Abstract：
BACKGROUND: There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants.
METHODS: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately.
RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]).
CONCLUSIONS: When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.
METHODS: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately.
RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]).
CONCLUSIONS: When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.
摘要：
背景：有一些证据表明炎症与精神障碍的发病机制有关。可溶性尿激酶型纤溶酶原激活物受体（suPAR）是慢性炎症的生物标志物，与更广泛使用的生物标志物相比，它提供了更稳定的全身性炎症指标。这篇综述旨在综合研究，测量患有精神疾病的个体的suPAR浓度，以确定与健康参与者相比，这些浓度是否发生了变化。
方法：从开始到2023年10月，对五个相关数据库进行了全面的文献检索(PubMed，WebofScience,Embase,Scopus,APAPsychInfo）。进行随机效应荟萃分析以比较患有任何精神疾病的个体相对于对照的血液suPAR水平(即血浆或血清)的标准化平均差异。对精神分裂症或其他精神病和抑郁症患者的suPAR水平进行了单独的荟萃分析。使用纽卡斯尔渥太华量表评估偏倚风险。事后敏感性分析包括排除偏倚高风险研究，以及分别测量血清或血浆中suPAR浓度的研究分析。
结果：文献检索确定了149条记录。筛选了10项全文研究的资格，并纳入了9项研究进行审查。初步分析显示，与对照组相比，患有任何精神疾病的个体之间的suPAR水平没有显着差异（k=7，SMD=0.42，95％CI[-0.20，1.04]）。然而,与对照组相比,抑郁症患者的suPAR水平升高(k=3,SMD=0.61,95%CI[0.34,0.87]).同样，二级分析显示，当排除偏倚高风险研究时，没有证据表明患有任何精神疾病的个体的suPAR水平存在显着差异(k=6，SMD=0.54，95%CI[-0.14，1.22])，但发现精神分裂症或其他精神病患者的suPAR浓度升高(k=3,SMD=0.98,95%CI[0.39,1.58]).此外，分析血浆suPAR浓度的研究发现，相对于对照组，患有任何精神疾病的个体的血浆suPAR水平升高（k=5，SMD=0.84，95％CI[0.38，1.29]），而测量任何精神疾病患者血清suPAR水平的研究均未发现差异(k=2,SMD=-0.61,95%CI[-1.27,0.04]).对于等离子体，精神分裂症或其他精神病患者的suPAR浓度也升高(k=3,SMD=0.98,95%CI[0.39,1.58]).
结论：当考虑仅测量血清或仅测量血浆suPAR的研究时，在精神疾病组之间观察到suPAR水平没有显着差异，尽管在中度至重度抑郁症患者中检测到suPAR水平显著升高。然而,与对照组相比，患有任何精神疾病的患者的血浆suPAR水平显着升高，而血清样本没有发现差异。精神分裂症或其他精神病性障碍也有类似的发现。血浆发现表明，慢性炎症失调可能导致精神分裂症和抑郁症的病理。需要进一步的纵向研究来充分阐明该标记物在这些疾病的精神病理学中的作用。
方法：从开始到2023年10月，对五个相关数据库进行了全面的文献检索(PubMed，WebofScience,Embase,Scopus,APAPsychInfo）。进行随机效应荟萃分析以比较患有任何精神疾病的个体相对于对照的血液suPAR水平(即血浆或血清)的标准化平均差异。对精神分裂症或其他精神病和抑郁症患者的suPAR水平进行了单独的荟萃分析。使用纽卡斯尔渥太华量表评估偏倚风险。事后敏感性分析包括排除偏倚高风险研究，以及分别测量血清或血浆中suPAR浓度的研究分析。
结果：文献检索确定了149条记录。筛选了10项全文研究的资格，并纳入了9项研究进行审查。初步分析显示，与对照组相比，患有任何精神疾病的个体之间的suPAR水平没有显着差异（k=7，SMD=0.42，95％CI[-0.20，1.04]）。然而,与对照组相比,抑郁症患者的suPAR水平升高(k=3,SMD=0.61,95%CI[0.34,0.87]).同样，二级分析显示，当排除偏倚高风险研究时，没有证据表明患有任何精神疾病的个体的suPAR水平存在显着差异(k=6，SMD=0.54，95%CI[-0.14，1.22])，但发现精神分裂症或其他精神病患者的suPAR浓度升高(k=3,SMD=0.98,95%CI[0.39,1.58]).此外，分析血浆suPAR浓度的研究发现，相对于对照组，患有任何精神疾病的个体的血浆suPAR水平升高（k=5，SMD=0.84，95％CI[0.38，1.29]），而测量任何精神疾病患者血清suPAR水平的研究均未发现差异(k=2,SMD=-0.61,95%CI[-1.27,0.04]).对于等离子体，精神分裂症或其他精神病患者的suPAR浓度也升高(k=3,SMD=0.98,95%CI[0.39,1.58]).
结论：当考虑仅测量血清或仅测量血浆suPAR的研究时，在精神疾病组之间观察到suPAR水平没有显着差异，尽管在中度至重度抑郁症患者中检测到suPAR水平显著升高。然而,与对照组相比，患有任何精神疾病的患者的血浆suPAR水平显着升高，而血清样本没有发现差异。精神分裂症或其他精神病性障碍也有类似的发现。血浆发现表明，慢性炎症失调可能导致精神分裂症和抑郁症的病理。需要进一步的纵向研究来充分阐明该标记物在这些疾病的精神病理学中的作用。
