A magnetic resonance imaging study of corpus callosum size in familial schizophrenic subjects,their relatives, and normal controls
Introduction
The corpus callosum is one of a number of brain regions that may be abnormal in schizophrenia. Woodruff et al. (1993) measured the mid-sagittal area of the corpus callosum in 30 schizophrenics and 44 normals and found that the middle section of the corpus callosum was significantly smaller in the schizophrenics, this remaining so after allowing for differences arising from head size and age. Since this part of the corpus callosum is known to connect the left and right temporal lobes including the superior temporal gyri (Witelson, 1989), Woodruff and colleagues proposed that reduction in this middle section may accord with evidence of diminution of the temporal lobe (Suddath et al., 1990) and superior temporal gyral volume in schizophrenia (Shenton et al., 1992). A meta-analysis of the size of the corpus callosum examined 11 studies with a total of 313 schizophrenic patients and 281 controls, and found a statistically significant reduction in corpus callosum area in schizophrenic patients (Woodruff et al., 1995). However, it was noted that in ten of these 11 studies, correcting for brain size by means of the corpus callosum:brain area ratio resulted in no between-group difference, a finding that could be explained by a reduced generalized brain size or increased ventricular:brain ratio in schizophrenia (Woodruff et al., 1995).
We sought to investigate whether there are any structural abnormalities of the corpus callosum in multiply-affected families in which more than one member has schizophrenia (‘familial schizophrenia’). The risk of schizophrenia increases with genetic proximity, i.e. the more closely related the individual is to an affected person (Gottesman and Shields, 1972). Studies in twins have shown that there is a recognized genetic influence on the size of the lateral ventricles, and these structures are situated in close proximity to the corpus callosum (Reveley et al., 1982). Indeed, enlargement of the lateral ventricles has been thought to account for shape distortion of the corpus callosum in a study of 15 pairs of monozygotic twins discordant for schizophrenia, in which the size (i.e. area, length and vertical thickness) of the corpus callosum was found to be statistically similar for each pair of twins (Casanova et al., 1990). Since the study did not include a control group, it was not possible to say whether the corpus callosum was actually abnormal in size. This point is of potential interest, since the healthy monozygotic twin of a schizophrenic patient is at maximal genetic risk (50%) of schizophrenia, and sharing similar brain morphology such as the size of the corpus callosum may indicate a risk of developing or transmitting the disorder. Accordingly, our study has investigated the size of this structure in first-degree relatives of multiply affected schizophrenic patients compared to normal controls. The patients and their relatives were derived from families where there were at least two schizophrenic individuals. We postulated that the corpus callosum of the familial schizophrenics would be smaller than that of the normal controls, and that of their relatives would be intermediate between the two groups. Our objective was to determine whether abnormal corpus callosum size is found in healthy relatives who are genetically at a greater than normal risk of developing or transmitting the disorder.
Section snippets
Sample
One hundred and fifteen subjects participated in the study (Table 1), comprising 27 with a diagnosis of schizophrenia according to DSMIIIR criteria (American Psychiatric Association, 1987) and 53 healthy first-degree relatives and 35 healthy volunteers. The schizophrenic subjects were selected from 16 families in which there were at least two members with schizophrenia, presumed ‘familial’ schizophrenics. Relatives included 11 presumed ‘obligate carriers’ i.e. non-psychotic relatives who were
Clinical and demographic variables by group
There was no significant difference between the groups in sex, social class, handedness or years of education. However, the distribution of age was significantly different between groups (ANOVA, F=10.10, df=2,122, p<0.001), and thus age was used as a covariate in the subsequent analyses. In addition, whole brain volume was also entered into the analysis since whole brain size is closely correlated with the size of brain structures, and in this sample, whole brain volume in effect correlated
Discussion
We found no significant difference, either in the mid-sagittal area of the corpus callosum or in that of its four subsections, between the groups. Adjusting for the effects of age and whole brain area did not alter these findings. A traditional case–sibling pair analysis showed that the mid-posterior section of the corpus callosum was significantly larger in the schizophrenics than in their control siblings. However, given that there is little evidence that the corpus callosum is larger in
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