Evidence continues to stack up about the environmentally responsive ways of our epigenome, but most of the time when we hear about it, it’s usually about some bad news. However, Dr. Shiva Singh and his colleagues at Western University (Canada) have come across an interesting case where epigenetics mechanisms appear to cause the therapeutic effects of antipsychotics.
Singh frames an interesting problem faced by psychiatry. He shares that, “What causes Schizophrenia remains a scientific challenge, even though it’s treated using antipsychotics, which block the dopamine D2 receptor. The effect of such drugs is variable across patients, may take weeks, and may result in variety of side effects.” So despite the current belief of the mechanism of action of this popular antipsychotic drug (via dopamine blockade), it seems that epigenetics has a thing or two to offer psychiatry in regards to the interaction between genome and environment. In their research, the group administered a therapeutic dose of an antipsychotic drug (olanzapine) and observed the effect on DNA methylation in two neural (hippocampus, cerebellum) tissues and one non-neural (liver) tissue in vivo.
Here’s what the group found (under all that snow):
- Olanzapine attenuates stress (as measured by locomotor activity) in rats that were previously exposed stress inducing tail pinches.
- Olanzapine causes methylation changes in genes encoding for dopamine related processes, including receptors, a transporter, dopamine synthesis, and metabolism.
- Most genes showed increases in methylation.
- In silico analysis points towards a strong potential for the observed changes in gene promoters to repress transcription.
Lead author Dr. Melkaye Melka shares that “Chronic olanzapine treatment may reduce dopamine activity by altering gene methylation. It may also explain the delayed therapeutic effect of antipsychotics, which occurs despite rapid dopamine blockade. The findings highlight the likely therapeutic effect of olanzapine through epigenetic mechanisms.” The authors also share that they have seen epigenetic changes that explain some of the associated side effects (metabolic disorders and sexual dysfunction), which is currently in press with Clinical Epigenetics. Ultimately, Singh concludes, “The novel results offer an independent support for the Dopamine hypothesis of schizophrenia and may account for variable drug response across patients. They also implicate DNA methylation as a potential mechanism of causation and therapeutic option in such disorders.”
Learn more about the epigenetics of the brain in the Journal of Molecular Psychiatry, November 2013