COMT and bipolar disorder: More recently, methylation of CpG sites in the promoter region of COMT has been linked to psychiatric diagnoses such as schizophrenia (Murphy et al., 2005; Abdolmaleky et al., 2006), bipolar disorder (Abdolmaleky et al., 2006), and nicotine dependence (Xu et al., 2010) as well as prefrontal cognition and activity (Ursini et al., 2011).