Biochemical link found between adversity, depression, and death

Kathleen Blanchard's picture

Researchers have used a unique way to determine a link between adverse life events that trigger stress and depression and lead to disease and increased risk of death. Interactions that occur between genes and the environment, in response to stress vary among individuals.

People with a rare form of the gene IL6 seem to be immune to dying from adverse life events and depression that can lead to poor health.

Steven Cole, a member of the UCLA Cousins Center for Psychoneuroimmunology and an associate professor of medicine in the division of hematology-oncology, and his colleagues used a computational model to discover that IL6, a gene that promotes inflammation, differs among individuals and changes the way adverse life events that trigger depression and misery affects individual health.

People who experience depression from adverse life events, whose IL6 gene activation pathway is blocked, seem to be immune from cardiovascular disease, neurodegeneration and some types of cancer that in other individuals produces depression that leads to disease and increased chances of death.

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"The IL6 gene controls immune responses but can also serve as 'fertilizer' for cardiovascular disease and certain kinds of cancer," said Cole, who is also a member of UCLA's Jonsson Comprehensive Cancer Center and UCLA's Molecular Biology Institute. "Our studies were able to trace a biochemical pathway through which adverse life circumstances — fight-or-flight stress responses — can activate the IL6 gene.

We also identified the specific genetic sequence in this gene that serves as a target of that signaling pathway, and we discovered that a well-known variation in that sequence can block that path and disconnect IL6 responses from the effects of stress."

The scientists found that individuals who possess the most common IL6 gene were at higher risk of death for approximately eleven years from depression brought about by adverse life events.

The authors write, “This opens a new era in which we can begin to understand the influence of adversity on physical health by modeling the basic biology that allows the world outside us to influence the molecular processes going on inside our cells." Stress that lead to misery is now found to be linked to death from inflammation that promotes heart disease, some types of cancer, and neurodegenerative disease.

The IL6 gene varies among individuals. The researchers discovered through epidemiological studies and by using a computer model, that people with the rarer variant of the IL6 gene, were immune from the ill effects of adverse life events that leads to depression, misery and death.

UCLA Newsroom