Relationship between Toxoplasma gondii infection and schizophrenia: a Meta-analysis
-
摘要:
目的 分析和评价弓形虫感染与精神分裂症发生风险的关系。 方法 计算机检索PubMed、EMBASE、Web of Science、Google Scholar、Cochrane Library、中国知网、万方数据知识服务平台、维普资讯中文期刊服务平台，收集1953年1月至2022年4月发表的弓形虫感染与精神分裂症发生风险的队列研究及其衍生类型的研究。 文献筛选、数据提取以及质量评价均由2名研究者独立完成，并采用R 4.1.1软件进行Meta分析。 结果 纳入9项研究（队列研究3项，巢式病例对照研究6项），样本量为55 352人。 Meta分析结果显示，弓形虫感染可使精神分裂症的发生风险增加47.1%［比值比（OR）＝1.471，95%置信区间（CI）：1.137～1.904，P=0.003］；异质性检验及亚组分析结果显示，研究异质性主要来源于发表时间、研究方法、弓形虫抗体检测方法以及精神分裂症诊断依据。 结论 本研究验证了弓形虫感染可增加精神分裂症的发生风险，为今后如何有效预防和控制弓形虫感染人群发生精神分裂症具有重要指导意义。 Abstract:Objective To analyze and assess the relationship between Toxoplasma gondii infection and the risk for schizophrenia. Methods PubMed, EMBASE, Web of Science, Google Scholar, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Databases for Chinese Technical Periodicals were used for the retrieval of literatures of cohort studies of the relationship between Toxoplasma gondii infection and the risk for schizophrenia and related studies published from January 1953 to April 2022. After two researchers independently screened the literature, extracted the data and evaluated the quality of the literatures included in the study, software R 4.1.1 was used for a Meta-analysis. Results Nine studies were included (3 cohort studies and 6 nested case-control studies) with a sample size of 55 352 people. The results of meta-analysis showed that Toxoplasma gondii infection increased the risk for schizophrenia by 47.1% [odds ratio (OR)=1.471, 95% confidence interval (CI): 1.137–1.904, P=0.003)]. The results of heterogeneity test and subgroup analysis showed that the heterogeneity of the study mainly came from publication time, research methods, Toxoplasma gondii antibody detection methods and diagnostic basis for schizophrenia. Conclusion This study confirmed that Toxoplasma gondii infection can increase the risk for schizophrenia, the study result is important for the effective prevention and control of schizophrenia in people infected with Toxoplasma gondii in the future. -
Key words:
- Toxoplasma gondii infection /
- Schizophrenia /
- Cohort study /
- Meta-analysis
-
图 2 弓形虫感染与精神分裂症发病风险关系的Meta分析
Figure 2. Meta-analysis on relationship between Toxoplasma gondii infection and schizophrenia
图 3 弓形虫感染与精神分裂症发病风险关系敏感性分析
Figure 3. Sensitivity analysis on relationship between Toxoplasma gondii infection and schizophrenia
图 5 剪补法填补后文献发表偏倚漏斗图
Figure 5. Publication bias funnel plot before and after fill by trim method
表 1 Meta分析纳入的9篇文献基本信息
Table 1. Basic characteristics of 9 studies included in Meta-analysis
纳入研究 国家 设计类型 样本量
（人）暴露组/病
例组人数
（人）对照组
人数
（人）弓形虫
抗体检
测方法精神分
裂症诊
断依据RR/HR/OR
（95%CI）调整的混杂因素 Pedersen MG 2011［15］ 丹麦 前瞻性队列研究 45 609 12 223 33 386 EIA ICD 1.420
（0.880～2.240）分娩时间、分娩年龄、父母精神病史和分娩时居住地 Lin HA 2020［16］ 中国 回顾性队列研究 1 295 259 1 036 ICD ICD 1.140
