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Article(id=1241522854085325624, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522846384583426, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202306258, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1686585600000, receivedDateStr=2023-06-13, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773931714793, onlineDateStr=2026-03-19, pubDate=1707494400000, pubDateStr=2024-02-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773931714793, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773931714793, creator=13701087609, updateTime=1773931714793, updator=13701087609, issue=Issue{id=1241522846384583426, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='3', pageStart='385', pageEnd='576', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773931712956, creator=13701087609, updateTime=1773931842201, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241523388544504301, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522846384583426, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241523388544504302, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241522846384583426, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=401, endPage=406, ext={EN=ArticleExt(id=1241522855733687102, articleId=1241522854085325624, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=A Mendelian randomization study on the relationship between mental disorders and the risk of psoriasis, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To study the causal effects of generalized anxiety disorder, major depressive disorder, schizophrenia, sleep disorder, and psoriasis by two-sample Mendelian randomization analysis.

Methods

The single nucleotide polymorphisms (SNPs) associated with four psychiatric traits and psoriasis were screened from the genome-wide association study (GWAS) data base. The relationships between exposures and outcome were analyzed by inverse variance weighting (IVW) method, weighted median (WM) method, and MR-Egger method. The results were mainly evaluated by P value of IVW, odds ratio (OR), and 95% confidence interval (CI). IVW, MR Egger, and MR-PRESSO were used for sensitivity analysis.

Results

The IVW results showed that there was a causal effect between schizophrenia and the risk of psoriasis (OR=1.002,95%CI: 1.000-1.003, P=0.023). In the heterogeneity test, the Cochran’s Q test of the IVW method reported P value of 0.104 and I2 of 19.06%, the MR-PRESSO test in the pleiotropy test reported P value of 0.106, and the regression intercept of MR Egger reported P value of 0.272. The sensitivity analysis results were robust, and the results did not show heterogeneity and pleiotropy. No causal relationship was found for generalized anxiety disorder (OR=1.000, 95%CI: 0.999-1.001, P=0.791), major depressive disorder (OR=1.002, 95%CI: 0.998-1.005, P=0.246), sleep disorder (OR=0.999, 95%CI: 0.996-1.001, P=0.614) with psoriasis.

Conclusion

There is a causal relationship between schizophrenia and the risk of psoriasis. Patients with schizophrenia should strengthen the screening and prevention of psoriasis in order to reduce the risk of psoriasis.

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目的

采用两样本孟德尔随机化方法研究广泛性焦虑障碍、重度抑郁、精神分裂症、睡眠障碍和银屑病发病风险的因果效应。

方法

在全基因组关联研究数据库（genome wide association study，GWAS）中筛选符合条件的四种精神心理特征及银屑病的单核苷酸多态性（single nucleotide polymorphism，SNP）。通过逆方差加权法(inverse-variance weighted, IVW)、加权中位数法(weighted median, WM)、MR-Egger等方法分析暴露与结局之间的发病风险，结果主要以IVW的P值、优势比(odds ratio, OR)和95%可信区间(confidence interval, CI)评估。采用IVW、MR-Egger、MR-PRESSO等方法进行敏感性分析。

结果

IVW结果显示精神分裂症与银屑病发病风险存在因果效应(OR=1.002，95%CI:1.000～1.003，P=0.023)。异质性检验中IVW法Cochran Q test检验的P=0.104，I2=19.60%，多效性检验中MR-PRESSO结果P=0.106，MR-Egger回归截距P=0.272，各项敏感性分析结果稳健，结果不存在异质性及多效性。未发现广泛性焦虑障碍(OR=1.000，95 %CI：0.999～1.001，P=0.791)、重度抑郁(OR=1.002，95%CI:0.998～1.005，P=0.246)、睡眠障碍(OR=0.999，95%CI:0.996～1.001，P=0.614)与银屑病发病存在因果关系。

结论

精神分裂症与银屑病风险存在因果关系，精神分裂症患者应加强对银屑病的筛查及预防，以降低患银屑病的风险。

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卢传坚 E-mail：
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=24rTZNuRLQa+rfkoveJs5g==, magXml=OuaWqjXvaTBq+sH6kkjbAg==, pdfUrl=null, pdf=g5ONaEGJ2n2yt5pwTDBtXQ==, pdfFileSize=2419032, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=JUWVxgas7H0UtK+dxwDagg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=TKQW28TLuNd1l5TQml1TgQ==, mapNumber=null, authorCompany=null, fund=null, authors=

