The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

Abstract

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.

Abnormal features of human self‐domestication in bipolar disorder

“…Finally, we found that genes that are candidates for both domestication and BD are significantly associated to human pathological phenotypes impacting the renin‐angiotensin system (HP:0003351, HP:0000847, HP:0000841, HP:0000848), which is mostly involved in the regulation of blood pressure and electrolyte balance, as well as vascular resistance, but which has been also linked to mood disorders (Mohite et al, 2019). Patients with BD show higher plasma renin activity compared with controls (Barbosa et al, 2020). In animals, the inhibition of selected components of the renin‐angiotensin system reverses the hypertension and cognitive deficits associated with mood disorders (Mohite et al, 2019).…”

Lithium Treatment Improves Cardiac Dysfunction in Rats Deprived of Rapid Eye Movement Sleep

“…The findings are consistent with those of previous studies [ 7 , 8 , 9 ], illustrating the development of cardiac fibrogenesis and ventricular dysfunction in rats deprived of REM sleep. This study suggests that lithium treatment may rescue cardiac remodeling in patients with bipolar disorder because the profibrotic signaling regulated by lithium in REM sleep-deprived hearts is also involved in the pathophysiology of bipolar disorder [ 18 , 19 , 20 ].…”

Abnormal features of human self-domestication in bipolar disorder

“…Finally, genes that are candidates for both domestication and BD are significantly associated to human pathological phenotypes impacting the renin-angiotensin system (HP:0003351, HP:0000847, HP:0000841, HP:0000848), which is mostly involved in the regulation of blood pressure and electrolyte balance, as well as vascular resistance, but which has been also linked to mood disorders (Mohite et al, 2019). Patients with BD show higher plasma renin activity compared to controls (Barbosa et al, 2020). In animals, the inhibition of selected components of the renin-angiotensin system reverses the hypertension and cognitive deficits associated with mood disorders (Mohite et al 2019).…”