首发精神分裂症患者伴发糖脂代谢异常的研究

发布时间：2018-03-13 15:14

本文选题：精神分裂症　切入点：糖脂代谢相关因子　出处：《天津医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的：精神分裂症患者在抗精神病药物治疗中伴发的糖脂代谢异常及相关问题日益凸现,严重影响精神疾病的治疗,已成为抗精神病药物临床治疗中的棘手问题。目前普遍认为精神分裂症治疗中出现的糖脂代谢异常是由抗精神病药引起的,然而,有研究资料证明首发的、未曾用过抗精神病药的分裂症患者存在代谢异常；因此,精神分裂症是否与代谢障碍存在遗传共病、抗精神病药是如何影响糖脂代谢的调节却不清楚。本课题拟通过对首次发病、未曾用过抗精神病药物的精神分裂症患者在抗精神病药物治疗中不同服药时间内糖脂代谢情况进行研究,同时对其家系成员中一级亲属的糖脂代谢进行系统研究,试图提供精神分裂症患者伴发糖脂代谢异常的临床证据以及糖脂代谢异常发生与服药时间之间的关系,为精神分裂症治疗过程中伴发的糖脂代谢异常问题的临床治疗和预防提供理论依据。方法：本课题由动物实验和临床试验组成,共分三部分。第一部分实验旨在探讨抗精神病药物对正常个体糖脂代谢的影响。本部分试验采用正常SD大鼠,给予6周的抗精神病药物(氟哌啶醇组、阿立哌唑组、奥氮平组)观察,生理盐水组做对照,观察用药后第6周大鼠进食水、体重、GH、COR、Leptin、INS、IGF-1、IGFBP-1、IGFBP-3的变化及各组间的变化。第二部分试验旨在探讨首发精神分裂症患者药物治疗12周后疗效及治疗期间糖脂代谢水平的变化,并探讨与服药时间之间的关系。本部分临床试验收集首发精神分裂症患者61例,观察比较首次发病、未曾用过抗精神病药物的精神分裂症患者用抗精神病药物奥氮平治疗前、治疗开始后第1、4、8、12周末体重指数、腰围、血浆血糖、CHOL、TGL、HDL、VLDL等糖脂代谢相关因子水平变化；同时采用阳性与阴性症状量表(PANSS)评定治疗前后精神症状变化。第三部分试验旨在探讨精神分裂症患者的正常一级亲属糖脂代谢情况。本部分收集精神分裂症患者的正常一级亲属32例,正常人群对照37例,比较精神分裂症患者一级亲属和正常人群对照腹围、体重指数、血浆血糖、胰岛素、IGF-1、Leptin以及GH等糖代谢相关因子水平。结果：第一部分：实验结果显示,给予6周抗精神病药物后,给予奥氮平组大鼠表现出明显的进食水的增多,差异有统计学意义(P0.05)：给药三组大鼠血浆GH、COR、Leptin、INS、IGFBP-1、IGFBP-3水平降低,但无统计学差异；给予奥氮平组大鼠血浆的IGF-1水平明显低于阿立哌唑、氟哌啶醇及生理盐水各组,差异有统计学意义(P0.05)；阿立哌唑、氟哌啶醇组与生理盐水组相比,差异无统计学意义(P0.05)。第二部分：结果显示,给予奥氮平12周治疗后患者的PANSS总分与治疗前相比降低,差异有统计学意义(P0.05)；血浆CHOL、TGL、VLDL水平在4周末便有明显的升高(P0.01),8周、12周血浆CHOL、TGL、VLDL水平也一直维持在较高的水平。血浆HDL水平在奥氮平治疗的4周、8周、12周与治疗前均未见明显的改变,各组间的比较无差异(P0.05)。第三部分：结果显示,精神分裂症患者正常一级亲属体重指数、腰围与正常人群相比,差异无统计学意义(P0.05)；患者正常一级亲属存在明显的胰岛素抵抗,与正常对照组相比,差异有统计学意义(P0.05)；患者正常一级亲属的血浆胰岛素水平高于正常对照组,差异有统计学意义(P0.05),但IGF-1水平明显低于正常对照组,差异有统计学意义(P0.05) 结论：本研究通过动物实验和临床试验相结合,探讨了首发精神分裂症患者在抗精神病药物治疗中伴发的糖脂代谢水平。主要结论如下： (1)抗精神病药物可能影响正常个体的糖脂代谢水平,其中非典型抗精神病药奥氮平对糖脂代谢的影响更明显。 (2)奥氮平明显改善精神病性症状,在为期12周的奥氮平治疗中PANSS量表评分明显减低,提示奥氮平作为首发精神分裂症患者治疗的首选用药,疗效明显；在奥氮平治疗后的第4周,脂代谢的相关因子指标明显增高,在给药后的8周、12周始终维持在较高水平。 (3)精神分裂症患者正常一级亲属血浆胰岛素水平明显高于正常对照组,IGF-1明显的低于正常对照组,提示精神分裂症一级亲属存在糖脂代谢异常的高危因素。总之,本研究通过动物实验和临床观察,观察到抗精神病药物对正常大鼠糖脂代谢的影响,同时,临床试验则采用单一用药(奥氮平)治疗首发、未用药的精神分裂症患者,并分别在不同的治疗时间段检测其血浆糖脂代谢水平,可以更为准确全面的评价精神分裂症患者治疗中伴发的糖脂代谢的变化。本研究为精神分裂症治疗过程中伴发的代谢障碍问题的临床治疗和预防提供了理论依据。
[Abstract]:Objective: in patients with schizophrenia antipsychotics are associated with abnormal glucose and lipid metabolism and related problems have become increasingly prominent, seriously affected the treatment of mental illness, has become a thorny problem in clinical treatment of psychiatric drugs. It is generally believed that the resistance in glucose and lipid metabolism in schizophrenia however appear in the treatment of abnormal is caused by antipsychotics medicine, research data show that, first, never used antipsychotic drugs for schizophrenia patients with metabolic disorders; therefore, schizophrenia and metabolic disorders are genetic diseases, antipsychotics is how to influence lipid metabolism regulation is not clear. The aim of this episode for the first time and never used antipsychotic drugs for schizophrenia research spirit of glycolipid metabolism in patients with different medication time in antipsychotic drug treatment, at the same time of first-degree relatives of family members in the Glucose and lipid metabolism were studied, to provide the relationship between the schizophrenia patients associated with abnormal glucose and lipid metabolism and clinical evidence of abnormal glucose and lipid metabolism and medication time, clinical treatment and prognosis of abnormal glucose and lipid metabolism for the treatment of schizophrenia in the process associated with the prevention and provide a theoretical basis.
Methods: the subject was composed of animal experiments and clinical trials, which were divided into three parts.
The first part of the experiment was designed to investigate the effects of antipsychotic drugs on lipid metabolism in normal individuals. This part of the test with normal SD rats were given antipsychotic drugs for 6 weeks (haloperidol group, aripiprazole, olanzapine group) were observed, the normal saline group as control group, observe the drug sixth weeks after rats were fed with water, weight GH, COR, Leptin, INS, IGF-1, IGFBP-1, and IGFBP-3, the changes between the groups.
The second part of the first experiment was to investigate the changes of patients with schizophrenia drug metabolism of glucose and lipid levels during treatment and 12 weeks after treatment, and to explore the relationship between time and medication. The collection of clinical trials in first-episode schizophrenic patients in 61 cases, were compared between the first onset, had never used antipsychotic drugs in schizophrenia patients with the antipsychotic olanzapine before treatment, after treatment after 1,4,8,12 week BMI, waist circumference, blood glucose, CHOL, TGL, HDL, factor level changes related to glucose and lipid metabolism in VLDL; at the same time, the positive and negative symptoms scale (PANSS) changes of psychiatric symptoms were assessed before and after treatment.
