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Surprise Find Links Mental Illness With Inflammation
"We've found a mechanism that directly links inflammation to mental illness," says Carroll. "This discovery has huge implications for a range of central nervous system diseases." – Dr. Michael Carroll
(Boston, MA) — Up to 75 percent of patients with systemic lupus erythematosus — an incurable autoimmune disease commonly known as lupus — experience neuropsychiatric symptoms. But so far, our understanding of the mechanisms underlying lupus' effects on the brain has remained murky. Now, new research from Boston Children's Hospital has shed light on the mystery and points to a potential new drug for protecting the brain from the neuropsychiatric effects of lupus and other central nervous system (CNS) diseases. The team has published its surprising findings in Nature. (Photo Credit: Boston Children's Hospital)
"In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis," says Allison Bialas, PhD, first author on the study and a research fellow working in the lab of Michael Carroll, PhD, senior author on the study, who are part of the Boston Children's Program in Cellular and Molecular Medicine. "But their cause has not been clear — for a long time it wasn't even appreciated that these were symptoms of the disease.
Collectively, lupus' neuropsychiatric symptoms are known as central nervous system (CNS) lupus. Carroll's team wondered if changes in the immune system in lupus patients were directly causing these symptoms from a pathological standpoint.
"How does chronic inflammation affect the brain?"
Lupus, which affects at least 1.5 million Americans, causes the immune systems to attack the body's tissues and organs. This causes the body's white blood cells to release type 1 interferon-alpha, a small cytokine protein that acts as a systemic alarm, triggering a cascade of additional immune activity as it binds with receptors in different tissues.
Until now, however, these circulating cytokines were not thought to be able to cross the blood brain barrier, the highly-selective membrane that controls the transfer of materials between circulating blood and the central nervous system (CNS) fluids.
"There had not been any indication that type 1 interferon could get into the brain and set off immune responses there," says Carroll, who is also professor of pediatrics at Harvard Medical School.
So, working with a mouse model of lupus, it was quite unexpected when Carroll's team discovered that enough interferon-alpha did indeed appear to permeate the blood brain barrier to cause changes in the brain. Once across the barrier, it launched microglia — the immune defense cells of the CNS — into attack mode on the brain's neuronal synapses. This caused synapses to be lost in the frontal cortex.
"We've found a mechanism that directly links inflammation to mental illness," says Carroll. "This discovery has huge implications for a range of central nervous system diseases."
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Boston Children’s Hospital