About one third of people with depression have high levels of inflammation markers in their blood. New research indicates that persistent inflammation affects the brain in ways that are connected with stubborn symptoms of depression, such as anhedonia, the inability to experience pleasure.
The results were published online on Nov. 10 in Molecular Psychiatry.
The findings bolster the case that the high-inflammation form of depression is distinct, and are guiding researchers' plans to test treatments tailored for it.
Anhedonia is a core symptom of depression that is particularly difficult to treat, says lead author Jennifer Felger, PhD, assistant professor of psychiatry and behavioral sciences at Emory University School of Medicine and Winship Cancer Institute.
"Some patients taking antidepressants continue to suffer from anhedonia," Felger says. "Our data suggest that by blocking inflammation or its effects on the brain, we may be able to reverse anhedonia and help depressed individuals who fail to respond to antidepressants."
In a study of 48 patients with depression, high levels of the inflammatory marker CRP (C-reactive protein) were linked with a "failure to communicate", seen through brain imaging, between regions of the brain important for motivation and reward.
High CRP levels were also correlated with patients' reports of anhedonia: an inability to derive enjoyment from everyday activities, such as food or time with family and friends. Low connectivity between another region of the striatum and the ventromedial prefrontal cortex was linked to a different symptom: slow motor function, as measured by finger tapping speed.
As a next step, Felger is planning to test whether L-DOPA, a medicine that targets the brain chemical dopamine, can increase connectivity in reward-related brain regions in patients with high-inflammation depression. This upcoming study is being supported by the Dana Foundation.
Felger's previous research in non-human primates suggests that inflammation leads to reduced dopamine release. L-DOPA is a precursor for dopamine and often given to people with Parkinson's disease.
Inflammation linked to weakened reward circuits in depression
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