The prevalence rate for depression in the United States is nearly 7%, yet standard antidepressants produce full remission in only 30-40% of patients.  Even when treatment is effective, patients require 2-4 weeks to achieve the full therapeutic effects. Adding to the problem, there are currently no biological diagnostic tests to predict depression, forcing clinicians to diagnose based upon clusters of non-specific overlapping behavioral symptoms.  Thus, in the Russo lab, we are interested in identifying novel biological targets to predict depression and treat it more rapidly and effectively.

In order to achieve our goals we take a multidisciplinary approach, working closely with clinicians to identify true disease mechanisms in humans with depression and performing proof-of-concept studies in rodent models.  We often start a project by obtaining blood or brain samples from depressed human patients to probe for any biological abnormalities.  Blood samples are very useful because they can be readily obtained from willing participants and monitored over time.  Out of necessity, brain samples can only be obtained at the time of death when a person willingly donates their body to science, however they can provide unique insight into brain abnormalities in depression.  Together these samples have been critical to understanding the biological nature of depression.

In recent years, we’ve identified a number of interesting potential causes of depression.  For example, by sampling blood from depressed patients we found that they exhibit sustained elevations in immune modulators, such as Interleukin-6 (IL-6).  IL-6 is a protein secreted by white blood cells in response to viral/bacterial exposure or physical insult. Our studies suggest that too much IL-6 can cause depressive symptoms.  We have also found that depressed patients exhibit sustained changes in brain plasticity factors that act to “re-wire” brain circuitry and cause long-lasting change in social behavior and pleasure seeking.   Armed with this information, we are utilizing animal models of depression to determine efficacy and safety of new therapeutic strategies to normalize these changes and prevent depression associated behavioral symptoms.

Dr. Scott J. Russo is Assistant Professor of Neuroscience at Icahn School of Medicine at Mount Sinai. His research is focused on understanding how the brain adapts to stress and drugs to guide future behaviors that are relevant to addiction and depression.

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