[Depression, stress and brain function]

Many patients with major depression have elevated serum cortisol, which cannot be suppressed with dexamethasone. This points to a disturbance in the hypothalamus-pituitary-adrenal (HPA) axis, which might have pathogenetic importance. Recent investigations with MRI have shown an increased frequency of generalised, as well as localised atrophy in the brains of depressed patients. The reduced volume of the hippocampus is particularly interesting, because of the participation of this structure in the regulation of the individual's stress response. Furthermore, the hippocampus is of major importance for cognitive processes. There is evidence that the increased cortisol concentration is neurotoxic and may cause atrophy, as is known from Cushing's disease. This is supported by studies of the accumulated duration of depressive episodes, and also by the fact that drugs that dampen the HPA axis have proved to have antidepressant properties in clinical controlled, double-blind studies. This points to new principles in the treatment of major depression and underlines the importance of early intervention in order to prevent cerebral atrophy, which is probably reversible at the beginning of the disease process.