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Excessive Extracellular Volume Reveals a Neurodegenerative Pattern in Schizophrenia Onset

Institution:
1Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2Laboratory for Mathematical Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
3Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
4Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA.
5Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
6Surgical Planning Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Publisher:
HighWire Press
Publication Date:
Nov-2012
Journal:
J Neurosci
Volume Number:
32
Issue Number:
48
Pages:
17365-72
Citation:
J Neurosci. 2012 Nov 28;32(48):17365-72.
Links:
http://dx.doi.org/10.1523/JNEUROSCI.2904-12.2012
PubMed ID:
23197727
PMCID:
PMC3549332
Keywords:
Schizophrenia, Neuroinflammation, Neurodegeneration, Diffusion MRI, Free-water
Appears in Collections:
LMI, NAC, PNL, SLICER, SPL
Sponsors:
M01 RR001032/RR/NCRR NIH HHS/United States
P41 RR013218/RR/NCRR NIH HHS/United States
P50 MH080272/MH/NIMH NIH HHS/United States
R01 MH050740/MH/NIMH NIH HHS/United States
R01 MH082918/MH/NIMH NIH HHS/United States
R01 MH050740/MH/NIMH NIH HHS/United States
R01 MH074794/MH/NIMH NIH HHS/United States
R01 MH082918/MH/NIMH NIH HHS/United States
Generated Citation:
Pasternak O., Westin C-F., Bouix S., Seidman L.J., Goldstein J.M., Woo T-U.W., Petryshen T.L., Mesholam-Gately R.I., McCarley R.W., Kikinis R., Shenton M.E., Kubicki M. Excessive Extracellular Volume Reveals a Neurodegenerative Pattern in Schizophrenia Onset. J Neurosci. 2012 Nov 28;32(48):17365-72. PMID: 23197727. PMCID: PMC3549332.
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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.

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