The third part experiment was conducted to investigate schizophrenia in first-degree relatives with normal glucose and lipid metabolism in patients with the situation. This part of the collection of schizophrenic patients with normal first-degree relatives of 32 cases, 37 cases of normal control group, comparison of first-degree relatives of schizophrenic patients and normal controls abdominal circumference, body weight index, plasma glucose, insulin, IGF-1. The level of glucose metabolism related factors Leptin and GH.
Results: the first part: the experimental results show that with 6 weeks of antipsychotics, olanzapine group rats showed significantly increased intake of food and water, the difference was statistically significant (P0.05): Administration of plasma GH, COR in the three groups of rats, Leptin, INS, IGFBP-1, IGFBP-3 levels decreased, but no significant difference; olanzapine group rats received plasma IGF-1 levels were significantly lower than aripiprazole, haloperidol and saline groups, the difference was statistically significant (P0.05); aripiprazole, haloperidol group compared with the saline group, the difference was not statistically significant (P0.05).
The second part: the results showed that olanzapine 12 weeks after treatment PANSS score and treatment of patients with lower than before, the difference was statistically significant (P0.05); plasma CHOL, TGL, VLDL level in the 4 weekend was significantly increased (P0.01), 8 weeks, 12 weeks of plasma CHOL, TGL, VLDL level has been maintained at a high level. The level of plasma HDL in olanzapine in the treatment of 4 weeks, 8 weeks, 12 weeks before and after treatment showed no obvious change between groups were no difference (P0.05).
The third part: the results showed that patients with schizophrenia in first-degree relatives with normal BMI, waist circumference compared with the control group, the difference was not statistically significant (P0.05); patients with normal first-degree relatives have obvious insulin resistance, compared with the normal control group, the difference was statistically significant (P0.05); plasma insulin levels in patients with normal first-degree relatives the higher than the normal control group, the difference was statistically significant (P0.05), but the level of IGF-1 was significantly lower than the normal control group, the difference was statistically significant (P0.05)
Conclusion: This study explored the glucose and lipid metabolism in first-episode schizophrenics treated with antipsychotic drugs through animal experiments and clinical trials.
(1) antipsychotic drugs may affect the level of glycolipid metabolism in normal individuals, and the atypical antipsychotic olanzapine has a more obvious effect on glycolipid metabolism.
(2) olanzapine significantly improved psychotic symptoms in olanzapine in the treatment of 12 weeks in the PANSS score decreased significantly, suggesting that the drug of choice, olanzapine as patients with first-episode schizophrenia treatment significantly; at fourth weeks after treatment with olanzapine, factors related to lipid metabolism index increased significantly after the administration of 8 weeks, 12 weeks is always maintained at a high level.
(3) the plasma insulin level of the first-degree relatives of schizophrenic patients is significantly higher than that of the normal control group. IGF-1 is significantly lower than that of the normal control group, suggesting that there is a high risk factor of abnormal glucose and lipid metabolism in first-degree relatives of schizophrenia.
In conclusion, this study by animal experiment and clinical observation, to observe effects of antipsychotic drugs on lipid metabolism in normal rats at the same time, clinical trials using single drug (olanzapine) treatment of first-episode, drug naive schizophrenic patients, and to detect the level of plasma glucose and lipid metabolism in different treatment time, can a more accurate and comprehensive evaluation of changes in glucose and lipid metabolism in patients with schizophrenia treated with hair. Provide a theoretical basis for clinical treatment and prevention of metabolic disorders the research for schizophrenia treatments are associated with.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.3

【引证文献】