ArticleBrain, behavior, and immunity2019
Inflammation and decreased functional connectivity in a widely-distributed network in depression: Centralized effects in the ventral medial prefrontal cortex.
Article in Brain, behavior, and immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Gene-disease association study of tumor necrosis factor-α G-308A gene polymorphism with risk of major depressive disorder: A systematic review and meta-analysis.Brain and behavior · 2020Pooled 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
- Upregulation of reward mesolimbic activity and immune response to vaccination: a randomized controlled trial.Nature medicine · 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
- Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study.Molecular psychiatry · 2022Trial
- Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals.Molecular psychiatry · 2021Trial
- Impact of Inflammation on White Matter Integrity and Functional Connectivity in Chronic Major Depressive Disorder.Biological psychiatry · 2026Article
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Inflammatory and MRI perfusion biomarkers in predicting persistence of depression: a 6-month Longitudinal Study.Translational psychiatry · 2025Article
- Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Neural Correlates of Peripheral Inflammation in Major Depressive Disorder and Their Transcriptomic Architecture, Neurochemical Basis, and Behavioral Relevance.Human brain mapping · 2025Article
- Therapeutic Effects of Intranasal Administration of Mesenchymal Stem Cell-Derived Secretome in Rats Exposed to Chronic Unpredictable Mild Stress.Pharmaceutics · 2025Article
- Neurotransmitter and metabolic effects of interferon-alpha in association with decreased striatal dopamine in a non-human primate model of cytokine-Induced depression.Brain, behavior, and immunity · 2025Article
- Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges.Brain sciences · 2025Review
- Lipids and C-reactive protein predict anhedonia and reward circuit functional connectivity responses to anti-cytokine and dopaminergic therapies in patients with depression.Comprehensive psychoneuroendocrinology · 2025Article
- Major Depressive Disorder in Long COVID and Exposure to Pro-Inflammatory Cytokines During Infection by SARS-CoV-2.Psychiatric research and clinical practice · 2025Article
- Neural and immune interactions linking early life stress and anhedonia.Brain, behavior, & immunity - health · 2024Article
- Medial prefrontal cortex connectivity with the nucleus accumbens is related to HIV serostatus, perceptions of psychological stress, and monocyte expression of TNF-a.Brain, behavior, & immunity - health · 2024Article
- Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?Brain, behavior, and immunity · 2024Article
- Neural substrates of predicting anhedonia symptoms in major depressive disorder via connectome-based modeling.CNS neuroscience & therapeutics · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Major depressive disorder is a heterogeneous disease involving widespread disruptions in functional brain networks, the neurobiological mechanisms of which are poorly understood. Amassing evidence supports innate immune activation as one pathophysiologic mechanism contributing to depression in a subgroup of patients with elevated inflammatory markers. Although inflammation is known to alter monoamine and glutamate neurotransmitters, little work has been done to understand its role in network dysfunction in patients with depression. Here we conducted a large-scale network-based analyses of resting-state functional magnetic resonance imaging (rfMRI) data acquired from depressed patients with varying levels of inflammation to develop a comprehensive characterization of network alterations as an effect of inflammation. Complementary approaches of global brain connectivity and parcellation-based network analysis applied to the whole brain revealed that increased plasma C-reactive protein (CRP) was associated with reduced functional connectivity in a widely-distributed network including ventral striatum, parahippocampal gyrus/amygdala, orbitofrontal and insular cortices, and posterior cingulate cortex. These broad alterations were centralized in the ventral medial prefrontal cortex (vmPFC), representing a hub for the effects of inflammation on network function in the whole brain. When feeding the identified multivariate network features into a machine learning algorithm of support vector regression, we achieved high prediction accuracies for depressive symptoms that have been associated with inflammation in previous studies including anhedonia and motor slowing. These findings extend and broaden previous observations from hypothesis-driven studies, providing further support for inflammation as a distinct contributing factor to network dysfunction and symptom severity in depression.
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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.