. The result is increased cortisol levels because there is nothing indicating to the body enough cortisol has been produced. 

Elevated cortisol levels appear to be dependent on the current state of the person. If the person is depressed, levels will be elevated. Once the depressive episode has resolved or the person has been effectively treated with antidepressants the HPA axis appears to normalize. 

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