Increased Density of Glutamate-immunoreactive Vertical Processes in Superficial Laminae in Cingulate Cortex of Schizophrenic Brain

Abstract

Recent postmortem investigations have suggested that schizophrenia may involve a defect in associative information processing in the upper layers of limbic cortex. One of these studies reported that vertical processes visualized with antibodies against the neurofilament 200K subunit (NFP-200K) of the axon cytoskeleton were increased in density in layer II and upper portions of layer IIIa of the cingulate region of schizophrenic individuals. Based on this tatter finding, it was hypothesized that there may he a superabundance of associa tive afferents to this region. To explore this possibility further, an immunoperoxidase localization of the amino acid glutamate has been employed to visualize vertical fibers in layers II and lila of postmortem anterior cingulate cortex in both normal controls (n = 15) and schizophrenics (n = 17). Vertical fibers were distinguished according to small or large calibers and were differentially counted with a blind computer-assisted technique. The schizophrenic group showed a markedly higher density (77.8%) of small-caliber glutamate-immunoreactive vertical fibers when compared to controls; the density of large-caliber vertical fibers also showed a similar, though smaller (30.2%), increase in the schizophrenic group. There were no differences in the density of either small- or large-caliber processes in prefrontal cortex of the two groups. The effects of age, postmortern interval, fixation, and neuroleptic exposure do not account for the differences between the normal and schizophrenic subjects. Taking together their small caliber, vertical orientation, localization in superficial layers, and marked glutamate immunoreactivity, it seems plausible that the fibers showing an increased density in schizophrenics may be glutamatergic afferents, possibly ones that are associative in nature. Thus, the data presented here are consistent with earlier findings based on NFP-200K-immunostained axons and support the hypothesis that alterations of associative information processing in the anterior cingulate cortex may be one component to the pathophysiology of schizophrenia.