Asking whether E. Kraepelin's early dementia praecox and disease concepts (1896) are still valid today, we condensed his early theory into four theses:1) schizophrenia is a disease entity, distinguishable from affective psychosis. 2) It is caused by a specific neuropathology. 3) It usually manifests itself in adolescence or early adulthood. 4) Underlying schizo- phrenia is a progressive disease process that leads to defects and dementia.

Having tested whether Kraepelin's dementia praecox and modern schizophrenia are actually comparable, we studied 1) how schizophrenia and depression are linked or separable in terms of symptoms, risk factors and illness course from onset until five years after first treatment contact. The analyses are based on a population-based sample of 130 first admissions because of schiz- ophrenia, 130 age- and sex-matched first admissions because of unipolar depressive disorder and 130 “healthy” population con- trols from the study area. 2) Results will be presented that, though not very specific, confirm Kraepelin's farsighted hypothesis of a neuropathological basis of the disorder. In this context it will be discussed whether the brain changes are developmental or degenerative in origin. 3) The distribution of age of onset extends far into old age. In a sample of 1109 consecutive first admis- sions because of nonaffective psychosis from the total age range it was shown that age-dependent developmental factors mod- ify certain components of symptomatology linearly and significantly. The main risk factors, too, significantly change with age. 4) Long-term course was examined in three studies of epidemiologically recruited first-episode samples: Study 1 included five cross sections over 5 years, Study 2 was a prospective pre-post-comparison over 12 years supplemented by a retrospective assessment of the illness course (IRAOS) and Study 3 encompassed 10 cross sections over fifteen years. Finally, the disease concept of schizophrenia, as it presents itself in the light of current knowledge, will be outlined and compared with Kraepelin's earlier and later view of the disorder.

the paper is based on a lecture (Lettura magistrale) presented at the SIEP Sesto Congresso Nazionale, “Gli Esiti della Schizofrenia - Trattamenti, Pratica nei Servizi, Valutazione” in Sirmione, November 6-8, 2003. Unfortunately, the illustrations shown there and some 20 % of the relevant references could not be included in this printed ver- sion for lack of space. This paper was written within the framework of the German Research Network on Schizophrenia and was funded by the German Federal Ministry for Education and Research BMBF (grant 01GI 0236). The ABC study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) as part of the Special Research Branch (Sonderforschungsbereich) 258 at the Central Institute of Mental Health until December 1998. From January 1999 to Sept. 2002 it was continued to be funded by the DFG.