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基于神经营养因子及其他生物标志物的精神分裂症诊断模型的建立

[Establishment of diagnostic model for schizophrenia based on neurotrophic factor and other biomarkers].

作者信息

Pang L J, Li X, Yuan X X, Hei G R, Zhang L Y, Wang S Y, Chen Y S, Song P L, Song X Q

机构信息

Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Henan International Joint Laboratory of Biological Psychiatry, Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou 450052, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2023 May 9;103(17):1310-1315. doi: 10.3760/cma.j.cn112137-20221212-02631.

DOI:10.3760/cma.j.cn112137-20221212-02631
PMID:37150680
Abstract

To construct a diagnostic model of schizophrenia (SCZ) based on biomarkers such as serum neurotrophic factor. Patients of schizophrenia (SCZ group) and healthy controls (HC group) who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were prospectively selected. In the SCZ group, the mental symptoms were assessed by the positive and negative symptom scale (PANSS), cognitive function was assessed by the MATRICS consensus cognitive battery (MCCB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), fasting glucose (FGB) and fasting insulin (FINS) levels were detected, and insulin resistance (HOMA-IR) was calculated. The same methods were used to evaluate cognitive function, measure BDNF, GDNF, FGB and FINS levels, and calculate HOMA-IR in HC group. The indexes with statistically significant differences between the two groups were selected to be included in the model. The diagnostic model was constructed by machine learning and verified by cross-validation method, the receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity and specificity were calculated. (1) A total of 142 patients (70 males and 72 females) with schizophrenia were finally included, and aged (25±4) years. Meanwhile, 140 healthy controls (72 males and 68 females) were also enrolled, and aged (26±4) years. In SCZ group, scores in all areas of cognitive function were lower than those in HC group (all <0.001), the levels of serum BDNF and GDNF [(6.7±1.8) ng/ml and (405±93) pg/ml] were also lower than those in HC group [(12.3±3.2) ng/ml and (574±139) pg/ml] (both <0.001), but the levels of FINS and HOMA-IR [(8.4±0.8) μU/ml and 1.7±0.3] were higher than those in HC group [(6.7±0.9) μU/ml and 1.4±0.3] (both <0.001). (2) Correlation analysis showed that the level of serum BDNF had a negative correlation with negative symptom scores and total scores (=-0.31, <0.001; =-0.17, =0.040), but had a positive correlation with attention/alertness (CPT-IP) T scores, working memory (WSM-Ⅲ) T scores and visual learning (BVMT) T scores in SCZ group (=0.39, 0.37 and 0.29, all <0.001). The level of serum GDNF also had a positive correlation with CPT-IP T scores, WSM-Ⅲ T scores and BVMT T scores (=0.32, <0.001; =0.23, =0.007; =0.40, <0.001). The values of HOMA-IR had a positive correlation with social cognition (MSCEIT) T scores in SCZ group (=0.18, =0.033). (3) AUC of the early diagnosis model constructed by combining BDNF, GDNF and HOMA-IR was 0.890 (95%: 0.832-0.940), the accuracy was 0.89, the sensitivity and specificity was 0.94 and 0.82, respectively. The final diagnostic model based on biomarkers of serum neurotrophic factor has good diagnostic efficiency for SCZ, but large-scale independent sample verification is still needed.

摘要

构建基于血清神经营养因子等生物标志物的精神分裂症诊断模型。前瞻性选取2017年1月至2019年12月在郑州大学第一附属医院就诊的精神分裂症患者(精神分裂症组)和健康对照者(健康对照组)。在精神分裂症组中,采用阳性与阴性症状量表(PANSS)评估精神症状,采用精神分裂症认知功能成套测验共识版(MCCB)评估认知功能,检测脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)、空腹血糖(FGB)和空腹胰岛素(FINS)水平,并计算胰岛素抵抗(HOMA-IR)。采用相同方法评估健康对照组的认知功能,检测BDNF、GDNF、FGB和FINS水平,并计算HOMA-IR。选取两组间差异有统计学意义的指标纳入模型。采用机器学习构建诊断模型,并通过交叉验证法进行验证,绘制受试者工作特征曲线(ROC),计算曲线下面积(AUC)、灵敏度和特异度。(1)最终纳入精神分裂症患者142例(男70例,女72例),年龄(25±4)岁。同时纳入健康对照者140例(男72例,女68例),年龄(26±4)岁。精神分裂症组认知功能各领域得分均低于健康对照组(均P<0.001),血清BDNF和GDNF水平[(6.7±1.8)ng/ml和(405±93)pg/ml]也低于健康对照组[(12.3±3.2)ng/ml和(574±139)pg/ml](均P<0.001),但FINS和HOMA-IR水平[(8.4±0.8)μU/ml和1.7±0.3]高于健康对照组[(6.7±0.9)μU/ml和1.4±0.3](均P<0.001)。(2)相关性分析显示,精神分裂症组血清BDNF水平与阴性症状评分及总分呈负相关(r=-0.31,P<0.001;r=-0.17,P=0.040),但与注意力/警觉性(CPT-IP)T分、工作记忆(WSM-Ⅲ)T分和视觉学习(BVMT)T分呈正相关(r=0.39、0.37和0.29,均P<0.001)。血清GDNF水平也与CPT-IP T分、WSM-Ⅲ T分和BVMT T分呈正相关(r=0.32,P<0.001;r=0.23,P=0.007;r=0.40,P<0.001)。精神分裂症组HOMA-IR值与社会认知(MSCEIT)T分呈正相关(r=0.18,P=0.033)。(3)联合BDNF、GDNF和HOMA-IR构建的早期诊断模型的AUC为0.890(95%CI:0.832~0.940),准确率为0.89,灵敏度和特异度分别为0.94和0.82。基于血清神经营养因子生物标志物的最终诊断模型对精神分裂症具有良好的诊断效能,但仍需大样本独立验证。

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