Glucocorticoids mood disorder

STRESS, GLUCOCORTICOIDS AND NEUROPLASTICITY IN THE PATHOLOGY OF MOOD DISORDERS 895... 

The potential hyperactivation of the HPA axis in mood disorders has been revisited in recent years, in large part due to the growing recognition of the specific brain areas in which atrophy (loss), a neuroplastic event, may be present in many patients. To what extent these findings of atrophy represent the sequelae of the biochemical changes (for example, in glucocorticoid levels) accompanying repeated affective episodes, remains to be fully elucidated. 

Whereas it is conceivable that a CRH/vasopressin hyperdrive contributes to behavioral, emotional, and hormonal symptoms of mood disorders, the question remains which mechanisms mediate this hyperactivity of CRH and vasopressin-secreting neurons. The gene expression of both neuropeptides is suppressed by ligand-activated glucocorticoid receptors. The efficiency of this negative feedback action of circulating corticosteroids depends on the number of corticosteroid receptors, their affinity, and the degree of interaction with other factors (e.g., heat shock protein) involved in the transcription machinery. 

McEwen BS Glucocorticoids, depression, and mood disorders Structural remodeling in the brain. Metabolism 2005 54(5 Suppl 1) 20. 

The authors suggested that the recurrence of the manic symptoms could have been due to premedication with prednisolone. Exacerbation of manic symptoms after the use of glucocorticoids has been documented before, but never in a case of short-term premedication before contrast-enhanced radiographic examination. This report shows that even a short-term course of glucocorticoids can have significant adverse effects in patients with a history of mood disorders. 

Steroids have mineralocorticoid and glucocorticoid effects. Betamethasone has little, if any, mineralocorticoid effect. However, it should be used with caution in patients predisposed to hypertension since mineralocorticoid effects may lead to sodium and water retention and an increase in blood pressure. When used systemically, especially at high doses, steroid therapy is associated with a risk of psychiatric reactions such as euphoria, irritability, mood lability and sleep disorders. Glucocorticoid side-effects include diabetes and osteoporosis. 

Yehuda R, Boisoneau D, Mason JW, Giller EL (1993a) Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders. Biol Psychiatry 34 18-25... 

Treatment with steroids may initially evoke euphoria. This reaction can be a consequence of the salutary effects of the steroids on the inflammatory process or a direct effect on the psyche. The expression of the unpredictable and often profound effects exerted by steroids on mental processes generally reflects the personality of the individual. Psychiatric side effects induced by glucocorticoids may include mania, depression, or mood disturbances. Restlessness and early-morning insomnia may be forerunners of severe psychotic reactions. In such situations, cessation of treatment might be considered, especially in patients with a history of personality disorders. In addition, patients may become psychically dependent on steroids as a result of their euphoric effect, and withdrawal of the treatment may precipitate an emotional crisis, with suicide or psychosis as a consequence. Patients with Cushing s syndrome may also exhibit mood changes, which are reversed by effective treatment of the hypercortisolism. 

The authors commented that the manic symptoms had probably been caused by glucocorticoids or glucocorticoid withdrawal. They concluded that patients with cluster headache and a history of affective disorder should not be treated with glucocorticoids, but with valproate or lithium, which are effective in both conditions. Lamotrigine, an anticonvulsive drug with mood-stabilizing effects, may prevent glucocorticoid-induced mania in patients for whom valproate or lithium are not possible (101). 

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