Effect of Inflammation on Cognition, Behavior, & Psychiatric Illness

Study the effects of inflammatory diseases on the brain to support new approaches for reducing anxiety and depression

Full Project Name:Effect of Inflammation on Cognition, Behavior, & Psychiatric IllnessPrincipal Investigator:William Drobyski, MD, MedicineCo-Investigator:Cecilia Hillard, PhD, Pharmacology and Toxicology; Jennifer M. Knight, MD, PsychiatryAward Amount:$200,000

Award Date

July2015

Project Duration:24 months

Project Description Narrative:

Reports indicate that between 35-40% of cancer patients experience elevated levels of anxiety, depression and adjustment disorders. Cancer patients are not alone, however, as cognitive difficulties and depression can occur in a number of human diseases that do not seem to have anything to do with the brain, including heart disease and infections.

Emerging evidence indicates that inflammation is a major contributor in brain function. Inflammation is an underlying characteristic of virtually all significant human disease states, including cancer, infections, heart disease and other disorders that can affect the brain. The cognitive and emotional challenges that can accompany these diseases have profound adverse effects on patient quality of life and can persist even after the underlying disease has been resolved.

Researchers aim to expand on preliminary data showing that the protein interleukin 6 can reduce brain inflammation and study the effects of inflammatory diseases, such as graft-versus-host-disease, on the brain in rodents and in a clinical trial, which may lead to the development of new approaches for reducing anxiety and depression.

Outcomes & Lessons Learned:

Investigated the effectiveness of an available drug in reducing cognitive dysfunction, anxiety and depression in stem cell transplant patients being treated to prevent graft-versus-host-disease
Demonstrated that systemic inflammation leads to behavioral and cognitive dysfunction in a well-characterized animal model. Furthermore, the researchers discovered that systemic inflammation directly promotes inflammation within the brain
Completed a clinical trial that assessed how an inflammatory molecule, termed interleukin 6, affects behavioral function. These preliminary clinical results will form the basis for a subsequent clinical trial in which patients are treated with either Tocilizumab or a placebo to determine whether mood and cognitive function can be improved in patients with underlying inflammatory disorders
Showed for the first time that interleukin 6 plays a pivotal role in mediating inflammation in the brain during graft-versus-host-disease which is the primary complication of bone marrow transplants. Since agents to block the effects of interleukin 6 are commercially available, there is now the potential to determine whether inhibition of the effects of interleukin 6 may improve behavioral function and reduce brain inflammation in these patients
Advanced knowledge regarding the relationship of inflammation and brain function, which may lead to new, targeted treatments that are applicable to a broad range of disorders