C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications
C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications
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DOI：
10.1038/mp.2015.87
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发表时间：
2016-04-01
影响因子：
11
通讯作者：
Berk, M.
中科院分区：
文献类型：
--
作者：
Fernandes, B. S.;Steiner, J.;Berk, M.
精神分裂症（SZ）的炎症假说认为炎症过程和神经免疫相互作用参与其发病机制，并可能支持其一些神经生物学相关性。SZ是造成最严重疾病负担的精神障碍，这不仅是由于其精神损害，而且还由于其显著的医学合并症。C-反应蛋白（CRP）是全球范围内常用的全身性炎症生物标志物。关于CRP在SZ中的行为，存在一些相互矛盾的结果。本研究的目的是验证周围CRP水平是否确实增加SZ，是否不同类别的抗精神病药物不同调节CRP水平，以及其水平是否与阳性和阴性精神病学相关。考虑到这一点，我们对SZ与健康受试者的血清和血浆CRP水平进行了荟萃分析。此外，我们评估了抗精神病药物使用前后CRP水平的纵向研究。我们对SZ患者CRP的荟萃分析共包括26项横断面或纵向研究，包括85000例受试者。无论是否使用抗精神病药物，SZ患者的CRP水平均中度升高，并且在精神病首次发作和SZ进展之间没有变化（g = 0.66，95%置信区间（95% CI）0.43至0.88，P < 0.001，24组间比较，n = 82 962）。外周血CRP水平升高的程度与阳性症状的严重程度相关，但与阴性症状的严重程度无关。CRP水平也与体重指数增加一致。相反，年龄越大，SZ患者和对照组之间CRP水平的差异越小。此外，CRP水平在开始抗精神病药物治疗后没有增加，无论这些药物是典型的还是非典型的抗精神病药物（g = 0.01，95% CI -0.20至0.22，P = 0.803，8组内比较，n = 713）。总之，我们的研究为SZ的炎症假说提供了进一步的证据。高CRP水平与SZ的发展和精神病性症状的加重之间是否存在因果关系，或者它们是否仅仅是SZ全身性低度炎症的标志物，仍有待澄清。
The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g = 0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P < 0.001, 24 between-group comparisons, n = 82 962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g = 0.01, 95% CI -0.20 to 0.22, P = 0.803, 8 within-group comparisons, n = 713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.