SynthesisJAMA psychiatry2025
Differential Associations of Dopamine and Serotonin With Reward and Punishment Processes in Humans: A Systematic Review and Meta-Analysis.
Synthesis in JAMA psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Real-world analysis of depression-related adverse events associated with the adsorbed anthrax vaccine: integrating pharmacovigilance signals, machine learning risk prediction, and transcriptomic mechanisms.Infectious diseases of poverty · 2026Article
- Multicenter retrospective study on perceived effectiveness, reported side effects, and cognitive outcomes of SSRIs in 22q11.2 deletion syndrome.European child & adolescent psychiatry · 2026Article
- Fluorescent Biosensor for Rapid and Accurate Detection of Dopamine Based on Oxidized Single-Walled Carbon Nanohorns and Cryonase Enzyme.Molecules (Basel, Switzerland) · 2026Article
- Early reduction in aversive Pavlovian bias as a mediator of anhedonia improvement during Behavioural Activation in realistic treatment settings.PLoS computational biology · 2026Observational
- Dopamine and serotonin inversely modulate D2 medium spiny neurons to regulate cocaine reward.Nature communications · 2026Article
- Clinical review of how glucagon-like peptide-1 agonist obesity medications decrease sexual desire, and a biopsychosocial model for why we don't 'see' it.Obesity pillars · 2026Review
- Multicenter retrospective study on effectiveness, reported side effects, and cognitive outcomes of SSRIs in 22q11.2 deletion syndrome.Research square · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Importance: Mechanistic biomarkers for guiding treatment selection require selective sensitivity to specific pharmacological interventions. Reinforcement learning processes show potential, but there have been conflicting and sometimes inconsistent reports on how dopamine and serotonin-2 key targets in treating common mental illnesses-affect reinforcement learning in humans. Objective: To perform a meta-analysis of pharmacological manipulations of dopamine and serotonin and examine whether they show distinct associations with reinforcement learning components in humans. Data Sources: Ovid MEDLINE/PubMed, Embase, and PsycInfo databases were searched for studies published between January 1, 1946, and January 19, 2023 (repeated April 9, 2024, and October 15, 2024), investigating dopaminergic or serotonergic effects on reward and punishment processes in humans according to PRISMA guidelines. Study Selection: Studies reporting randomized, placebo-controlled, dopaminergic or serotonergic manipulations on a behavioral outcome from a reward or punishment processing task in healthy humans were included. Data Extraction and Synthesis: Standardized mean difference (SMD) scores were calculated for the comparison between each drug (dopamine or serotonin) and placebo on a behavioral reward or punishment outcome and quantified in random-effects models for overall reward or punishment processes and 4 main subcategories. Study quality (Cochrane Collaboration tool), moderators, heterogeneity, and publication bias were also assessed. Main Outcomes and Measures: Performance on reward or punishment processing tasks. Results: In total, 102 studies conducted among healthy volunteers were included (2291 participants receiving dopamine vs 2284 receiving placebo and 1491 receiving serotonin vs 1523 receiving placebo). Dopamine was associated with an increase in overall reward (SMD, 0.18; 95% CI, 0.09 to 0.28) but not punishment function (SMD, -0.06; 95% CI, -0.26 to 0.13). Serotonin was not meaningfully associated with overall punishment (SMD, 0.22; 95% CI, -0.04 to 0.49) or reward (SMD, 0.02; 95% CI, -0.33 to 0.36). Dopaminergic and serotonergic manipulations had distinct associations with subcomponents. Dopamine was associated with reward learning or sensitivity (SMD, 0.26; 95% CI, 0.11 to 0.40), reward discounting (SMD, -0.08; 95% CI, -0.14 to -0.01), and reward vigor (SMD, 0.32; 95% CI, 0.11 to 0.54). By contrast, serotonin was associated with punishment learning or sensitivity (SMD, 0.32; 95% CI, 0.05 to 0.59), reward discounting (SMD, -0.35; 95% CI, -0.67 to -0.02), and aversive pavlovian processes (within-participant studies only; SMD, 0.36; 95% CI, 0.20 to 0.53). Conclusions and Relevance: In this study, pharmacological manipulations of both dopamine and serotonin had measurable associations with reinforcement learning in humans. The selective associations with different components suggest that reinforcement learning tasks could form the basis of selective, mechanistically interpretable biomarkers to support treatment assignment.
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