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Article(id=1322168286423396582, tenantId=1146029695717560320, journalId=1220038315760373764, issueId=1322168262247432815, articleNumber=null, orderNo=null, doi=10.12102/j.issn.1009-6493.2026.05.006, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1741708800000, receivedDateStr=2025-03-12, revisedDate=1763308800000, revisedDateStr=2025-11-17, acceptedDate=null, acceptedDateStr=null, onlineDate=1793159084181, onlineDateStr=2026-10-28, pubDate=1773072000000, pubDateStr=2026-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793159084181, onlineIssueDateStr=2026-10-28, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793159084181, creator=13701087609, updateTime=1793159084181, updator=13701087609, issue=Issue{id=1322168262247432815, tenantId=1146029695717560320, journalId=1220038315760373764, year='2026', volume='40', issue='5', pageStart='705', pageEnd='880', issueExtLink='null', onlineDate='null', pubDate='1773072000000', pubDateStr='2026-03-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793159078418, creator='13701087609', updateTime=1793159078418, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=749, endPage=755, ext={EN=ArticleExt(id=1322168286628917479, articleId=1322168286423396582, tenantId=1146029695717560320, journalId=1220038315760373764, language=EN, title=Correlation between serum total bilirubin,albumin levels and cognitive function in first-episode drug-naïve patients with schizophrenia, columnId=1220689484526572183, journalTitle=Chinese Nursing Research, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the correlation between peripheral non-enzymatic antioxidant levels,such as serum uric acid(UA),total bilirubin(TBIL),and albumin(ALB),and cognitive impairment in first-episode drug-naïve(FEDN) patients with schizophrenia(SZ).

Methods

A total of 167 FEDN schizophrenia patients from the department of psychiatry,First Hospital of Shanxi Medical University,were enrolled as the case group from October 2022 to October 2024,along with 103 matched healthy volunteers as the control group.Fasting venous blood was collected to measure serum UA,TBIL,and ALB levels. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).

Results

The case group showed significantly lower serum ALB and TBIL levels compared to the healthy control group(P<0.001).Total scores of RBANS as well as scores across all domains were also lower in the case group(P<0.001).After adjusting for confounding factors,serum TBIL levels were positively correlated with immediate memory(β=0.67,P<0.001),delayed memory(β=1.06,P<0.001),and the RBANS total scores(β=0.47,P<0.001).Serum ALB levels were positively correlated with immediate memory(β=0.60,P<0.001) and delayed memory scores(β=1.39,P<0.001).However,no significant correlations were observed between serum TBIL or ALB levels and the RBANS scores in the healthy control group.

Conclusions

In clinical practice,early correction of peripheral non-enzymatic antioxidant levels,such as specifically serum total bilirubin and albumin, in FEDN schizophrenia patients may enhance antioxidant capacity and improve cognitive function,particularly memory,highlighting its clinical importance.

, authors=Weinan DU1, Xiao'e LANG2, authorsList=Weinan DU, Xiao'e LANG, authorCompany=null, correspAuthors=Xiao'e LANG, authorNote=null, correspAuthorsNote=
LANG Xiao'e, E-mail:
, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322168288138866932, articleId=1322168286423396582, tenantId=1146029695717560320, journalId=1220038315760373764, language=CN, title=首发未用药精神分裂症病人血清总胆红素、白蛋白水平与认知功能的相关性, columnId=1220689484681761433, journalTitle=护理研究, columnName=科研论著, runingTitle=null, highlight=null, articleAbstract=
目的

探讨首发未用药精神分裂症病人的外周非酶类抗氧化物血清尿酸、总胆红素、白蛋白水平与其认知功能受损的相关性。

方法

选取2022年10月—2024年10月就诊于山西医科大学第一医院精神卫生科的167例首发未用药精神分裂症病人作为病例组，招募103名与病例组相匹配的健康志愿者作为健康对照组，抽取空腹静脉血分别测定两组研究对象的血清尿酸、总胆红素和血清白蛋白水平，采用重复性成套神经心理状态测验量表（RBANS）评估两组研究对象的认知功能。

结果

病例组的血清白蛋白和总胆红素水平均低于健康对照组（P<0.001），且RBANS总分及各维度得分均低于健康对照组（P<0.001）。调整混杂因素后，血清总胆红素水平与即刻记忆分值（β=0.67）、延时记忆分值（β=1.06）以及RBANS总分值（β=0.47）呈正相关（P<0.001）。血清白蛋白水平与即刻记忆分值（β=0.60）、延时记忆分值（β=1.39）呈正相关（P<0.001）。而在健康对照组中并未发现血清总胆红素、白蛋白与RBANS总分及各维度分值的相关性。

