Evidence for white matter abnormalities in schizophrenia

Abstract

Purpose of review: The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is cast within the context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research.

Recent findings: White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely. This has come about as a result of advances in neuroimaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia.

Summary: Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia.

Figure 1. Automatic segmentation of white matter

Magnetic resonance imaging structural data acquired on a 1.5 T magnet (courtesy of Sylvain Bouix).

Figure 2. Diffusion tensor images acquired on 1.5 T magnetic resonance magnet

On the left is a fractional anisotropy map, and on the right is a tensor map with the colors corresponding to fiber orientation (i.e. blue = superior to inferior, red = left to right, and green = posterior to anterior).

Figure 3. Map of magnetization transfer ratio showing distribution of myelin in the brain

The red color indicates higher myelin density in the white matter (note the highest myelin density is in the corpus callosum), while the yellow color indicates lower myelin density in the gray matter.

Figure 4. Fiber tractography

Based on diffusion data acquired on a 3 T magnet demonstrating major long fiber tracts of the brain (courtesy of Hae-Jeong Park PhD, currently at Laboratory of Molecular Neuroimaging, Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, South Korea).

Figure 5. Fiber tractography of the uncinate fasciculus

Fiber tractography of the uncinate fasciculus is co-registered with a fractional anisotropy coronal image, and shows the relationship of this fiber bundle to surrounding structures.