Posttranslational histone modifications and the neurobiology of psychosis

Schizophrenia and related major psychiatric disease is typically defined by the conspicuous absence of a defining neuropathology and a lack of straightforward identifiable genetic factors in the majority of affected individuals. On the other hand, there is increasing evidence that a distinct set of RNAs, many of which encode proteins of critical importance for myelin regulation and oligodendrocyte function, or GABAergic inhibitory and glutamatergic excitatory neurotransmission are expressed at altered levels in diseased brain. This chapter explores the mechanisms by which epigenetic regulators of gene expression, including covalent histone modifications, could contribute to dysregulation of gene expression in schizophrenia. There is also discussion on the methodological and scientific limitations of histone-focused approaches, as it pertains to the human (postmortem) brain, as well as brief remarks on the topic of epigenetic heritability of chromatin structures potentially altered in schizophrenia. The authors predict that the study of histone modifications, both at defined candidate gene loci and genome-wide, will become an important tool in the investigation of gene expression abnormalities and potential epigenetic dysregulation in the brains of subjects on the psychosis spectrum.