Scientists Find Link Between Bipolar Disorder and Neuroinflammation

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A doctor looking at a picture of a human brain taken by a positron emission tomography scanner, also called PET scan, on Jan. 9, 2019, at the Regional and University Hospital Center of Brest in France.
A doctor looking at a picture of a human brain taken by a positron emission tomography scanner, also called PET scan, on Jan. 9, 2019, at the Regional and University Hospital Center of Brest in France.
Photo: Fred Tanneau (Getty Images)

Scientists may be closer to understanding how the brain can function differently in people who have bipolar disorder. In a new study, researchers say they’ve found evidence that certain brain cells trigger inflammation more easily in those who have bipolar disorder, and that these wayward cells can be linked to decreased neural activity that could be harmful to our mental health. The findings, published on Thursday in Stem Cell Reports, could hint at a new way to treat bipolar disorder someday, though more research is still needed.

Scientists have been studying the connection between inflammation and mental illness for some time, including bipolar disorder. People with bipolar disorder experience uncontrollable mood swings that can leave them severely depressed one moment and manic the next. People with bipolar disorder are known to be more likely to have other conditions associated with chronic inflammation, such as hypertension and diabetes. Some studies have also shown that bipolar disorder patients can have higher levels of proteins that goad the body into becoming inflamed, especially when they’re in the middle of a manic episode. These proteins include interleukin 6 (IL-6), which plays many roles in the body, such as guiding the body’s acute response to infection.

In their new study, researchers at the Salk Institute for Biological Studies, the University of California, San Diego, and the Institute of Psychiatry and Neuroscience of Paris decided to look at a specific type of brain cell, the astrocyte. These are star-shaped cells in the brain that carry out a number of important functions that help support neurons. One of these functions include being part of the chain of command that triggers inflammation in the brain and surrounding nervous system, which is meant to help the brain respond to injury or infection. The researchers theorized that this generally useful process can go awry in people with bipolar disorder, and that astrocytes can have a part in this dysfunctional inflammation.


“Due to a growing understanding of the role of neuroinflammation in psychiatric disorders, we asked whether altered inflammation-driven signaling in astrocytes was associated with bipolar disorder,” study author Fred Gage, president of the Salk Institute for Biological Studies, said in an email.

Gage and his team used stem cells derived from six people with bipolar disorder as well as four controls without bipolar disorder, then had them develop into astrocytes that were studied in the lab. (They had figured out how to create these cells from earlier research.) Compared to the control group, the astrocytes from patients with bipolar disorder were noticeably different. The cells had higher expression of their IL-6 gene and as a result, they secreted more IL-6 than the control astrocytes. When they exposed neurons to these astrocytes, the team saw decreased levels of neural activity, compared to the astrocytes from the controls. And when the researchers introduced an antibody that suppressed IL-6 into the mix, the neurons were less hampered by the astrocytes, further implicating IL-6. Lastly, the blood of bipolar disorder patients also contained more IL-6 than controls.


“Our study suggests that normal function of astrocytes is affected in bipolar disorder patients’ brains, contributing to neuroinflammation,” co-author Renata Santos, a researcher at the Salk Institute as well as the Institute of Psychiatry and Neuroscience of Paris, said.

The findings are certainly intriguing, but the researchers warn there’s still a long road to go before we can confirm a clear, causal link between impaired astrocytes, IL-6, and bipolar disorder, much less something that could lead to meaningful new treatments. Lab-grown astrocytes might be different from those found in our brain in important ways, for instance. (One difference is that these cells are less mature.) And since the brain is plenty complicated, there are likely other aspects of our biology, including in the brain, that could play an important role in causing bipolar disorder.


“Our findings elucidate aspects of the understudied role of astrocytes in neuroinflammation in psychiatric disorders, with relevance for altered IL-6 and inflammatory signaling in bipolar disorder patient astrocytes,” lead author Krishna Vadodaria, a research associate at the Salk Institute, said.

If the researchers are onto something here, it’s possible astrocytes could not only help provide further insight on bipolar disorder, but other mental illnesses linked to inflammation, such as schizophrenia, according to study author Carol Marchetto, now an anthropology researcher at UC San Diego. And they hope their work will help propel future research into astrocytes and inflammation—research that could lead to the development of treatments that might reverse the harmful bodily changes seen in those with bipolar disorder and similar conditions.