Modifying responses to antipsychotic drugs

Chronic treatment with antipsychotic drugs induces modifications to histones, the proteins around which DNA wraps, which may hinder the responses to these drugs. These findings from this mouse study, reported online this week in Nature Neuroscience, suggest that inhibiting the modification of histones may improve their efficacy.

Javier Gonzalez-Maeso and colleagues report that mice treated chronically with antipsychotic drugs have modifications to histones that reduced the expression of glutamate receptors in the frontal cortex of mice. This reduction in glutamate receptors was also associated with increased schizophrenia-like behaviors in the mice. Treating the mice with a drug that prevented these histone modifications reversed this effect.

Previous clinical studies have found that combining antipsychotic drugs with valproate, a drug that is known to prevent the histone modifications studied here, can increase the therapeutic benefits of antipsychotic drugs. This study suggests a mechanism by which valproate (and other drugs that target histone modifications) could increase the therapeutic benefit of antipsychotic treatment.