杨玉洁（1996—），女，博士在读，研究方向：银屑病基础与临床研究方向

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杨玉洁（1996—），女，博士在读，研究方向：银屑病基础与临床研究方向

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杨玉洁（1996—），女，博士在读，研究方向：银屑病基础与临床研究方向

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2.广东省中医院皮肤科，广东 广州 510120
3.广州中医药大学第二附属医院省部共建中医湿证国家重点实验室，广东 广州 510120
4.粤港澳中医药与免疫疾病研究联合实验室，广东 广州 510120
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label=Table 1, caption=

Basic information of exposure and outcome

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暴露/结局年份（年）人种样本量SNP数量PMIDGWAS ID
广泛性焦虑障碍2021欧洲人200 27316 380 388—finn-b-F5_GAD
重度抑郁2019欧洲人500 199—30718901ieu-b-102
睡眠障碍2021欧洲人216 70016 380 458—finn-b-SLEEP
精神分裂2022欧洲人127 906—35396580ieu-b-5102
银屑病2017欧洲人337 15910 894 596—ukb-a-100
), ArticleFig(id=1241680467641028825, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241522854085325624, language=CN, label=表1, caption=

暴露与结局的基本信息表

, figureFileSmall=null, figureFileBig=null, tableContent=
暴露/结局年份（年）人种样本量SNP数量PMIDGWAS ID
广泛性焦虑障碍2021欧洲人200 27316 380 388—finn-b-F5_GAD
重度抑郁2019欧洲人500 199—30718901ieu-b-102
睡眠障碍2021欧洲人216 70016 380 458—finn-b-SLEEP
精神分裂2022欧洲人127 906—35396580ieu-b-5102
银屑病2017欧洲人337 15910 894 596—ukb-a-100
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精神心理障碍与银屑病发病风险的孟德尔随机化研究
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杨玉洁 1 , 莫念 1 , 郑旭威 1 , 唐斌 1, 2, 3, 4, 5 , 罗倩倩 1 , 毕洋 1 , 陈海明 1, 2, 3, 4, 5 , 卢传坚 1, 2, 3, 4, 5
现代预防医学 | 流行病与统计方法 2024,51(3): 401-406
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现代预防医学 | 流行病与统计方法 2024, 51(3): 401-406
精神心理障碍与银屑病发病风险的孟德尔随机化研究
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杨玉洁1, 莫念1, 郑旭威1, 唐斌1, 2, 3, 4, 5, 罗倩倩1, 毕洋1, 陈海明1, 2, 3, 4, 5, 卢传坚1, 2, 3, 4, 5
作者信息
  • 1.广州中医药大学第二临床医学院，广东 广州 510006
  • 2.广东省中医院皮肤科，广东 广州 510120
  • 3.广州中医药大学第二附属医院省部共建中医湿证国家重点实验室，广东 广州 510120
  • 4.粤港澳中医药与免疫疾病研究联合实验室，广东 广州 510120
  • 5.广东省中医证候临床研究重点实验室，广东 广州 510120

    • 杨玉洁（1996—），女，博士在读，研究方向：银屑病基础与临床研究方向

通讯作者:

卢传坚 E-mail：
A Mendelian randomization study on the relationship between mental disorders and the risk of psoriasis
Yu-jie YANG1, Nian MO1, Xu-wei ZHENG1, Bin TANG1, 2, 3, 4, 5, Qian-qian LUO1, Yang BI1, Hai-ming CHEN1, 2, 3, 4, 5, Chuan-jian LU1, 2, 3, 4, 5
Affiliations
  • The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China
出版时间: 2024-02-10 doi: 10.20043/j.cnki.MPM.202306258
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摘要
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目的

采用两样本孟德尔随机化方法研究广泛性焦虑障碍、重度抑郁、精神分裂症、睡眠障碍和银屑病发病风险的因果效应。

方法

在全基因组关联研究数据库（genome wide association study，GWAS）中筛选符合条件的四种精神心理特征及银屑病的单核苷酸多态性（single nucleotide polymorphism，SNP）。通过逆方差加权法(inverse-variance weighted, IVW)、加权中位数法(weighted median, WM)、MR-Egger等方法分析暴露与结局之间的发病风险，结果主要以IVW的P值、优势比(odds ratio, OR)和95%可信区间(confidence interval, CI)评估。采用IVW、MR-Egger、MR-PRESSO等方法进行敏感性分析。

