Excessive Extracellular Volume Reveals a Neurodegenerative Pattern in Schizophrenia Onset

被引:226
|
作者
Pasternak, Ofer [1 ]
Westin, Carl-Fredrik [2 ]
Bouix, Sylvain [1 ]
Seidman, Larry J. [4 ,6 ]
Goldstein, Jill M. [1 ,3 ,4 ]
Woo, Tsung-Ung W. [5 ]
Petryshen, Tracey L. [6 ,7 ,8 ]
Mesholam-Gately, Raquelle I. [4 ]
McCarley, Robert W. [4 ,9 ]
Kikinis, Ron [2 ]
Shenton, Martha E. [1 ,9 ]
Kubicki, Marek [1 ]
机构
[1] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr,Publ Psychiat Div, Boston, MA 02215 USA
[5] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA
[6] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA
[7] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA 02142 USA
[8] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02144 USA
[9] Vet Affairs Boston Healthcare Syst, Brockton Div, Dept Psychiat, Brockton, MA 02301 USA
来源
JOURNAL OF NEUROSCIENCE | 2012年 / 32卷 / 48期
基金
美国国家卫生研究院;
关键词
MATTER VOLUME; DIFFUSION; ABNORMALITIES; DEGENERATION; INFLAMMATION; MICROGLIA; PATHOLOGY; DENSITY; CORTEX; GRAY;
D O I
10.1523/JNEUROSCI.2904-12.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Diffusion MRI has been successful in identifying the existence of white matter abnormalities in schizophrenia in vivo. However, the role of these abnormalities in the etiology of schizophrenia is not well understood. Accumulating evidence from imaging, histological, genetic, and immunochemical studies support the involvement of axonal degeneration and neuroinflammation-ubiquitous components of neurodegenerative disorders-as the underlying pathologies of these abnormalities. Nevertheless, the current imaging modalities cannot distinguish neuroinflammation from axonal degeneration, and therefore provide little specificity with respect to the pathophysiology progression and whether it is related to a neurodegenerative process. Free-water imaging is a new methodology that is sensitive to water molecules diffusing in the extracellular space. Excessive extracellular volume is a surrogate biomarker for neuroinflammation and can be separated out to reveal abnormalities such as axonal degeneration that affect diffusion characteristics in the tissue. We applied free-water imaging on diffusion MRI data acquired from schizophrenia-diagnosed human subjects with a first psychotic episode. We found a significant increase in the extracellular volume in both white and gray matter. In contrast, significant signs of axonal degeneration were limited to focal areas in the frontal lobe white matter. Our findings demonstrate that neuroinflammation is more prominent than axonal degeneration in the early stage of schizophrenia, revealing a pattern shared by many neurodegenerative disorders, in which prolonged inflammation leads to axonal degeneration. These findings promote anti-inflammatory treatment for early diagnosed schizophrenia patients.
引用
收藏
页码:17365 / U792
页数:9
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