This raises several biological questions that I am curious about. How does the immune system play a role in schizophrenia? For instance, differentially methylated regions overlap with the major histocompatibility complex. What role does expression of the major histocompatibility complex play in the development and course of schizophrenia? Is there a specific theory as to the role of the immune system in the development of schizophrenia in patients?

The presence of abnormal DNA methylation in utero is very interesting. It raises obvious questions of important clinical significance. Are there specific environmental conditions that the mothers were exposed to that resulted in the abnormal methylation of fetal DNA in utero? If so, what can be done to prevent such negative environmental conditions?

It is very interesting that clozapine, a drug for treating schizophrenia, can cause epigenetic modifications like DNA methylation. This raises questions about how many of the pharmaceutical drugs (and other drugs) that people take can result in epigenetic modification thereby having unanticipated effects on gene expression that may outlast the taking of the drug. What is the mechanism by which clozaphine causes DNA methylation at various sites? These are interesting quesitons that are not often discussed when looking at the mechanism of action of a drug.

It is very interesting that epigenetic modification relating to schizophrenia can be different in the genders because it is not obvious that this would be the case. Why would the same disease, schizophrenia, be cause by different epigenetic modification in men versus women? Given that the onset of schizophrenia commonly occurs between the late teens and late 20s, is there any evidence that changes in puberty are associated with any of these modifications such that they would be different in different genders? If the epigenetic modifications are different in different genders, does that suggest that the underlying mechanism may be different or that there should be a different approach to treatment of schizophrenics based on gender?

While it is not surprising that schizophrenia is polygenic, it is interesting that all of the known loci associated with schizophrenia have "minor" contributions and that there are no specific genes that are "major" contributors to the development of schizophrenia.

This is consistent with what we learned in class. As we learned, acetylation of histones is associated with gene expression whereas methylation of histones has been associated with with a decreased level of expression. The fact that the section on histone modifications is short as compared to the sections on DNA methylation suggests that the role of histone modifications in the epigenetics of schizophrenia is less well studied than the role of DNA methylation.

We learned about the miRNAs regulating translation in class by either repressing translation or causing degradation of mRNAs. It is interesting that such translational regulation plays a role in schizophrenia because this means that epigenetic factors that play a role in schizophrenia include both DNA methylation affecting transcription of certain genes and miRNAs affecting the translation of certain genes. This adds complexity to understanding the epigenetic mechanisms associated with schizophrenia. For example, in research studies, testing for the level of expression of a gene through quantifying mRNA as a proxy for expression of the protein can be misleading due to the regulation of translation by miRNAs.

Given that schizophreania is known to have a genetic component, it is interesting that the incidence has noticeably increased. The implication is that this may be due to environmental or epigenetic factors. Is there a hypothesis or explanation as to what environmental factors may have led to the increased incidence of schizophrenia? What factors are different now than 20 years ago accounting for the increased incidence?