结果

IVW结果显示精神分裂症与银屑病发病风险存在因果效应(OR=1.002，95%CI:1.000～1.003，P=0.023)。异质性检验中IVW法Cochran Q test检验的P=0.104，I2=19.60%，多效性检验中MR-PRESSO结果P=0.106，MR-Egger回归截距P=0.272，各项敏感性分析结果稳健，结果不存在异质性及多效性。未发现广泛性焦虑障碍(OR=1.000，95 %CI：0.999～1.001，P=0.791)、重度抑郁(OR=1.002，95%CI:0.998～1.005，P=0.246)、睡眠障碍(OR=0.999，95%CI:0.996～1.001，P=0.614)与银屑病发病存在因果关系。

结论

精神分裂症与银屑病风险存在因果关系，精神分裂症患者应加强对银屑病的筛查及预防，以降低患银屑病的风险。

银屑病  /  精神心理障碍  /  孟德尔随机化  /  因果效应
Objective

To study the causal effects of generalized anxiety disorder, major depressive disorder, schizophrenia, sleep disorder, and psoriasis by two-sample Mendelian randomization analysis.

Methods

The single nucleotide polymorphisms (SNPs) associated with four psychiatric traits and psoriasis were screened from the genome-wide association study (GWAS) data base. The relationships between exposures and outcome were analyzed by inverse variance weighting (IVW) method, weighted median (WM) method, and MR-Egger method. The results were mainly evaluated by P value of IVW, odds ratio (OR), and 95% confidence interval (CI). IVW, MR Egger, and MR-PRESSO were used for sensitivity analysis.

Results

The IVW results showed that there was a causal effect between schizophrenia and the risk of psoriasis (OR=1.002,95%CI: 1.000-1.003, P=0.023). In the heterogeneity test, the Cochran’s Q test of the IVW method reported P value of 0.104 and I2 of 19.06%, the MR-PRESSO test in the pleiotropy test reported P value of 0.106, and the regression intercept of MR Egger reported P value of 0.272. The sensitivity analysis results were robust, and the results did not show heterogeneity and pleiotropy. No causal relationship was found for generalized anxiety disorder (OR=1.000, 95%CI: 0.999-1.001, P=0.791), major depressive disorder (OR=1.002, 95%CI: 0.998-1.005, P=0.246), sleep disorder (OR=0.999, 95%CI: 0.996-1.001, P=0.614) with psoriasis.

Conclusion

There is a causal relationship between schizophrenia and the risk of psoriasis. Patients with schizophrenia should strengthen the screening and prevention of psoriasis in order to reduce the risk of psoriasis.

