[Serotoninergic system and limbic-hypothalamic-pituitary-adrenal axis (LHPA axis) in depression]

Depression is associated with the dysfunction in the serotoninergic (5-HT, 5-hydroxytryptamine) transmission and dysregulation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA axis). In depression, the 5-HT system exhibits impaired presynaptic activity of 5-HT neurones, an increased activity of central postsynaptic 5-HT2A receptors, decreased activity of postsynaptic 5-HT1A receptors and altered synaptic 5-HT uptake. The coexistent dysregulation of the LHPA axis is predominantly linked to GR (glucocorticoid receptor) dysfunction within the limbic system along with hypercortisolemia, MR (mineralocorticoid receptor) and GR receptors imbalance which results in impaired negative feedback mechanisms in the LHPA axis loops. Several clinical and animal studies revealed the involvement of 5-HT1A system in LHPA axis regulatory mechanisms. That association seems to be dependent on the corticoid levels. The impaired GR receptor function and MR/GR receptors imbalance alter the negative feedback regulation within the LHPA axis which is followed by its dysregulation and hypercortisolemia that is further associated with the decreased activity of postsynaptic 5-HT1A receptors resulting in a serotoninergic dysfunction. The aim of this paper is to discuss and review the current data on the existence of the hypothetical relationship between the activity of the serotoninergic system, predominantly 5-HT1A receptors, and LHPA axis in depression.