BMI SEMINAR // Neuroimmune mechanisms of depression

Major depressive disorder (MDD) is the leading cause of worldwide disability with some reports estimating prevalence rates around 6.7%.  ~30% of depressed patients experience heightened inflammation, putting them at increased risk of comorbid physical illness such as cardiovascular disease, diabetes, metabolic disorder, asthma, or rheumatoid arthritis. Scott Russo, Ph.D. and his team at the Mount Sinai School of Medicine have set out to test whether overactive, unresolved inflammation might ultimately lead to the development of mood disorders.  To achieve this goal, Dr. Russo has partnered with a broad team of experts across Psychiatry, Immunology and Vascular Biology here at Mount Sinai, adopting a back translational approach, which first identified elevations of the inflammatory molecule IL-6 in humans with treatment resistant depression. His lab later went on to show that by neutralizing IL-6 in the periphery and preventing it from entering the brain, they could produce antidepressant-like effects in a mouse model of depression (Hodes et. al. PNAS, 2014).  As a result of Dr. Russo’s preclinical work, which tested a novel antibody neutralization strategy to sequester peripheral IL-6, Janssen Pharmaceuticals has initiated a phase II clinical trial to test efficacy of IL-6 neutralization in treatment of unipolar depression (https://clinicaltrials.gov/ct2/show/NCT02473289).