结论

在临床诊疗过程中，应尽早纠正首发未用药精神分裂症病人的外周非酶类抗氧化物血清总胆红素水平与血清白蛋白水平，对提高其抗氧化能力，进而改善首发未用药精神分裂症病人的认知功能，尤其是对改善其记忆功能具有重要的临床意义。

, authors=杜伟楠1, 郎小娥2, *, *, authorsList=杜伟楠, 郎小娥, authorCompany=null, correspAuthors=郎小娥, authorNote=

杜伟楠，硕士研究生在读

, correspAuthorsNote=
郎小娥，E-mail：
LANG Xiao'e, E-mail:
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K,BOROVCANIN M M.The influence of serum uric acid on the brain and cognitive dysfunction[J].Frontiers in Psychiatry,2022,13:828476., articleTitle=The influence of serum uric acid on the brain and cognitive dysfunction, refAbstract=null), Reference(id=1322530452745863375, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, doi=null, pmid=null, pmcid=null, year=2020, volume=292, issue=null, pageStart=113305, pageEnd=null, url=null, language=null, rfNumber=28, rfOrder=27, authorNames=HE Q X, YOU Y T, YU L, journalName=Psychiatry Research, refType=null, unstructuredReference=HE Q X,YOU Y T,YU L,et al.Uric acid levels in subjects with schizophrenia:a systematic review and meta-analysis[J].Psychiatry Research,2020,292:113305., articleTitle=Uric acid levels in subjects with schizophrenia:a systematic review and meta-analysis, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1322530444751519874, tenantId=1146029695717560320, 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tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=图1, caption=血清总胆红素、白蛋白与认知功能的相关性, figureFileSmall=YwcEH52ml7ettD786E5mww==, figureFileBig=2V+5fegde95IY5gTB/bh+w==, tableContent=null), ArticleFig(id=1322530448165683364, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Figure 2, caption=Relationship between serum albumin level and immediate memory in FEDN schizophrenia patients, figureFileSmall=tQWPhrvyo3CohgEQ67qvcw==, figureFileBig=SAHwyRZ0ygPyYxsCZOEXXg==, tableContent=null), ArticleFig(id=1322530448228597925, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=图2, caption=首发未用药精神分裂症病人血清白蛋白水平与即刻记忆的关系

（红色线条表示变量之间的平滑曲线拟合，上下两条蓝色线条表示由此拟合得出的95%CI）

, figureFileSmall=tQWPhrvyo3CohgEQ67qvcw==, figureFileBig=SAHwyRZ0ygPyYxsCZOEXXg==, tableContent=null), ArticleFig(id=1322530448291512486, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Figure 3, caption=Relationship between serum albumin level and delayed memory in FEDN schizophrenia patients, figureFileSmall=WFKGlGAtsgmiaRwo3MZ3nA==, figureFileBig=CY+PTc31tQJM80I8p5PsJQ==, tableContent=null), ArticleFig(id=1322530448358621351, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=图3, caption=首发未用药精神分裂症病人血清白蛋白水平与延时记忆的关系

（红色线条表示变量之间的平滑曲线拟合，上下两条蓝色线条表示由此拟合得出的95%CI）

, figureFileSmall=WFKGlGAtsgmiaRwo3MZ3nA==, figureFileBig=CY+PTc31tQJM80I8p5PsJQ==, tableContent=null), ArticleFig(id=1322530448425730216, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Figure 4, caption=Relationship between serum total bilirubin level and immediate memory in FEDN schizophrenia patients, figureFileSmall=qyWnut3Oh7dvWCHSzZk/dA==, figureFileBig=VSADFlHNaxHawhrMfCPh+A==, tableContent=null), ArticleFig(id=1322530448497033385, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=图4, caption=首发未用药精神分裂症病人血清总胆红素水平与即刻记忆的关系

（红色线条表示变量之间的平滑曲线拟合，上下两条蓝色线条表示由此拟合得出的95%CI）

, figureFileSmall=qyWnut3Oh7dvWCHSzZk/dA==, figureFileBig=VSADFlHNaxHawhrMfCPh+A==, tableContent=null), ArticleFig(id=1322530448559947946, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Figure 5, caption=Relationship between serum total bilirubin level and delayed memory in FEDN schizophrenia patients, figureFileSmall=FFbT5zUc4gLgvOY43H7XlQ==, figureFileBig=DpUHC8QJy5ObbmisLgs12g==, tableContent=null), ArticleFig(id=1322530448618668203, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=图5, caption=首发未用药精神分裂症病人血清总胆红素水平与延时记忆的关系

