The schizophrenia high-risk project in Copenhagen: three decades of progress

We describe the design, theoretical approach and major recent findings of a prospective longitudinal study of the offspring of schizophrenic mothers and controls, initiated in 1962 by Sarnoff Mednick and Fini Schulsinger in Copenhagen, Denmark. Over 90% of the original 207 high-risk and 104 low-risk subjects have been successfully followed up since the initial assessment. At the time of the most recent assessment (1989), the subjects averaged 42 years of age and were nearly completely through the risk period for developing schizophrenia. By relating the lifetime psychiatric diagnoses of the subjects back to information on their premorbid experiences and functioning, we have identified several precursors of schizophrenia. This paper reviews our recent findings concerning whether outcomes of schizophrenia that differ in the relative prominence of negative versus positive symptoms represent discrete longitudinal syndromes. Predominantly negative and predominantly positive symptom schizophrenia were found to follow different patterns of symptom development from adolescence through the adult course of illness and were predicted by different combinations of genetic and environmental influences. Taken together, the findings suggest that the pathological processes underlying these two forms of schizophrenia are 1) partly independent of each other, 2) at least partly active during the premorbid state and 3) to some degree stable in the adult course of illness.