Structural neuroimaging in schizophrenia: from methods to insights to treatments

Abstract

Historically, Kraepelin speculated that dementia praecox resulted from damage to the cerebral cortex, most notably the frontal and temporal cortices. It is only recently, however, that tools have been available to test this hypothesis. Now, more than a century later, we know that schizophrenia is a brain disorder. This knowledge comes from critical advances in imaging technology--including computerized axial tomography, magnetic resonance imaging, and diffusion imaging--all of which provide an unprecedented view of neuroanatomical structures, in vivo. Here, we review evidence for structural neuroimaging abnormalities, beginning with evidence for focal brain abnormalities, primarily in gray matter, and proceeding to the quest to identify abnormalities in brain systems and circuits by focusing on damage to white matter connections in the brain. We then review future prospects that need to be explored and pursued in order to translate our current knowledge into an understanding of the neurobiology of schizophrenia, which can then be translated into novel treatments.

Figure 1.. This CT scan shows separation of brain from fluid, including CSF and blood. This is a CT scan, post-contrast, of a patient with a bleed from an aneurysm (black color is blood and CSF). CT, computed tomography; CSF, cerebrospinal fluid

Figure 2.. This MR scan shows one coronal slice through the superior aspects of the lateral ventricles. Note the clear differentiation between gray and white matter. Gray matter appears gray and can be seen in the ribbon around the cortex, as well as in subcortical brain regions. White matter appears white, and the lateral ventricles are black. MR, magnetic resonance

Figure 3.. Graph of MRI studies in schizophrenia between 1984 and April 2010. MRI, magnetic resonance imaging

Figure 4.. Graph of DTI studies in schizophrenia between 1998 and Apri 201 0. DTI, diffusion tensor imaging

Figure 5.. The anisotropy map in the left panel shows increased fractiona anisotropy (FA) in areas where the water diffusion is restricted, such as in the corpus callosum. Areas with increased FA are visible as white. The color map in the right panel shows the directions of the diffusion in x, y z space, with the colors red, blue, and green, respectively.

Figure 6.. Three-dimensional image reconstructed based on diffusion data acquired on a 3T GE scanner at Brigham and Women's Hospital, Harvard Medical School, Boston, MA. This image shows several major white matter fiber bundles identified through diffusion tensor imaging: fornix (magenta), right cingulum (green), right inferior longitudinal fasciculus (yellow), right uncinate fasciculus (blue), corpus callosum (orange). Adapted from ref 24: Shenton ME, Kubicki M. Structural brain imaging in schizophrenia. In: Sadock BJ, Sadock VA, Ruiz P, eds. Sadock's Comprehensive Textbook of Psychiatry. 9th ed. New York: NY: Lippincott Williams, and Wilkins; 2009:1494-1506. Copyright © Lippincott, Williams and Wilkins, 2009.