Because the hippocampus and amygdala help form some of the walls of the lateral ventricles, ventricular enlargement in patients with schizophrenia might arise from atrophy or destruction of these adjacent regions. Indeed, comparing twins who are discordant for schizophrenia reveals that the hippocampus and the amygdala are smaller in the twin with schizophrenia.

Postmortem studies of patients with schizophrenia have revealed cellular abnormalities in several parts of the limbic system, including the hippocampus, amygdala, and parahippocampal regions. Kovelman and Scheibel (1984), comparing the brains of chronic sufferers of schizophrenia with those of medical patients of the same age that did not exhibit brain pathology, especially noted changes in the hippocampus. Figure 1 shows an example of these cellular differences. The hippocampal pyramidal cells of chronic sufferers of schizophrenia exhibit a characteristic disorganization, possibly resulting from abnormal synaptic arrangements of both the inputs and outputs of these cells. The degree of cellular disorientation reportedly reflects the severity of the disorder: the most impaired individuals exhibit the greatest disorganization (Conrad et al., 1991). Abnormalities are also evident in other limbic system structures, including the entorhinal cortex, parahippocampal cortex, and cingulate cortex (Shapiro, 1993).

Figure 1  Cellular Disarray of the Hippocampus in Chronic Schizophrenia
(a) This horizontal section of the cerebral hemispheres shows the location of the hippocampus. (b) Enlargements of the hippocampus and fornix show the location of anterior, middle, and posterior hippocampal segments. (c) The hippocampus and dentate gyrus are enlarged in this cross section. (d) The hippocampus is subdivided into three regions: CA1, CA2, and CA3 (“CA” stands for cornu ammonis, or “Ammon’s horn,” another name for the hippocampus). (e) Orientations of the pyramidal cells of a control subject (top) and a patient with schizophrenia (bottom) are compared in these hippocampal cross sections. (f, g) Histological cross sections show differences in tissue between a normal control (f) and a patient with schizophrenia (g). (After Kovelman and Scheibel, 1984; f and g courtesy of Arnold Scheibel.)

The cellular derangement in schizophrenia probably arises during early cell development (Mednick et al., 1994). These abnormalities of cellular arrangement in the hippocampus also resemble those of mutant mice that show disordered neurogenesis in the hippocampus (Scheibel and Conrad, 1993). Since we now know that humans make new neurons throughout life, especially in the hippocampus, we can surmise that abnormal neurogenesis or disordered integration of newly born cells might be a contributing factor in the development of schizophrenia in humans.

References

Conrad, A. J., Abebe, T., Austin, R., Forsythe, S., et al. (1991). Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Archives of General Psychiatry 48: 413–417.

Kovelman, J. A., and Scheibel, A. B. (1984). A neurohistological correlate of schizophrenia. Biological Psychiatry 19: 1601.

Mednick, S. A., Huttunen, M. O., and Machon, R. A. (1994). Prenatal influenza infections and adult schizophrenia. Schizophrenia Bulletin 20: 263–267.

Scheibel, A. B., and Conrad, A. S. (1993). Hippocampal dysgenesis in mutant mouse and schizophrenic man: Is there a relationship? Schizophrenia Bulletin 19: 21–33.

Shapiro, R. M. (1993). Regional neuropathology in schizophrenia: Where are we? Where are we going? Schizophrenia Research 10: 187–239.