（红色线条表示变量之间的平滑曲线拟合，上下两条蓝色线条表示由此拟合得出的95%CI）

, figureFileSmall=FFbT5zUc4gLgvOY43H7XlQ==, figureFileBig=DpUHC8QJy5ObbmisLgs12g==, tableContent=null), ArticleFig(id=1322530448677388460, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Figure 6, caption=Relationship between serum total bilirubin level and rbans total score in FEDN schizophrenia patients, figureFileSmall=AEiwsysuZQNvPoLXeiP9sQ==, figureFileBig=idhm/ZgBKGkIUQ7A+U7SEA==, tableContent=null), ArticleFig(id=1322530448778051757, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=图6, caption=首发未用药精神分裂症病人血清总胆红素水平与RBANS总分的关系

（红色线条表示变量之间的平滑曲线拟合，上下两条蓝色线条表示由此拟合得出的95%CI）

, figureFileSmall=AEiwsysuZQNvPoLXeiP9sQ==, figureFileBig=idhm/ZgBKGkIUQ7A+U7SEA==, tableContent=null), ArticleFig(id=1322530448840966318, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Table 1, caption=

Comparison of indicators between the two groups

, figureFileSmall=null, figureFileBig=null, tableContent=
项目分类健康对照组(n=103)病例组(n=167)统计值P
年龄(岁)28.83±6.2930.22±11.33F=1.650.200
性别（例）女5598χ2=0.720.395
男4869
教育年限(年)12.33±3.4912.16±3.34F=0.170.682
BMI(kg/m2)23.10±3.1524.01±4.95F=3.460.064
吸烟史（例）有90142χ2=0.290.590
无1325
饮酒史（例）有98151χ2=1.980.159
无516
PANSS（分）总分77.31±11.66
阳性症状16.49±4.35
阴性症状18.68±5.29
一般精神病理42.13±7.55
RBANS（分）总分83.42±11.5760.86±6.17F=333.12<0.001
即刻记忆81.98±12.9463.75±6.26F=178.52<0.001
视觉广度85.82±17.6170.41±8.35F=69.27<0.001
言语功能93.94±16.2570.12±8.98F=186.32<0.001
注意89.56±12.8469.20±8.74F=201.48<0.001
延时记忆85.24±14.0471.37±10.21F=75.88<0.001
血清尿酸（μmol/L）363.11±101.95358.40±104.79F=0.130.717
血清白蛋白（g/L)46.96±2.6041.86±3.39F=193.64<0.001
总胆红素（μmol/L)15.71±6.9212.71±6.27F=13.474<0.001
), ArticleFig(id=1322530448912269487, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=表1, caption=

两组各项指标比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目分类健康对照组(n=103)病例组(n=167)统计值P
年龄(岁)28.83±6.2930.22±11.33F=1.650.200
性别（例）女5598χ2=0.720.395
男4869
教育年限(年)12.33±3.4912.16±3.34F=0.170.682
BMI(kg/m2)23.10±3.1524.01±4.95F=3.460.064
吸烟史（例）有90142χ2=0.290.590
无1325
饮酒史（例）有98151χ2=1.980.159
无516
PANSS（分）总分77.31±11.66
阳性症状16.49±4.35
阴性症状18.68±5.29
一般精神病理42.13±7.55
RBANS（分）总分83.42±11.5760.86±6.17F=333.12<0.001
即刻记忆81.98±12.9463.75±6.26F=178.52<0.001
视觉广度85.82±17.6170.41±8.35F=69.27<0.001
言语功能93.94±16.2570.12±8.98F=186.32<0.001
注意89.56±12.8469.20±8.74F=201.48<0.001
延时记忆85.24±14.0471.37±10.21F=75.88<0.001
血清尿酸（μmol/L）363.11±101.95358.40±104.79F=0.130.717
血清白蛋白（g/L)46.96±2.6041.86±3.39F=193.64<0.001
总胆红素（μmol/L)15.71±6.9212.71±6.27F=13.474<0.001
), ArticleFig(id=1322530448983572656, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Table 2, caption=

Linear regression analysis of total bilirubin on cognitive function in the case group

, figureFileSmall=null, figureFileBig=null, tableContent=
项目模型Ⅰ模型Ⅱ模型Ⅲ
β(95%CI)Pβ(95%CI)Pβ(95%CI)P
即刻记忆0.67[0.56,0.79]<0.0010.68[0.56,0.79]<0.0010.67[0.56,0.79]<0.001
延时记忆1.07[0.88,1.26]<0.0011.06[0.87,1.25]<0.0011.06[0.86,1.25]<0.001
RBANS总分0.45[0.32,0.58]<0.0010.48[0.34,0.61]<0.0010.47[0.33,0.60]<0.001
), ArticleFig(id=1322530449063264433, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=表2, caption=