Psoriasis  /  Mental disorder  /  Mendelian randomization  /  Causal effect
杨玉洁, 莫念, 郑旭威, 唐斌, 罗倩倩, 毕洋, 陈海明, 卢传坚. 精神心理障碍与银屑病发病风险的孟德尔随机化研究. 现代预防医学, 2024 , 51 (3) : 401 -406 . DOI: 10.20043/j.cnki.MPM.202306258
Yu-jie YANG, Nian MO, Xu-wei ZHENG, Bin TANG, Qian-qian LUO, Yang BI, Hai-ming CHEN, Chuan-jian LU. A Mendelian randomization study on the relationship between mental disorders and the risk of psoriasis[J]. Modern Preventive Medicine, 2024 , 51 (3) : 401 -406 . DOI: 10.20043/j.cnki.MPM.202306258
正文
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精神心理障碍是指脑功能受生物、心理及社会因素影响而紊乱，导致个体认知、情感、意志和行为的障碍。银屑病是一种免疫介导的心身共病性疾病，大量研究表明银屑病与多种精神心理障碍密切相关，如自卑、抑郁症、焦虑症、睡眠障碍、精神分裂等[1-2]。一项基于2项回顾性队列研究和4项病例对照研究（约610万参与者）的系统回顾和荟萃分析结果显示：与没有精神分裂症的受试者相比，精神分裂症患者患银屑病的风险增加1.83倍[3]。而在丹麦13 675名银屑病患者的精神障碍风险研究中发现精神分裂症、双相情感障碍、单向抑郁症、广泛性焦虑症和人格障碍的风险比(hazardrate, HR)及95%CI分别为1.64（1.01～2.65）、2.33（1.59～3.41）、1.72（1.49～1.98）、1.88（1.08～3.30）、2.06（1.55～2.73）[4]，心理精神障碍相关疾病或症状在银屑病中的发病率升高。由于银屑病的损容性皮损常分布于躯体暴露部位，对患者的生活及社交造成较大困扰，使患者易产生自卑、紧张等心理反应。另外银屑病不可治愈及反复易发性的特点也加重了患者精神心理负担。虽然诸多研究已证明银屑病与精神心理障碍存在相关性，但两者之间共同的发病机制尚不明确，也鲜有研究对两者的发病风险进行因果推断。
孟德尔随机化（Mendelian randomisation, MR）研究是一种基于孟德尔独立分布定律的流行病学研究设计和数据分析方法，已被广泛用于评估暴露因素与疾病之间的因果效应。MR采用遗传变异，即单核苷酸多态性（single nucleotide polymorphisms,SNP）作为工具变量（instrumental variables, IVs），可以减少环境因素、疾病过程及其他因素对遗传变异的影响，增强暴露与结局的关系，并消除反向因果关系，从而加强因果推断，被称为“大自然的随机效应”[5-6]。本研究旨在运用MR方法，探讨不同心理精神障碍与银屑病发病的潜在因果关系及关联强度，从遗传联系层面探讨两者的发病风险，以期为临床加强筛查及防范提供新的依据。
1　对象与方法
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1.1　研究设计
本研究是基于全基因组关联研究数据库（genome wide association study，GWAS）汇总的公开数据进行的一项双样本MR研究。暴露因素分别为广泛性焦虑障碍、重度抑郁、精神分裂症、睡眠障碍，结局变量为银屑病。MR分析要求工具变量满足三个核心假设，见图1。
（1）相关性假设：工具变量与暴露因素相关。本研究中在全基因组水平上选择与暴露因素显著相关的SNPs（相关的阈值为：P<5×10-8），设置参数r2<0.001, kb=10 000以排除连锁不平衡的干扰[7]。若所得IVs过少不足以支撑分析，将相关性的阈值放宽至P<5×10-6[8-9]。IVs的相关性强度通过计算统计量F衡量，当统计量F>10时，IVs被认为与暴露具有强相关性，相关计算公式, ，其中N为暴露因素的样本量，K为所纳入工具变量个数，R2为工具变量解释的暴露因素变异比例，EAF是效应等位基因频率，β是效应值是β值的标准误差[10]。
（2）排他性假设：IVs仅通过暴露影响结果。若IVs通过其他途径对结局产生影响，则表示相关遗传变异具有多效性，多效性的存在违反排他性假设，因此本研究通过多种敏感性分析方法检测多效性以确保结果稳健，P>0.05表明结果不存在多效性。
（3）独立性假设：IVs与任何潜在影响暴露及结局的混杂因素无关。本研究通过Phenoscanner数据库查询并剔除与混杂因素相关的SNPs[11]。剔除混杂因素包括心血管性疾病（冠心病，心肌梗死、血压异常等）、代谢异常（肥胖、糖尿病、BMI、脂质代谢异常如总胆固醇、高密度脂蛋白等）、消化系统疾病（乳糜泻、炎症性肠病等）、骨关节疾病（风湿性关节炎、骨关节炎等）、生活习惯（抽烟、饮酒等）、与暴露相关的情绪因素（神经质、双向情感障碍、惊恐、烦躁、易激惹等）等。
