精神分裂症是一种影响患者思维、情感和行为的严重的神经系统疾病。作为人类最常见的疾病之一，精神分裂症影响了大约1%的人口。由于病因复杂，反复发作以及大多在青壮年发病，精神分裂症严重影响患者生活，同时也给患者家属和社会带来了沉重的负担。目前的研究表明遗传因素和环境因素在精神分裂症的发生中都有作用，其中又以遗传因素为主(精神分裂症遗传力达到0.8左右)，精神分裂症的遗传机制和致病机理仍不清楚。

实验室主要围绕精神分裂症的遗传机制和发病机理进行深入的系统研究。结合人类遗传学、生物信息学以及神经生物学，从分子、细胞、模式动物和人等多个层次进行重要精神分裂症易感基因的功能及其机制研究，主要目标是阐明精神分裂症遗传机制和致病机理，最终为预防和治疗精神分裂症提供诊断及预后的分子标志物以及治疗靶标。目前研究兴趣集中在探索和发现新的精神分裂症易感基因，并深入研究这些精神分裂症易感基因如何影响神经系统发育和功能，最终导致精神分裂症发生。目前研究方向主要集中在以下三个方面：

1.利用人类遗传学和整合生物信息学研究精神分裂症的遗传机制：

虽然精神分裂症的遗传学研究已经取得显著进展，然而精神分裂症遗传基础仍不清楚。精神分裂症是多基因疾病，多个微效基因的累加效应结合环境因素共同作用导致精神分裂症发生。目前的人类遗传学研究（包括遗传连锁、相关、GWAS、外显子测序等）已经鉴别到大量的精神分裂症易感基因，然而这些基因仅仅只能解释精神分裂症一小部分遗传力（heritability）,暗示着大量效应较小的精神分裂症易感基因仍有待进一步的发现。利用人类遗传学和整合生物信息学，本课题组将系统性分析和鉴别新的精神分裂症易感基因。

2.运用小鼠和灵长类动物模型研究精神分裂症的致病机理：

目前精神分裂症的病因仍不清楚，累积的研究表明精神分裂症是由神经系统发育异常导致的。 因此，了解精神分裂症易感基因如何影响神经系统发育对了解精神分裂症发生至关重要。本课题组利用基因敲除方法在小鼠和灵长类动物模型中深入研究精神分裂症易感基因在神经系统发育中的作用，探索精神分裂症易感基因的分子功能和致病机理。

3.探索精神分裂症的潜在治疗靶标和开发抗精神疾病药物：

依托昆明动物所丰富的灵长类资源，本课题组将尝试建立精神分裂症灵长类动物模型，并利用灵长类动物模型探索精神分裂症的潜在治疗靶标和开发抗精神疾病药物

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2. Xiong-Jian Luo^#,*, Chen Zhang^#. Down-regulation of SIRT1 in major depressive disorder. The American Journal of Psychiatry. 2016. 173(10):1046.  

3. Yong-Xia Huo^#, Liang Huang^#, Deng-Feng Zhang, Yong-Gang Yao, Yi-Ru Fang, Chen Zhang*, Xiong-Jian Luo*. Identification of SLC25A37 as a major depressive disorder risk gene. Journal of Psychiatric Research. 2016. 83:168-175.   

4. Ming Li^#, Liang Huang^#, Kai-Qin Li^#, Yong-Xia Huo^#, Chun-Hui Chen, Jin-Kai Wang, Jie-Wei Liu, Zhen-Wu Luo, Chuan-Sheng Chen, Qi Dong, Yong-Gang Yao, Bing Su, Xiong？Jian Luo*. Adaptive Evolution of Interleukin-3 (IL3), a Gene Associated with Brain Volume Variation in General Human Populations. Human Genetics. 2016. 135(4):377-392.  

5. Ming Li^#,*, Dong-Dong Wu^#, Yong-Gang Yao, Yong-Xia Huo, Jie-Wei Liu, Bing Su, Daniel I. Chasman, Audrey Y. Chu, Tao Huang, Lu Qi, Yan Zheng, CHARGE Nutrition Working Group, DietGen Consortium, Xiong-Jian Luo^#,*. Recent Positive Selection Drives the Expansion of a Schizophrenia Risk Non-synonymous Variant at SLC39A8 in Europeans. Schizophrenia Bulletin. 2016. 42(1):178–190.    

6. Ming Li^#, Liang Huang^#, Jin-Kai Wang^#, Bing Su*, Xiong-Jian Luo*. No Association Between Schizophrenia Susceptibility Variants and Macroscopic Structural Brain Volume Variation in Healthy Subjects. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2016. 171B(2):160–168.   

7. Ming Li^#,*, Xiong-Jian Luo^#, Mikael Landén, Sarah E. Bergen, Christina M. Hultman, Xiao Li, Wen Zhang, Yong-Gang Yao, Chen Zhang, Jie-Wei Liu, Manuel Mattheisen, Sven Cichon, Thomas W. Mühleisen, Franziska A. Degenhardt, Markus M. Northen, Thomas G. Schulze, Maria Grigoroiu-Serbanescu, Hao Li, Chris K. Fuller, Chun-Hui Chen, Qi Dong, Chuan-Sheng Chen, StéphaneJamain, Marion Leboyer, Frank Bellivier, Bruno Etain, Jean-Pierre Kahn, Chantal Henry, Martin Preisig, ZoltánKutalik, Enrique Castelao, MooDS Bipolar Consortium, The Swedish Bipolar Study Group, Marcella Rietschel, Bing Su*. Impact of a Cis-associated Gene Expression SNP on Chromosome 20q11.22 on Bipolar Disorder Susceptibility, Hippocampal Structure and Cognitive Performance. British Journal of Psychiatry. 2016. 208(2):128-137.   

8. Xiao Xiao^#, Xiong-Jian Luo^#, Hong Chang^#, Zi-Chao Liu, Ming Li*. Evaluation of European Schizophrenia GWAS Loci in Asian Populations via Comprehensive Meta-Analyses. Molecular Neurobiology. 2016. DOI 10.1007/s12035-016-9990-3.   

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10. Xiong-Jian Luo*, Liang Huang, Edwin J. van den Oord, Karolina A. Aberg, Lin Gan, Zhong-Ming Zhao, Yong-Gang Yao. Common Variants in the MKL1 Gene Confer Risk of Schizophrenia. Schizophrenia Bulletin. 2015. 41(3):715-727.   

11. Zi-Chao Liu^#, Liang Huang^#, Xiong-Jian Luo, Li-Chuan Wu* , Ming Li*. MAOA Variants and Genetic Susceptibility to Major Psychiatric Disorders. Molecular Neurobiology. 2015. 53(7):4319-4327.  

12. Jie-Wei Liu^#, Yin Mo^#, Tian Ge^#, Yi Wang, Xiong-Jian Luo, Jian-Feng Feng, Ming Li, Bing Su*. Allelic Variation at 5-HTTLPRIs Associated with Brain Morphology in a Chinese population. Psychiatry Research. 2015. 226(1):399-402.  

13. Xiao Li, Wen Zhang, Jin-Song Tang, Li-Wen Tan, Xiong-Jian Luo, Xiao-Gang Chen*, Yong-Gang Yao*. Do Nuclear-encoded Core Subunits of Mitochondrial Complex I Confer Genetic Susceptibility to Schizophrenia in Han Chinese Populations? Scientific Reports. 2015. 5:11076.  

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