（0.200～6.590）年龄、性别、保险费、诊断季节、医院护理水平、城市化水平、Charlson共病指数 Sugden K 2016［17］ 新西兰 前瞻性队列研究 837 236 601 EIA DSM 1.310
（0.550～3.120）性别 Mortensen PB 2007［18］ 丹麦 巢式病例对照研究 755 71 684 EIA ICD 1.790
（1.010～3.150）性别、出生年份、出生地和精神障碍家族史 Xiao JC 2009［19］ 美国 巢式病例对照研究 466 120 346 EIA DSM 1.280
（0.830～1.970）城市和出生日期、种族/民族和性别 Brown AS 2005［20］ 美国 巢式病例对照研究 186 63 123 Sabin-
Feldman
染色试验ICD 2.610
（1.000～6.820）产妇年龄 Burgdorf KS 2019［21］ 丹麦 巢式病例对照研究 5 321 28 5 293 EIA ICD 2.780
（1.270～6.090）父母精神病史、性别和年龄 Blomström A 2012［22］ 瑞典 巢式病例对照研究 171 47 124 EIA DSM和ICD 2.100
（1.000～4.500）性别、出生日期和出生医院 Niebuhr DW 2008［23］ 美国 巢式病例对照研究 712 180 532 EIA ICD 1.040
（0.970～1.120）出生日期、入伍日期、性别、种族、兵役科室和可用的血清样本数量 注：文献检索时间范围为1953年1月至2022年4月；EIA. 酶免疫测定法；ICD. 疾病和有关健康问题的国际统计分类；DSM. 精神障碍统计与诊断手册；RR. 相对危险度；HR. 风险函数比；OR. 比值比；CI. 置信区间 
下载: 导出CSV
表 2 纳入研究的纽卡斯尔−渥太华量表质量评价
Table 2. Quality evaluation of studies involved with Newcastle-Ottawa Scale
研究 研究类型 研究对象的选择（分） 可比性（分） 结局（分） 质量评分（分） Pedersen MG 2011［15］ 前瞻性队列研究 3 2 3 8 Lin HA 2020［16］ 回顾性队列研究 4 2 3 9 Sugden K 2016［17］ 前瞻性队列研究 3 2 1 6 Mortensen PB 2007［18］ 巢式病例对照研究 2 2 3 7 Xiao JC 2009［19］ 巢式病例对照研究 4 2 3 9 Brown AS 2005［20］ 巢式病例对照研究 3 2 3 8 Burgdorf KS 2019［21］ 巢式病例对照研究 1 2 3 6 Blomström A 2012［22］ 巢式病例对照研究 3 2 2 7 Niebuhr DW 2008［23］ 巢式病例对照研究 3 2 3 8 注：满分为9分，7～9分为高质量，4～6分为中等质量，0～3分为低质量
下载: 导出CSV
表 3 弓形虫感染与精神分裂症发病风险关系亚组分析
Table 3. Subgroup analysis on relationship between Toxoplasma gondii infection and schizophrenia
分组因素 分组 文献数（篇） 异质性 效应模型 效应值 I 2值（%） Q值 P值 OR值（95%CI） P值 效应值 RR［15–16，21］ 3 11.9 2.270 0.322 FEM 1.660（1.123～2.454） 0.011 OR［17–20，22–23］ 6 54.6 11.010 0.051 REM 1.395（1.039～1.874） 0.027 研究地区 欧洲［15，18，21–22］ 4 0.0 2.330 0.507 FEM 1.780（1.318～2.404） < 0.001 亚洲［16］ 1 − − − − 1.140（0.199～6.544） 0.897 大洋洲［17］ 1 − − − − 1.310（0.550～3.120） 0.540 北美洲［19–20，23］ 3 53.8 4.330 0.115 REM 1.200（0.879～1.639） 0.252 发表时间 2010年以后［15–17，21–22］ 5 0.0 2.930 0.570 FEM 1.678（1.216～2.315） 0.002 2010年以前［18–20，23］ 4 60.8 7.650 0.054 REM 1.335（0.955～1.868） 0.091 研究方法 队列研究［15–17］ 3 0.0 0.070 0.964 FEM 1.380（0.925～2.059） 0.115 巢式病例对照研究［19–24］ 6 69.7 16.500 0.006 REM 1.585（1.119～2.246） 0.010 样本含量（人） ≥1000［15–16，21］ 3 11.9 2.270 0.322 FEM 1.660（1.123～2.455） 0.011 < 1000［17–20，22–23］ 6 54.6 11.010 0.051 REM 1.395（1.039～1.874） 0.027 研究质量 高［15-16，18-20，22-23］ 7 50.9 12.220 0.057 REM 1.381（1.063～1.794） 0.016 中［17，21］ 2 37.1 1.590 0.207 FEM 1.983（1.108～3.547） 0.021 弓形虫抗体检测方法 EIA［15，17–19，21–23］ 7 59.4 14.780 0.022 REM 1.420（1.093～1.845） 0.009 ICD［16］ 1 − − − − 1.140（0.199～6.544） 0.897 Sabin-Feldman染料试验［20］ 1 − − − − 2.610（0.999～6.816） 0.051 精神分裂症诊断依据 ICD［15–16，18，20–21，23］ 6 64.7 14.180 0.015 REM 1.538（1.070～2.212） 0.020 DSM［17］ 2 0.0 0.000 0.963 FEM 1.286（0.873～1.893） 0.203 ICD和DSM［22］ 1 − − − − 2.100（0.990～4.455） 0.266 注：FEM. 固定效应模型；REM. 随机效应模型；–. 无相关数据；RR.相对危险度；OR. 比值比；CI. 置信区间
