Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA.
Schizophr Res. 2013 Aug;148(1-3):130-7. doi: 10.1016/j.schres.2013.05.018. Epub 2013 Jun 6.
The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies. The two cohorts were composed of the following: (1) n=141 schizophrenia, n=75 bipolar disorder, n=78 controls; (2) n=78 antipsychotic-naïve first-episode schizophrenia, n=38 medicated first-episode schizophrenia. sCD14 seropositivity conferred a 3.1-fold increased odds of association with schizophrenia (multivariate regressions, OR=3.09, p<0.0001) compared to controls. Case-control differences in sCD14 were not matched by LBP. Quantitative levels of LBP, but not sCD14, correlated with BMI in schizophrenia (R(2)=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R(2)=0.26-0.27, p<0.0001) and elevated in females compared to males (p<0.01). Antipsychotic treatment generally did not impact sCD14 or LBP levels except for significant correlations, especially sCD14, with gluten antibodies in antipsychotic-naïve schizophrenia (R(2)=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R(2)=0.37, p<0.001). In conclusion, these bacterial translocation markers produced discordant and complex patterns of activity, a finding that may reflect an imbalanced, activated innate immune state. Whereas both markers may upregulate following systemic exposure to Gram-negative bacteria, non-lipopolysaccharide-based monocyte activation, autoimmunity and metabolic dysfunction may also contribute to the observed marker profiles.
精神疾病炎症的起源尚不清楚。共生微生物从胃肠道屏障易位可导致持续低度免疫激活和/或炎症。我们测量了两个精神疾病队列的细菌易位血清学替代标志物（可溶性 CD14（sCD14）和脂多糖结合蛋白（LBP）），并将这些水平与 C 反应蛋白（CRP）、体重指数（BMI）、食物相关和自身抗体进行了比较。两个队列由以下人群组成：（1）n=141 例精神分裂症，n=75 例双相情感障碍，n=78 例对照组；（2）n=78 例抗精神病药初发精神分裂症，n=38 例药物初发精神分裂症。sCD14 阳性与精神分裂症的相关性为 3.1 倍（多元回归，OR=3.09，p<0.0001）。sCD14 和 LBP 与 BMI 在精神分裂症中呈正相关（R(2)=0.21，p<0.0001）。与对照组相比，sCD14 的病例对照差异与 LBP 不匹配。sCD14 和 LBP 在精神分裂症中也有一定的一致性，两者均与 CRP 显著相关（R(2)=0.26-0.27，p<0.0001），与女性相比，男性 sCD14 和 LBP 水平升高（p<0.01）。抗精神病药物治疗一般不会影响 sCD14 或 LBP 水平，除了在初发精神分裂症中，sCD14 与谷蛋白抗体有显著相关性（R(2)=0.27，p<0.0001）。在双相情感障碍中，sCD14 水平与抗组织转谷氨酰胺酶 IgG 显著相关（R(2)=0.37，p<0.001）。总之，这些细菌易位标志物表现出不一致和复杂的活性模式，这一发现可能反映了不平衡的、激活的固有免疫状态。虽然这两种标志物都可能在全身接触革兰氏阴性菌后上调，但非脂多糖单核细胞激活、自身免疫和代谢功能障碍也可能导致观察到的标志物谱。
