Alterations in GABA activity have been shown to be a result of lower GAD1 expression induced by epigenetic mechanisms.40, 41 Lower GABA concentrations were found in patients with mood disorder, bipolar disorder or depression compared with controls.42, 43, 44 Another gene, which might regulate GABA neuronal excitability, is COMT (ref. 45). This evidence concerns the gene COMT and bipolar disorder.