Depression is often associated with sadness, but it can also cause a powerful loss of motivation. People may find it difficult to start everyday activities, work toward goals, or feel that rewards are worth the effort.
This loss of drive can make recovery especially difficult. Standard antidepressants can help many people, but motivation problems do not always improve fully, leading scientists to search for other ways to treat this symptom.
A study from Emory University suggests that inflammation in the body may be part of the problem for some people. Researchers found that an anti-inflammatory drug called infliximab improved measures of motivation in patients with depression who also had high levels of inflammation.
Infliximab is not normally used as an antidepressant. It is a powerful medicine that blocks tumor necrosis factor, or TNF, an inflammatory substance involved in the body’s immune response, and it is used to treat illnesses such as rheumatoid arthritis and inflammatory bowel disease.
Scientists have become increasingly interested in the connection between inflammation and depression. Long-lasting inflammation may affect chemical signals and brain networks involved in mood, energy, pleasure, and the willingness to make an effort for a reward.
The Emory researchers studied 42 adults with depression who were not taking other antidepressant medicines. All had evidence of increased inflammation, measured using a blood marker called C-reactive protein, or CRP.
CRP is produced by the liver when inflammation is present in the body. The participants had CRP levels above 3 milligrams per liter, a level commonly used to indicate elevated inflammation.
Participants were randomly assigned to receive either one dose of infliximab or a placebo. Neither the participants nor the researchers assessing them knew which treatment each person had received, helping reduce the risk of bias.
Over the following two weeks, the team measured motivation in several ways. Participants completed questionnaires and tasks that tested how much effort they were willing to make to receive a reward.
The researchers also used functional magnetic resonance imaging, or fMRI, to examine activity in the brain. They were particularly interested in brain areas involved in motivation and reward.
People who received infliximab showed improvements in their willingness to work for rewards compared with those who received the placebo. The researchers also detected changes in brain activity in regions including the prefrontal cortex and ventral striatum.
These brain areas help people evaluate rewards, make decisions, and decide whether something is worth the effort. The findings therefore offer a possible biological explanation for how reducing inflammation could influence motivation.
Lead author Michael Treadway of Emory University said the research helps connect an anti-inflammatory treatment with changes in brain circuits related to motivation. Co-author Andrew Miller has also studied how immune activity and inflammation may contribute to depression.
The findings do not mean that infliximab should now be used routinely to treat depression. The study was small, involved a carefully selected group with elevated inflammation, and followed participants for only a short period, so larger studies are needed.
Still, the results may point toward a more personalized approach to depression treatment. In the future, doctors may be able to identify people whose symptoms are partly driven by inflammation and choose treatments that target that biological pathway.
The study was published in the journal Molecular Psychiatry. It adds to growing evidence that depression can involve both the brain and the body’s immune system, and that understanding this connection could lead to new treatments for difficult symptoms such as loss of motivation.
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