TY - JOUR
T1 - Free water alterations in different inflammatory subgroups in schizophrenia
AU - Wu, Dongsheng
AU - Wu, Qi
AU - Li, Fei
AU - Wang, Yaxuan
AU - Zeng, Jiaxin
AU - Tang, Biqiu
AU - Bishop, Jeffrey R.
AU - Xiao, Li
AU - Lui, Su
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/1
Y1 - 2024/1
N2 - Background: Accumulating evidence suggests that inflammatory dysregulation both in blood and the brain is implicated in the pathogenesis of schizophrenia. Alterations in peripheral cytokines are not evident in all patients and there may be discrete altered inflammatory subgroups in schizophrenia. Recent studies using a novel and in vivo free-water imaging to detect inflammatory processes, have shown increased free water in white matter in schizophrenia. However, no studies to date have investigated the free water alterations in different inflammatory subgroups in schizophrenia. Methods: Forty-four patients with schizophrenia and 49 controls were recruited. The serum levels of interleukin-1 beta (IL-1β), IL-6, IL-10, and IL-12p70 were measured and used for cluster analysis with K-means and hierarchical algorithms. Diffusion tensor imaging (DTI) images were collected for all participants and voxel-wise free water and fractional anisotropy of tissue (FA-t) were compared between groups with Randomise running in FSL. Partial correlation analysis was employed to explore the association of the peripheral cytokine levels with free water. Results: We identified two statistically quantifiable discrete subgroups of patients based on the cluster analysis of cytokine measures. The peripheral levels of IL-1β (P < 0.001), IL-10 (P = 0.041), and IL-12p70 (P < 0.001) showed significant differences between the two different inflammatory subgroups. In the inflammatory subgroup with a predominantly higher IL-1β level, increased free water values in white matter were found mainly in the left posterior limb of the internal capsule, posterior corona radiata, and partly in the left sagittal stratum. These affected areas did not overlap with the regions that showed significant free water differences between patients and healthy controls. In the inflammatory subgroup with lower IL-1β levels, peripheral IL-1β was significantly associated with free water values in white matter while no such association was detected in the patient group. Conclusions: Localized free water differences were demonstrated between the two identified inflammatory subgroups in our data, and free water appears to be a feasible in vivo neuroimaging biomarker guiding the target of inflammatory intervention and development of new therapeutic strategies in an individualized manner in schizophrenia.
AB - Background: Accumulating evidence suggests that inflammatory dysregulation both in blood and the brain is implicated in the pathogenesis of schizophrenia. Alterations in peripheral cytokines are not evident in all patients and there may be discrete altered inflammatory subgroups in schizophrenia. Recent studies using a novel and in vivo free-water imaging to detect inflammatory processes, have shown increased free water in white matter in schizophrenia. However, no studies to date have investigated the free water alterations in different inflammatory subgroups in schizophrenia. Methods: Forty-four patients with schizophrenia and 49 controls were recruited. The serum levels of interleukin-1 beta (IL-1β), IL-6, IL-10, and IL-12p70 were measured and used for cluster analysis with K-means and hierarchical algorithms. Diffusion tensor imaging (DTI) images were collected for all participants and voxel-wise free water and fractional anisotropy of tissue (FA-t) were compared between groups with Randomise running in FSL. Partial correlation analysis was employed to explore the association of the peripheral cytokine levels with free water. Results: We identified two statistically quantifiable discrete subgroups of patients based on the cluster analysis of cytokine measures. The peripheral levels of IL-1β (P < 0.001), IL-10 (P = 0.041), and IL-12p70 (P < 0.001) showed significant differences between the two different inflammatory subgroups. In the inflammatory subgroup with a predominantly higher IL-1β level, increased free water values in white matter were found mainly in the left posterior limb of the internal capsule, posterior corona radiata, and partly in the left sagittal stratum. These affected areas did not overlap with the regions that showed significant free water differences between patients and healthy controls. In the inflammatory subgroup with lower IL-1β levels, peripheral IL-1β was significantly associated with free water values in white matter while no such association was detected in the patient group. Conclusions: Localized free water differences were demonstrated between the two identified inflammatory subgroups in our data, and free water appears to be a feasible in vivo neuroimaging biomarker guiding the target of inflammatory intervention and development of new therapeutic strategies in an individualized manner in schizophrenia.
KW - Cluster analysis
KW - Diffusion tension imaging
KW - Free water
KW - Inflammation
KW - Schizophrenia
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U2 - 10.1016/j.bbi.2023.11.006
DO - 10.1016/j.bbi.2023.11.006
M3 - Article
C2 - 37972880
AN - SCOPUS:85178285710
SN - 0889-1591
VL - 115
SP - 557
EP - 564
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -