Diagnostic Value of Serum SHBG，NCAM and CCL2 Levels in Cognitive Dysfunction in First-episode Patients with Schizophrenia
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摘要:
目的 探究首发精神分裂症（first-episode schizophrenia，FES）患者血清性激素结合球蛋白（sex hormone-binding globulin，SHBG）、神经细胞黏附分子（neural cell adhesion molecule，NCAM）、CC基序趋化因子配体2（c-c motif chemokine ligand 2，CCL2）水平对认知功能障碍的诊断价值。 方法 选择2023年7月至2025年6月诊治的125例FES患者为研究组，另选132例同期在玉林市荣军优抚医院体检的健康志愿者为对照组，根据研究组是否发生认知功能障碍分为非障碍组（n = 72）和障碍组（n = 53）。ELISA检测血清SHBG、NCAM、CCL2水平，阳性与阴性症状量表（positive and negative syndrome scale，PANSS）评估患者精神分裂症严重程度，蒙特利尔认知评估表（montreal cognitive assessment，MoCA）评估患者是否发生认知功能障碍，精神分裂症认知功能成套测验共识版（measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery，MCCB）评分评估患者认知障碍程度。Pearson相关性分析SHBG、NCAM、CCL2水平与PANSS评分、MCCB评分的相关性；ROC曲线分析SHBG、NCAM、CCL2对FES患者发生认知功能障碍的诊断价值，Z检验比较AUC的差异。 结果 与对照组相比，研究组SHBG、CCL2水平较高，NCAM水平较低（P < 0.05）；与非障碍组相比，障碍组SHBG、CCL2水平较高，NCAM水平较低（P < 0.05）；与非障碍组相比，障碍组PANSS评分（阳性症状、阴性症状、一般病理症状、总分）较高，MCCB评分（社会认知、推理和问题解决能力、视觉学习、词语学习、工作记忆、注意/警觉性、信息处理速度、总分）较低（P < 0.05）；障碍组血清SHBG、CCL2水平与PANSS评分各项及总分呈正向相关，与MCCB评分各项及总分呈负相关，NCAM水平与PANSS评分各项及总分呈负向相关，与MCCB评分各项及总分呈正相关（P < 0.05）；SHBG、NCAM、CCL2联合诊断FES患者发生认知功能障碍的AUC为0.955，优于各自单独诊断（0.795、0.814、0.824）（P < 0.05）。 结论 FES患者SHBG、CCL2水平较高，NCAM水平较低，三者与疾病严重程度及认知障碍严重程度具有相关性，联合诊断具有一定的临床意义。 Abstract:Objective To explore the diagnostic value of the levels of serum sex hormone-binding globulin （SHBG）, neural cell adhesion molecule （NCAM）, and C-C motif chemokine ligand 2 （CCL2） in cognitive dysfunction among patients with first-episode schizophrenia （FES）. Methods A total of 125 FES patients treated between July 2023 and June 2025 were selected as the study group, and 132 healthy volunteers who underwent physical examination in Yulin City Veterans' Hospital（Yulin City Fourth People's Hospital） during the same period were selected as the control group. The study group was further divided into a non-dysfunction group （n = 72） and a dysfunction group （n = 53） based on whether cognitive dysfunction occurred. Serum levels of SHBG, NCAM, and CCL2 were detected using ELISA. The Positive and Negative Syndrome Scale （PANSS） was used to assess the severity of schizophrenia, the Montreal Cognitive Assessment （MoCA） was used to assess the presence of cognitive dysfunction, and the MATRICS Consensus Cognitive Battery （MCCB） score was used to assess the degree of cognitive impairment. Pearson correlation analysis was used to analyze the correlations between the levels of SHBG, NCAM, and CCL2 and the PANSS score and MCCB scores. The ROC curve was used to analyze the diagnostic value of SHBG, NCAM, and CCL2 for cognitive dysfunction in FES patients, and the Z-test was used to compare the differences in the area under the curve （AUC）. Results Compared with the control group, the study group had higher SHBG and CCL2 levels and lower NCAM levels （P < 0.05）. Compared with the non-dysfunction group, the dysfunction group had higher SHBG and CCL2 levels and lower NCAM levels （P < 0.05）. Compared with the non-dysfunction group, the dysfunction group had higher PANSS scores （positive symptoms, negative symptoms, general psychopathology, and total score） and lower MCCB scores （social cognition, reasoning and problem-solving ability, visual learning, verbal learning, working memory, attention/vigilance, information processing speed, and total score） （P < 0.05）. In the dysfunction group, serum SHBG and CCL2 levels were positively correlated with each item and total score of PANSS and negatively correlated with each item and total score of MCCB, while NCAM levels were negatively correlated with each item and total score of PANSS and positively correlated with each item and total score of MCCB （P < 0.05）. The AUC for combined diagnosis of cognitive dysfunction in FES patients using SHBG, NCAM, and CCL2 was 0.955, which was superior to individual diagnoses（0.795, 0.814, 0.824） （P < 0.05）. Conclusion FES patients have elevated SHBG and CCL2 levels and reduced NCAM levels. These three markers are correlated with disease severity and cognitive impairment severity. Combined diagnosis has certain clinical significance and provides a data foundation for clinical diagnosis and related drug development. -
图 1 SHBG、NCAM、CCL2诊断FES患者发生认知功能障碍的ROC
Figure 1. ROC curves of SHBG，NCAM，and CCL2 in diagnosing cognitive dysfunction in FES patients
表 1 对照组和研究组一般资料血清SHBG、NCAM、CCL2水平比较 [n（%）/（$ \bar x \pm s $）]
Table 1. Comparison of general data and serum SHBG，NCAM，and CCL2 levels between the control group and the study group [n（%）/（$ \bar x \pm s $）]
项目 对照组（n = 132） 研究组（n = 125） t/χ2 P 年龄（岁） 29.63 ± 6.14 28.49 ± 5.62 1.550 0.122 BMI（kg/m2） 22.48 ± 2.32 22.38 ± 2.28 0.348 0.728 性别 0.509 0.476 男 67（50.76） 69（55.20） 女 65（49.24） 56（55.20） 吸烟 2.002 0.157 是 57（43.18） 65（52.00） 否 75（56.82） 60（48.00） 饮酒 1.235 0.266 是 45（34.09） 51（40.80） 否 84（5.16） 74（59.20） SHBG（ng/mL） 208.24 ± 53.12 311.53 ± 74.68 12.829 < 0.001* NCAM（μg/mL） 127.62 ± 34.29 77.75 ± 21.48 13.883 < 0.001* CCL2（pg/mL） 252.28 ± 63.74 370.45 ± 105.48 10.935 < 0.001* *P < 0.05。 
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表 2 非障碍组和障碍组血清SHBG、NCAM、CCL2水平比较 [n（%）/（$ \bar x \pm s $）]
Table 2. Comparison of serum SHBG，NCAM，and CCL2 levels between non-dysfunction group and dysfunction group [n（%）/ （$\bar x \pm s $）]
