A review of MRI findings in schizophrenia

Abstract

After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described 'dementia praecox' and the 'schizophrenias', were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82-120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92% of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63% of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. (ABSTRACT TRUNCATED)

Figures

Fig. 1

This image shows the ventricular system derived from 1.5-mm contiguous MR images which were segmented to delineate the ventricles. A three-dimensional reconstruction surface rendering program was used to visualize the labeled MR data set. The component parts of the ventricular system (see labels) include: the lateral ventricles (body, temporal horns, frontal horns, occipital horns), and third and fourth ventricles. [Courtesy of Aleksandra Ciszewski, B.A., Marianna Jakab, M.S., Marek Kubicki, M.D., PhD, Elizabeth David, A.B., and Michael Halle, PhD Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, and Surgical Planning Laboratory, Department of Radiology, Harvard Medical School.]

Fig. 2

Photograph of a lateral view of the human brain. [From Carpenter, Human Neuroanatomy, 1983, reprinted with permission of Williams & Witkins, New York, New York.]

Fig. 3

Coronal 1.5-mm slice showing medial temporal lobe and neocortical structures. The region delineated in white on the left side of the image (subject’s right) is the temporal lobe. The regions delineated in white on the right side of the image (subject’s left) include the superior temporal gyrus, which borders the Sylvian fissure, the amygdala (almond shaped region in the medial temporal lobe), and the parahippocampal gyrus, delineated beneath the amygdala. [Reprinted with permission of The New England Journal of Medicine, Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf D, Coleman M, McCarley RW, 327, 602, 1992, Copyright (1992), Massachusetts Medical Society.]

Fig. 4

Coronal 1.5-mm slice of a normal control (left panel) and a schizophrenic patient (right panel). Note the increased CSF (black) in the left Sylvian fissure in the patient image (right panel, viewer’s right), as well as the increased CSF in the left temporal horn which surrounds the amygdala (see white arrow), and tissue reduction in the left superior temporal gyrus. The lateral ventricles are also enlarged in the patient image as can be seen by the black CSF regions in the center of the image. Contrast this with the slice at approximately the same neuroanatomical level for the normal control (left panel). [Reprinted with permission of The New England Journal of Medicine, Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf D, Coleman M, McCarley RW, 327, 602, 1992, Copyright (1992), Massachusetts Medical Society.]

Fig. 5

3D surface rendering of the superior, middle and frontal lobe gyri is shown along with a coronal 1.5-mm slice that illustrates the relationship of the gyri to the coronal slice. The side view depicts the gyri just at the beginning of the amygdala (top), and the front view (bottom) shows the same slice and 3D reconstruction but in a different orientation. Superior frontal (flesh/aqua color), middle frontal (blue/peach color), and inferior frontal (gold/yellow) gyri are depicted.[Courtesy of Aleksandra Ciszewski, B.A. and Marianna Jakab, M.S., Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, and Surgical Planning Laboratory, Department of Radiology, Harvard Medical School.]

Fig. 6

MR brain diffusion tensor image map of a normal control subject. The diffusion tensor map is displayed as eigenvectors with the blue lines representing the direction of the in-plane components of each eigenvector which correspond to the largest eigenvalue. Note the orientation of the fibers in the corpus callosum which can be readily appreciated. In gray matter, where spherical diffusion is predominant, the eigenvectors points in a random direction. The displayed lines corresponding to the largest eigenvectors are also very short. Harder to visualize are the green and orange colored dots, where the in- and out-of-plane components of the largest eigenvector barely exceed threshold. This figure demonstrates the possibilities that this new technology affords. We call particular attention to the white matter fiber tracts of the corpus callosum, because we think they strongly illustrate the power of this technique in visualizing heretofore unseen fiber tracts in vivo. [Courtesy of Marek Kubicki, M.D., PhD, Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, and Surgical Planning Laboratory, Department of Radiology, Harvard Medical School.]