Corticosteroid-induced psychiatric disorders: genetic studies are needed

Excerpt

Glucocorticoids are steroid hormones, secreted by the adrenal glands, that bind with high affinity to brain mineralocorticoid receptors (MR) and lower affinity to glucocorticoid receptors (GR). GR are widely distributed throughout the brain, whereas MR are mainly found in the hippocampus. Cortisol exerts predominantly its tonic influences via hippocampal MR, whereas feedback actions at the level of the pituitary as well as actions at the amygdala level are mediated by GR. In addition, glucocorticoid responsive elements are found in the regulatory regions of many genes in the brain. Glucocorticoids are involved in different processes such as glucose metabolism, inflammation, immunity, etc. The stress responsive hypothalamic pituitary adrenal (HPA) axis regulates glucocorticoid production and is implicated in the pathophysiology of anxiety and depression as well as in cognitive functioning or the development and relapse of psychotic disorders. Major depression may be associated with a dysregulation of MR and/or GR within the HPA axis; elevated HPA activity could be more often associated with depression with psychotic features. Elevated cortisol secretion has also been positively linked with symptom severity in people with psychotic disorders. Antiglucocorticoid and related drugs that target the HPA axis may be useful for the treatment of people with psychosis and were also studied in the treatment of depressive disorders or in the improvement of cognitive dysfunction associated with these disorders [1]. Moreover, inflammation plays a significant role in the pathophysiology of major psychiatric disorders. …