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Inflammation Linked to Weakened Reward System in Depression

Inflammation Tied to Weakened Reward System in Depression

A new study indicates that persistent inflammation is linked to anhedonia, a stubborn symptom of depression defined as the inability to experience pleasure.

The condition significantly weakens the brain’s reward system, the driving force that motivates us to accomplish things.

The findings add to the growing body of research showing that certain forms of depression are tied closely to inflammation. In fact, it has been found that about one-third of people with depression have markers of high levels of inflammation in their blood.

Anhedonia is a core symptom of depression that is particularly difficult to treat, says lead author Jennifer Felger, Ph.D., 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 said. “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 brain imaging study of 48 patients with depression, high levels of the inflammatory marker CRP (C-reactive protein) were linked with a “failure to communicate” between regions of the brain important for motivation and reward.

While observing a brain with magnetic resonance imaging, neuroscientists can infer that two regions of the brain are talking to each other by whether they light up at the same time or in the same patterns, even when someone is not doing anything in particular. They describe this as “functional connectivity.”

In patients with high CRP, the researchers observed a lack of connectivity between the ventromedial prefrontal cortex and the ventral striatum. In contrast, patients with low CRP had robust connectivity.

“We were interested in these regions of the brain because of their known importance for response to reward,” she said. “In addition, we had seen reduced activation of these areas in people receiving immuno-stimulatory treatments for hepatitis C virus or cancer, which suggested that they may be sensitive to inflammation.”

High CRP levels were also linked to 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.

During the brain imaging portion of the study, participants were not taking antidepressants, anti-inflammatory drugs, or other medications for at least four weeks, and CRP was measured on repeat visits to make sure its levels were stable.

An earlier study of people with difficult-to-treat depression found that those with high inflammation (as measured with CRP), improved in response to the anti-inflammatory antibody infliximab.

In future research, Felger would like 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.

“We hope our investigations may lead to new therapies to treat anhedonia in high-inflammation depression,” she said.

The results are published online in the journal Molecular Psychiatry.

Source: Emory Health Sciences
Woman looking out window photo by shutterstock.

Inflammation Tied to Weakened Reward System in Depression

Traci Pedersen

Traci Pedersen is a professional writer with over a decade of experience. Her work consists of writing for both print and online publishers in a variety of genres including science chapter books, college and career articles, and elementary school curriculum.

APA Reference
Pedersen, T. (2018). Inflammation Tied to Weakened Reward System in Depression. Psych Central. Retrieved on September 25, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 21 Nov 2015)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
Published on Psych All rights reserved.