精神分裂症患者炎症与免疫指标及其临床价值分析
文献类型：学位论文
| 作者 | 王晓宇 |
| 答辩日期 | 2021-12 |
| 文献子类 | 继续教育硕士 |
| 授予单位 | 中国科学院大学 |
| 授予地点 | 中国科学院心理研究所 |
| 其他责任者 | 王晶 |
| 关键词 | 精神分裂症 炎症指标 抗核抗体 血脂代谢 糖代谢 |
| 学位名称 | 理学硕士 |
| 学位专业 | 应用心理学 |
| 其他题名 | Analysis of inflammatory and immune indexes and their clinical value in patients with schizophrenia |
| 中文摘要 | BackgroundSchizophrenia is a serious chronic mental disease. Its occurrence is related to pro-inflammatory risk genes, environmental stress factors and changes of immune system. A large number of epidemiological and clinical studies have proved that inflammation and immunity play a role in schizophrenia, and various infection factors are the risk factors of schizophrenia. In addition, schizophrenia is also a heterogeneous mental disease with a wide range of clinical and biological manifestations. However, due to the lack of objective tests or biomarkers, its accurate diagnosis and the choice of effective treatment is still challenging. In terms of clinical characteristics, schizophrenia may be more prone to insulin resistance, lipid abnormalities and weight gain. The risk of metabolic abnormalities is higher than that of the general population. Inflammation is also an important pathophysiological factor of metabolic disorders such as type 2 diabetes. Therefore, it is speculated that the high risk of metabolic abnormalities in patients with schizophrenia may also be related to their inflammation. In this study, biomarkers related to immune inflammation were selected to study in patients with schizophrenia. High sensitivity C-reactive protein (hs-CRP) is an acute inflammatory protein. Neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) are newly found inflammatory markers positively correlated with hs-CRP. Homocysteine (Hcy) can affect vascular endothelial cells through various ways to induce oxidative stress and inflammatory response and participate in the occurrence and development of schizophrenia. Antinuclear antibody (ANA) is an immune biomarker and an autoantibody against a series of nuclear components. In conclusion, this study hypothesized that NLR, RDW, hs-CRP, Hcy and ANA may be highly expressed in schizophrenic patients and have a certain impact on the disorder of glucose and lipid metabolism. In addition, the above indicators may also have some auxiliary diagnostic value for schizophrenia, and are expected to become potential biomarkers for early detection and prevention of schizophrenia and its accompanying glycolipid metabolism disorders.ObjectiveTo detect the expression of NLR, RDW, hs-CRP, Hcy and ANA in patients with schizophrenia, analyze their relationship with various dimensions of schizophrenia (different stages of onset, different clinical characteristics and before and after antipsychotic treatment) and accompanying abnormal glucose and lipid metabolism.To explore the efficacy of the above indexes in the auxiliary diagnosis of first-episode and recurrent schizophrenia, so as to seek the clinical value of these inflammatory indexes in schizophrenia.Methods114 schizophrenic patients treated in Beijing Huilongguan Hospital from January to December 2019 were selected as case group, and 48 healthy subjects were selected as control group. The levels of NLR, RDW, hs-CRP and Hcy at admission were detected and