The specificity of stress responses to different nocuous stimuli: neurosteroids and depression

The role that adrenal cortex and neurosteroid hormones may have in the etiology and/or maintenance of depressive diseases is discussed. Selye's concept of stress as the summation of unspecific body responses of the autonomic central nervous system (CNS) and hypothalamic pituitary adrenal axis (HPAA) as the main characteristic of it is contrasted with Mason's view of stress responses as being specific for different stimuli, i.e., the neuroendocrine system responds with the production of a hormonal profile individualized and characteristic for the various stimuli applied. The data reviewed provides support for Mason's interpretation of stress as fundamentally a behavioral response. In turn, the high relevance of emotional factors in the determination of stress responses led to a reconsideration of cognitive-affective interactions in nervous systems. Recent results revealed that improvement in depression treated with antidepressants (ADs) is associated with an increase in the neurosteroid 3alpha 5alpha tetrahydroprogesterone, both in the blood and cerebrospinal fluid of recovered patients. The increase occurs with both selective serotonin reuptake inhibitors and tricyclic ADs. An evaluation of the possible and putative roles for neurosteroids in the CNS is presented and suggestions for enhancing the type of supporting data from the laboratory diagnosis of depressions are advanced.