病例组病人总胆红素与认知功能的线性回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
项目模型Ⅰ模型Ⅱ模型Ⅲ
β(95%CI)Pβ(95%CI)Pβ(95%CI)P
即刻记忆0.67[0.56,0.79]<0.0010.68[0.56,0.79]<0.0010.67[0.56,0.79]<0.001
延时记忆1.07[0.88,1.26]<0.0011.06[0.87,1.25]<0.0011.06[0.86,1.25]<0.001
RBANS总分0.45[0.32,0.58]<0.0010.48[0.34,0.61]<0.0010.47[0.33,0.60]<0.001
), ArticleFig(id=1322530449130373298, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=EN, label=Table 3, caption=

Linear regression analysis of albumin on cognitive function in the case group

, figureFileSmall=null, figureFileBig=null, tableContent=
项目模型Ⅰ模型Ⅱ模型Ⅲ
β(95%CI)Pβ(95%CI)Pβ(95%CI)P
即刻记忆0.53[0.26,0.80]<0.0010.58[0.28,0.87]<0.0010.60[0.30,0.89]<0.001
延时记忆1.23[0.81,1.65]<0.0011.38[0.93,1.82]<0.0011.39[0.94,1.83]<0.001
), ArticleFig(id=1322530449205870771, tenantId=1146029695717560320, journalId=1220038315760373764, articleId=1322168286423396582, language=CN, label=表3, caption=

病例组病人血清白蛋白与认知功能的线性回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
项目模型Ⅰ模型Ⅱ模型Ⅲ
β(95%CI)Pβ(95%CI)Pβ(95%CI)P
即刻记忆0.53[0.26,0.80]<0.0010.58[0.28,0.87]<0.0010.60[0.30,0.89]<0.001
延时记忆1.23[0.81,1.65]<0.0011.38[0.93,1.82]<0.0011.39[0.94,1.83]<0.001
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首发未用药精神分裂症病人血清总胆红素、白蛋白水平与认知功能的相关性
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杜伟楠 1 , 郎小娥 2, *, *
护理研究 | 科研论著 2026,40(5): 749-755
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护理研究 |科研论著 2026 , 40 (5) : 749 -755
首发未用药精神分裂症病人血清总胆红素、白蛋白水平与认知功能的相关性
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杜伟楠1, 郎小娥2, *, *
作者信息
  • 1山西医科大学第一临床医学院，山西 030001
  • 2山西医科大学第一医院
通讯作者:
郎小娥，E-mail：
LANG Xiao'e, E-mail:
作者简介:

杜伟楠，硕士研究生在读

Correlation between serum total bilirubin,albumin levels and cognitive function in first-episode drug-naïve patients with schizophrenia
Weinan DU1, Xiao'e LANG2
Affiliations
  • 1The First Clinical College of Medicine, Shanxi Medical University, Shanxi 030001 China
  • 2First Hospital of Shanxi Medical University
    • Corresponding Author:
    LANG Xiao'e, E-mail:
出版时间: 2026-03-10 doi: 10.12102/j.issn.1009-6493.2026.05.006
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摘要
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目的

探讨首发未用药精神分裂症病人的外周非酶类抗氧化物血清尿酸、总胆红素、白蛋白水平与其认知功能受损的相关性。

方法

选取2022年10月—2024年10月就诊于山西医科大学第一医院精神卫生科的167例首发未用药精神分裂症病人作为病例组，招募103名与病例组相匹配的健康志愿者作为健康对照组，抽取空腹静脉血分别测定两组研究对象的血清尿酸、总胆红素和血清白蛋白水平，采用重复性成套神经心理状态测验量表（RBANS）评估两组研究对象的认知功能。

结果

病例组的血清白蛋白和总胆红素水平均低于健康对照组（P<0.001），且RBANS总分及各维度得分均低于健康对照组（P<0.001）。调整混杂因素后，血清总胆红素水平与即刻记忆分值（β=0.67）、延时记忆分值（β=1.06）以及RBANS总分值（β=0.47）呈正相关（P<0.001）。血清白蛋白水平与即刻记忆分值（β=0.60）、延时记忆分值（β=1.39）呈正相关（P<0.001）。而在健康对照组中并未发现血清总胆红素、白蛋白与RBANS总分及各维度分值的相关性。

结论

在临床诊疗过程中，应尽早纠正首发未用药精神分裂症病人的外周非酶类抗氧化物血清总胆红素水平与血清白蛋白水平，对提高其抗氧化能力，进而改善首发未用药精神分裂症病人的认知功能，尤其是对改善其记忆功能具有重要的临床意义。

精神分裂症  /  首发  /  尿酸  /  总胆红素  /  血清白蛋白  /  认知功能  /  记忆功能  /  相关性
Objective

To investigate the correlation between peripheral non-enzymatic antioxidant levels,such as serum uric acid(UA),total bilirubin(TBIL),and albumin(ALB),and cognitive impairment in first-episode drug-naïve(FEDN) patients with schizophrenia(SZ).

