Statins: Neurobiological underpinnings and mechanisms in mood disorders

• Published in: Neuroscience and biobehavioral reviews 2021-09, Vol.128, p.693-708
• Main Authors: Walker, Adam J., Kim, Yesul, Borissiouk, Igor, Rehder, Rodolfo, Dodd, Seetal, Morris, Gerwyn, Nierenberg, Andrew A., Maes, Michael, Fernandes, Brisa S., Dean, Olivia M., Williams, Lana J., Eyre, Harris A., Kim, Sung-Wan, Zoungas, Sophia, Carvalho, Andre F., Berk, Michael
• Format: Article
• Language: English
• Subjects: Bipolar disorder; Cholesterol; Depression; Inflammation; Mental disorders; Mood disorders; Neuroprogression; Neuroscience; Psychiatry; Statins; Treatment
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2021.07.012

•Mood disorders can feature disturbances in lipid metabolism, oxidative stress and inflammation.•Statins are extensively prescribed for cardiovascular disease for their lipid-lowering properties.•Pleiotropic effects of statins include anti-inflammatory and anti-oxidative action.•Growing evidence suggests statins may have potential as adjunctive psychotropic agents.•Larger scale clinical trials are needed to better assess the utility of statins in mood disorders. 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.