Cavum Septum Pellucidum and Its Increased Prevalence in Schizophrenia: A Neuroembryological Classification

Table 1 shows the prevalence of CSP in both groups, with a statistically significant increased frequency in schizophrenia patients, as compared to control subjects. Fourteen of the 32 patients (43.75%) had ratings of Type I, Type II, or Type III of CSP (Table 2). One patient was rated with a CSP Type III while no control subjects were rated “3.” There was a clear tendency for schizophrenia patients to have higher abnormal ratings, although the difference when compared with each specific type was not statistically significant (Table 2). Cavum vergae and Cavum velum interpositum were not disclosed in any of the analyzed images. Correlational analysis using Spearman's rho was calculated between the severity ratings for the CSP and the sizes of ventricles, temporal lobes, area of corpus callosum and total brain volumes. Other variables such as age, educational level, length of disease, neuroleptic doses, and positive or negative symptoms were studied in relation to differences between absence or presence of cavum. No statistically significant correlations were found. Correlations between age and surface of corpus callosum, whether CSP was present or not, disclosed a significant decrease in the surface of the corpus callosum with age in the schizophrenia group (r_s −0.46 p < 0.05). In the control group, the surface was not altered with age. The negative sign of the correlation in the schizophrenia group indicates that the area of the corpus callosum, contrary to what happens in the control group, decreases with the increment of age. These results are reported in detail elsewhere.¹⁴

Our results showed a prevalence of CSP in chronic schizoprenia of 43.7% and 10.5% in control subjects, even though we studied a highly selected population of Caucasian, female patients with residual schizophrenia who were compared to normal subjects matched for sex and age. Several imaging studies have shown that the frequency of CSP in chronic schizophrenia is high, ranging from 15%,¹⁵ 21%,¹ 36%,¹⁶ and 44.8%.² Nonetheless, when the CSP was studied with different imaging techniques, as well as in different subtypes of schizophrenia, the prevalence varied consistently in patients and normal subjects. DeGreef et al.¹⁷ found 23% of CSP in first-episode patients versus a 2% in control subjects. Also in first-episode patients, Kwon et al.¹⁶ found a 25% of CSP in patients versus a 10% in controls. Others such as Fukuzako et al.¹⁰ disclosed a 47% presence of CSP in patients and 38% in controls, while Rajarethinam et al.¹⁸ found a 60% presence of septum anomaly in schizophrenics and 42% in normal subjects. On the other hand, Nopoulus et al.¹¹ presented a meticulous imaging technique to report this anomaly and disclosed a 58% presence of CSP in patients and controls as well. Following this report, the same author¹⁹ defined abnormal enlargement of CSP as those greater than 6 mm in length and reported a 12.5% of enlarged CSP in childhood-onset schizophrenia. The results of previous studies seem highly variable in both patients and controls. The inconsistencies in incidences could be regarded, in part, for technical reasons (i.e., magnetic resonance imaging (MRI) acquisitions protocols). Variances in the characteristics of the samples related to race, sex, or age might not be available. Regarding the interpretation of our data, it is clear that a majority of patients with schizophrenia do not have a cavum, and some controls do, and the statistical association in our study could represent nothing more than epiphenomena.

It is our intention to make several hypotheses about the relationship between the CSP and other neuromorphological findings previously described in several studies. First, the possibility that the primary atrophy found in these patients (e.g., smaller frontal lobes,²⁰ smaller temporal lobes,²¹ reduced hemispheric volumes,⁷ increased ventricular volumes)²² could secondarily impact on the SP conforming a postembryonary cavum.

The strict anatomical relationship of the fornix with the septum leaflets is evident. The fornix has its origin in the subiculum, alveus of the hippocampus, and the hippocampal pyramidal cells. It belongs to the limbic system and is directly or indirectly connected to the thalamus, hypothalamus, and reticular formation. Disarray of hippocampal pyramidal cells,²³ reduced parahippocampal white matter²⁴ and volume gyrus,²⁵ reduced volumes of hippocampus and amygdalas,^26,27 and lower neuronal densities in the cingulate gyrus²⁸ are limbic disturbances that have been noted in schizophrenics. Other qualitative abnormalities of the limbic system disclosed in schizophrenia included gliosis of the hippocampus⁶ and cellular changes in the ansa lenticularis²⁹ and rostral enthorrinal region,³⁰ among others. It is possible that these abnormalities anatomically impact the fornix and in the septum.

Third, the abnormalities of the corpus callosum and septum pelucidum have been previously described in schizophrenia.^14,15 An involution of the corpus callosum, specifically of the genu due to less interconnection of frontal fibers, could lead to a secondary effect in the anterior septum developing the CSP.

Another possibility is that the CSP in schizophrenia is a persisting anomaly from the prenatal period and not a secondary developmental anomaly. One possible way to study this hypothesis is to perform MRIs of neonates and children with predisposing factors such as direct family members with schizophrenia. It is important to recognize that more systematic studies will require thousands of subjects and many years of follow-up. However, the finding of developmental anomalies supports the theory that increased susceptibility to schizophrenia may result from a prenatal disturbance in brain development.^2,31

An interconnected web among all these factors could lead to a conformation of a CSP in patients with schizophrenia. The theory that anatomical structures such as the basal ganglia, thalamus, and hippocampus have possible implications in the mechanisms of cognition, consciousness, intelligence, and creativity³² is applicable in patients with schizophrenia. Empirical data that confirms or refutes these hypotheses are still lacking.

Our studies disclosed an increased prevalence of CSP in female patients with residual schizophrenia, compared with a control group matched by age and gender. We believe that a more anatomo-embryological-based classification of the CSP, such as the one presented here, would be more appropriate to distinguish this particular anomaly in schizophrenia patients. It is our opinion that the presence of a CSP in this disease is merely a developmental anomaly and is not adequate, per se, to produce schizophrenia, although it is related to other structural abnormalities that could not be established in the present study.

The authors thank Mrs. Sue Ware for English assistance.