Methods

A total of 167 FEDN schizophrenia patients from the department of psychiatry,First Hospital of Shanxi Medical University,were enrolled as the case group from October 2022 to October 2024,along with 103 matched healthy volunteers as the control group.Fasting venous blood was collected to measure serum UA,TBIL,and ALB levels. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).

Results

The case group showed significantly lower serum ALB and TBIL levels compared to the healthy control group(P<0.001).Total scores of RBANS as well as scores across all domains were also lower in the case group(P<0.001).After adjusting for confounding factors,serum TBIL levels were positively correlated with immediate memory(β=0.67,P<0.001),delayed memory(β=1.06,P<0.001),and the RBANS total scores(β=0.47,P<0.001).Serum ALB levels were positively correlated with immediate memory(β=0.60,P<0.001) and delayed memory scores(β=1.39,P<0.001).However,no significant correlations were observed between serum TBIL or ALB levels and the RBANS scores in the healthy control group.

Conclusions

In clinical practice,early correction of peripheral non-enzymatic antioxidant levels,such as specifically serum total bilirubin and albumin, in FEDN schizophrenia patients may enhance antioxidant capacity and improve cognitive function,particularly memory,highlighting its clinical importance.

schizophrenia  /  first-episode  /  uric acid  /  total bilirubin  /  albumin  /  cognitive function  /  memory function  /  correlation
杜伟楠, 郎小娥. 首发未用药精神分裂症病人血清总胆红素、白蛋白水平与认知功能的相关性. 护理研究, 2026 , 40 (5) : 749 -755 . DOI: 10.12102/j.issn.1009-6493.2026.05.006
Weinan DU, Xiao'e LANG. Correlation between serum total bilirubin,albumin levels and cognitive function in first-episode drug-naïve patients with schizophrenia[J]. Chinese Nursing Research, 2026 , 40 (5) : 749 -755 . DOI: 10.12102/j.issn.1009-6493.2026.05.006
正文
