Schizophrenia: Refining the phenotype, resolving endophenotypes

The conceptual history of the diagnosis of schizophrenia is reviewed and the current definition of the illness is examined (e.g. DSM-IV). A dimensional alternative to the traditional categorical model of diagnosis is discussed with a specific emphasis on the four dimensions of psychopathology represented by reality distortion (hallucinations, delusions), disorganization (positive formal thought disorder, bizarre behavior), negative symptoms (flattened affect, avolition, alogia, asociality), and premorbid social functioning. Also discussed is the development of structured psychiatric interviews that emerged from the clinical/research context that gave rise to explicit (i.e. operational) diagnostic criteria for schizophrenia. The general methodological approach used to detect valid endophenotypes for schizophrenia liability-i.e. indicators of liability not visible to the unaided naked eye-as well as their potential diagnostic and research utility is presented in overview. The rationale for linking such indicators to schizophrenia liability, which is conceptualized as a latent construct, is also reviewed. Future directions in the development and refinement of the diagnostic approach to schizophrenia and schizophrenia liability are highlighted. Copyright (C) 1999 Elsevier Science Ltd.