项目 非障碍组（n = 72） 障碍组（n = 53） t/χ2 P 年龄（岁） 28.35 ± 5.26 28.68 ± 5.84 0.331 0.741 BMI（kg/m2） 22.35 ± 2.31 22.42 ± 2.47 0.163 0.871 性别 0.209 0.648 男 41（56.94） 28（52.83） 女 31（43.06） 25（47.17） 吸烟 1.553 0.213 是 34（47.22） 31（58.49） 否 28（52.78） 22（41.51） 饮酒 0.766 0.382 是 27（37.50） 24（45.28） 否 45（62.50） 29（54.72） 精神药物使用情况 利培酮 20（27.78） 15（28.30） 0.004 0.949 奥氮平 14（19.44） 12（22.64） 0.189 0.663 喹硫平 11（15.28） 7（13.21） 0.106 0.745 用药时长（d） 25.12 ± 4.86 26.73 ± 5.21 1.775 0.078 出现症状至治疗时间（d） 32.14 ± 5.46 30.79 ± 6.37 1.272 0.206 SHBG（ng/mL） 274.26 ± 71.42 362.15 ± 76.31 6.605 < 0.001* NCAM（μg/mL） 85.35 ± 16.84 67.42 ± 11.47 6.690 < 0.001* CCL2（pg/mL） 314.73 ± 96.12 446.15 ± 112.87 7.013 < 0.001* *P < 0.05。
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表 3 非障碍组和障碍组疾病严重程度及认知障碍程度比较[ （$ \bar x \pm s $），分]
Table 3. Comparison of disease severity and cognitive impairment between non-dysfunction group and dysfunction group [（$ \bar x \pm s $），scores]
项目 非障碍组（n = 72） 障碍组（n = 53） t/χ2 P PANSS评分 阳性症状 19.47 ± 5.32 24.85 ± 7.13 4.833 < 0.001* 阴性症状 15.62 ± 3.74 18.25 ± 4.34 3.629 < 0.001* 一般病理症状 31.54 ± 7.28 35.87 ± 8.56 3.049 0.003* 总分 66.63 ± 10.32 78.96 ± 12.57 6.015 < 0.001* MCCB评分 社会认知 40.38 ± 6.47 34.65 ± 5.24 5.293 < 0.001* 推理和问题解决能力 38.21 ± 5.36 35.72 ± 4.87 2.667 < 0.001* 视觉学习 43.57 ± 7.14 37.21 ± 5.83 5.310 < 0.001* 词语学习 39.25 ± 6.27 33.72 ± 4.47 5.475 < 0.001* 工作记忆 46.35 ± 6.84 43.68 ± 6.32 2.227 < 0.001* 注意/警觉性 35.49 ± 5.36 31.75 ± 4.83 4.018 < 0.001* 信息处理速度 36.82 ± 5.74 32.15 ± 5.21 4.673 < 0.001* 总分 280.07 ± 35.21 248.89 ± 30.47 5.175 < 0.001* *P < 0.05。
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表 4 障碍组血清SHBG、NCAM、CCL2水平与PANSS评分、MCCB评分相关性分析
Table 4. Correlation analysis of serum SHBG，NCAM，and CCL2 levels with PANSS scores and MCCB scores in the dysfunction group
项目 SHBG NCAM CCL2 r P r P r P PANSS评分 阳性症状 0.448 < 0.001* −0.474 < 0.001* 0.421 < 0.001* 阴性症状 0.439 < 0.001* −0.518 < 0.001* 0.443 < 0.001* 一般病理症状 0.469 < 0.001* −0.526 < 0.001* 0.412 < 0.001* 总分 0.422 < 0.001* −0.542 < 0.001* 0.446 < 0.001* MCCB评分 社会认知 −0.443 < 0.001* 0.439 < 0.001* −0.478 < 0.001* 推理和问题解决能力 −0.430 < 0.001* 0.454 < 0.001* −0.447 < 0.001* 视觉学习 −0.488 < 0.001* 0.525 < 0.001* −0.451 < 0.001* 词语学习 −0.471 < 0.001* 0.454 < 0.001* −0.483 < 0.001* 工作记忆 −0.478 < 0.001* 0.466 < 0.001* −0.519 < 0.001* 注意/警觉性 −0.481 < 0.001* 0.457 < 0.001* −0.457 < 0.001* 信息处理速度 −0.524 < 0.001* 0.432 < 0.001* −0.516 < 0.001* 总分 −0.487 < 0.001* 0.560 < 0.001* −0.542 < 0.001* *P < 0.05。
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表 5 SHBG，NCAM，CCL2对FES患者发生认知功能障碍的诊断价值
Table 5. Diagnostic value of SHBG，NCAM，and CCL2 for cognitive dysfunction in FES patients
指标 AUC 95%CI P 截断值 敏感度（%） 特异度（%） 约登指数 SHBG 0.795 0.714～0.862 < 0.001* 328.365 ng/mL 60.38 87.50 0.479 NCAM 0.814 0.734～0.878 < 0.001* 78.724 μg/mL 73.58 73.61 0.472 CCL2 0.824 0.746～0.886 < 0.001* 439.645 pg/mL 54.72 94.44 0.492 联合诊断 0.955 0.902～0.984 < 0.001* − 94.34 86.11 0.805 *P < 0.05。
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