Objectives. The aim of thepaper is to discuss the role of two neurosteroids: dehydroepiandosterone (DHEA) and pregnenolone in schizophrenia, in the light of experimental and clinical studies.
Background Neurosteroids are precursors or metabolites of steroid hormones that regulate the nervous system excitability. Since neurosteroids modulate a number of receptors implicated in pathophysiology of schizophrenia, investigation of the physiology and patho-physiology of neurosteroid metabolism in the CNS seems to be important for our better understanding of thepathomechanism of schizophrenia. Among neuroactive steroids the followingplay a major role in the pathophysiology of psychotic symptoms:progesterone, dehydroepiandosterone (DHEA), pregnenolone sulfate (PREGS), and dehydroepiandosterone sulfate (DHEAS). All the four substances modulate NMDA receptors positively and GABA-A receptors-negatively. In patients with schizophrenia elevated plasma levels of circulating DHEA, DHEAS, testosterone, cortisol, progesterone, and estradiol can be seen, although clinical significance of these findings remains unclear. DHEA, DHEAS, progesterone or its derivative, allopregnenolone, manifest clinical anxiolytic, antidepressant, and antipsychotic action.
Conclusions. Studies conducted so far allow to conclude that in the course of schizophrenia a disturbance of neurosteroid balance occurs. Moreover, a positive response to neuroleptic treatment was shown to be related to changes in plasma levels of a number of neurosteroids. Finding out whether this is a random effect or whether some neurosteroids perhaps mediate the positive response to antipsychotic treatment would be a significant development in psychopharmacotherapy of schizophrenia.