About 30% of patients with schizophrenia do not respond to antipsychotic drugs. The authors showed that chronic administration of atypical antipsychotics downregulates metabotropic glutamate 2 receptor (mGlu2) expression in the frontal cortex in mice and in patients with schizophrenia, and this was due to a serotonin receptor 2A-dependent increase in histone deacetylase 2 (Hdac2) expression and HDAC2 binding to the mGlu2 promoter. Chronic administration of HDAC inhibitors improved the effects of antipsychotic drugs in a mouse model of schizophrenia, pointing to their potential clinical use in treatment-resistant schizophrenia.
ORIGINAL RESEARCH PAPER
Kurita, M. et al. HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nature Neurosci. 5 Aug 2012 (doi:10.1038/nn.3181)
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Welberg, L. Improving responses to antipsychotics. Nat Rev Neurosci 13, 603 (2012). https://doi.org/10.1038/nrn3333