Main risk factors for schizophrenia: increased familial loading and pre- and peri-natal complications antagonize the protective effect of oestrogen in women

Women fall ill with schizophrenia 3 to 4 years later than men. The neurobio logical mechanism, explaining the delay of onset in women until menopause, is presumably due to a sensitivity reducing effect of oestrogen on central D-2 receptors, as we have previously shown in animal experiments and in a c ontrolled clinical study. The gender difference in age at onset seems to di sappear in familial cases with schizophrenia, but it increases to highly si gnificant values of 5 years or more in isolated cases according to a recent study by Albus and Maier (Schizophrenia Research 18:51-57, 1995). We tried to replicate these findings and to test the hypothesis of a functi onal antagonism between genetic predisposition to illness and the protectiv e effect of oestrogen in a population-based sample of 232 first illness epi sodes of schizophrenia. In woman with at least one first-degree relative suffering from schizophren ia, age at onset defined by first psychotic symptom was significantly reduc ed by several years and the difference with men disappeared. In sporadic fe male cases (no mental disorder in first-degree relatives) the age at onset was slightly increased compared with the total sample, which was in accorda nce with our hypothesis. In men with familial schizophrenia, but without a protective agent like oestrogen, the age at onset was only slightly and non -significantly reduced compared with the total group and with sporadic case s. This was in line with Albus and Maier and with our hypothesis that only the protective effect of oestrogen could be antagonized by a strong genetic disposition. The second main risk factor for schizophrenia is pre- and peri-natal compli cations. We compared men and women from our sample of first illness episode s with a history of pre- and peri-natal complications with those without a history of obstetric complications. In women the age at first psychotic sym ptom was markedly reduced, but due to small case numbers not significantly, compared with women without the risk factor and with the total group. Agai n, schizophrenic men with a history of pre- and peri-natal complications sh owed only a small, non-significant reduction of age at onset compared with the total and the group without the risk factor. Therefore, we concluded th at the degree of genetically determined vulnerability and, presumably to a slightly lesser extent, the degree of pre- and perinatal brain injury antag onizes the onset delaying effect of oestrogen in schizophrenia. (C) 2000 El sevier Science B.V. All rights reserved.