Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood,
cognition, and functioning. BD is associated with several psychiatric conditions as well clinical
comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and
multifactorial and several systems have been implicated. Considering that the Renin Angiotensin
System (RAS) plays an important role in cardiovascular diseases and that recently evidence has
suggested its role in psychiatric disorders, the aim of the present study is to summarize and to
discuss recent findings related to the modulation of RAS components in BD. A systematic search of
the literature using the electronic databases MEDLINE and LILACS was conducted through March
2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”;
“Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included
original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially
retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8),
the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls.
BD patients presented higher plasma renin activity in comparison with controls. The studies
evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a
potential role of RAS in BD. Further studies are necessary to investigate this relationship.