ABNORMAL CHOLECYSTOKININ MESSENGER-RNA LEVELS IN ENTORHINAL CORTEX OFSCHIZOPHRENICS

Limbic cortical regions, including anterior cingulate cortex (ACC), pr efrontal cortex (PFC) and entorhinal cortex (ERC), have been implicate d in the neuropathology of schizophrenia. Glutamate projection neurons connect these limbic cortical regions to each other, as well as to th e terminal fields of the striatal/accumbens dopamine neurons. Subsets of these glutamate projection neurons, and of the GABA interneurons in cortex, contain the neuropeptide cholecystokinin (CCK). In an effort to study the limbic cortical glutamate projection neurons and GABA int erneurons in schizophrenia, we have measured CCK mRNA with in situ hyb ridization histochemistry in postmortem samples of dorsolateral (DL)PF C, ACC and ERC of seven schizophrenics, nine nonpsychotic suicides and seven normal controls. CCK mRNA is decreased in ERC (especially layer s iii-vi) and subiculum in schizophrenics relative to controls. Cellul ar analysis indicates that there is a decrease in density of CCK mRNA in labelled neurons. In so far as ERC CCK mRNA is not reduced in rats treated chronically with haloperidol, this decrease in schizophrenics does not appear to be related to neuroleptic treatment. In contrast, i n DLPFC, where schizophrenics do not differ from normals, the suicide victims have elevated CCK mRNA (especially in layers v and vi), and in creased cellular density of CCK mRNA, relative to both normals and sch izophrenics. These results lend further support for the involvement of ERC and hippocampus in schizophrenia, suggesting that neurons that ut ilize CCK may be particularly important. Similarly, an increase in CCK mRNA levels in the PFC of suicides adds to a growing body of evidence implicating this structure in this pathological state. In so far as C CK is co-localized with GABA or glutamate in cortical neurons, both of these neuronal populations need to be studied further in schizophreni a and suicide. (C) 1997 Elsevier Science Ltd.