Statins: Neurobiological underpinnings and mechanisms 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 path-ogenesis 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 antide-pressant 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 re-mains 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.Adam J. Walkera, Yesul Kima, Igor Borissiouka, Rodolfo Rehdera, b, Seetal Dodda, c, d, Gerwyn Morrisa, Andrew A. Nierenberga, e, f, Michael Maesa, g, h, Brisa S. Fernandesa, Olivia M. Deana, i, Lana J. Williamsa, Harris A. Eyrea, j, k, l, Sung-Wan Kimm, Sophia Zoungasn, Andre F. Carvalhoa, Michael Be