ArticleMolecular psychiatry2023
Characterization of the extracellular free water signal in schizophrenia using multi-site diffusion MRI harmonization.
Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Early identification of vascular cognitive impairment from a multimodal perspective: a combined diagnosis from targeted cognitive assessments, imaging biomarkers, and molecular fluid biomarkers to ecological behavioral characteristics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A frontotemporal free water signature associated to interleukin-8 and cognitive impairment in schizophrenia with comorbidity of metabolic syndrome.Brain, behavior, & immunity - health · 2026Article
- Saturated Fatty Acids and White Matter Microstructure in Individuals With At-risk Mental State.Schizophrenia bulletin · 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
- White matter microstructure alterations in early psychosis and schizophrenia.Translational psychiatry · 2025Article
- Elevated Extracellular Free Water in the Brain Predicts Clinical Improvement in First-Episode Psychosis.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Article
- Gyrification across psychotic disorders: A bipolar-schizophrenia network of intermediate phenotypes study.Schizophrenia research · 2024Article
- A diffusion MRI tractography atlas for concurrent white matter mapping across Eastern and Western populations.Scientific data · 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
- Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Reduction of N-acetyl aspartate (NAA) in association with relapse in early-stage psychosis: a 7-Tesla MRS study.Schizophrenia (Heidelberg, Germany) · 2024Article
- Harmonized diffusion MRI data and white matter measures from the Adolescent Brain Cognitive Development Study.Scientific data · 2024Article
- Poor self-reported sleep is associated with prolonged white matter T2 relaxation in psychotic disorders.Frontiers in psychiatry · 2024Article
- Microstructural Cortical Gray Matter Changes Preceding Accelerated Volume Changes in Individuals at Clinical High Risk for Psychosis.Research square · 2023Article
Corrections and comments
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Authors and funding
26 authors at 15 institutions in 7 countries.
Funding
Abstract
Studies applying Free Water Imaging have consistently reported significant global increases in extracellular free water (FW) in populations of individuals with early psychosis. However, these published studies focused on homogenous clinical participant groups (e.g., only first episode or chronic), thereby limiting our understanding of the time course of free water elevations across illness stages. Moreover, the relationship between FW and duration of illness has yet to be directly tested. Leveraging our multi-site diffusion magnetic resonance imaging(dMRI) harmonization approach, we analyzed dMRI scans collected by 12 international sites from 441 healthy controls and 434 individuals diagnosed with schizophrenia-spectrum disorders at different illness stages and ages (15-58 years). We characterized the pattern of age-related FW changes by assessing whole brain white matter in individuals with schizophrenia and healthy controls. In individuals with schizophrenia, average whole brain FW was higher than in controls across all ages, with the greatest FW values observed from 15 to 23 years (effect size range = [0.70-0.87]). Following this peak, FW exhibited a monotonic decrease until reaching a minima at the age of 39 years. After 39 years, an attenuated monotonic increase in FW was observed, but with markedly smaller effect sizes when compared to younger patients (effect size range = [0.32-0.43]). Importantly, FW was found to be negatively associated with duration of illness in schizophrenia (p = 0.006), independent of the effects of other clinical and demographic data. In summary, our study finds in a large, age-diverse sample that participants with schizophrenia with a shorter duration of illness showed higher FW values compared to participants with more prolonged illness. Our findings provide further evidence that elevations in the FW are present in individuals with schizophrenia, with the greatest differences in the FW being observed in those at the early stages of the disorder, which might suggest acute extracellular processes.
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