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nferen1104 Am J Psychiatry 159:7, July 2002

Clinical Case Conference
A Case of “Pfropfschizophrenia”:
Kraepelin’s Bridge Between Neurodegenerative
and Neurodevelopmental Conceptions of Schizophrenia

Avram H. Mack, M.D.
James J. Feldman, M.D., M.P.H.
Ming T. Tsuang, M.D., Ph.D., D.Sc.


The notion that schizophrenia, as conceived by Kraepelin,is a neurodegenerative disorder has been challenged by new research on the nature of the cognitive impairment in this disease; instead, schizophrenia is increasingly described as a neurodevelopmental disorder (1). For Kraepelin, the unifying observation among the catatonic, hebephrenic, and paranoid types of dementia praecox was a continued decline of intellectual function. However, empirical findings have demonstrated that cognitive function does not universally decline in patients with schizophrenia. Some authors have suggested that low intellectual functioning is a premorbid and fixed feature (2). Others have sought to separate patients according to different “trajectories” of lifetime intellectual function that include subsets of schizophrenic patients with intellectual functioning that was either compromised from a very early age or preserved at normal premorbid levels (3, 4). Finally, there have been attempts to determine if there are differences in change among cognitive functions (intellect, memory, executive, and attention) in schizophrenia (3). These data seem to be mutually exclusive of some of Kraepelin’s most important observations, and they generally support the “static encephalopathy” concept that asserts that schizophrenia is due to a stable neurodevelopmental brain lesion (5). The increasing dominance of the neurodevelopmental paradigm is illustrated by the American Academy of Child and Adolescent Psychiatry’s declaration that “schizophrenia is a neurodevelopmental disorder” (6) and also by Prusiner’s exclusion of schizophrenia (7) from the neurodegenerative disorders, all of which, in his perspective, “result from abnormalities in the processing of proteins.” One wonders whether this dichotomous landscape has room for only one perspective at a time. Download

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