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

本研究旨在阐明感染和免疫活动在精神分裂症发展中的作用，它们可能与神经发育相互作用。遗传和环境因素，更具体地说，HLA基因型及其邻近基因座和出生季节进行了调查。关于HLA，我们研究了精神分裂症患者中i类的频率，重点研究了HLA- a24和26，这两种基因在80年代包括东日本人群在内的几个人群的精神分裂症患者中反复出现升高。因此，无论是在日本东部人群还是在日本西南部（长崎）人群中，均未观察到任何i类特异性（包括A24和A26）与精神分裂症之间的关联。这与hla II类（DR1）与精神分裂症之间的关联形成对比，这在日本东部人群的日本受试者中一直被观察到。未观察到精神分裂症与HLA位点相邻的位点（包括Notch-4和TNF）之间的关联。在出生季节方面，夏季出生对日本人的精神分裂症有显著的保护作用，尤其是男性。然而，冬季出生的有害影响尚不清楚。然而，当研究对象仅限于出生在日本北部的人时，冬季出生的影响就更明显了，尤其是在男性研究对象中。我们正计划进一步研究HLA ii类和其他HLA位点附近的基因在精神分裂症中的作用。它们与出生季节的相互作用特别有趣。此外，我们正在研究日本地区精神分裂症的出生季节效应的变化，在日本，各个地区的天气都有很大的变化。

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.