Longitudinal Assessment of Gray and White Matter in Chronic Schizophrenia: A Combined Diffusion-Tensor and Structural Magnetic Resonance Imaging Study

Serge A Mitelman1, *, Emily L Canfield1, Randall E Newmark1, Adam M Brickman2, Yuliya Torosjan1, King-Wai Chu1, Erin A Hazlett1, M. Mehmet Haznedar1, Lina Shihabuddin1, Monte S Buchsbaum3
1 Department of Psychiatry, Mount Sinai School of Medicine, New York, USA
2 Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA
3 Departments of Psychiatry and Radiology, University of California, San Diego, USA

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© Mitelman et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Mount Sinai Medical Center, Department of Psychiatry, Box 1505, Neuroscience Positron Emission Tomography Laboratory, One Gustave L. Levy Place, New York, New York 10029, USA; Tel: 1 (212) 241-5294; Fax: 1 (212) 423-0819; E-mail:


Previous studies have reported continued focal gray matter loss after the clinical onset of schizophrenia. Longitudinal assessments in chronic illness, of white matter in particular, have been less conclusive.

We used diffusion-tensor and structural magnetic resonance imaging in 16 healthy subjects and 49 chronic schizophrenia patients, subdivided into good-outcome (n=23) and poor-outcome (n=26) groups, scanned twice 4 years apart. Fractional anisotropy, gray matter and white matter volumes were parcellated into the Brodmann’s areas and entered into multiway ANCOVAs.

At baseline, schizophrenia patients had 1) lower anisotropy in frontoparietal white matter, 2) larger posterior frontal white matter volumes, and 3) smaller frontal, temporal, and parietal gray matter volumes. On follow-up, healthy subjects showed a more pronounced 1) decline in anisotropy, 2) expansion of regional white matter volumes, and 3) reduction in regional gray matter volumes than schizophrenia patients. Good-outcome patients showed a more pronounced decline in white matter anisotropy and a less pronounced increase in white matter volumes than poor-outcome patients. Poor-outcome patients displayed a greater gray matter loss throughout the brain than good-outcome patients.

In the chronic phase of the illness, longitudinal changes in both gray and white matter are in the direction of an effacement of between-group differences among schizophrenia patients and healthy subjects. Similarly, preexisting white matter differences between good-outcome and poor-outcome patients diminish over time. In contrast, gray matter volumes in poor-outcome patients continue to decline more rapidly than in patients with good outcome. These patterns are consistent with earlier onset of aging-associated changes in schizophrenia.

Key Words: Kraepelinian schizophrenia, poor outcome, anisotropy, white matter, illness progression.