Role of neuroactive steroids in mechnanism of action of clozapine (NU20-04-00389)

Basic information

Investigator: RNDr. Karel Valeš, Ph.D.
Main recipient: National Institute of Mental Health (NIMH)
Co-recipient: Institute of Endocrinology, Institute of Physiology of the Czech Academy of Science
Research period: 1/5/2020 - 31/12/2023
Total budget: 18,949,000 CZK
NIMH budget: 8,358,000 CZK
Supported by: Czech Health Research Council (AZV ČR)

Annotation

In our previous projects, we have demonstrated the role of neurosteroids in schizophrenia in both the animal model and clinical research. Furthermore, we demonstrated the effect of pragnanolone derivatives in the animal model of schizophrenia. A number of studies suggest that different levels of neurosteroids may explain differences in the therapeutic response. Antipsychotics can normalize altered levels of neurosteroids, but they also have their own antipsychotic potential and can be used as adjuvant therapy to affect the negative and cognitive symptoms of schizophrenia. It is in this direction that our research will go. In the preclinical part, we will study changes in neurosteroid levels in the CNS in the animal model of schizophrenia in response to the application of typical and atypical antipsychotics. Consequently, adjuvant therapy with pregnane derivatives will study the potential for an increase in the antipsychotic effect of antipsychotics. In the clinical part, we will focus on steroid changes in the blood of schizophrenia patients who can predict response to clozapine.