The clinical potentials of endogenous neurosteroids

Stress increases plasma and brain concentrations of the neurosteroids allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC), which can have potent effects on GABAA receptors in the brain. Blockade of the formation of neurosteroids prevents specific biochemical and behavioral effects of stress, suggesting that those effects are dependent upon the actions of GABA(A)-receptor active neurosteroids. Recent investigations provide a better understanding of the role of endogenous neurosteroids in normal neuronal development and in the pathophysiology of brain disorders. Physiological neurosteroid fluctuations have potential implications for stress-sensitive neurological conditions such as epilepsy, infantile spasms, as well as psychiatric disorders such as schizophrenia, posttraumatic stress disorder and depression. Future studies may provide important new evidence that may not only explain acute actions of stress, but also reveal the clinical importance of neurosteroid mechanisms during chronic stress.