A systematic review and meta-analysis by Murri and others found that cortisol levels are "associated with the manic phase" of BD. Likewise, various other studies support an important role for hypothalamic-pituitary-adrenal axis (HPA axis).

Risk for BD is thought to be influenced by genetics, environment, and ADHD. In one respect (heritability), genetic factors may account for up to 70-90% of the risk of developing BD.