Fiber Content of the Fornix in Schizophrenia: Lack of Evidence for a Primary Limbic Encephalopathy

OBJECTIVE: There have been claims that schizophrenia is a disease of the limbic circuit and that the volume of the hippocampus and its content of neurons are low in schizophrenia. The fornix is a major pathway through which neurons project to and from the hippo­campus. The authors investigated whether the fiber number or structure of the fornix is abnormal in schizophrenia, as was suggested by an earlier MRI study. METHOD: A section of fornix was removed from each hemisphere of postmortem brains of 16 male and 13 female schizophrenic patients and a comparison group of 19 men and 14 women. Cross-sectional area, fiber density, and total fiber number were examined for differences between diagnostic groups and between genders. RESULTS: The men had a lower fiber density in the fornix than the women. Fiber density on the left side was greater in the schizophrenic men than in the comparison men. For total fiber number (density multiplied by area) there were no differences between groups. Density was found to decrease with increasing area, suggesting that these measures may be affected by degree of myelination. CONCLUSIONS: The fornix does not show the abnormalities in cross-sectional area or total fiber number that would be expected if the primary impact of schizophrenia is on the hippocampus and limbic system. The greater density on the left in schizophrenic men suggests an effect of schizophrenia on myelination related to sex and asymmetry, which may reflect one aspect of a global delay in brain development.