In this study of whole-brain measures in subjects with schizotypal personality disorder, ANOVAs demonstrated a main effect of diagnosis and an interaction between diagnosis and the brain’s three main tissue classes. Follow-up planned comparisons showed larger CSF volume in the schizotypal subjects than in normal comparison subjects. As lateral ventricle size did not differ, this difference in CSF volume derived from other sources. In addition, there was also a nonsignificantly smaller (p=0.07) cortical gray matter volume with a moderate to large effect size (0.78), suggesting that an increase in the subject number would result in statistically significant differences between groups in total cortical gray matter. Calculations based on this effect size indicated that a subject pool of fewer than 30 subjects per group would yield a statistically significant result.
These data suggest that the abnormalities in schizotypal personality disorder are not confined to the temporal lobe (7
) but may be more widespread. As subarachnoid CSF accounts for the major portion of the nonventricular CSF (about 87% of whole-brain CSF) (9
), we think it likely that this component is larger than normal, a finding consistent with results of a previous computerized tomography (CT) study (27
). The most likely reason for a large CSF volume is a small volume of underlying gray or white matter. Our findings of no difference in white matter but smaller than normal cortical gray matter (although not statistically significant) suggest it may be primarily this latter component. Nonetheless, additional studies of gray matter volume in different cortical regions will be required to determine whether the larger CSF volume is accompanied by diffusely small gray matter volume or is better characterized by disproportionate abnormalities among regions, as has been true in the great majority of studies of schizophrenia (86%) (15
In an important MRI study (28
) examining the possible role of genetics in overall brain morphology, schizophrenic subjects and their siblings—10% of whom had schizotypal personality disorder—were shown to have smaller cortical gray matter volumes and larger sulcal CSF volumes. However, only the schizophrenic subjects had large lateral ventricles and concurrently small white matter volumes. The authors hypothesized that genetics contributed to the small cortical gray matter volume and that psychotic illness effects or “nonshared causative effects” contributed to the large ventricular volumes (28
). Their finding is similar to ours: the subjects with schizotypal personality disorder showed a tendency for smaller cortical gray matter, no abnormality in ventricular volume, but a significantly larger than normal subarachnoid CSF volume.
Also, consistent with the preceding hypothesis, Buchsbaum and co-workers (29
) showed no abnormality in lateral ventricle size in subjects with schizotypal personality disorder. However, they did find large temporal horns in those subjects. Possible reasons for the difference in temporal horn findings are their 1) use of a clinic population, 2) inclusion of both men and women, 3) inclusion of both right- and left-handed subjects, 4) use of axial images rather than coronal images, and 5) different tracing procedures. Indeed, only one study (30
) showed high ventricle-brain ratios (VBRs) in subjects with schizotypal personality disorder, although these subjects may have VBRs intermediate between those of schizophrenic and comparison subjects (31
) and larger VBRs than those of nonaffected siblings (32
Overall, although there are differences in the technology used, populations sampled, and brain regions measured, there appears to be an emerging consensus from the literature. In terms of global measures, schizotypal personality disorder appears to be associated with large CSF volume and, possibly, small cortical gray matter volume. The exact area of the large CSF volume may differ among studies, and more work is needed to understand these differences.
The nonnormal distribution of CSF volume demonstrated in this study may not be unusual as a skew toward the right (toward higher values) has also been reported in chronic schizophrenia (33
). Thus, in the schizophrenia spectrum disorders, the skew toward higher values may reflect a severity factor affecting CSF volume. Although the reported CSF volume for this comparison group was not statistically different from a normal distribution, there are literature reports of a “tail” of higher CSF values in the general population (34
), where mean CSF volume is usually between 130 and 140 ml (35
). Our mean value of 137 ml and our finding that two comparison subjects had CSF volumes 100 ml above the mean are consistent with these reports.
Moreover, the size of the lateral ventricles may also vary greatly in the general population. In a postmortem study of 183 grossly normal brains (37
), the mean lateral ventricle size was 7 ml and the range was 2 to 39 ml, values that are consistent with our current findings of large lateral ventricles in two comparison subjects. No history of head trauma or developmental abnormalities was noted for either subject. (Removing these two normal subjects from the analysis had no effect on the absence of a statistically significant difference in lateral ventricle size between the schizotypal and comparison subjects.) The present data thus appear compatible with literature reports of variability of CSF and ventricle size in the general population and with a tendency for distributions to be skewed toward higher values.
Although there was no difference in total gray matter volume between the two groups, when total gray matter was more carefully delineated into cortical gray matter only, the subjects with schizotypal personality disorder showed nonsignificantly smaller volumes. In studies of schizophrenia, measurements of gray matter have yielded conflicting results: some studies have demonstrated a smaller than normal total gray matter volume (38
) or cortical gray matter volume (39
) and others have not (9
). From our review of such studies (15
), however, the evidence suggests a nonuniform distribution of gray matter volume deficits in schizophrenia, i.e., that the deficits are greater in some areas than in others. One CT study (30
) of subjects with personality disorders in the schizophrenia spectrum (the majority of whom had schizotypal personality disorder) used a visual scale to show “cortical atrophy” (greater sulcal prominence), which likely is compatible with our finding of larger than normal subarachnoid CSF volume.
The ability to generalize these findings to all persons with schizotypal personality disorder is limited by the relatively small number of subjects and the use of only male subjects. Future plans include the study of female subjects. Drawing subjects from the community may yield subjects less severely affected than in clinic groups but has the important advantage of finding subjects not yet exposed to neuroleptics or other psychotropic medications. In addition, these data do not address the issue of whether the abnormalities are neurodevelopmental and/or degenerative in nature, as this was not a longitudinal study designed to study changes over time.
The finding of larger than normal overall CSF volume and suggestive evidence for smaller cortical gray matter volume, taken together with previous findings of focal deficits in the temporal lobes of the same subjects, suggest that neuroanatomic abnormalities in schizotypal personality disorder may be present in widespread locations but may be greater in some regions than in others, not unlike what is seen in schizophrenia (15