Large-Scale Evidence for an Association Between Peripheral Inflammation and White Matter Free Water in Schizophrenia and Healthy Individuals

被引:54
作者
Di Biase, Maria A. [1 ,2 ,3 ]
Zalesky, Andrew [1 ,2 ,4 ]
Cetin-Karayumak, Suheyla [3 ]
Rathi, Yogesh [3 ,5 ]
Lv, Jinglei [6 ]
Boerrigter, Danny [7 ,8 ]
North, Hayley [7 ,8 ]
Tooney, Paul [9 ]
Pantelis, Christos [1 ,2 ,4 ]
Pasternak, Ofer [3 ,5 ]
Weickert, Cynthia Shannon [7 ,8 ,10 ]
Cropley, Vanessa L. [1 ,2 ,11 ]
机构
[1] Univ Melbourne, Melbourne Neuropsychiat Ctr, Dept Psychiat, Level 3,Alan Gilbert Bld 161 Barry St, Carlton, Vic, Australia
[2] Melbourne Hlth, Carlton, Vic, Australia
[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA
[4] Univ Melbourne, Melbourne Sch Engn, Parkville, Vic, Australia
[5] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA
[6] Univ Sydney, Sch Biomed Engn, Camperdown, NSW, Australia
[7] Neurosci Res Australia, Randwick, NSW, Australia
[8] Univ New South Wales, Sch Psychiat, Sydney, NSW, Australia
[9] Univ Newcastle, Sch Biomed Sci & Pharm, Hunter Med Res Inst, Newcastle, NSW, Australia
[10] Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA
[11] Swinburne Univ, Fac Hlth Arts & Design, Ctr Mental Hlth, Melbourne, Vic, Australia
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
diffusion-weighted imaging; magnetic resonance imaging; DWI; MRI; cytokines;
D O I
10.1093/schbul/sbaa134
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Introduction: Clarifying 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. Methods: All 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-ianti-inflammatory cytokines related to FW in brain white matter, imaged in a subset (n = 308) of patients and controls. Results: Patients 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 TNF alpha (t = 4.30, P < .0001). Higher proinflammatory signaling of IL-6 (t = 3.4, P = .0007) and TNF alpha (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. Conclusions: We report widespread deregulation of cytokines in schizophrenia and identify inflammation as a putative mechanism underlying increases in brain FW levels.
引用
收藏
页码:542 / 551
页数:10
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