Statins: Neurobiological underpinnings and mechanisms in mood disorders

Adam J Walker; Yesul Kim; Igor Borissiouk; Rodolfo Rehder; Seetal Dodd; Gerwyn Morris; Andrew A Nierenberg; Michael Maes; Brisa S Fernandes; Olivia M Dean; Lana J Williams; Harris A Eyre; Sung-Wan Kim; Sophia Zoungas; Andre F Carvalho; Michael Berk

doi:10.1016/j.neubiorev.2021.07.012

Statins: Neurobiological underpinnings and mechanisms in mood disorders

Neurosci Biobehav Rev. 2021 Sep:128:693-708. doi: 10.1016/j.neubiorev.2021.07.012. Epub 2021 Jul 13.

Authors

Affiliations

¹ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia.
² Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; Federal University of São Paulo (UNIFESP), São Paulo, Brazil.
³ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia.
⁴ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁵ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; Department of Psychiatry, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Bangkok, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria.
⁶ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia.
⁷ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; OECD-PRODEO Institute Neuroscience-inspired Policy Initiative, Paris, France; Global Brain Health Institute, University of California, San Francisco, CA, USA; Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁸ Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁹ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹⁰ Deakin University, IMPACT - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, VIC, Australia; Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia; Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia. Electronic address: michael.berk@deakin.edu.au.

PMID: 34265321
DOI: 10.1016/j.neubiorev.2021.07.012

Abstract

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) treat dyslipidaemia and cardiovascular disease by inhibiting cholesterol biosynthesis. They also have immunomodulatory and anti-inflammatory properties. Beyond cardiovascular disease, cholesterol and inflammation appear to be components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Statins may therefore afford some therapeutic benefit in mood disorders. In this paper, we review the pathophysiology of mood disorders with a focus on pharmacologically relevant pathways, using major depressive disorder and bipolar disorder as exemplars. Statins are discussed in the context of these disorders, with particular focus on the putative mechanisms involved in their anti-inflammatory and immunomodulatory effects. Recent clinical data suggest that statins may have antidepressant properties, however given their interactions with many known biological pathways, it has not been fully elucidated which of these are the major determinants of clinical outcomes in mood disorders. Moreover, it remains unclear what the appropriate dose, or appropriate patient phenotype for adjunctive treatment may be. High quality randomised control trials in concert with complementary biological investigations are needed if the potential clinical effects of statins on mood disorders, as well as their biological correlates, are to be better understood.

Keywords: Bipolar disorder; Cholesterol; Depression; Inflammation; Mental disorders; Mood disorders; Neuroprogression; Neuroscience; Psychiatry; Statins; Treatment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antidepressive Agents / therapeutic use
Bipolar Disorder* / drug therapy
Depressive Disorder, Major* / drug therapy
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Mood Disorders / drug therapy

Substances

Antidepressive Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors