Investigation of HCA, neurodevelopmental genes and related environmental factors in schizophrenia

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This study aimed to elucidate a role of infection and immune activity, which may interact with neurodevelopment, in the development of schizophrenia. Both genetic and environmental factors, more specifically, genotypes of HLA and its adjacent loci as well as season of birth, were investigated. Regarding HLA, frequencies of class-I in schizophrenia patients were studied, focusing on HLA-A24 and 26, which were repeatedly reported to increase in schizophrenia patients from several populations, including the East-Japan population, in 80s.As a result, no association between any class-I specificities, including A24 and A26, and schizophrenia was observed either from the East-Japan population or from the South-West Japan (Nagasaki) population. This was in contrast to an association between HLA-class II (DR1) and schizophrenia, which has been consistently observed in Japanese subjects from the East-Japan population. No association between schizophrenia and loci adjacent to the HLA loci, including Notch-4 and TNF, was observed. As for season of birth, significant protective effect of summer birth against schizophrenia was observed in the Japanese subjects, especially in male subjects. However, a harmful effect of winter birth was not clear. When the subjects were confined to those born in the Northern part of Japan, however, the effect of winter birth was more clearly observed, especially in male subjects. We are planning to further investigate a role of HLA class-II and other genes adjacent to the HLA loci in schizophrenia. Their interaction with season of birth is of special interest. Also, we are studying a variation of the season of birth effect in schizophrenia across the areas of Japan, where a significant variation of weather is observed across the regions.