Механизм резистентности к лечению шизофрении

Scientists have discovered a molecular mechanism for resistance to antipsychotic medications, a finding that may pave the way for the development of new drugs to treat a significant proportion of schizophrenia patients who do not respond to these medications.

Investigators led by Javier González-Maeso, PhD, assistant professor of psychiatry and neurology, Mount Sinai School of Medicine in New York City, found that long-term administration of atypical antipsychotic drugs selectively upregulates expression of the enzyme histone deacetylase 2 (HDAC2) in both mouse and human frontal cortex.

This epigenetic change, which is dependent on serotonin 5-hydroxytryptamine 2A (5-HT2A) upregulation, leads to lower expression of the metabotropic glutamate 2 receptor (mGlu2), thereby limiting the therapeutic effects of atypical antipsychotic therapy, often leading to a recurrence of psychotic symptoms.

According to investigators, blocking this cascade of events with HDAC inhibitors may improve responses to atypical antipsychotic drug therapy.

"Together, these data suggest that HDAC2 may be a new therapeutic target to augment the treatment of schizophrenia.... Specifically, our findings encourage the development and testing of HDAC2-selective inhibitors for schizophrenia," the investigators write.

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