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精神分裂症（schizophrenia,SZ）是一种致残率很高的重性精神疾病[1]，精神分裂症的核心症状主要包括阳性症状、阴性症状和认知损害症状。其中，认知损害被认为是精神分裂症病人精神残疾的强预测因子[2]。精神分裂症相关认知障碍包括注意力不集中、记忆力减退、执行功能受损、信息处理速度减慢以及决策能力下降等多个方面[3]。高达80%以上的精神分裂症病人在认知功能的多个维度上存在损害，尤其是在注意力、记忆力和执行功能方面[4]。精神分裂症相关认知障碍具有高发、严重、广泛、持久等多重特点，是导致精神残疾和严重疾病负担的主要原因[5]。越来越多的研究发现，精神分裂症病人体内存在氧化应激的增加和抗氧化物活性的降低[6-8]，且有研究表明，精神分裂症病人认知受损越严重，其抗氧化能力越弱[9-10]。人体内存在两大类抗氧化系统：酶类抗氧化物和非酶类抗氧化物，其中非酶类抗氧化系统主要由外周血清尿酸、总胆红素、白蛋白等组成。这些非酶类抗氧化物通过与金属离子螯合、直接俘获羟和/或碳中心/自由基等方式缓解氧化应激，占血浆总抗氧化能力的85%以上，非酶类抗氧化物参与了精神分裂症的发生发展[11]，血清总胆红素、白蛋白、尿酸可被视作氧化应激的标志物，反映体内的氧化应激程度[12-14]。总胆红素具有抗氧化特性和潜在的细胞毒性双重作用，一项基于431 699名成人的前瞻性队列研究发现，总胆红素水平与认知功能呈正相关[15]，且Becklén[16]的研究中发现首发精神分裂症病人体内的总胆红素水平低于正常人，而在另一项纳入89例急性发作且未用药精神分裂症病人和100名正常人的研究中却发现，精神分裂症病人体内总胆红素水平高于正常人[17]，关于总胆红素在精神分裂症病人中的研究结果并不一致。尿酸作为一种外周血中的抗氧化剂，同时也是一种细胞内的促氧化剂。体内高尿酸水平可以增强机体的氧化应激能力，但过高的尿酸水平可能导致脱氧核糖核酸（DNA）损伤、炎性细胞因子的产生，甚至细胞凋亡[14]。有研究发现，维持期精神分裂症病人中尿酸水平与认知功能呈正相关[18]，而在同期的研究发现精神分裂症病人中尿酸水平与认知功能呈负相关[19]，关于尿酸对精神分裂症病人认知损害的研究结果存在矛盾且复杂。此外，白蛋白已被证明对精神分裂症病人的认知功能具有保护作用，但相关研究较少[20]，其具体机制尚未明确。既往关于非酶类抗氧化物对精神分裂症病人认知受损的影响研究结果并不一致，且非酶类抗氧化物在首发未用药精神分裂症病人中的报道尚少。因此，本研究探讨非酶类抗氧化物对首发未用药精神分裂症认知功能的潜在影响，以期为临床精神分裂症认知功能的评估和认知障碍的精神分裂症病人个性化护理方案提供思路。
1　对象与方法
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1.1　研究对象
选择2022年10月—2024年10月就诊于山西医科大学第一医院精神卫生科的167例首发未用药精神分裂症病人作为病例组。纳入标准：1）符合《精神障碍诊断与统计手册》第5版（DSM-5）中关于精神分裂症的诊断标准；2）首次发病且未接受过任何治疗；3）阳性与阴性症状量表（PANSS）评分≥60分；4）年龄16~60岁；5）右利手。排除标准：1）患有高血压、糖尿病以及肝、胆、肾等躯体疾病；2）有药物或乙醇滥用及依赖史；3）有其他神经精神疾病；4）尿妊娠试验阳性和哺乳期女性；5）近期服用过可能影响血清尿酸、总胆红素、白蛋白水平的药物，如噻嗪类利尿剂、类固醇、布洛芬、维生素E、肌苷、辅酶Q10等。此外，招募并按性别和年龄与病例组进行配对，共有103名健康志愿者纳入健康对照组。研究方案已获得山西医科大学第一医院伦理委员会的审查批准（审批号：K045），且所有参与者或其合法监护人均已签署知情同意书。
1.2　资料收集方法
1）一般资料：收集病例组与健康对照组的基本信息和人口统计学资料，涵盖性别、年龄、教育年限、体质指数（BMI）以及吸烟、饮酒史；2）PANSS评分：由2名经过一致性培训的主治医师职称以上的精神科医生收集病例组病人PANSS评分；3）认知功能：采用重复性成套神经心理状态测验（RBANS）评估首发未用药精神分裂症病例组和健康对照组的认知功能，该系统分为即刻记忆、言语功能、视觉广度、注意、延时记忆5个神经心理状态因子，包括12个分测验，RBANS总分的确定方法是将5个因子分数相加，然后根据RBANS转化量表得出总分。分数越高，表明认知功能越好；4）尿酸、白蛋白和总胆红素水平：在清晨空腹状态下，研究人员抽取参与者静脉血液样本，测量血清中的尿酸、白蛋白和总胆红素水平。样本收集后，研究人员随即使用贝克曼库尔特公司的AU5800A和AU5800B全自动生化分析仪对这些血清指标进行测定。
1.3　统计学方法
数据分析采用SPSS 27.0和RStudio 4.4.2软件。符合正态分布的定量资料以均值±标准差（x±s）描述，定性资料采用例数、百分比（%）描述。符合正态分布的定量资料比较采用单因素方差分析（ANOVA），并应用Bonferroni校正进行多重比较，以控制Ⅰ型错误。定性资料比较采用χ2检验。采用Spearman相关性分析探讨病例组和健康对照组外周非酶类抗氧化物水平与认知功能的关联。此外，为了更准确地评估外周非酶类抗氧化水平与认知功能之间的关系，本研究构建了3个线性回归模型：模型Ⅰ未进行调整；模型Ⅱ调整了年龄和性别；模型Ⅲ进一步调整了教育年限、吸烟、饮酒、BMI。此外，还采用广义可加模型来探索外周非酶类抗氧化物水平与即刻记忆、延时记忆及RBANS总分之间的线性或非线性关系，并调整了性别、年龄、教育年限、吸烟、饮酒、BMI等混杂因素。以P<0.05为差异有统计学意义。
