The renin–angiotensin system: a possible new target for depression

Abstract

Depression remains a debilitating condition with an uncertain aetiology. Recently, attention has been given to the renin–angiotensin system. In the central nervous system, angiotensin II may be important in multiple pathways related to neurodevelopment and regulation of the stress response. Studies of drugs targeting the renin–angiotensin system have yielded promising results. Here, we review the potential beneficial effects of angiotensin blockers in depression and their mechanisms of action. Drugs blocking the angiotensin system have efficacy in several animal models of depression. While no randomised clinical trials were found, case reports and observational studies showed that angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had positive effects on depression, whereas other antihypertensive agents did not. Drugs targeting the renin–angiotensin system act on inflammatory pathways implicated in depression. Both preclinical and clinical data suggest that these drugs possess antidepressant properties. In light of these results, angiotensin system-blocking agents offer new horizons in mood disorder treatment.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Examples include statins, aspirin and angiotensin antagonists 788, 789, 790, 791, 792, 793. The implications are that clinicians should be actively engaged in the management of these disorders, and should select therapies from those agents that may have benefit in mood symptoms.…”

The Effect of Hypo-Hydration on Mood and Cognition is Influenced by Electrolyte in a Drink and Its Colour: A Randomised Trial

“…Clinical data, although not as yet double-blind trials, have suggested that drugs, such as anti-hypertensive drugs that block the production of Angiotensin II, help mood disorders and produce a positive outcome in animal models of depression. It has been proposed that aldosterone has a role in depression [33][34][35], and that the level of this hormone predicts the outcome of the disorder [36]. Therefore, future research should monitor the levels of hormones associated with the renin-angiotensin-aldosterone system, and relate these to psychological functioning.…”

Neuroimaging genomic studies in major depressive disorder: A systematic review

“…Recent evidence indicates that the RAA system may be involved in the pathophysiology of MDD and be a potential target for depression treatment . Diverse studies have found that neuroimaging alterations in MDD were associated with angiotensin‐converting enzyme insertion/deletion (ACE I/D) and type 1 angiotensin II receptor (AGTR1) genes.…”

“…Recent evidence indicates that the RAA system may be involved in the pathophysiology of MDD and be a potential target for depression treatment. 109,110 Diverse studies have found that neuroimaging alterations in MDD were associated with angiotensin-converting enzyme insertion/deletion (ACE I/D) and type 1 angiotensin II receptor (AGTR1) genes. ACE-D carriers showed significantly smaller anterior cingulate gyrus volumes and larger middle temporal gyrus volumes, 46 as well as decreased default-mode network activity in remitted geriatric depression.…”