下载: 导出CSV
-
[1] 欧阳净, 陈耀凯. 弓形虫感染与精神分裂症相关性的研究进展[J]. 中国寄生虫学与寄生虫病杂志,2019,37(1):102–106. DOI:10.12140/j.issn.1000−7423.2019.01.019.Ouyang J, Chen YK. Progress in research on the correlation between Toxoplasma gondii infection and schizophrenia[J]. Chin J Parasitol Parasit Dis, 2019, 37(1): 102–106. DOI: 10.12140/j.issn.1000−7423.2019.01.019. [2] Charlson FJ, Ferrari AJ, Santomauro DF, et al. Global epidemiology and burden of schizophrenia: Findings from the global burden of disease study 2016[J]. Schizophr Bull, 2018, 44(6): 1195–1203. DOI: 10.1093/schbul/sby058. [3] Radua J, Ramella-Cravaro V, Ioannidis JPA, et al. What causes psychosis? An umbrella review of risk and protective factors[J]. World Psychiatry, 2018, 17(1): 49–66. DOI: 10.1002/wps.20490. [4] 胡一菲. 关于精神分裂症患者家属的负担研究[D]. 广州: 华南理工大学, 2019.Hu YF. A Study on the burden of family members of schizophrenic patients [D]. Guangzhou: South China University of Technology, 2019. [5] Nicolle C, Manceaux LH. On a leishman body infection (or related organisms) of the gondi. 1908[J]. Int J Parasitol, 2009, 39(8): 863–864. DOI: 10.1016/j.ijpara.2009.02.001. [6] Milne G, Webster JP, Walker M. Toxoplasma gondii: An underestimated threat[J]. Trends Parasitol, 2020, 36(12): 959–969. DOI: 10.1016/j.pt.2020.08.005. [7] Hernandez AV, Thota P, Pellegrino D, et al. A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim-sulfamethoxazole a real option[J]. HIV Med, 2017, 18(2): 115–124. DOI: 10.1111/hiv.12402. [8] Torrey EF, Bartko JJ, Lun ZR, et al. Antibodies to Toxoplasma gondii in patients with schizophrenia: a Meta-analysis[J]. Schizophr Bull, 2007, 33(3): 729–736. DOI: 10.1093/schbul/sbl050. [9] Sutterland AL, Fond G, Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and Meta-analysis[J]. Acta Psychiatr Scand, 2015, 132(3): 161–179. DOI: 10.1111/acps.12423. [10] 黎文鸿, 武丽, 李紫薇, 等. 弓形虫感染与精神分裂症的两样本孟德尔随机化研究[J]. 现代预防医学,2022,49(7):1153–1158. DOI:10.3969/j.issn.1003−8507.2022.7.xdyfyx202207001.Li WH, Wu L, Li ZW, et al. Analysis of the association between toxoplasma gondii infection and schizophrenia with two-sample Mendelian randomization method[J]. Mod Prev Med, 2022, 49(7): 1153–1158. DOI: 10.3969/j.issn.1003−8507.2022.7.xdyfyx202207001. [11] Arias I, Sorlozano A, Villegas E, et al. Infectious agents associated with schizophrenia: a Meta-analysis[J]. Schizophr Res, 2012, 136(1/3): 128–136. DOI: 10.1016/j.schres.2011.10.026. [12] Valle R. Schizophrenia in ICD-11: Comparison of ICD-10 and DSM-5[J]. Rev Psiquiatr Salud Ment (Engl Ed), 2020, 13(2): 95–104. DOI: 10.1016/j.rpsm.2020.01.001. [13] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in Meta-analyses[J]. Eur J Epidemiol, 2010, 25(9): 603–605. DOI: 10.1007/s10654−010−9491−z. [14] 王丹, 翟俊霞, 牟振云, 等. Meta分析中的异质性及其处理方法[J]. 