Abstract
Mental disorders are frequently preceded by stressful events or situations. Depression is a typical case in point. This raises the question, is depression--or possibly better: are certain forms of depression--caused by stress? Can stress be a true pathogenic factor? Phrased differently: can stress destabilize neuronal systems in the central nervous system (CNS) to such an extent that depressive symptoms are generated? This question is discussed with the corticotropin releasing hormone (CRH) and MA systems and hypothalamic-pituitary-adrenal (HPA) axis as major foci. The following issues are explored: the effect of antidepressants on corticosteroid receptor gene expression; the behavioral sequellae of CRH administration; CRH disturbances in depression; the impact of early life adversity on the development of the CRH system and on stress reactivity; the interrelationships of stress hormones and monoaminergic (MA ergic) transmission and finally the therapeutic potential of CRH and cortisol antagonists. The available data suggest that CRH overdrive and cortisol overproduction may play a pathogenic role in the occurrence of certain types of depression, directly and/or indirectly, i.e. by induction or exacerbation of disturbances in MA ergic transmission. Stress should, thus, become a major focus of biological depression research.