Genome-wide mapping of epigenetic modifications in the brain suggest an important role for epigenetic processes in neurodevelopment (Lister et al, 2013). It is hypothesized that epigenetic alterations mediate neurodevelopmental diseases such as schizophrenia or autism, as well as other mental health conditions such as addiction and dementia.

The main appeal of this hypothesis is that, since epigenetic modifications are catalyzed by reversible enzymatic reactions they could be modulated by pharmacological agents, potentially reprogramming pathological states. There is strong preclinical evidence that learning and memory involve changes in DNA methylation and histone acetylation (Heyward and Sweatt, 2015). The involvement of DNA methylation and histone acetylation/deacetylation enzymes in learning and memory raises the possibility that they might be targeted to attenuate remote memories for treatment of PTSD(Graff et al, 2014). HDAC inhibition enhances cognitive performance in a mouse model of impaired cognition, and CREB pathway-specific selected HDAC inhibitor crebinostat was shown to significantly improve memory (Fass et al, 2013). It is unclear, however, whether this approach works in humans. If indeed the clinical data replicates animal studies, isotype-specific HDAC inhibitors should have a large impact on the treatment of cognitive decline and dementia, and perhaps PTSD.

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