Background and Objectives: Testing Kraepelin´s dichotomy model, we studied the separability of schizophrenia and affective disorders by their symptoms and course. Methods: To this end symptoms and illness course were assessed retrospectively in individually matched untreated probands with schizophrenia and depression (n=130 each) from first admission back to illness onset in comparison with 130 "healthy" controls. In a second study these same variables were studied prospectively in 107 patients with schizophrenia over a homogenised follow-up of 134 months (11.2 years). The actual mean length of the follow-up period was 12.3 years. Results: The symptom most frequently marking the onset of both schizophrenia and depression was depressive mood. Both disorders exhibited the same prodromal core syndrome. It was not until the emergence of positive symptoms that the disorders became separable by the international classification systems. Depression remained the most frequent syndrome over the course of schizophrenia. Conclusions: Obviously, depression does not represent comorbidity, but an integral part of psychosis. A dimensional disease model based on (successively emerging) hierarchical symptom patterns of the human brain with increasing brain dysfunction in the course of schizophrenia and several neuro-degenerative disorders, not unknown to the later Kraepelin, is offered as an explanation.
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