Causes and Consequences of the Gender Difference in Age at Onset of Schizophrenia

The ABC (age, beginning, course) schizophrenia study was commenced in 1987 to generate and test hypothe-ses about pathogenic aspects of schizophrenia. One of the main branches of the study focused on how gender influences the age distribution of onset, symptomatol-ogy, illness behavior, and early course in schizophre-nia. Proceeding from one of the rare, strikingly deviat-ing, consistent findings—the gender difference in age at first admission—we launched a systematic search for explanations by generating and testing hypotheses in a series of substudies. We moved from the epidemio-logical to the neurobiological and finally to the clinical level. The present article is an attempt to provide a brief overview of the individual stages of the ABC study and the different levels of investigation involved in formulating and testing the estrogen hypothesis in animal experiments and in demonstrating its applica-bility to human schizophrenia. From these results, three hypotheses were formulated and tested on data from an ABC study sample of 232 first-episode cases of schizophrenia. The analyses described here represent the latest stages of the ABC study. Key words: Gender differences, age at onset, early course