Anti-inflammatory drug can increase motivation in patients with depression, study shows

A new study published this week in Molecular Psychiatry by researchers at Emory University has demonstrated a promising new approach to treating motivational deficits in patients with depression.

Motivational deficits are a central component of depression and have long been associated with poor treatment outcomes, reduced quality of life, and increased suicide risk. Increasing evidence suggests that one possible cause of lack of motivation may be persistent inflammation that suppresses activity in key brain circuits.

This study is the first of its kind to examine the effects of infliximab – an antagonist of the inflammatory molecule tumor necrosis factor (TNF) – on behavioral and brain markers of motivation in a group of 42 medically stable, drug-naïve depressed patients.

Importantly, the study focused on patients who were not only depressed but also had signs of severe inflammation, as measured by C-reactive protein (CRP) levels above 3 mg/L. CRP is a blood test that is widely available in clinics and hospitals throughout the United States.

The research team believed that in some patients with depression, the additional presence of high levels of inflammation may play a key role in reduced motivation.

Patients were randomly assigned to receive either a single dose of infliximab (a powerful anti-inflammatory drug used to treat rheumatoid arthritis and other inflammatory diseases) or a placebo.

Over a two-week period, researchers assessed changes in patients' motivation using a variety of methods, including an effort-based decision-making task, self-report questionnaires, and functional magnetic resonance imaging (fMRI) to monitor brain activity.

Patients receiving infliximab showed a greater willingness to exert effort for rewards than patients receiving a placebo. This increase in effort behavior was closely associated with a reduction in the signaling pathways directly targeted by infliximab, particularly TNF.

Furthermore, these changes were reflected in changes in brain activity in key regions associated with motivation, such as the dorsomedial prefrontal cortex, ventral striatum, and putamen, as well as in the functional connectivity between these areas.

“This is the first study to demonstrate the effects of an anti-inflammatory drug on brain circuits associated with motivation,” says lead author Michael Treadway, Ph.D., professor of psychology at Emory University. “It's exciting to see how modulating inflammation can directly affect motivation, one of the most difficult-to-treat symptoms in depression.”

Importantly, the study found that the association between infliximab treatment and improved motivation was mediated by the observed changes in TNF signaling and brain activity. Furthermore, reductions in motivational deficits were associated with increased responses in a brain network sensitive to reward.

“These findings build on growing evidence that anti-inflammatory treatments are a promising new approach to treating motivational deficits in depression,” says lead author Andrew Miller, professor of psychiatry and behavioral sciences at Emory University School of Medicine.

“By targeting inflammation, we not only address the biological causes of these deficits, but also offer new hope for more effective treatment options.”