A drug that increases dopamine can reverse the effects of inflammation on the brain in depression
summary: Levodopa, a drug commonly prescribed to treat Parkinson’s disease that increases dopamine in the brain, has been found to reverse the effects of neuroinflammation on the reward system and improve symptoms associated with depression.
Source: Emory University
Emory University study published in Molecular Psychiatry Levodopa, a drug that increases dopamine in the brain, is shown to have the ability to reverse the effects of inflammation on the brain’s reward circuits, ultimately improving symptoms of depression.
Numerous labs around the world have shown that inflammation causes decreased motivation and anhedonia, a core symptom of depression, by affecting reward pathways in the brain.
Previous research from the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine has linked the effects of inflammation on the brain to decreased release of dopamine, a chemical neurotransmitter that regulates motivation and motor activity in the ventral striatum.
In the study, the researchers showed that levodopa reversed the effects of inflammation on brain functional connectivity in the reward circuitry and anhedonia (inability to feel pleasure) in depressed individuals who had C-reactive protein (CRP), a blood biomarker produced and released by the liver in response to inflammation.
Inflammation levels can be easily measured with simple blood tests, such as CRP, which are readily available in clinics and hospitals across the United States.
The study involved 40 depressed patients with a range of high-to-low CRP levels who underwent functional brain scans at two visits after randomly receiving either a placebo or levodopa, a drug often prescribed for disorders such as Parkinson’s disease.
Levodopa improved functional connectivity in a classical ventral striatum to the ventral prefrontal cortex reward circuit but only in patients with higher levels of CRP. This improvement in reward circuits in depressed individuals with a higher CRP level is also associated with a reduction in symptoms of anhedonia after levodopa.
“This research demonstrates translational potential for using inflammation-related deficiencies in functional connectivity and could have important implications for future investigations of precision therapies for psychiatric patients with severe inflammation,” says lead investigator and lead author Jennifer C. Felger, PhD. Ph.D., Assistant Professor of Psychiatry and Behavioral Sciences, Emory College of Medicine.
Felger says the study’s findings are crucial for two reasons. First, they suggest that depressed patients with severe inflammation may respond particularly well to drugs that increase dopamine.
Secondly, these findings also provide additional evidence that functional connectivity in the reward circuitry may serve as a reliable brain biomarker for the effects of inflammation on the brain, says Villiger.
“Furthermore, because the effect of levodopa was specific to depressed patients with higher inflammation, this functional connection could be used to assess the brain’s response to novel therapies that might target this subtype of depressed patients in future studies and clinical trials,” Felger says.
About this news Psychopharmacology and Depression Research
author: Jennifer Johnson McQueen
Source: Emory University
Contact: Jennifer Johnson McQueen – Emory University
picture: The image is in the public domain
Original search: open access.
“Functional connectivity in reward circuits and anhedonia symptoms as treatment targets in depression with severe inflammation: evidence from the dopamine challenge study.by Mandakh Bekhbat et al. Molecular Psychiatry
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Functional connectivity in reward circuits and anhedonia symptoms as treatment targets in depression with severe inflammation: evidence from the dopamine challenge study.
Increased inflammation in major depressive disorder (MDD) has been associated with decreased functional connectivity (FC) in cortical reward circuits and symptoms of anhedonia, relationships that may involve the effect of inflammation on dopamine synthesis and release.
To test this hypothesis while creating a platform to examine the targeted engagement of potential therapies in patients with increased inflammation, medically stable, untreated adult MDD patients with an inflammation range (as indexed by plasma C-reactive protein) were enrolled. [CRP] Levels) were studied at two visits involving an acute challenge with the dopamine precursor levodopa (L-DOPA, 250 mg) and placebo (double-blind, randomized ~1 week apart).
The resting-state raw score (rs) FC was calculated in a classical ventral striatum to the ventral prefrontal cortex reward circuit using a pre-targeted approach.
Data available before and after the challenge (n= 31/40) stabilized rsFC across visits and defined a CRP >2 mg/L as the cut-off point for patients who showed positive responses of FC (post-minus pre) to L-DOPA versus placebo (s<0.01).
An elevated L-DOPA FC level was confirmed in patients with CRP >2 mg/L in all patients (n= 40) where rsFC data was available after challenge (B= 0.15, s= 0.006), and in those with (tb)FC during reward expectation (B= 0.15, s= 0.013).
Whereas effort-based motivation outside the scanner correlated positively with rsFC regardless of treatment or CRP, change in anhedonia scores correlated negatively with rsFC after L-DOPA only in patients with CRP >2 mg/L (s= -0.56, s= 0.012).
FC in the reward circuit should be further validated in larger samples as a biomarker for targeted engagement of potential therapies including dopaminergic agents in MDD patients with increased inflammation.