Corticosteroids in relation to fear, anxiety and psychopathology

Corticosteroids play extremely important roles in fear and anxiety. The mechanisms 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 behavioral outcomes more likely in certain contexts as a result of the strengthening or weakening of particular neural pathways. The timing of corticosteroid increase (before, during or after exposure to a stressor) determines whether and how behavior is affected. The present review shows that different aspects of fear and anxiety are affected differentially by the occupation of the mineralocorticoid receptor (MR) or glucocorticoid receptor (GR) at different phases of the stress response. Corticosteroids, at low circulating levels, exert a permissive action via brain MRs on the mediation of acute freezing behavior and acute fear-related plus-maze behavior. Corticosteroids, at high circulating levels, enhance acquisition, conditioning and consolidation of an inescapable stressful experience via GR-mechanisms. Brain GR-occupation also promotes processes underlying fear potentiation. Fear potentiation can be seen as an adjustment in anticipation of changing demands. However, such feed-forward regulation may be particularly vulnerable to dysfunction. MR and/or GR mechanisms are involved in fear extinction. Brain MRs may be involved in the extinction of passive avoidance, and GRs may be involved in mediating the extinction of active avoidance. In the developing brain, corticosteroids play a facilitatory role in the ontogeny of freezing behavior, probably via GRs in the dorsal hippocampus, and their influence on the development of the septo-hippocampal cholinergic system. Corticosteroids 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 after psychosocial stress, prolonged stress, prenatal stress or postnatal stress, especially when maternal care or social support is absent, because these can chronically dysregulate the central MR/GR balance. In such circumstances the normally adaptive corticosteroid responses can become maladaptive.