The mechanism of valproic acid (Depakote) is inhibition of histone de-acetylases. For a mood-stabilizer and anti-epileptic, this has struck many people as unexpected. A paper by Tang at Scripps in Translational Psychiatry now strengthens the link, showing the acetylation levels at some promoter regions of genes implicated in schizophrenia and bipolar disorder (samples were taken from PFC). In non-psychiatric patients the levels drop consistently with age, but in the psychiatric patients they didn't. Treatment with a novel HDAC inhibitor altered expression of the homologous genes in treated mice.
Maybe a heavy epigenetic bias to the pathophysiology of schizophrenia is the reason we've had such trouble making schizophrenia markers stick.
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