overview: Commonly prescribed as a treatment for Parkinson’s disease by increasing dopamine in the brain, levodopa was found to reverse the effects of neuroinflammation on the reward system and improve symptoms associated with depression.
sauce: Emory University
Emory University study published in molecular psychiatry Levodopa, a drug that increases dopamine in the brain, has been shown to reverse the effects of inflammation on the brain’s reward circuits, ultimately potentially improving symptoms of depression.
Numerous laboratories around the world have shown that inflammation affects reward pathways in the brain, leading to decreased motivation and anhedonia, a major symptom of depression.
A previous study conducted by the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine examined the effects of inflammation on the brain on the release of dopamine, a chemical neurotransmitter that regulates motivation and motor activity, in the ventral striatum. associated with decline.
In this study, researchers investigated the effect of levodopa on the brain’s functional connections in the brain’s reward circuits and the effects of inflammation on brain functional connections and C-reactive protein (CRP), which is produced and released by the brain. demonstrated a reversal of the effect on anhedonia (inability to feel pleasure) in depressed patients with elevated blood biomarkers. Liver in response to inflammation.
The level of inflammation can be easily measured with a simple blood test such as CRP, readily available in clinics and hospitals across the United States.
The study included 40 depressed patients ranging from high to low CRP levels who were given either placebo or levodopa (a drug often prescribed for disorders such as Parkinson’s disease). After randomized dosing, functional brain scans were performed at two visits.
Levodopa improved functional connectivity from the classical ventral striatum to ventromedial prefrontal cortex reward circuitry, but only in patients with high levels of CRP. This improvement in reward circuitry in depressed patients with high CRP was also correlated with reduced anhedonia symptoms after levodopa.
“This study demonstrates the translational potential of using inflammation-associated deficits in functional connectivity and may have important implications for future research into precision therapy for psychiatric patients with high-grade inflammation. D., Associate Professor of Psychiatry and Behavioral Sciences, Emory College of Medicine.
Felger says the findings are important for two reasons. First, they suggest that depressed patients with high inflammation may respond specifically to drugs that increase dopamine.
Second, Felger says these findings also provide additional evidence that functional connections in reward circuits may serve as reliable brain biomarkers for the effects of inflammation on the brain.
“Furthermore, because the effects of levodopa were unique to depressed patients with high inflammation, this functional connectivity could be used to target this subtype of depressed patients in future studies and clinical trials.” It allows us to assess the brain’s responsiveness to potentially novel therapeutics,” says Felger.
About this psychopharmacology and depression research news
Original research: open access.
“Functional connections in reward circuits and symptoms of anhedonia as therapeutic targets for depression with hyperinflammation: Evidence from a dopamine challenge study.’ Mandakh Bekhbat et al. molecular psychiatry
Functional connections in reward circuits and symptoms of anhedonia as therapeutic targets for depression with hyperinflammation: Evidence from a dopamine challenge study.
Increased inflammation in major depressive disorder (MDD) may be associated with decreased functional connectivity (FC) in the corticostriatal reward circuit and symptoms of anhedonia, an effect of inflammation on dopamine synthesis and release associated with sexual relationships.
To test this hypothesis, medically stable naïve adult MDD outpatients were enrolled to establish a platform to examine the target engagement of potential therapies in patients with increased inflammation. inflammation (indexed by plasma C-reactive protein) [CRP] Levels) were studied at two visits including acute challenge with the dopamine precursor levodopa (L-DOPA; 250 mg) and placebo (double-blind, randomized order ~1 week apart).
The main outcome of the resting-state (rs) FC from the classical ventral striatum to the ventromedial prefrontal cortex reward circuit was calculated using a targeted a priori approach.
Data available both pre-challenge and post-challenge (n= 31/40) to establish rsFC stability across visits and determined CRP > 2 mg/L as the cutpoint for patients exhibiting a positive FC response (post-minus pre) to L-DOPA versus placebo (p< 0.01).
Higher values after L-DOPA FC in patients with CRP >2 mg/L were confirmed in all patients (n= 40) where rsFC data were available after challenge (B.= 0.15, p= 0.006), and for task-based (tb)FC during reward prediction (B.= 0.15, p= 0.013).
Off-scanner effort-based motivation was positively correlated with rsFC independently of treatment or CRP, whereas changes in anhedonia scores were associated with rsFC after L-DOPA only in patients with CRP >2 mg/L. was negatively correlated with (r= -0.56, p= 0.012).
The reward circuit FC needs further validation in larger samples as a biomarker of target engagement for potential treatments, including dopamine agonists, in MDD patients with increased inflammation.