1.2　研究数据
从GWAS汇总数据库（https://gwas.mrcieu.ac.uk）中获取本研究相关的遗传数据，所有遗传数据均为合法公开的研究数据。银屑病遗传数据是由Neale于2017年发布的，分别包含337 159例样本。精神分裂症相关遗传数据来源于Trubetskoy V于2022年发表的文章，分别包含127 906例样本[12]。其余数据基本信息见表1。
1.3　MR方法
使用逆方差加权法(inverse-variance weighted, IVW)、MR-Egger、加权中位数法(weighted median, WM)评估不同暴露因素与银屑病的因果效应。IVW方法综合了多种遗传变异的因果效应评估，且不受异质性和多效性的干扰，当所选择的遗传变异均为有效的IVs时，IVW将提供最精确的结果[9, 13]，因此以IVW的P值结果作为评价的主要指标。其他方法用以辅助评估MR效应值，其中不同方法的效应量（β值）方向与IVW一致表明结果稳健。
敏感性分析中的异质性检验主要采用IVW、“留一法”评估，并通过漏斗图可视化整体异质性。IVW异质性主要通过Cochran Q test和I2统计量进行检测，Cochran Q test统计量P>0.05，I2统计量小于40%则表明结果不存在异质性[14]。若存在异质性，则需采用随机效应IVW方法进行分析，若不存在异质性，则采用固定效应IVW分析方法[15]。
“留一法”是在逐个剔除SNP后，再次计算剩余SNP的效应量，以评估单个SNP的效应量对整体的影响，可检测造成整体效应值变化较大的SNP[16]。敏感性分析中的多效性检验主要采用MR-Egger、MR-PRESSO方法进行。MR-PRESSO方法能检测并校正可能存在的异常值，通过去除异常值来消除水平多效性[17]，P>0.05表明结果不存在多效性。MR-Egger采用基因结局系数对基因暴露系数的加权线性回归，因果效应的估计用线性回归的斜率表示，遗传变异的平均水平多效性效应的估计值用截距表示[18]，P>0.05表明结果不存在多效性。MR分析均在R软件(4.2.1版本)中的 Two Sample MR软件包中实现，检验水准α=0.05。
2　结果
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2.1　重度抑郁与银屑病风险的因果效应
重度抑郁数据以P<5×10-8为筛选阈值，在排除连锁不平衡及删除回文序列后提取到45个SNPs，经过筛选和剔除后共纳入33个SNPs作为研究的IVs，分析结果未发现重度抑郁与银屑病的发病间存在因果关系(OR=1.002，95%CI: 0.998～1.005；PIVW=0.246，PEgger=0.934，PWM=0.453)。
2.2　广泛性焦虑障碍与银屑病风险的因果效应
广泛性焦虑障碍以P<5×10-8为筛选阈值未提取到符合条件的SNPs，将阈值调整至P<5×10-6后，纳入7个符合筛选条件的SNPs，分析结果未发现广泛性焦虑障碍与银屑病的发病间存在因果关系(OR=1.000，95%CI：0.999～1.001；PIVW=0.791，PEgger=0.212，PWM=0.215)。
2.3　睡眠障碍与银屑病风险的因果效应
睡眠障碍以P<5×10-8为筛选阈值共提取到3个SNPs，放宽阈值至P<5×10-6，排除连锁不平衡及删除回文序列后获得25个SNPs，剔除混杂后最终纳入13个SNPs。分析结果未发现睡眠障碍与银屑病的发病间存在因果关系(OR=0.999，95%CI: 0.996～1.001；PIVW=0.614，PEgger=0.627，PWM=0.517)。
2.4　精神分裂症与银屑病风险的因果效应
精神分裂症数据中符合筛选阈值且无连锁不平衡的SNPs共154个，剔除与银屑病及混杂因素相关的SNPs后，共纳入57个SNPs作为本次研究的工具变量，计算F值均>10，表明所纳入的SNPs均为强工具变量。MR分析IVW结果提示精神分裂与银屑病存在相关性和正向因果关系（OR=1.002，95%CI: 1.000～1.003，P=0.023），MR-Egger（OR=1.005，95%CI: 0.998～1.012，P=0.128）、WM（OR=1.001，95%CI: 0.999～1.002，P=0.367）虽无统计学意义，但β值与IVW方向一致，见图2。异质性检验中IVW法Cochran Q检验P=0.104，I2=19.60%，结果不存在异质性。留一法未发现对因果关联估计值影响较大的SNPs，见图3，漏斗图中IVW分界线（浅蓝色）两侧散点分布较为均匀，提示整体结果不存在潜在偏倚，见图4。多效性检验中MR PRESSO分析结果P=0.106，未发现异常SNPs，MR-Egger回归的截距P=0.272，两种方法均表明暴露因素和结局变量不存在多效性。不同分析方法在4种精神心理障碍与银屑病风险的因果效应汇总，见图5。
3　讨论
