Trial reportMolecular psychiatry2025
A randomized proof-of-mechanism trial of TNF antagonism for motivational deficits and related corticostriatal circuitry in depressed patients with high inflammation.
Trial report in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of Anti-Inflammatory Treatment on Depressive Symptom Severity and Anhedonia in Depressed Individuals With Elevated Inflammation: Systematic Review and Meta-Analysis of Randomized Controlled Trials.The American journal of psychiatry · 2026Pooled it
- Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation.Brain, behavior, and immunity · 2026Trial
- Consummatory deficits in close social reward predict inflammation-induced depressed mood.Psychoneuroendocrinology · 2026Trial
- Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation.Brain, behavior, and immunity · 2025Trial
- Compound Ciwujia Granules Attenuate Stress-Induced Anxiety- and Depression-Like Behaviors via Inhibition of TNF-α-Associated Neuroinflammation in the dmPFC.CNS neuroscience & therapeutics · 2026Article
- Stressful life events and lifestyle factors are associated with elevated peripheral TNF-α levels in adults with depression without physical diseases.European archives of psychiatry and clinical neuroscience · 2026Article
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- Voluntary wheel running in male mice mitigates select hyperglycemia-induced depressive-like behaviors and modulates BDNF andBrain, behavior, & immunity - health · 2026Article
- Designing Clinical Trials for an Inflammatory Subtype of Major Depressive Disorder.Biological psychiatry · 2026Article
- Sigma-1R-CD36 axis in myeloid cells contributes to the alleviation of depression-like behaviors.Journal of translational medicine · 2026Article
- Anti-inflammatories for depression: challenges and ASPIRations.The lancet. Psychiatry · 2026Article
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Basal Ganglia Dopamine Availability and Immune Activation Interact and Relate to Anhedonia Severity among Youth with Depression.Research square · 2026Article
- Interleukin-6 and tumor necrosis factor alpha as predictive biomarkers for depression and mania in young adults with depressive and bipolar disorder.Journal of psychiatric research · 2026Article
- From Monoamines to Systems Psychiatry: Rewiring Depression Science and Care (1960s-2025).Biomedicines · 2025Article
- Networks and clusters of immunometabolic biomarkers and depression-associated features in middle-aged and older community-dwelling US adults with and without depression.Brain, behavior, & immunity - health · 2025Article
- An interoceptive model of energy allostasis linking metabolic and mental health.Science advances · 2025Review
- Predicting antidepressant response via local-global graph neural network and neuroimaging biomarkers.NPJ digital medicine · 2025Article
- Advancing an Inflammatory Subtype of Major Depression.The American journal of psychiatry · 2025Review
- Anhedonia as a Core Symptom of Depression and a Construct for Biological Research.Focus (American Psychiatric Publishing) · 2025Article
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein >3 mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5 mg/kg) versus placebo. Behavioral performance on an effort-based decision-making task, self-report questionnaires, and neural responses during event-related functional magnetic resonance imaging were assessed at baseline and 2 weeks following infusion. We found that relative to placebo, patients receiving infliximab were more willing to expend effort for rewards. Moreover, increase in effortful choices was associated with reduced TNF signaling as indexed by decreased soluble TNF receptor type 2 (sTNFR2). Changes in effort-based decision-making and sTNFR2 were also associated with changes in task-related activity in a network of brain areas, including dorsomedial prefrontal cortex (dmPFC), ventral striatum, and putamen, as well as the functional connectivity between these regions. Changes in sTNFR2 also mediated the relationships between drug condition and behavioral and neuroimaging measures. Finally, changes in self-reported anhedonia symptoms and effort-discounting behavior were associated with greater responses of an independently validated whole-brain predictive model (aka "neural signature") sensitive to monetary rewards. Taken together, these data support the use of anti-inflammatory treatment to improve effort-based decision-making and associated brain circuitry in depressed patients with high inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.