Neuroactive steroids as modulators of depression and anxiety.

In addition to the well-known genomic effects of steroid molecules, certain neuroactive steroids control neurotransmission through the modulation of specific neurotransmitter receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety and depression-related behavior and may contribute to the therapeutic effects of antidepressant drugs. However, nonpharmacological antidepressant treatment strategies did not affect neuroactive steroid composition. These studies suggest that the changes in neuroactive steroids observed after antidepressant pharmacotherapy probably reflect distinct pharmacological properties of antidepressants, rather than the clinical response. Nevertheless, initial studies investigating the antidepressive effects of exogenously administered dehydroepiandosterone revealed promising results. In addition, in various anxiety disorders, alterations of neuroactive steroid levels have been observed. In conclusion, neuroactive steroids contribute to the pathophysiology of affective disorders and the mechanisms of action of antidepressants. They are important endogenous modulators of depression and anxiety and might offer new targets for the development of novel anxiolytic compounds.