Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.

Andrea L Cordero; Madeleine R Frazier; Geneva M Jost; Camelia E Hostinar; Johnna R Swartz

doi:10.1016/j.bbi.2026.106827

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Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.

Andrea L Cordero·Madeleine R Frazier·Geneva M Jost·Camelia E Hostinar·Johnna R Swartz

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Abstract

Research shows that cytokines are associated with psychiatric disorders, including major depression, and multiple aspects of brain structure and function. Accumulating data suggest that different cytokines may have unique profiles of biological activity, particularly in their neuromodulatory roles, but it is currently unclear whether they have unique associations with specific neural circuits in humans. In this paper, we systematically review magnetic resonance imaging studies conducted with depressed or healthy control human participants under age 65 that examine associations between peripheral cytokines and brain structure and function, with the goal of evaluating evidence for the specificity of these cytokine-brain associations. We find that across multiple measures of brain structure and function, the majority of studies reviewed reported unique associations between individual cytokines and brain outcomes. A synthesis of findings across studies also suggests a preliminary hypothesis of specific associations of interleukin-6 levels in circulation with the default mode network and tumor necrosis factor-alpha with the salience network, which could be tested in future research. We conclude the review with future directions for research that can strengthen understanding of these associations.

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Humans Magnetic Resonance Imaging Brain Cytokines Interleukin-6 Tumor Necrosis Factor-alpha Major Depressive Disorder Neural Pathways Brain function Brain structure Inflammation Magnetic resonance imaging Journal Article Systematic Review Review

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Andrea L Cordero, Madeleine R Frazier, Geneva M Jost, Camelia E Hostinar, Johnna R Swartz. 2026-05-20. Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.. https://doi.org/10.1016/j.bbi.2026.106827

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Brain subject Cytokines subject Humans subject Interleukin-6 subject Journal Article subject Journal Article; Systematic Review; Review resource Magnetic Resonance Imaging subject Major Depressive Disorder subject Neural Pathways subject Systematic reviews study inflammation subject

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