Levodopa May Improve Depressive Symptoms by Reducing Brain Inflammation

Levodopa, a drug that increases dopamine in the brain and is often prescribed for disorders like Parkinson disease, may improve depressive symptoms by reversing the effects of inflammation on brain reward circuits. Study findings examining this application of the drug were published in Molecular Psychiatry.

“A significant portion of patients with major depressive disorder (MDD) reliably exhibit evidence of increased inflammation, which has received considerable attention as one pathophysiologic pathway contributing to symptoms of depression and particularly anhedonia,” wrote Mandakh Bekhbat, PhD, postdoctoral fellow, Department of Psychiatry and Behavioral Sciences, Emory University, and co-authors.

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Past research conducted by the same research team showed how increased inflammation in the brain reduced the release of dopamine, especially in depressed patients with higher C-reactive protein (CRP) levels. CRP is a blood biomarker that originates in the liver and is released in response to inflammation.

The study included 40 depressed individuals who ranged from high to low concentrations of CRP. Patients completed 2 functional brain scans on 2 occasions after randomly receiving either placebo or levodopa. Researchers found that patients with a concentration of CRP greater than 2mg/L responded most significantly to treatment with levodopa.

“These results suggest that our targeted, a priori method for assessing FC in reward circuitry that has been reproducibly associated with both increased inflammation and anhedonia is a potentially modifiable brain biomarker to assess target engagement in relation to behavioral efficacy of treatments to reverse the impact of inflammation on the brain in MDD,” the authors concluded. “In this regard, these findings also suggest that MDD patients with higher CRP may have low dopamine availability and potential for therapeutic benefit from therapies with dopaminergic activity.”

References

McEwen JJ. A drug that increased dopamine can reverse the effects of inflammation on the brain in depression. Medical Xpress. Published online January 27, 2023. Accessed March 7, 2023.

Bekhbat M, Li Z, Mehta ND, et al. Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study. Mol Psychiatry. 27(2022):4113-4121. doi:10.1038/s41380-022-01715-3