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

Serge A Mitelman,Adam M Brickman,Lina Shihabuddin,M Mehmet Haznedar,King-Wai Chu,Erin A Hazlett,Yuliya Torosjan,Emily L Canfield,Randall E Newmark,Monte S Buchsbaum

doi:10.2174/1874440000903010031

Abstract

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.

Highlights

Illness progression remains a debated topic in schizophrenia neuroimaging research [1, 2]
In comparison to healthy subjects and in alliance with a large body of neuroimaging literature, middle-aged patients with chronic schizophrenia entered this study with lower anisotropy over extensive frontal and parietal white matter regions and with larger posterior frontal white matter volumes
A similar regional finding of larger white matter volumes at the frontoparietal junction was recently presented by Whitford et al in first-episode schizophrenia patients [36]

Summary

Introduction

Illness progression remains a debated topic in schizophrenia neuroimaging research [1, 2]. Some authors reported a progressive decline in gray matter volumes in chronic schizophrenia patients as had been shown after the first psychotic outbreak [5], the interpretation of these results gained a degree of controversy when. Weinberger and McClure [6] proposed that these findings may be epiphenomenal, reflecting the methodological and/or physiological vicissitudes rather than a true tissue loss. This claim sprang from a rather obvious conjecture that by extrapolating the reported rate of excessive gray matter loss early in the illness (2-7% per year in various studies) in due time schizophrenia patients risk being left void of gray matter altogether. A more recent review of the still rare longitudinal MRI studies in chronic schizophrenia patients, concludes that this may be the case and that, unlike normal aging, the rate of regional changes in both gray and white matter volumes in patients with schizophrenia slows down with age [8]

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