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运用MR的方法，本研究分析了四种精神心理特征对银屑病的影响，包括广泛性焦虑障碍、重度抑郁、精神分裂症、睡眠障碍。IVW结果表明精神分裂症与银屑病发病风险存在正向因果效应(OR=1.002，95%CI: 1.000～1.003，P=0.023)，其余两种MR方法虽无统计学意义，但其结果β值方向与IVW一致，同样认可精神分裂患者的银屑病风险增高[19-20]。MR结果提示从遗传变异的角度银屑病是精神分裂症患者的危险因素，精神分裂症患者的银屑病患病风险增高。暂未发现广泛性焦虑障碍、重度抑郁、睡眠障碍与银屑病发病风险存在因果关系。
对银屑病及精神分裂症的遗传学研究发现在中国汉族人群中人类白细胞抗原基因区的五种变异最有可能与银屑病及精神分裂症相关，两者共同产生显著的风险效应（最高四分位数的比值比=6.03，P<2.0×10-16），且对银屑病和精神分裂症之间的共同遗传成分贡献最大的变体在抗原处理和细胞内质网中富集[21]。既往回顾性队列研究及观察性研究亦发现精神分裂症患者银屑病的15年累积发病率为2.82%，非精神分裂症患者为1.17%（P<0.001），且精神分裂症患者中银屑病的风险男性（矫正OR=1.60，95% CI：1.08～2.36）显著高于女性（矫正OR=1.15，95% CI：0.86～2.44）[3, 22-23]。本研究结果与先前研究相一致，即精神分裂症与银屑病发病相关（P<0.05），但两者的因果效应与先前的研究存在较大差异，可能是由于个体间的遗传变异较大所致，应对人群特征进行更为细致的分层分析，受限于原始的样本数据，暂无法实现。但不可否认的是，精神分裂症患者的银屑病风险增加，这种增加的风险可能需要精神及心理从业者对精神分裂症患者的皮肤健康给予更多的关注。本研究从遗传联系的角度建立了银屑病和精神分裂症之间的因果联系，可为临床精神障碍患者加强银屑病的筛查及防范提供新的依据。
银屑病属于心身疾病的范畴，睡眠障碍及抑郁焦虑在银屑病中尤为常见。在中国人群中，分别有13.9%和10.6%的银屑病患者患有中度至重度抑郁和焦虑[24]，10%～58%的银屑病患者会出现失眠，而失眠既是抑郁症的主要表现，又可增加行为障碍、抑郁及银屑病的风险[25]。当前研究注重对银屑病患者精神心理状况的筛查，缺乏对精神心理障碍患者皮肤疾病的关注，但对脑-皮轴的研究已证实不良精神心理因素可通过影响内分泌激素、神经介质、压力信号等影响银屑病的发展[26]。本研究中广泛性焦虑障碍、重度抑郁及睡眠障碍与银屑病发病结果与既往研究有所差异，考虑与以下因素相关，第一，在放宽筛选阈值后符合纳入标准的工具变量仍较少（睡眠障碍为25个，广泛性焦虑障碍为7个），因此结果可能受到一定的影响，应扩大样本并联合meta分析，增加符合筛选条件的工具变量的纳入。第二，MR分析中以遗传变异进行因果推断，基因型的分布时间早于后天暴露，受环境影响较小，而实际临床观察中精神心理障碍的发生发展受社会环境因素、个体心理敏感程度的影响，因此可能存在差异。
本研究虽为精神分裂症及银屑病的因果关联提供了统计学证据，但因果效应与临床研究仍存在一定差异，因此仍需通过大样本前瞻性队列研究进行综合探讨。
基金
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  • 国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202204)
  • 广东省科技计划项目(2020B1212030006; 2023B1212060063)
  • 广州市科技计划项目(202206080006; 202201020353)
文献
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doi: 10.20043/j.cnki.MPM.202306258
  • 接收时间：2023-06-13
  • 首发时间：2026-03-19
  • 出版时间：2024-02-10
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  • 收稿日期：2023-06-13
基金
国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202204)
广东省科技计划项目(2020B1212030006; 2023B1212060063)
广州市科技计划项目(202206080006; 202201020353)
作者信息
    1.广州中医药大学第二临床医学院，广东 广州 510006
    2.广东省中医院皮肤科，广东 广州 510120
    3.广州中医药大学第二附属医院省部共建中医湿证国家重点实验室，广东 广州 510120
    4.粤港澳中医药与免疫疾病研究联合实验室，广东 广州 510120
    5.广东省中医证候临床研究重点实验室，广东 广州 510120

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