RT Journal Article SR Electronic T1 Excessive Extracellular Volume Reveals a Neurodegenerative Pattern in Schizophrenia Onset JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 17365 OP 17372 DO 10.1523/JNEUROSCI.2904-12.2012 VO 32 IS 48 A1 Pasternak, Ofer A1 Westin, Carl-Fredrik A1 Bouix, Sylvain A1 Seidman, Larry J. A1 Goldstein, Jill M. A1 Woo, Tsung-Ung W. A1 Petryshen, Tracey L. A1 Mesholam-Gately, Raquelle I. A1 McCarley, Robert W. A1 Kikinis, Ron A1 Shenton, Martha E. A1 Kubicki, Marek YR 2012 UL http://www.jneurosci.org/content/32/48/17365.abstract AB 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.