BMAL1 and major depressive disorder: CpG2 site methylation is also positively correlated with the ability to make quick decisions and mind flexibility, whereas CpG3 and CpG5 are associated with nighttime wakefulness, and CpG4 is correlated with symptoms of depression in AD patients, indicating that fine epigenetic BMAL1 gene regulation plays a critical role in AD pathogenesis [18].