Aims: 

A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported in several psychiatric a neurological disorders. In depression, a dysbalance at all levels of the HPA axis has been reported. It is suggested that chronic exposure to stress situations and particularly the neurotoxic effects of glucocorticoids contribute to the development of mood disorders. This general belief neglects the already known variability and specificity of the stress response.

Methods: 

We have studied several models of psychiatric disorders, such as chronic mild stress and spontaneous anhedonia as models of depression, and enriched environment (EE) as a model of increased neural plasticity.

Results: 

The results show that a prolonged rise in plasma corticosterone may, but need not to be observed in the models of depression as well as in the EE inducing a positive physiological outcome. Main neurochemical changes observed in the brain were those in gene expression of CRH and ionotropic glutamate receptor subunits. Many intensive stress situations in humans, both under daily life conditions and in stress models, were not associated with increased cortisol release. Moreover, high trait anxiety in healthy subjects was accompanied by lower cortisol response during psychosocial stress. In anxious subjects, low cortisol responses during stress correlated with exaggerated perception of stress and worse mental performance.

Conclusions: 

Our findings do not support the corticosteroid neurotoxicity hypothesis. More complex neuroendocrine changes have to be considered in evaluating the risk factors of the development of mood disorders.

The study was supported by grants of APVV LPP-0194-06 and VEGA 5064.