ArticleSchizophrenia bulletin2021
Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals.
Article in Schizophrenia bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Effects of IL-6/IL-6R axis alterations in serum, plasma and cerebrospinal fluid with the schizophrenia: an updated review and meta-analysis of 58 studies.Molecular and cellular biochemistry · 2024Pooled it
- Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after ketamine treatment - A pilot study.Journal of affective disorders · 2022Trial
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Putative glymphatic function and free water in schizophrenia: A 7T DTI study across psychosis stages.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Myo-inositol concentration in the medial prefrontal cortex is associated with changes in brain white matter microstructure in early psychosis.Translational psychiatry · 2026Article
- A frontotemporal free water signature associated to interleukin-8 and cognitive impairment in schizophrenia with comorbidity of metabolic syndrome.Brain, behavior, & immunity - health · 2026Article
- Amyloid-beta statuses prediction with free water MR imaging features in Alzheimer's disease using machine learning models.BMC medical imaging · 2026Article
- Free Water Elevation in Alzheimer's Disease: Influence of Amyloid-Beta Deposition Beyond Brain Cell Loss.Journal of Korean medical science · 2026Article
- Gray and White matter microstructural alterations in major depressive disorder: a multi-center diffusion imaging study.Translational psychiatry · 2026Article
- Microvascular and microstructural brain abnormalities in paediatric haematological cancer survivors are related to cognitive deficits: An IVIM-FWI MRI study.British journal of haematology · 2026Article
- Differential effect of cannabis use and antipsychotic medication on extracellular free-water in the brain of individuals with early psychosis and controls.Molecular psychiatry · 2026Article
- Decreased diffusivity along the perivascular spaces in bipolar disorder: an MRI-based cross-sectional and Mendelian randomization study.Translational psychiatry · 2025Article
- MRI-based neuroimaging alterations in immune-related skin diseases: a comprehensive review.Archives of dermatological research · 2025Review
- Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.Human brain mapping · 2025Article
- Review
- Magnetic resonance imaging of postmortem human brain specimens: methodological considerations and prospects in psychoradiology.Psychoradiology · 2025Article
- Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis.Molecular psychiatry · 2024Article
- Gyrification across psychotic disorders: A bipolar-schizophrenia network of intermediate phenotypes study.Schizophrenia research · 2024Article
- Executive functioning, behavior, and white matter microstructure in the chronic phase after pediatric mild traumatic brain injury: results from the adolescent brain cognitive development study.Psychological medicine · 2024Article
- Longitudinal microstructural alterations surrounding subcortical ischemic stroke lesions detected by free-water imaging.Human brain mapping · 2024Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
introductionClarifying the role of neuroinflammation in schizophrenia is subject to its detection in the living brain. Free-water (FW) imaging is an in vivo diffusion-weighted magnetic resonance imaging (dMRI) technique that measures water molecules freely diffusing in the brain and is hypothesized to detect inflammatory processes. Here, we aimed to establish a link between peripheral markers of inflammation and FW in brain white matter.
methodsAll data were obtained from the Australian Schizophrenia Research Bank (ASRB) across 5 Australian states and territories. We first tested for the presence of peripheral cytokine deregulation in schizophrenia, using a large sample (N = 1143) comprising the ASRB. We next determined the extent to which individual variation in 8 circulating pro-/anti-inflammatory cytokines related to FW in brain white matter, imaged in a subset (n = 308) of patients and controls.
resultsPatients with schizophrenia showed reduced interleukin-2 (IL-2) (t = -3.56, P = .0004) and IL-12(p70) (t = -2.84, P = .005) and increased IL-6 (t = 3.56, P = .0004), IL-8 (t = 3.8, P = .0002), and TNFα (t = 4.30, P < .0001). Higher proinflammatory signaling of IL-6 (t = 3.4, P = .0007) and TNFα (t = 2.7, P = .0007) was associated with higher FW levels in white matter. The reciprocal increases in serum cytokines and FW were spatially widespread in patients encompassing most major fibers; conversely, in controls, the relationship was confined to the anterior corpus callosum and thalamic radiations. No relationships were observed with alternative dMRI measures, including the fractional anisotropy and tissue-related FA.
conclusionsWe report widespread deregulation of cytokines in schizophrenia and identify inflammation as a putative mechanism underlying increases in brain FW levels.
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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.