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

UMMS Affiliation

Department of Psychiatry; Implementation Science and Practice Advances Research Center; Psychotic Disorders Program, UMass Memorial Medical Center; School of Medicine

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Document Type



Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Mental and Social Health | Mental Disorders | Nervous System | Neuroscience and Neurobiology | Pharmacology, Toxicology and Environmental Health | Psychiatry | Psychiatry and Psychology | Therapeutics


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)-gamma, 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.

DOI of Published Version



CNS Drugs. 2019 Jun;33(6):539-547. doi: 10.1007/s40263-019-00632-4. Link to article on publisher's site

Journal/Book/Conference Title

CNS drugs

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Link to Article in PubMed

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