Depression and epilepsy: do glucocorticoids and glutamate explain their relationship?

Depression is the most common psychiatric comorbidity in people with epilepsy, but it remains underrecognized and undertreated. In addition to its negative impact on quality of life, depressive disorders are predictive of a worse response to pharmacologic and surgical treatment of seizure disorders. This phenomenon is probably an expression of a bidirectional relationship between epilepsy and depression, which in turn is indicative of common pathogenic mechanisms that are operant in the two conditions. The abnormal role of the hypothalamic-pituitary-adrenal axis is one of the common pathogenic mechanisms that explains why patients with depression are at greater risk for developing epilepsy and vice versa.