NLRP3 and bipolar disorder: Possible explanations include AII-mediated increases in substance P activity and heightened hypothalamic-pituitary-adrenal axis activity, provoking stress and anxiety.7,8,9 Moreover, polymorphisms associated with higher levels of AII have been associated with other mental health conditions, including major depression, bipolar disorder, panic disorder, and anxiety disorder.7,8,10,11,12 Furthermore, recent data13 suggest that users of ARBs, but not ACEIs, may have an increased risk of suicide compared with nonusers.