Stress-related inflammation may increase risk for depression

October 20, 2014, The Mount Sinai Hospital
Credit: George Hodan/Public Domain

Preexisting differences in the sensitivity of a key part of each individual's immune system to stress confer a greater risk of developing stress-related depression or anxiety, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published October 20 in the Proceedings of the National Academy of Sciences (PNAS).

Inflammation is the 's response to infection or disease, and has long been linked to stress. Previous studies have found depression and anxiety to be associated with elevated blood levels of inflammatory molecules and white blood cells after a confirmed diagnosis, but it has been unclear whether greater inflammation was present prior to the onset of disease or whether it is functionally related to depression symptomology.

Specifically, the new study measured the cytokine IL-6 in non-aggressive prior to and after repeated invoked by an aggressive mouse. They found that IL-6 levels were higher in mice that were more susceptible to stress than in "stress-resilient" mice. They also found the levels of leukocytes (white blood cells that release IL-6) were higher in stress susceptible mice before stress exposure. The researchers then validated the increased levels of IL-6 in two separate groups of human patients diagnosed with treatment-resistant Major Depressive Disorder.

The Mount Sinai study results revolve around the peripheral immune system, a set of biological structures and processes in the lymph nodes and other tissues that protect against disease. Inflammation is a culprit of many disease conditions when it happens in the wrong context or goes too far. Under normal conditions when the immune system perceives a threat (e.g. invading virus), inflammatory proteins called interleukins are released by as an adaptive mechanism to limit injury or infection. However, in some instances, the immune system may become hyper responsive to an "insult," leading to chronic dysregulation of inflammatory processes that ultimately cause disease.

"Our data suggests that pre-existing individual differences in the peripheral immune system predict and promote stress susceptibility," says lead author Georgia Hodes, PhD, Postdoctoral Researcher in Neuroscience. "Additionally, we found that when mice were given bone marrow transplants of stem cells that produce leukocytes lacking IL-6 or when injected with antibodies that block IL-6 prior to stress exposure, the development of social avoidance was reduced compared with their respective control groups, demonstrating that the emotional response to stress can be generated or blocked in the periphery."

Evidence in the current study is the first to suggest that Interleukin 6 response prior to social stress exposure can predict individual differences in vulnerability to a subsequent social stressor.

The research team, led by Scott Russo, PhD, Associate Professor of Neuroscience, exposed mice to two social stress models that are translational to social stressors experienced by humans. They measured blood levels of cytokines in non-aggressive mice before and after repeated social defeat stress invoked by exposure to an aggressive mouse for 10 minutes daily for 10 days or after 10 days of witnessing defeat of another mouse, a purely emotional stressor. The researchers classified the non-aggressive mice as susceptible based on a preference to spend more time near an empty cage rather than near a new mouse on a subsequent social interaction test, whereas resilient mice showed the opposite pattern. Interleukin-6 was the only cytokine significantly elevated in susceptible mice compared with unstressed and resilient mice.

As has been witnessed in humans, they found that chronic social subordinations in mice leads to depression-like behavior, including social avoidance, in a subset of mice termed susceptible, whereas resilient mice resist the development of such behavior.

"Interleukin-6 could be a risk factor for the development of depression in vulnerable individuals," says Dr. Russo. "We believe our studies could have significant impact on the development of new antidepressant therapeutics that inhibit IL-6, which may reduce stress-induced relapse in patients with ."

The new study provides experimental evidence that the emotional response to stress can be generated or blocked in the periphery, offering the potential for new forms of treatment for stress disorders and may eventually inform therapeutic strategies to reengineer a patient's immune system to reduce stress vulnerability. Given that disorders and inflammation are together associated with increased prevalence of many other chronic diseases, such as heart disease and stroke that are highly comorbid with emotional disturbances, these findings may provide insight into common pathways governing multiple diseases.

Human blood samples used in the study were collected at Mount Sinai and the University of Cambridge.

Explore further: Peripheral immune system may regulate vulnerability to depression

More information: Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1415191111

Related Stories

Peripheral immune system may regulate vulnerability to depression

December 12, 2013
A new study shows that immune cells outside the brain may regulate propensity to develop depression. The data were presented today at the American College of Neuropsychopharmacology (ACNP) Annual Meeting.

Study in mice raises question: Could PTSD involve immune response to stress?

February 20, 2014
Chronic stress that produces inflammation and anxiety in mice appears to prime their immune systems for a prolonged fight, causing the animals to have an excessive reaction to a single acute stressor weeks later, new research ...

Obesity and stress pack a double hit for health

September 22, 2014
If you're overweight, you may be at greater risk for stress-related diseases like type 2 diabetes, cardiovascular disease and cancer, according to a new study by Brandeis University.

Making old lungs look young again: Animal research suggests ibuprofen can reduce lung inflammation in elderly

October 2, 2014
New research shows that the lungs become more inflammatory with age and that ibuprofen can lower that inflammation.

A new brain-based marker of stress susceptibility

July 29, 2014
Some people can handle stressful situations better than others, and it's not all in their genes: Even identical twins show differences in how they respond.

Recommended for you

New neurons in the adult brain are involved in sensory learning

February 23, 2018
Although we have known for several years that the adult brain can produce new neurons, many questions about the properties conferred by these adult-born neurons were left unanswered. What advantages could they offer that ...

Do you see what I see? Researchers harness brain waves to reconstruct images of what we perceive

February 22, 2018
A new technique developed by neuroscientists at the University of Toronto Scarborough can, for the first time, reconstruct images of what people perceive based on their brain activity gathered by EEG.

Neuroscientists discover a brain signal that indicates whether speech has been understood

February 22, 2018
Neuroscientists from Trinity College Dublin and the University of Rochester have identified a specific brain signal associated with the conversion of speech into understanding. The signal is present when the listener has ...

Study in mice suggests personalized stem cell treatment may offer relief for multiple sclerosis

February 22, 2018
Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis ...

Biomarker, clues to possible therapy found in novel childhood neurogenetic disease

February 22, 2018
Researchers studying a rare genetic disorder that causes severe, progressive neurological problems in childhood have discovered insights into biological mechanisms that drive the disease, along with early clues that an amino ...

A look at the space between mouse brain cells

February 22, 2018
Between the brain's neurons and glial cells is a critical but understudied structure that's been called neuroscience's final frontier: the extracellular space. With a new imaging paradigm, scientists can now see into and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.