Epigenetics and Novel Treatments for Psychiatric Disorders

NEW TREND IN PSYCHOPHARMACOLOGY Modern formulations of psychiatric disorders hypothesize that mother nature goes awry, causing both genetic and epigenetic disease actions. Genetic disease actions are the consequences of naturally inherited risk genes that have an altered sequence of DNA. This altered DNA sequence theoretically leads to the production of altered gene products in neurons, causing inefficient information processing in various brain circuits, and biasing those circuits towards developing symptoms of a mental illness. Epigenetic disease actions are theorized either to activate risk genes to make an altered gene product or to activate normal genes to make normal gene products but at the wrong time. Epigenetic disease mechanisms theoretically turn normal genes into risk genes by causing normal genes to be expressed in neurons when these genes should be silenced or by causing normal genes to be silenced when they should be expressed. Such epigenetic disease actions are thought not only to be regulated by inherited mechanisms and to be triggered by stress and the environment; they are also hypothesized to contribute to inefficient information processing in brain circuits, increasing the chances of developing symptoms of a psychiatric disorder. Since manipulating genes themselves in psychiatric disorders may not be feasible, ethical, or safe (it is not nice to try to fool mother nature this way), targeting epigenetic mechanisms is increasingly being seen as a possible therapeutic approach for developing novel treatments of psychiatric illnesses (perhaps the nice way to fool mother nature?). Three specific epigenetic mechanisms currently under investigation include attempts to silence risk genes by enhancing the methylation of gene promoters or their downstream products; attempts to activate helpful genes by inhibiting an enzyme called histone deacetylase; and preventing the formation of defective or unwanted proteins in a neuron by interfering with RNA. Here we review the progress in applying such epigenetic therapeutics in psychiatry and determine whether such a strategy has shown any success in fooling mother nature's role in psychiatric disorders, emphasizing findings in schizophrenia.