Cerebral Ventricular Enlargement

One of the best replicated neuropathological findings in schizophrenia is that of enlargement of the fluid-filled spaces in the brain (cerebral ventricles), specifically the lateral ventricles and the third ventricle. Ventricular enlargements have been identified in postmortem studies, as well as in scanning studies of live patients using computerized tomography (CT) and magnetic resonance imaging (MRI). In a review of MRI studies, the ventricular size in schizophrenia patients is 40 percent larger than in controls (Lawrie and Abukmeil, 1998). It is important to note that the ventricular enlargement in patients with schizophrenia is present for the group as a whole and that there is some overlap in the range of ventricular size between schizophrenia patients and controls. Nonetheless, one recent study (Staal et al., 2001) showed a relationship between ventricular enlargement and schizophrenia outcome in that patients with poor outcomes have on average larger ventricles than patients with good outcomes (Fig. 9.2A-C). In studies of monozygotic twins discordant for schizophrenia, the affected twin usually has bigger ventricles (Stabenau and Pollin, 1993). The twin studies are important because they control for both genetic predisposition and environmental factors and show that this particular neuropathological abnormality is associated with the expression of the disease rather then being associated with the underlying genotype. However, people's genes do have an impact on the size of the ventricles such that the discordant twin who does not have schizophrenia will have larger ventricles than will other members of the family, and unaffected relatives have larger

Figure 9.2. Magnetic resonance imaging of coronal sections of the brains of a healthy comparison subject (A), a patient with schizophrenia with good outcome (B) and a patient with schizophrenia with poor outcome (C). Note that patients that have schizophrenia with bad outcome have larger ventricles than either patients with good outcome or healthy controls. Schizophrenia patients with good outcome did not differ significantly from healthy controls [Adapted from Staal, Am J Psychiatry 2001, 158(7):1140-1142. Copyright 2001, the American Psychiatric Association, http://ajp.psychiatryonline.org. Reprinted by permission.]

Figure 9.2. Magnetic resonance imaging of coronal sections of the brains of a healthy comparison subject (A), a patient with schizophrenia with good outcome (B) and a patient with schizophrenia with poor outcome (C). Note that patients that have schizophrenia with bad outcome have larger ventricles than either patients with good outcome or healthy controls. Schizophrenia patients with good outcome did not differ significantly from healthy controls [Adapted from Staal, Am J Psychiatry 2001, 158(7):1140-1142. Copyright 2001, the American Psychiatric Association, http://ajp.psychiatryonline.org. Reprinted by permission.]

ventricles than that of the control population. Ventricular enlargement does not appear to be due to a neurodegenerative process since there are no obvious signs of neuronal loss and no increase in gliotic cells, which would normally invade to remove any degenerating cells (Selemon and Goldman-Rakic, 1999). Rather, ventricular enlargement is likely related to changes in other brain structures, including thinning of the surrounding cortex.

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