Study Finds Critical Link Between Mental Illness and Inflammation
Most of the 1.5 million Americans with lupus suffer from anxiety, depression, and even psychosis, but the cause of the symptoms has been a mystery. As a result, lupus has been seen as an undefined cluster of symptoms rather than a well-defined disease.
Now a team led by Dr. Allison Bialas of Boston Children's Hospital may have found the mechanism that connects lupus and its symptoms via the body's own attempts to fight this debilitating disease.
The study published in Nature describes how the aggressive nature of lupus causes the body's immune system to attack tissues and organs, causing white blood cells to release a cytokine protein known as type 1 interferon-alpha. As it binds to receptors at other tissues, the protein triggers more immune activity, which leads to inflammation, which results in the symptoms.
What exactly does this mean for the brain? "There had not been any indication that type 1 interferon could get into the brain and set off immune responses there," says Dr. Michael Carroll, senior author of the study. Now, using a lupus mouse model, the study has determined otherwise.
Type 1 interferon not only crosses this barrier, it initiates a response of microglia -- the central nervous system's (CNS) cells' armor. This effect produces a war on the neuronal synapses of the brain, causing the loss of synapses in the frontal cortex, leading in turn to the devastating symptoms so common in lupus.
Carroll and his team were curious to see if a drug, anti-IFNAR, which blocks interferon-alpha's receptor, could decrease synapse loss. Consequently, they did indeed find that this drug has protective effects in the brains of mice with lupus, which not only reduced synapse loss in comparison to the control group, but also reduced behaviors associated with psychiatric disorders, such as anxiety.
This could be a breakthrough for other diseases of the nervous system as well.
"We've seen microglia dysfunction in other diseases like schizophrenia, and so now this allows us to connect lupus to other CNS diseases," Bialas says. "CNS lupus is not just an undefined cluster of neuropsychiatric symptoms, it's a real disease of the brain -- and it's something that we can potentially treat."