The underlying structural and functional pathology is insufficiently understood, and there is no objective diagnostic test or validated biological marker that could provide a secure anchor for either clinical decision-making or biological and epidemiological research. Recurrent controversies in schizophrenia

research concern its delimitation from other psychoses, bipolar affective disorder, and neurodevelopmental disorders; the validity of the schizophrenia spectrum concept and the existence Inhibitors,research,lifescience,medical of subclinical forms, such as schizotypal disorder; the utility of its categorical classification as compared with descriptive symptom dimensions or subtypes based on quantitative cognitive traits,2 and the discordances between the ICD-10 and DSM-IV criteria for its Inhibitors,research,lifescience,medical diagnosis. The aim of the present paper is to highlight aspects of the origin, evolution, and current state of the diagnostic concept of schizophrenia – ending with a

speculation about its future prospects. A brief overview of the history of the concept Kraepelin and the construction of dementia praecox The disease concept of schizophrenia is of a relatively recent origin, as compared with disorders such as Inhibitors,research,lifescience,medical melancholia, mania, or generic “PF-562271 chemical structure insanity,” all known since antiquity. By the middle of the 19th century, European psychiatrists began describing disorders of unknown causes, typically affecting the young, and often progressing to chronic deterioration. In France, Morel3 referred to such cases as démence précoce, while in Scotland, Clouston4 Inhibitors,research,lifescience,medical coined the term “adolescent insanity.” In Germany, Kahlbaum5 delineated the catatonic

syndrome, and his disciple Hecker6 described hebephrenia. However, it was Emil Kraepelin (1856-1926) who proposed to integrate those varied clinical pictures into a single nosological entity under the name of “dementia praecox,” based on his longitudinal observations of a large number of clinical cases exhibiting a common pattern of course which ultimately resulted in severe cognitive and behavioral decline. Elaborating on the description of the disorder in Inhibitors,research,lifescience,medical successive editions of his Textbook,7,8 Kraepelin acknowledged the diversity of the clinical pictures subsumed under dementia praecox and articulated nine different “clinical forms“ (Table I). Although the core features of the disorder could not always be identified reliably in the cross-section of the clinical presentation, Kraepelin emphasised that “we meet Florfenicol everywhere the same fundamental disorders in the different forms of dementia praecox [...] in very varied conjunctions, even though the clinical picture may appear at first sight ever so divergent. 8 The “fundamental disorders“ which supported the concept of the disease entity were cognitive deficit (a “general decay of mental efficiency”) and executive dysfunction (“loss of mastery over volitional action”), most clearly manifested in the residual, “terminal states“ of the illness.