基于18FDG PET在库欣病精神障碍及致病机制中的研究

Patients with cushing's disease often exhibit psychiatric disorders and cognitive function impairment, the pathogenic mechanisms are unknown. Studies have shown that high cortisol is its causes, but after the glucocorticoids decreased，the symptoms improved is poor. In our study, we found the cerebral glucose metabolism changed in the patients with cushing's disease, the whole body PET scans of some patients displayed high metabolism in muscle, but decreased hepatic metabolism, which suggests there maybe had the presence of hepatic insulin resistance. Through the data of cerebral PET scans, based on the statistical parametric mapping ( SPM ) software analysis, observed the changes of brain functional network after the resection of pituitary tumor. By the cortisol induced diabetic rat model and streptozotocin induced diabetic rat model, observed the regulation of plasma glucose and the distribution of glucose in vivo, as well as the effects on cerebral metabolism by micro PET. The results of animal experiments will apply in the patients with cushing's disease, to research the pathogenic mechanisms of high glucocorticoids and plasma glucose on cerebral cortex, and explore the new therapeutic targets, and further guide the clinical treatment. The method and technology can be directly applied to the studies of the pathogenic mechanism and psychiatric disorder in other metabolic diseases, such as diabetes and exogenous glucose cortisol hormone pulse therapy induced psychiatric disorders, or the research of insulin resistance. Therefore, this study is of great theoretical and clinical application values.

库欣病人常表现精神障碍和认知功能受损，致病机制不明，有研究认为高糖皮质醇激素是其致病原因，但抗皮质醇治疗后症状改善不佳，在我们研究中发现库欣病人脑葡萄糖代谢发生改变，躯干PET显示部分病人肌肉高代谢，肝脏代谢减低，提示肝胰岛素抵抗可能。本项目通过采集脑的PET数据，基于统计参数图（SPM）软件分析技术，观察库欣病脑各功能区状态，及在切除垂体瘤去除高皮质醇因素后脑功能改变。分别建立高皮质醇和链脲佐菌素致糖尿病鼠模型，通过microPET观察药物调节血糖前后葡萄糖在体内的分布，及对脑代谢的影响。实验结果应用于库欣病人借以深入了解糖皮质醇和血糖对脑功能的致病机制，并探讨新的治疗靶点，进一步指导临床治疗。该研究所建立的方法和技术平台，可直接应用于其它代谢性疾病精神障碍的致病机制研究，如糖尿病，外源性糖皮质醇激素冲击治疗后所致精神障碍及胰岛素抵抗的研究等。因此，本研究具有重大的理论和临床应用意义。

库欣病患者有认知、记忆情感方面的异常，表现为兴奋、抑郁、惊恐发作、自杀倾向、木僵，甚至感觉障碍，幻视、幻听、妄想等精神分裂症样症状。18FDG PET脑显像作为先进的分子影像技术，是研究各种生理及病理状态下脑功能变化的重要手段。基于像素水平的分析法是以脑功能成像图像的像素为基本单位，逐像素对数据做统计分析，不存在人为因素，并可由计算机自动处理，此方法灵敏度高，也相对客观，目前应用最广泛的是统计参数图(statistical parametric mapping，SPM)软件，可将不同个体的脑结构进行弹性空间重排或标准化成为标准立体空间，对各个脑区的代谢进行基于像素的统计分析，可客观灵敏地进行不同群体的比较，检出轻微代谢改变。目前对库欣病人的脑研究样本数少，需要采用先进的脑部统计学分析软件进行大样本的分析，及从全身的整体状态来分析库欣病人脑的葡萄糖代谢状态。 这也是我们此课题的研究方向和意义。