NEUROFIBRILLARY PATHOLOGY IN BRAINS OF ELDERLY SCHIZOPHRENICS TREATEDWITH NEUROLEPTICS

The clinical histories of 102 schizophrenics who died at 70 years of a ge or older were reviewed. The incidence of neurofibrillary tangles (N FTs) was two times higher in the patients who received (74%) than in t hose who did not receive (36%) treatment with neuroleptics. The develo pment of NFTs started earlier in the treated group. Further studies co mparing brains of nine schizophrenics (average age, 86 years) who did not receive treatment with neuroleptics and seven age-matched cases wh o received neuroleptics, both with neurofibrillary pathology and neuri tic plaques, showed characteristic differences. The numerical density of NFTs was slightly greater in the cornu Ammonis (CA1 and CA2) and su biculum of treated patients. Significantly lower numerical density and lower percentage of pretangles (stage 0) and early and mature tangles (stages 1 and 2) and increased number of end-stage tangles (stage 3) were found in the CA, subicular complex, and cerebral cortex of the tr eated group. These changes suggest accelerated neurofibrillary degener ation in neurons. A significant increase in the numerical density of t au-1-positive plaques was observed in sector CA1 of the CA (from 0.15/ mm(2) to 17.36/mm(2)), subiculum (from 0/mm(2) to 16.62/mm(2)), tempor al cortex (from 0.14/mm(2) to 9.46/mm(2)), and occipital cortex (from 0.08/mm(2) to 0.39/mm(2)). The higher numerical density of tau-1-posit ive plaques, but not of 4G8-positive plaques, indicates acceleration o f neurofibrillary changes in the plaques of patients treated with neur oleptics. The significant decrease (20-25%) in the numerical density o f neurons in the pyramidal layer of sectors 2-4 in the CA appears to b e associated with accelerated neurofibrillary changes in neurons and p laques in the treated group. This study demonstrates that chronic trea tment with neuroleptics-not schizophrenia itself-significantly increas es the risk of more frequent, earlier, and accelerated development of neurofibrillary pathology in the brains of elderly schizophrenics.