recorded, and the first-episode and recurrent patients were grouped with normal controls. The above indicators were compared and analyzed between the first episode、recurrence and the normal control group, and then the receiver operating characteristic curve ( ROC curve ) was used to analyze the auxiliary diagnostic value of high expression indicators in the case group for schizophrenia; The case group was divided into different subgroups according to clinical characteristics, and the levels of NLR, RDW, hs-CRP, Hcy were compared among all groups; Forty-eight patients were selected from the case group who received standard treatment of first-line second-generation antipsychotic drugs for 1 month, and the levels of NLR, RDW, hs-CRP and Hcy were compared before and after treatment; The univariate and multivariate binary logistic regression analysis were used to analyze the relationship between the above inflammatory indexes and the abnormal glucose and lipid metabolism in patients in the case group; The serum of 77 patients in the case group from April to October 2019 was collected at admission, and ANA was detected and compared with normal controls.ResultsCompared with the normal control group, NLR and Hcy in the first-episode schizophrenia group increased significantly (p<0.05), and NLR, RDW, hs-CRP and Hcy in the recurrent schizophrenia group also increased significantly (p<0.05). In addition, RDW and hs-CRP in the recurrent schizophrenia group increased significantly compared with the first-episode schizophrenia group (p<0.05); ROC curve analysis showed that NLR, Hcy alone and in combination had diagnostic value for first-episode schizophrenia (the areas under the ROC curve were 0.789, 0.774 and 0.853 respectively), and NLR, RDW, hs-CRP and Hcy alone and in combination had diagnostic value for recurrent schizophrenia (the areas under the ROC curve were 0.788, 0.669, 0.739, 0.795 and 0.918 respectively); The comparison of clinical subgroups of schizophrenia showed that the RDW of women was higher than that of men (p<0.05), the Hcy of men was higher than that of women (p<0.05), the hs-CRP in patients over 50 years old was higher than that in patients between 30 to 50 years old (p<0.05), the hs-CRP was higher in patients with first untreated period ≥1 year than that in patients with < 1 year (p<0.05), the NLR was higher in patients with recurrent disease duration ≥ 10 years than that in patients with disease duration < 10 years (p<0.05); After antipsychotic treatment, the NLR level of 48 patients decreased significantly compared with that before treatment (p<0.05), but there was no difference in hs-CRP, RDW and Hcy before and after treatment (p>0.05); Logistic regression analysis showed that hs-CRP was an independent risk factor for abnormal lipid metabolism in schizophrenic patients (OR=1.254, p<0.05). NLR and age were independent risk factors for abnormal fasting blood glucose metabolism in schizophrenic patients (OR was 1.642 and 1.060, respectively, p<0.05); The comparison of ANA positive rate showed that there was no difference between schizophrenia group and normal control group (p>0.05).ConclusionIn schizophrenic patients, the expression level of inflammatory indexes in patients with long course and recurrence is higher, suggesting that the inflammatory