Eighty-five percent of normal subjects, 77% of schizophrenic patients, 63% of patients with affective disorder, and 76% of patients with schizotypal personality disorder showed some degree of cavum septi pellucidi. Thus, regardless of diagnosis, most subjects evinced cavum septi pellucidi. These rates are high compared to those of other studies that used CT or MRI (16
), which have reported cavum septi pellucidi in 0.15% to 58.8% of schizophrenic patients. All of these studies, except that of Nopoulos et al. (23
), used imaging techniques with less spatial resolution than in our study. The study by Nopoulos et al. was, in fact, the first to use 1.5-mm contiguous slices, and they reported cavum septi pellucidi in 58.7% of normal subjects and 58.8% of schizophrenic patients. Their figures are lower than the percentages reported in the current study (i.e., 85% of normal subjects, 77% of schizophrenic patients). This discrepancy may be due to the higher proportion of men in our study (see later discussion). It would appear, nonetheless, that the presence of cavum septi pellucidi, in and of itself, may have no pathological significance.
We next considered the rating of 6 mm or more of cavum septi pellucidi as abnormal (corresponding to cavum septi pellucidi on four or more slices). Using this criterion, we found that 30.4% of schizophrenic patients (36.4% of chronic and 25.0% of first-episode patients) and 10.3% of normal subjects showed abnormal cavum septi pellucidi. This finding is consistent with previous studies (19
). Ratings of cavum septi pellucidi on four or more slices would therefore seem appropriate for classifying cavum septi pellucidi as abnormal, although it would, of course, need to be validated with a new group of subjects.
When we used the criteria of Nopoulos et al. (23
), we noted an increase in abnormal cavum septi pellucidi: 35.0% of schizophrenic patients (40.0% of chronic and 30.0% of first-episode patients) and 13.0% of normal subjects had abnormal cavum septi pellucidi. Degreef et al. (25
), in a postmortem study, reported abnormal cavum septi pellucidi in 32.1% of schizophrenic patients and 7.7% of normal subjects; these figures are similar to ours.
Eighteen percent of patients with schizotypal personality disorder showed abnormal cavum septi pellucidi on the basis of our criteria, in contrast to 27.3% on the basis of the Nopoulos et al. (23
) criteria. These ratings were intermediate between those of schizophrenic and normal subjects; this finding is consistent with a study in our laboratory of neuropsychological performance in patients with schizotypal personality disorder that was intermediate between that of schizophrenic and normal subjects (45
). It is also consistent with the report by Trestman et al. (46
) of auditory P300 amplitude reduction in patients with schizotypal personality disorder that was intermediate between that of normal and schizophrenic subjects. These findings suggest that schizotypal personality disorder may be a milder form on a continuum of schizophrenia spectrum disorders.
Abnormal cavum septi pellucidi was evident in 20.0% of patients with first-episode affective disorder. It would, however, be premature to conclude that the occurrence of abnormal cavum septi pellucidi in affective disorder is not different from that in normal subjects, particularly in light of the fact that our group was small. Shioiri et al. (28
), however, reported that cavum septi pellucidi in patients with bipolar disorder was not higher than that in normal subjects when small cavum septi pellucidi was excluded from the analysis; but the rate was higher than that in normal subjects when all ratings were included. Jurjus et al. (21
) reported a lower frequency of cavum septi pellucidi in patients with affective disorder than in schizophrenic patients (25% versus 10%); there was no difference between patients with affective disorder and normal subjects, which they attributed to a gender effect (i.e., their study had an excess of male schizophrenic subjects). Others have also reported a higher rate of cavum septi pellucidi in male than in female subjects (16
). Nopoulos et al. (23
), for example, reported cavum septi pellucidi in 67% of male subjects, compared to 46% of female subjects. This gender effect may be evident in other neurodevelopmental abnormalities (11
). Eight of our group of 113 subjects were female: two were normal subjects, three first-episode schizophrenic patients, and three patients with affective disorder. One of the eight women, a schizophrenic patient, did show abnormal cavum septi pellucidi. More careful studies, with a larger cohort of female subjects, will be needed to address further the issue of gender effects.
The first report of an association between cavum septi pellucidi and psychosis was done through use of CT (16
). This association was replicated by Mathew et al. (48
) through use of MR, and there have been several MR studies of cavum septi pellucidi (reviewed in reference 49
). More recently, Nopoulos et al. (50
) reported an association between abnormal cavum septi pellucidi and left temporal lobe volume reduction in male schizophrenic patients. In their first study (23
), six schizophrenic patients showed abnormal cavum septi pellucidi. This group, along with four new patients with abnormal cavum septi pellucidi, was the subject of the second study. In that study, 44 schizophrenic patients without cavum septi pellucidi were compared with 10 schizophrenic patients with abnormal cavum septi pellucidi. The schizophrenic patients with abnormal cavum septi pellucidi showed volume reduction only in the left temporal lobe, as well as a less severe decrease in total brain tissue, normal-sized frontal lobes, and pronounced asymmetry (right greater than left). In contrast, the schizophrenic patients with normal cavum septi pellucidi showed reduced volumes in overall brain and an increase in overall CSF. These investigators suggested that the pattern of structural abnormalities observed in schizophrenic patients with abnormal cavum septi pellucidi may reflect a regional, localized tissue reduction confined to the left temporal lobe in a subgroup of male schizophrenic patients.
In our study, we found an association between degree of cavum septi pellucidi and volume of hippocampus in male chronic schizophrenic patients. This finding is consistent with the hypothesis that growth of both the hippocampus and corpus callosum during fetal development results in a pushing together of the leaflets of septi pellucidi, which fuse; abnormalities in this process may lead to a lack of fusion (cavum septi pellucidi). Of note, the septum pellucidum is an important relay station with the hippocampus and hypothalamus, as well as being part of the limbic system that regulates emotion and motivational behavior (51
). Disturbances in this system may, therefore, lead to distortions of perception, cognition, and behavior seen in schizophrenia.
In conclusion, abnormal cavum septi pellucidi was confirmed in schizophrenia, and we noted an association between cavum septi pellucidi and hippocampal volume. These findings suggest that for at least a subgroup of patients, neurodevelopmental origins may be implicated in the pathogenesis of schizophrenia. A further study of patients with and without abnormal cavum septi pellucidi should help to clarify further the nature of these brain anomalies.