GLIAL FIBRILLARY ACIDIC PROTEIN-IMMUNOREACTIVE ASTROCYTOSIS IN ELDERLY PATIENTS WITH SCHIZOPHRENIA AND DEMENTIA

Clinical and neuropsychological studies of chronically institutionaliz ed patients with schizophrenia indicate that severe cognitive impairme nt and functional disability in late life are very prevalent. The biol ogical substrates for this dementia remain unknown. While subtle cytoa rchitectural and morphometric abnormalities have been described in pat ients with schizophrenia and interpreted as reflecting aberrant neurod evelopment, post-maturational injury or neurodegeneration associated w ith gliosis remain as plausible explanations of at least some of the c linical manifestations of schizophrenia. We monitored astrocytosis and neurofibrillary tangle (NFT) formation in 21 elderly patients with sc hizophrenia (14 with concurrent dementia, 7 without), and in 12 normal and 5 Alzheimer's disease (AD) control cases. Astrocytes in ventromed ial temporal, frontal, and calcarine cortices were immunohistochemical ly identified with monoclonal antibodies directed at glial fibrillary acidic protein (GFAP) and vimentin, and NFTs were labeled with an anti -tau antibody specific for paired helical filaments. There were no inc reases in GFAP- or vimentin-immunoreactive astrocyte counts, GFAP opti cal density, or NFT counts for the schizophrenic group as a whole comp ared to the non-neuropsychiatric group, while both groups differed fro m AD. When patients with schizophrenia were divided into demented and non-demented subtypes, those with dementia demonstrated significantly greater numbers of GFAP-positive astrocytes than those without dementi a. These data may reflect an up-regulation of GFAP in normal astrocyte s or the presence of reactive astrocytosis in a subgroup of schizophre nics. In the absence of any diagnostic neuropathological findings in t his subgroup, the implications of these observations for the pathogene sis of schizophrenia remain to be determined.