奥氮平影响食欲调节中枢导致食欲增加的机制研究

抗精神病药物是治疗精神分裂症的主要方法，但会引起严重的代谢障碍，其中以奥氮平对代谢的影响最为严重，目前对其发生机制不明。我们前期研究发现奥氮平引起的食欲增加及食物偏好的改变在其中起着非常重要的作用，约80%的患者服用奥氮平后出现食欲增加且与代谢障碍显著相关。由此我们提出假说：奥氮平可能通过直接影响食欲调节中枢导致食欲增加及食物偏好的改变。本项目拟对首发精神分裂症通过多模态磁共振技术分析使用奥氮平前后食欲调节中枢的结构与功能变化，利用靶向代谢组学等技术检测患者服用奥氮平前后的食欲调节相关激素变化，进一步分析出奥氮平对食欲调节中枢的脑功能连接与食欲调节相关激素变化的关系，找到奥氮平影响食欲调节中枢的关键神经环路，从而揭示奥氮平影响食欲调节中枢导致食欲增加的机制。本项目可为研发控制抗精神病药物引起食欲增加的药物、降低抗精神病药物引起的体重增加及代谢障碍的有效方法提供理论依据。

Antipsychotic medications are the main treatment for schizophrenia，but they induce severe metabolic disorders. Olanzapine produce the most severe effect on metabolism, and the mechanism remains unknown. In our previous studies, we found that increased appetite and changes in food preferences induced by olanzapine play a very important role in olanzapine-induced metabolic disorders. About 80% of patients after taking olanzapine had appetite increase and changes in food preferences, which was significantly associated with olanzapine-induced metabolic disorders. So, we hypothesise that olanzapine induces appetite increase and changes in food preferences through affecting appetite regulating center. In this project, we will use multi-mode MRI to analyze the structural and functional changes of appetite regulating center before and after olanzapine administration, and use targeted metabolomics to detect the changes of appetite-related hormones before and after olanzapine administration. We will further analyze the association between brain functional connection of appetite regulating center and appetite-regulate hormone after olanzapien treatment, and try to find the the key neuron circuit of olanzapine affecting the appetite regulating center, and then reveal the mechanisms of the effects of olanzapine on appetite regulating centers and then inducing appetite increase. This project can provide theoretical basis for the research and development of effective methods to control the appetite increase, weight gain and metabolic disorder induced by antipsychotics.