Olanzapine, a common antipsychotic drug used in schizophrenia treatment, is known to affect the epigenetic profile of the brain and other organs, explaining its efficacy in treating certain symptoms of the disease, as well as adverse side effects experienced by some patients.
Schizophrenia therapy has been a continuous struggle for over 50 years, which is still unsuccessful in finding universally effective treatments. The currently available drugs have the advantage of reducing schizophrenia symptoms with few neurological side effects, however, they are often associated with undesired systemic changes, such as metabolic syndrome and weight gain. Moreover, response to common antipsychotics is delayed in most patients, and show individual responsiveness, e.g. certain drugs are beneficial for some patients while completely ineffective in others, even if in general they have a similar mode of action.
Epigenetic changes, specifically DNA methylation, have been recently demonstrated to play a role in the development of characteristic schizophrenia symptoms, such as hallucinations and delusions. Research now shows that common antipsychotic drugs could alter DNA methylation status, thus affecting gene transcription and reducing schizophrenic symptoms indirectly.
A study published in Clinical Epigenetics demonstrates olanzapine is able to induce genome-wide DNA methylation changes in hippocampus, cerebellum and liver. These tissue-specific alterations are thought to disrupt the expression of critical genes involved in reversal of psychosis, as well as induction of unwanted side effects, such as weight gain.
The indirect mode of action would explain the delayed effect of the drug, since it often takes days or weeks after treatment with olanzapine for any changes to emerge. Moreover, olanzapine was demonstrated to be differentially effective in patients depending on their genotype. For example, certain genotypic status can be related to degradation and resistance to olanzapine. Thus, these patients would be unresponsive to this drug and may require alternative treatment.
Unraveling the mode of action of more antipsychotic drugs would help to identify genes and pathways involved in psychosis, opening up venues for more directed therapies, instead of using only universal treatments. Moreover, due to ambiguous etiology of schizophrenia, pin-pointing exact drug targets would be essential for creating personalized treatments, based on individual genotypic and epigenetic profiles. Such therapies would, without a doubt, be superior to conventional treatment plans developed mainly by trial-and-error.