近年精神分裂症的不同学科交叉研究受到关注。在本病中，认知功能损害可能早于症状的临床表现。申请者前期研究提示：听P300和N400参与本病认知缺损。参与者在脑源性神经营养因子（BDNF）中发现，BDNF也是本病认知缺损的重要生物学基础。但还有疑点未明？新近研究发现：BDNF介导的神经可塑性机制在语言发展及N400改变中发挥重要作用。在此基础上，申请者结合前述国自项目研究结果，进一步将遗传学和脑电生理加以整合。我们发现前额叶重要线索并假设：本病彩图成语N400缺陷机制在于BDNF信号通路异常引起的前额叶神经可塑性病理变化。本项目以BDNF和经颅磁刺激脑电（TMSEEG）为研究靶点，通过寻找交集聚焦靶点，寻找本病病因学新证据。预期结果：1论证BDNF在本病N400缺陷形成及消退过程中的作用，阐明部分机制。2建立TMSEEG检测。3通过随访为本病改变最终性质及研发新药提供线索。4研究转化临床应用。

Recently, Interdisciplinary study has received more and more attention in schizophrenia research. In schizophrenia, cognitive dysfunction may occur earlier than clinical symptoms. Our previous studies suggested that auditory P300 and N400 are critical factors in the development of cognitive deficits in schizophrenia. Other participants found brain-derived neurotropic factor（BDNF） may underlie the biological mechanism of cognitive dysfunction in schizophrenic patients. However, the underlying mechanisms are unclear. Recently, BDNF mediated neural plasticity were reported playing important role in language development and N400 impairment. In our previous national science foundation of China（NSFC） projects supported research, some clues of combining genetics(BDNF) and electrophysiology(N400) were found. The findings of prefrontal cortex dysfunction in schizophrenia made us hypothesized that the underlying mechanism of N400 deficits in schizophrenia may be due to abberant BDNF pathway induced changes in neuroplasticity of prefrontal cortex. In this study, we will focus on overlapped findings of BDNF, N400 and TMS-EEG change in schizophrenia, to explore the new evidence for BDNF pathology of schizophrenia. The aims of the study includes: 1. To verify the role of BDNF in the development and extinction of N400 in schizophrenia. 2. To set up the measurement of neuroplasticity by TMS-EEG. 3. To explore the changes of this disease and provide evidence for drug development. 4.To explore the translation medicine from preclinical study to clinic usage.