CLINICAL HANDBOOK OF SCHIZOPHRENIA

5. Neuropathology 47schizophrenia include the lateral ventricles as a whole, the temporal horn portion of thelateral ventricular system (particularly on the left), and the third ventricle (which is ofparticular importance given its proximity to the thalamus, discussed below). Rather thanuse an absolute measurement, ventricular size is often measured by ventricule–brain ratio(VBR), which adjusts for differences in subjects’ overall brain volumes. Schizophrenia hasbeen associated with a wide range of increases in VBR, from 20 to 75%, with a recent reviewciting a median enlargement of 40%. Although estimates of the size of this increaseremain somewhat variable, the enlargement of the ventricles in schizophrenia is a ubiquitousfinding. There is a significant amount of overlap in VBR between subjects withschizophrenia and controls, so it is worth noting that VBR has no diagnostic or predictiveability. Although overall brain volumes have often been found to be reduced in schizophreniaas described earlier, this decrease has not been shown to correlate with the degreeof VBR increase.Not only is the increase in VBR a common finding, but twin studies also lend supportto the idea that this may be partially a predisposing factor and partially a disease-specificfinding. On the one hand, in monozygotic twins discordant for schizophrenia, the ventriclesof the affected twin are larger than those of the unaffected sibling, along with reductionsin cortical and hippocampal size. These findings suggest that increased VBR is partof a schizophrenia phenotype; in other words, this increase accompanies the presentationof the disease and does not merely reflect an underlying genetic vulnerability. On theother hand, family studies that examine patients with schizophrenia and their unaffectedsiblings demonstrate that unaffected siblings have smaller ventricles than their siblingswith schizophrenia but larger ventricles than healthy controls who are not part of thefamily. This suggests, instead, that at least some aspect of ventricular size in schizophreniamay be under genetic influence.Prefrontal CortexCORTICAL FINDINGSThe prefrontal cortex is a region of interest in schizophrenia, because it is believed tomodulate many cognitive and behavioral tasks at which patients with schizophrenia aredeficient. Postmortem studies have shown prefrontal abnormalities, and although imagingstudies have not been as conclusive, the majority of such studies do find deficits in thisregion. Likely, the reason for the negative findings includes the fact that the frontal lobehas often been measured as a whole, and small regional abnormalities in these casesmight be missed. Importantly, when white matter and gray matter are examined differentially,studies have shown that each is reduced. Furthermore, when the frontal cortex issubdivided, differences do appear in dorsolateral regions, as well as in orbitofrontal (infemales) and dorsomedial (in males) regions. Investigations into subdivisions of the frontallobe have also revealed correlations with performance tests of verbal recall, visualmemory, semantic fluency, and negative symptoms, consistent with theories of schizophrenia’scognitive deficits residing in aberrations of frontal lobe structures.Increased neuronal packing density has been reported over the entire frontal lobe,particularly in the dorsolateral prefrontal cortex (DLPFC). Although negative findingshave been reported on this measure in these regions, the importance of the DLPFC inschizophrenia is largely accepted, because many of the symptom- and cognition-relatedfindings have been associated with alterations in DLPFC functioning. Of note, the absolutenumber of neurons in the DLPFC has not been found to be altered in patients withschizophrenia.