中国循证医学杂志,2009,9(10):1115–1118. DOI:10.3969/j.issn.1672−2531.2009.10.013.Wang D, Zhai JX, Mou ZY, et al. Discussing on the research of heterogeneity in Meta-analysis[J]. Chin J Evid-Based Med, 2009, 9(10): 1115–1118. DOI: 10.3969/j.issn.1672−2531.2009.10.013. [15] Pedersen MG, Stevens H, Pedersen CB, et al. Toxoplasma infection and later development of schizophrenia in mothers[J]. Am J Psychiatry, 2011, 168(8): 814–821. DOI: 10.1176/appi.ajp.2011.10091351. [16] Lin HA, Chien WC, Huang KY, et al. Infection with Toxoplasma gondii increases the risk of psychiatric disorders in Taiwan: a nationwide population-based cohort study[J]. Parasitology, 2020, 147(13): 1577–1586. DOI: 10.1017/S0031182020001183. [17] Sugden K, Moffitt TE, Pinto L, et al. Is Toxoplasma gondii infection related to brain and behavior impairments in humans? Evidence from a population-representative birth cohort[J]. PLoS One, 2016, 11(2): e0148435. DOI: 10.1371/journal.pone.0148435. [18] Mortensen PB, Nørgaard-Pedersen B, Waltoft BL, et al. Toxoplasma gondii as a risk factor for early-onset schizophrenia: analysis of filter paper blood samples obtained at birth[J]. Biol Psychiatry, 2007, 61(5): 688–693. DOI: 10.1016/j.biopsych.2006.05.024. [19] Xiao JC, Buka SL, Cannon TD, et al. Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring[J]. Microbes Infect, 2009, 11(13): 1011–1018. DOI: 10.1016/j.micinf.2009.07.007. [20] Brown AS, Schaefer CA, Quesenberry CP, et al. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring[J]. Am J Psychiatry, 2005, 162(4): 767–773. DOI: 10.1176/appi.ajp.162.4.767. [21] Burgdorf KS, Trabjerg BB, Pedersen MG, et al. Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders[J]. Brain Behav Immun, 2019, 79: 152–158. DOI: 10.1016/j.bbi.2019.01.026. [22] Blomström Å, Karlsson H, Wicks S, et al. Maternal antibodies to infectious agents and risk for non-affective psychoses in the offspring-a matched case-control study[J]. Schizophr Res, 2012, 140(1/3): 25–30. DOI: 10.1016/j.schres.2012.06.035. [23] Niebuhr DW, Millikan AM, Cowan DN, et al. Selected infectious agents and risk of schizophrenia among U. S. military personnel[J]. Am J Psychiatry, 2008, 165(1): 99–106. DOI: 10.1176/appi.ajp.2007.06081254. [24] Torrey EF, Bartko JJ, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: an update[J]. Schizophr Bull, 2012, 38(3): 642–647. DOI: 10.1093/schbul/sbs043. [25] Bergersen KV, Barnes A, Worth D, et al. Targeted transcriptomic analysis of C57BL/6 and BALB/c mice during progressive chronic Toxoplasma gondii infection reveals changes in host and parasite gene expression relating to neuropathology and resolution[J]. Front Cell Infect Microbiol, 2021, 11: 645778. DOI: 10.3389/fcimb.2021.645778. [26] English ED, Boyle JP. Impact of engineered expression of mitochondrial association factor 1b on Toxoplasma gondii infection and the host response in a mouse model[J]. mSphere, 2018, 3(5): e00471–18. DOI: 10.1128/mSphere.00471−18. [27] Wang AW, Avramopoulos D, Lori A, et al. Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2019, 92: 133–147. DOI: 10.1016/j.pnpbp.2018.12.019. [28] Nayeri T, Sarvi S, Daryani A. Toxoplasmosis: Targeting neurotransmitter systems in psychiatric disorders[J]. Metab Brain Dis, 2022, 37(1): 123–146. DOI: 10.1007/s11011−021−00824−2. [29] Xiao JC. Toxoplasma-induced behavioral changes: an aspecific consequence of neuroinflammation[J]. Trends Parasitol, 2020, 36(4): 317–318. DOI: 10.1016/j.pt.2020.01.005. [30] Karlsson H, Dal H, Gardner RM, et al. Birth month and later diagnosis of schizophrenia. A population-based cohort study in Sweden[J]. J Psychiatr Res, 2019, 116: 1–6. DOI: 10.1016/j.jpsychires.2019.05.025. [31] Swanenburg M, Gonzales JL, Bouwknegt M, et al. Large-scale serological screening of slaughter pigs for Toxoplasma gondii infections in the Netherlands during five years (2012–2016): Trends in seroprevalence over years, seasons, regions and farming systems[J]. Vet Parasitol, 2019, 276: 100017. DOI: 10.1016/j.vpoa.2019.100017. [32] Zhu YT, Webster MJ, Murphy CE, et al. Distinct phenotypes of inflammation associated macrophages and microglia in the prefrontal cortex schizophrenia compared to controls[J]. Front Neurosci, 2022, 16: 858989. DOI: 10.3389/fnins.2022.858989. [33] Blanchard N, Dunay IR, Schlüter D. Persistence of Toxoplasma gondii in the central nervous system: a fine-tuned balance between the parasite, the brain and the immune system[J]. Parasite Immunol, 2015, 37(3): 150–158. DOI: 10.1111/pim.12173. [34] Vlatkovic S, Sagud M, Svob Strac D, et al. Increased prevalence of Toxoplasma gondii seropositivity in patients with treatment-resistant schizophrenia[J]. Schizophr Res, 2018, 193: 480–481. DOI: 10.1016/j.schres.2017.08.006. [35] Kezai AM, Lecoeur C, Hot D, et al. Association between schizophrenia and Toxoplasma gondii infection in Algeria[J]. Psychiatry Res, 2020, 291: 113293. DOI: 10.1016/j.psychres.2020.113293. [36] Grada S, Mihu AG, Petrescu C, et al. Toxoplasma gondii infection in patients with psychiatric disorders from western Romania[J]. Medicina (Kaunas), 2022, 58(2): 208. DOI: 10.3390/medicina58020208. [37] Morais FB, Arantes TEFE, Muccioli C. Seroprevalence and manifestations of ocular toxoplasmosis in patients with schizophrenia[J]. Ocul Immunol Inflamm, 2019, 27(1): 134–137. DOI: 10.1080/09273948.2017.1408843. [38] Yin K, Xu C, Zhao GH, et al. Epigenetic manipulation of psychiatric behavioral disorders induced by Toxoplasma gondii[J]. Front Cell Infect Microbiol, 2022, 12: 803502. DOI: 10.3389/fcimb.2022.803502. -
点击查看大图
图(5) / 表(3)
计量
- 文章访问数: 115
- HTML全文浏览量: 55
- PDF下载量: 21
- 被引次数: 0