state may develop with the disease process, and the level of NLR after antipsychotic treatment is lower than that before treatment, suggesting that antipsychotics have an effect on NLR in schizophrenic patients; In addition, inflammatory indexes are also related to the risk of abnormal glucose and lipid metabolism in schizophrenic patients. Close monitoring of NLR and hs-CRP may help to evaluate and prevent the occurrence of glucose and lipid metabolism disorders in patients with schizophrenia; In clinical diagnosis, the single and combined detection of inflammatory indexes NLR, hs-CRP, RDW and Hcy has diagnostic value for schizophrenia, and the value of combined detection is greater than that of single detection. Key Words: Schizophrenia, Inflammatory index, Antinuclear antibody, Lipid metabolism, Glucose metabolism |
| 英文摘要 | 研究背景精神分裂症是一种严重的慢性精神疾病，其发生和促炎风险基因、环境压力因素以及免疫系统改变等有关。大量流行病学和临床研究证明，炎症和免疫在精神分裂症中发挥作用，各种感染因子是精神分裂症的危险因素。此外，精神分裂症还是一种异质性精神疾病，具有广泛的临床和生物学表现，但目前由于缺乏客观的测试或生物标志物，其准确诊断和有效治疗方法的选择仍具有挑战性。就临床特征而言，精神分裂症患者可能更容易出现胰岛素抵抗、脂质异常和体重增加，其代谢异常发生风险相较于普通人群是增高的，而炎症是2型糖尿病等代谢异常疾病的重要病理生理因素，因此，推测精神分裂症患者高代谢异常风险可能和其炎症也有相关。本研究选取免疫炎症相关生物标志物在精神分裂症患者中进行研究，其中超敏C反应蛋白(high sensitivity C-reactive protein, hs-CRP)是一种急性炎症蛋白；中性粒细胞与淋巴细胞比值(neutrophil-lymphocyte ratio, NLR)和红细胞分布宽度(red blood cell distribution width, RDW)是新近发现与hs-CRP呈正相关的炎症标志物；同型半胱氨酸(homocysteine, Hcy)可通过各种途径影响血管内皮细胞诱发氧化应激和炎性反应而参与精神分裂症的发生与发展；抗核抗体(antinuclear antibody, ANA) 则为免疫生物标志物，是针对一系列细胞核成分的自身抗体。综上，本研究假设NLR、RDW、hs-CRP、Hcy、ANA可能在精神分裂症患者中高表达，并且对伴发糖脂代谢紊乱有一定影响。此外，以上指标也有可能对精神分裂症具有一定辅助诊断价值，有望成为早期发现和预防精神分裂症及其伴发糖脂代谢紊乱的潜在生物标志物。目的检测精神分裂症患者NLR、RDW、hs-CRP、Hcy、ANA的表达水平，分析其与精神分裂症各个维度（不同发病阶段、不同临床特征以及抗精神病药物治疗前后）以及伴发糖脂代谢异常的关系，并探讨其对首发及复发精神分裂症辅助诊断效能，以寻求这些炎症指标在精神分裂症中的临床价值。方法选取2019年1-12月于北京回龙观医院进行治疗的精神分裂症患者114例作为病例组，选择同期健康体检者48例作为对照组。检测并记录患者入院时NLR、RDW、hs-CRP、Hcy的水平，并将首发与复发患者进行分组同正常对照一起比较分析上述指标，然后再利用受试者工作特征曲线（ROC曲线）分析病例组中高表达的指标对精神分裂症的辅助诊断价值；按临床特征将病例组分为不同亚组，比较各组NLR、RDW、hs-CRP、Hcy的水平差异；从病例组中选取经一线第2代抗精神病药物连续规范治疗达1个月的48例患者，比较治疗前后NLR、RDW、hs-CRP、Hcy的水平；采用单因素及多因素二元logistic回归分析上述炎症指标与病例组患者伴发糖脂代谢异常的关系；收集病例组中2019年4-10月的77例患者入院时血清，检测ANA并与正常对照进行比较分析。结果与正常对照组相比，首发精神分裂症组NLR和Hcy显著升高(p<0.05)，复发精神分裂症组NLR、RDW、hs-CRP、Hcy也显著升高(p<0.05)，此外，与首发精神分裂症组相比，复发精神分裂症组RDW、hs-CRP显著升高(p<0.05)；ROC曲线分析显示，NLR、Hcy单独及联合检测均对首发精神分裂症有诊断价值(ROC曲线下面积分别为0.789、0.774、0.853)，NLR、RDW、hs-CRP、Hcy单独及联合检测均对复发精神分裂症有诊断价值(ROC曲线下面积分别为0.788、0.669、0.739、0.795、0.918)；精神分裂症临床亚组比较显示：女性RDW高于男性(p<0.05)，男性Hcy高于女性(p<0.05)，>50岁患者hs-CRP高于30-50岁患者(p<0.05)，首发未治疗期≥1年患者hs-CRP高于<1年患者(p<0.05)，复发病程≥10年患者NLR高于病程<10年患者(p<0.05)；经抗精神病药物治疗后，48例患者的NLR水平较治疗前有显著下降(p<0.05)，但hs-CRP、RDW、Hcy治疗前后比较无差异(p>0.05)；logistics回归分析显示hs-CRP是精神分裂症患者伴发血脂代谢异常的独立危险因素(OR=1.254，p<0.05)，NLR和年龄是精神分裂症患者伴发空腹血糖代谢异常的独立危险因素(OR分别为1.642、1.060，p<0.05)；ANA阳性率比较显示，精神分裂症组和正常对照组之间无差异(p>0.05)。结论在精神分裂症患者中，长病程及复发患者的炎症指标表达水平更高，提示炎症状态可能会随着疾病进程而发展，且在经过抗精神病药物治疗后，NLR的水平较治疗前有下降，提示抗精神病药物对精神分裂症患者NLR有影响；此外，炎症指标与精神分裂症患者高糖脂代谢异常风险也有相关，通过密切监测NLR、hs-CRP等指标水平可能有助于评估与防范精神分裂症患者发生糖脂代谢紊乱；在临床诊断应用中，炎症指标NLR、hs-CRP、RDW、Hcy单独及联合检测均对精神分裂症有诊断价值，且联合检测的价值大于单独检测。 |
| 语种 | 中文 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/45234]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 推荐引用方式 GB/T 7714 | 王晓宇. 精神分裂症患者炎症与免疫指标及其临床价值分析[D]. 中国科学院心理研究所. 中国科学院大学. 2021. |
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来源：心理研究所
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