Exploring the evidence implicating the renin-angiotensin system (RAS) in the physiopathology of mood disorders

Mood disorders include Major Depressive Disorder (MDD), Bipolar Disorder (BD) and variations of both. Mood disorders has a public health significance with high comorbidity, suicidal mortality and economic burden on the health system. Research related to mood disorders has evolved over the years to relate it with systemic conditions. The Renin Angiotensin System (RAS) has been noticed to play major physiological roles beyond renal and cardiovascular systems. Recent studies have linked RAS not only with neuro-immunological processes, but also with psychiatric conditions like mood and anxiety disorders. In this comprehensive review, we integrated basic and clinical studies showing the associations between RAS and mood disorders. Animal studies on mood disorders models-either depression or mania-were focused on the reversal of behavioral and/or cognitive symptoms through the inhibition of RAS components like the Angiotensin-Converting Enzyme (ACE), Angiotensin II Type 1 receptor (AT1) or Mas receptors. ACE polymorphisms, namely insertion-deletion (I/D), were linked to mood disorders and suicidal behavior. Hypertension was associated with neurocognitive deficits in mood disorders, which reversed with RAS inhibition. Low levels of RAS components (renin activity or aldosterone) and mood symptoms improvement with ACE inhibitors or AT1 blockers were also observed in mood disorders. Overall, this review reiterates the strong and under-researched connection between RAS and mood disorders.