Catching the winter flu or common cold is difficult to avoid in the city—pathogens live every place you turn, from subway poles, to bus seats, to doorknobs at the office. If you have already gotten sick this season, you can attest to the fact that it is stressful, exhausting, and a downer. But it's no coincidence that when you are physically ill, you feel more depressed than usual.
Illnesses like the flu or the common cold can closely mimic and cause depressive symptoms by activating your immune response and inflammation in your body (Hall 1996, Smith 1999, Capuron 1999).
Our immune, neurologic, and psychological systems are closely intertwined. When there is a foreign invader in your body, like the influenza virus, your cells produce proinflammatory cytokines, non-antibody proteins that activate and organize your body’s immune response (Raison 2006).
These chemical proteins circulate throughout your body and communicate with your brain, which in turn produces its own cytokines. These brain cytokines lead to fever, fatigue, depressed mood, lack of appetite, lack of motivation, social withdrawal, poor concentration, and altered sleeping patterns. In other words, the physical sickness caused by the inflammatory response significantly overlaps with depressive symptoms.
A recently published study in JAMA Psychiatry adds important evidence on the link between depression and inflammation (Setiawan, et al. 2015). Researchers compared the positron emission tomography (PET) scans of 20 people diagnosed with a current major depressive episode with 20 healthy control participants. They measured a protein density known to be associated with neuroinflammation ("translocator protein density measured by distribution volume").
Levels of protein density measuring neuroinflammation were significantly elevated in all three brain regions that they examined: 26 percent higher in the prefrontal cortex, 32 percent higher in the anterior cingulate cortex (ACC), and 33 percent higher in the insula. Further, higher levels of this protein density—and, presumably, neuroinflammation—in the ACC were associated with increased severity of the depression.
This finding is consistent with the existing literature on the neuroinflammatory hypothesis of depression. In a 2001 study published in the New England Journal of Medicine, 40 patients who not depressed were given a pro-inflammatory cytokine named interferon alpha (i.e., these patients were being treated with big-dose interferon alfa therapy for their malignant melanoma) (Musselman 2001).
Nearly half of the patients developed major depression within 3 months of interferon alfa therapy. Patients who had been given the antidepressant paroxetine (Paxil) two weeks before the cytokine responded to the medication, and 95 percent did not become depressed. Only 1 of the 20 patients who had been pretreated with paroxetine had to stop interferon alfa due to severe depression.
Similar studies have shown that other types of cytokines, when given as for treatment of cancer or hepatitis C, are also associated with significant levels of depression (Meyers 1999). Antidepressants have been found to successfully treat depression associated with both the cytokine-induced depression as well as medical illness-associated depression.
These studies help to shed light on neuroinflammation as a potential pathway for depression. It also helps explain why, when you come down with the flu, you might also feel like you caught the blues, too.
Copyright Marlynn H. Wei, MD, PLLC © 2015
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