2　结果
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2.1　两组各项指标比较
两组性别、年龄、教育年限、BMI、吸烟史和饮酒史等比较差异均无统计学意义（P>0.05）。除血清尿酸外，病例组白蛋白和总胆红素水平均低于对照组（P<0.001）；此外，病例组的RBANS总分及其各维度评分均低于对照组（P<0.001）。详见表1。
2.2　血清总胆红素、白蛋白水平与认知功能的相关性
结果显示，在病例组中，血清总胆红素水平与RBANS总分值（r=0.523，P<0.001）及即刻记忆分值（r=0.650，P<0.001）、延时记忆分值（r=0.721，P<0.001）均呈正相关，血清白蛋白与即刻记忆分值（r=0.283，P<0.001）及延时记忆分值（r=0.403，P<0.001）呈正相关；在健康对照组中，血清总胆红素、白蛋白水平与RBANS总分及其各维度得分的相关性均无统计学意义（P>0.05）。表明这些外周非酶类抗氧化物水平可能对认知功能有影响，或许仅在精神分裂症病人中才有意义。见图1。
2.3　病例组病人总胆红素、白蛋白与认知功能的线性回归分析
本研究进一步采用线性回归模型分析血清总胆红素水平、血清白蛋白水平与首发未用药精神分裂症病人即刻记忆分值、延时记忆分值及总胆红素水平与RBANS总分之间的关系。线性回归模型分析结果见表2和表3。模型Ⅰ、模型Ⅱ和模型Ⅲ均显示，血清总胆红素水平、血清白蛋白水平与即刻记忆、延时记忆及血清总胆红素与RBANS总分值之间存在正相关关系（P<0.001）。在控制潜在混杂变量后（模型Ⅲ），血清总胆红素水平与即刻记忆分值（β=0.67)、延时记忆分值（β=1.06）以及RBANS总分值（β=0.47）的正相关关系仍有统计学意义（P<0.001）。血清白蛋白水平与即刻记忆分值（β=0.60）、延时记忆分值（β=1.39）正相关关系仍有统计学意义（P<0.001）。
2.4　广义可加模型
广义可加模型对识别线性或非线性相关性具有较高的敏感性。为验证线性回归分析结果的可靠性，本研究利用广义线性模型进一步探讨血清总胆红素水平与即刻记忆、延时记忆及RBANS总分值和血清白蛋白与即刻记忆、延时记忆分值之间的线性或非线性相关性。基于模型Ⅲ，本研究构建了平滑拟合曲线以可视化潜在的相关性。在调整了性别、年龄、教育年限、吸烟、饮酒、BMI等混杂变量后，结果显示，首发未用药精神分裂症病人的血清总胆红素水平与即刻记忆（P<0.001）、延时记忆（P<0.001）及RBANS总分（P<0.001）之间均存在线性正相关关系；血清白蛋白与即刻记忆（P<0.05）、延时记忆（P<0.001）之间均存在线性正相关关系。详见图2~图6。
3　讨论
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氧化应激是指体内自由基的产生与清除失衡时，过量的自由基和活性氧对细胞成分（如脂质、蛋白质、核酸）造成的损伤[21]。来自遗传学的研究证据表明，氧化应激相关基因的遗传多态性与精神分裂症的发病风险相关[22]。外周非酶类抗氧化水平反映了精神分裂症病人体内氧化应激水平的状态，在提示精神分裂症病人的认知功能受损程度中有着至关重要的作用。本研究发现，首发未用药精神分裂症病人血清总胆红素、白蛋白水平低于健康对照组，且血清总胆红素、白蛋白水平越低，其认知功能受损越严重。而在健康对照组中未发现血清尿酸、总胆红素、白蛋白与认知功能有上述相关性。
总胆红素是血红素代谢的最终产物，具有显著的抗氧化特性，能够清除超氧化物和过氧化物自由基，约占机体总抗氧化能力的30%左右[23]。本研究发现，首发未用药精神分裂症病人的血清总胆红素水平越低，即刻记忆功能受损越严重，这一结果与先前的研究结果[24]相一致。此外，本研究还发现，首发未用药精神分裂症病人的血清总胆红素水平与延时记忆分值与认知功能总分值也呈正相关性。研究表明，血清胆红素水平降低可引起深部脑白质病变，从而导致该类病人认知功能的延时记忆维度严重受损[25-26]。由此推断，本研究中首发未用药精神分裂症病人血清总胆红素水平降低导致其抗氧化防御能力减弱，引发其深部脑白质病变，从而导致其延时记忆功能受损。
血清白蛋白作为血清中的核心蛋白质成分，并且展现出显著的抗氧化功能，它能够与血液中的自由基以及重金属粒结合，从而降低氧化应激对细胞造成的损害。一项研究招募了133例服用8周抗精神病药物治疗的精神分裂症病人的血清白蛋白水平较健康对照组降低[20]，血清白蛋白水平与记忆功能呈正相关，本研究在首发未用药精神分裂症病人中发现相同的结果，推断白蛋白水平与记忆功能的关联可能独立于抗精神病药物治疗的影响，为理解精神分裂症的认知障碍提供了新的视角。记忆功能受损可能是由精神分裂症病人的血清白蛋白水平降低导致的抗氧化缺陷导致。然而，血清白蛋白水平易受到病人营养状况等因素的影响，由于本研究仅纳入病人的BMI，尚未对病人的营养状况进行进一步评估及对饮食进行严格控制，因此认为其对精神分裂症病人认知功能的影响仍为初步结果。未来的研究需在更为严格的营养状况和饮食条件下进行大样本探讨，进一步研究精神分裂症病人白蛋白水平与认知功能之间的关系，以探讨其作为生物学指标对精神分裂症病人的价值。
