CNS Drugs

, Volume 33, Issue 6, pp 539–547 | Cite as

The Possible Role of the Angiotensin System in the Pathophysiology of Schizophrenia: Implications for Pharmacotherapy

  • SeungJu Jackie Oh
  • Xiaoduo FanEmail author
Leading Article


A growing body of literature has elucidated the involvement of the central renin–angiotensin system (RAS) in various neuropsychiatric diseases. While consensus on the exact mechanism of the central RAS in schizophrenia pathophysiology does not currently exist, increasing evidence reveals promise in harnessing the therapeutic potential of RAS modulation in the treatment of schizophrenia. In this review, we examine how the central RAS affects inflammation, glutamate, dopamine, gamma-aminobutyric acid (GABA), and peroxisome proliferator-activated receptor (PPAR)-γ, all of which are associated with schizophrenia etiology. In addition, a recent study has demonstrated the therapeutic potential of RAS modulators, especially angiotensin II type 1 receptor blockers (ARBs), as adjunctive therapy to the currently available antipsychotic medications for schizophrenia treatment. With a greater understanding of how RAS inhibition directly modulates neurotransmitter balance in the brain, it is possible that compounds with RAS-inhibiting properties could be used to optimize physiological levels of glutamate, dopamine, and GABA, and the balance among the three neurotransmitters, analogously to how antipsychotic medications mediate the dopaminergic pathways. It can be hoped that a novel approach based on this concept, such as adjunctive telmisartan therapy, may offer practical interventional strategies to address currently unmet therapeutic needs in patients with schizophrenia, especially those with treatment-resistant schizophrenia.


Compliance with Ethical Standards


No sources of funding were used to conduct this review or prepare this manuscript.

Conflict of interest

XF has received research support or honoraria from Alkermes, Neurocrine, Avanir, Allergen, Otsuka, Lundbeck, Boehringer Ingelheim, and Janssen. SJO reports no competing interests.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.University of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Psychotic Disorders ProgramUMASS Memorial Medical CenterWorcesterUSA

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