Effects of simvastatin on innate and adaptive immunity in major depressive disorder with comorbid obesity: An ancillary study to the randomized controlled SIMCODE trial

• Applicants: Professor Dr. Manuel A. Friese; Professor Dr. Stefan M. Gold; Professor Dr. Christian Otte
• Subject Area: Biological Psychiatry ; Endocrinology, Diabetology, Metabolism
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 471126945

Major depressive disorder (MDD) and obesity are among the most common disorders in the general population and are associated with substantial disease burden and health care costs. Depression and obesity often co-occur and the presence of one increases the risk for developing the other.Converging lines of evidence from epidemiological and clinical studies as well as animal models have implicated inflammation and immune dysfunction in the pathogenesis of both depression and obesity, indicating a putative shared pathobiology. Intriguingly, evidence for an antidepressant effects of statins has emerged from animal models, epidemiological studies, and several small RCTs. These may - at least in part - be due to their pleiotropic effects on the immune system.We have recently received funding for a multicenter trial to test the efficacy of simvastatin as an add-on to escitalopram for patients with comorbid depression and obesity in a double blind, randomized controlled trial. Here, we are now applying for funding to conduct an ancillary study to explore the potential effects of this therapy on immune function in these patients. We propose to test the effects on read-outs of innate immunity (monocyte phenotype, metabolic function, and transcriptional profiles), adaptive immunity (T cell phenotype, metabolic function, and antiviral T cell responses) as well as systemic markers of inflammation (CRP, IL-6, TNF). This study will provide novel insights into the putative mechanisms of statins in depression and help to elucidate the cause effect relationship between markers of immune function and depression severity in patients with comorbid MDD and obesity.

• DFG Programme: Research Grants