Corticosteroids in relation to fear, anxiety and psychopathology

Corticosteroids play extremely important roles in fear and anxiety. The mec hanisms by which corticosteroids exert their effects on behavior are often indirect, because, although corticosteroids do not regulate behavior, they induce chemical changes in particular sets of neurons making certain behavi oral outcomes more likely in certain contexts as a result of the strengthen ing or weakening of particular neural pathways. The timing of corticosteroi d increase (before, during or after exposure to a stressor) determines whet her and how behavior is affected. The present review shows that different a spects of fear and anxiety are affected differentially by the occupation of the mineralocorticoid receptor (MR) or glucocorticoid receptor (GR) at dif ferent phases of the stress response. Corticosteroids, at low circulating l evels, exert a permissive action via brain MRs on the mediation of acute fr eezing behavior and acute fear-related plus-maze behavior. Corticosteroids, at high circulating levels, enhance acquisition, conditioning and consolid ation of an inescapable stressful experience via GR-mechanisms. Brain GR-oc cupation also promotes processes underlying fear potentiation. Fear potenti ation can be seen as an adjustment in anticipation of changing demands. How ever, such feed-forward regulation may be particularly vulnerable to dysfun ction. MR and/or GR mechansisms are involved in fear extinction. Brain MRs may be involved in the extinction of passive avoidance, and GRs may be invo lved in mediating the extinction of active avoidance. In the developing bra in, corticosteroids play a facilitatory role in the ontogeny of freezing be havior, probably via GRs in the dorsal hippocampus, and their influence on the development of the septo-hippocampal cholinergic system. Corticosteroid s can exert maladaptive rather than adaptive effects when their actions via MRs and GRs are chronically unbalanced due to chronic stress. Both mental health of humans and animal welfare is likely to be seriously threatened af ter psychosocial stress, prolonged stress, prenatal stress or postnatal str ess, especially when maternal care or social support is absent, because the se can chronically dysregulate the central MR/GR balance. In such circumsta nces the normally adaptive corticosteroid responses can become maladaptive. (C) 2001 Elsevier Science Ltd. All rights reserved.