Infliximab, an anti-inflammatory drug used to treat rheumatoid arthritis, may boost motivation in people with depression.
- Compared with placebo, depressed patients receiving infliximab, an anti-inflammatory drug, had a greater willingness to exert effort to obtain rewards.
- This increase in effortful behavior was closely related to a reduction in signaling pathways directly targeted by the drug, particularly reduced tumor necrosis factor.
- Changes in decision making were also associated with changes in task-related activity in a network of brain areas, including the dorsomedial prefrontal cortex, ventral striatum, and putamen, as well as functional connectivity between these regions.
Lack of motivation is a core component of depression and has long been linked to poor treatment outcomes, decreased quality of life, and increased risk of suicide. Growing evidence suggests that a potential cause of this low motivation may be “low-grade chronic inflammation”which suppresses activity in key brain circuits.
42 depressed patients received a dose of infliximab or a placebo
Researchers at Emory University (USA) wanted to study the effects of infliximab on behavioral and brain markers of motivation in depressed adults. This drug is an antagonist of tumor necrosis factor, an inflammatory molecule, indicated in cases of rheumatoid arthritis and other inflammatory diseases. As part of a study, the team recruited 42 people suffering from medically stable depression and showing signs of high inflammation (measured by a C-reactive protein (CRP) greater than 3 mg/L).
In one intervention, participants were divided into two groups. The first received a dose of 5 mg/kg of infliximab. The rest of the volunteers received a placebo. Over the course of two weeks, the authors assessed changes in the patients’ motivation using a variety of methods, including an effort-based decision-making task, self-report questionnaires, and functional magnetic resonance imaging (fMRI) to observe brain activity.
Depression: “Anti-inflammatories show promise for treating” lack of motivation
The results, published in the journal Molecular Psychiatryshowed that depressed people who took infliximab were more willing to exert effort to obtain rewards than those who received placebo. This was associated with reduced tumor necrosis factor signaling. Furthermore, these changes were reflected in alterations in brain activity in key regions associated with motivation, such as the dorsomedial prefrontal cortex, ventral striatum, and putamen, as well as functional connectivity between these areas.
“This research builds on growing evidence that anti-inflammatory treatments hold promise as a novel approach to treating motivational deficits in depression. By targeting inflammation, we not only address the biological causes of these deficits, but also offer new hope for more effective treatment options,” concluded Andrew Millerlead author of the work.
