VOL. 21, NO. 1, 1995 Gender Differences in Schizophrenia: Hormonal Effect or Subtypes? by David J. Castle, Kathryn Abel, Noriyoshi Takei, and Robin M. Murray At Issue The At Issue section of the Schizophrenia Bulletin contains viewpoints and arguments on contro- versial issues. Articles published in this section may not meet the strict editorial and scientific standards that are applied to major articles in the Bulletin. In addition, the viewpoints expressed in the following articles do not necessarily represent those of the staff or the Editorial Advisory Board of the Bulletin.—The Editors. Abstract Compared with their male coun- terparts, females with schizophre- nia, on average, show better pre- morbid functioning, later onset, and a more benign course of ill- ness. They are also more likely to have a family history of schizophrenia and/or affective ill- ness, to exhibit "atypical" and affective features, and to show a seasonal pattern of hospital ad- mission that mimics that of pa- tients with mania. However, there exists a paradox. Although schizophrenia in females has much in common with affective disorder, the "schizophrenogenic" effect of maternal influenza also appears to be more significant in female than in male schizophre- nia. Perhaps females with a pre- disposition to affective psychosis who have also been subject to the effects of maternal viral in- fection during gestation develop some subtle neurodevelopmental damage that renders their psy- chosis schizophrenia-like. Schizophrenia Bulletin, 21(1): 1-12, 1995. Schizophrenia has a later onset in females than in males; the dif- ference has been found to be about 5 years in most studies (see Lewine 1988). The sex difference in age at onset is consistent across cultures (Hambrecht et al. 1992) and is robust to definition of "onset" (Loranger 1984; Riecher et al. 1989; Hafner et al. 1991) as well as to definition of illness (Loranger 1984; Shimizu et al. 1988). Furthermore, the age-at- onset distribution curves for schizophrenia differ between women and men. In a study of 392 consecutive first admissions from a defined catchment area with a diagnosis of schizophrenia or paranoid disorder (the ABC study), Hafner and colleagues (1991) found that males showed a single marked peak in their early twenties, while for females there was a second peak of onset in the 45-54-year age group. This finding is echoed in the distribution of pooled data from the World Health Organization Determinants of Outcome study (Hambrecht et al. 1992). We (Castle et al. 1993) recently investigated gender dif- ferences in a catchment-area sam- ple of 470 patients with schizo- phrenia across all ages and found that a surprisingly large number (n = 134, 28%) had an onset of ill- ness after age 45 and even after age 60 (n = 56, 12%). Males had a dramatic early peak followed by a monotonous decline; females showed a second peak in the late forties and an even more emphatic peak in very old age. Thus, not only do females have a later mean age at onset of ill- ness than males, but the age-at- onset distribution curves for females and males are very dif- Reprint requests should be sent to Prof. R.M. Murray, Institute of Psychi- atry, De Crespigny Park, London SE5 8AF, United Kingdom. by guest on May 31, 2013 http://schizophreniabulletin.oxfordjournals.org/ Downloaded from