Evidence for separate diseases?: Stages of one disease or different combinations of symptom dimensions?

Objective We tested Kraepelin's dichotomy model by studying the separability of schizophrenia and depression on the basis of symptoms and illness course. Materials and methods Matched untreated patients with schizophrenia and depression (n = 130 each) and 130 "healthy'' controls were assessed from onset to first admission. In a second study the same variables were studied in 107 patients with schizophrenia over a homogenised follow-up of 134 months (11.2 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 entire course of schizophrenia. Conclusion Depression does not represent comorbidity, but an integral part of psychosis. A dimensional disease model based on successively emerging hierarchical symptom patterns, not unknown to the later Kraepelin, is offered as an explanation.