尿酸作为一种高效的自由基清除剂，在人体中的抗氧化作用极为重要。另一方面，尿酸通过与其他各种氧化剂反应形成自由基而成为促氧化剂，引起炎症[27]，因此，尿酸具有促氧化剂和抗氧化剂的双重作用。这两种作用之间的平衡取决于多种因素之间的复杂相互作用，在这种情况下，大脑的抗氧化能力低于其他器官，这使得其特别容易受到氧化应激的损害[18]。目前，血清尿酸水平和精神分裂症的关系仍存在争议。在既往研究中，Hu等[19]发现82例首发精神分裂症病人的血清尿酸水平高于健康对照组，而He等[28]的系统综述和荟萃分析发现首发精神分裂症病人的尿酸水平低于健康对照组，但在未服用抗精神病学药物的精神分裂症病人中，尿酸水平与健康对照组比较差异无统计学意义。本研究在首发未用药精神分裂症病人与健康对照组之间并未发现尿酸水平的显著差异，这一结果进一步强调了尿酸水平在首发精神分裂症中的复杂性，并提示尿酸可能并非精神分裂症的特异性生物标志物。尿酸水平的变化可能受到多种因素的影响，包括疾病阶段、药物使用以及潜在的生物学异质性，这为未来的研究提供了重要的方向，特别是在探索尿酸作为生物标志物的潜力以及其在疾病早期阶段的作用时，需要更加谨慎地考虑这些因素。
4　本研究的不足
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1）样本量较小，未来研究将进一步增大样本量，增强研究的代表性和可靠性。2）本研究仅测量了血清尿酸、总胆红素、白蛋白的水平，限制了对外周非酶类抗氧化物全面的评估，后续的研究将包括其他非酶类抗氧化物指标，如谷胱甘肽、生育酚、维生素A与维生素C。3）本研究为横断面设计，后续需开展更多纵向设计的研究，探讨首发未用药精神分裂症病人外周非酶类抗氧化物与认知功能的因果关系。
5　小结
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综上所述，本研究为首发未用药精神分裂症病人的外周非酶类抗氧化物水平与认知功能之间的关系提供了初步数据支持。研究结果显示，首发未用药精神分裂症病人的血清总胆红素和血清白蛋白水平低于健康对照组，且水平越低，病人的记忆功能受损越严重。提示应尽早纠正首发未用药精神分裂症病人的外周非酶类抗氧化物血清总胆红素水平与血清白蛋白水平，对提高其抗氧化能力从而改善首发未用药精神分裂症病人的认知功能，尤其是改善其记忆功能具有重要的临床意义。
血清总胆红素和血清白蛋白水平作为生物标志物，在精神分裂症病人认知功能评估中展现出其独特的优势。与传统的脑影像学检测方法相比，这两种生物标志物具有接受度高、价格低廉的特点，能够广泛应用于初级保健的常规血液筛查。通过检测外周血中血清总胆红素和血清白蛋白的水平变化，护理人员可以快速识别病人记忆功能受损的程度，从而简化专科护理的转诊流程，提高护理效率。首发未用药精神分裂症病人血清总胆红素与血清白蛋白水平的降低与记忆功能损害密切相关，这一发现为临床护理提供了新的评估手段，有助于推动护理实践从传统的症状管理向基于生物标志物的精准护理模式转变。通过监测这些指标，护理人员能够更早地识别出可能存在认知障碍风险的病人，并及时启动针对性的护理干预措施，如认知训练和营养支持，以改善病人的认知功能。此外，定期监测这些指标还可帮助医护人员动态监测病人的病情变化，及时调整治疗和护理方案。同时，提示护理人员可以利用病人的常规化验指标和量表评估结果开展护理研究。

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2026年第40卷第5期
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doi: 10.12102/j.issn.1009-6493.2026.05.006
  • 接收时间：2025-03-12
  • 首发时间：2026-10-28
  • 出版时间：2026-03-10
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  • 收稿日期：2025-03-12
  • 修回日期：2025-11-17
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    1山西医科大学第一临床医学院，山西 030001
    2山西医科大学第一医院

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
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光柄菇属 Pluteus 5 2.39
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