Abstract：
Increased peripheral cytokine levels have been observed in patients with psychotic disorders; however, large high-quality studies with individually matched healthy controls have been lacking regarding cytokines in cerebrospinal fluid (CSF) of individuals with psychotic disorders.
Patients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22-29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria\'s except for the psychiatric diagnoses. All participants were aged 18-50 years and individuals with neurological or immunological disorders were excluded. CSF cytokines were analyzed with MesoScale V-PLEX neuroinflammation panel. Co-primary outcomes were CSF interleukin-6 (IL-6) and IL-8.
We included 104 patients and 104 healthy controls, matching on age, sex and BMI. No significant differences were found for the primary outcomes IL-6 (relative mean difference (MD): 0.97, 95 %CI: 0.84-1.11, p = 0.637) or IL-8 (MD: 1.01, 95 %CI: 0.93-1.09, p = 0.895). Secondary analyses found patients to have higher IL-4 (MD: 1.30, 95 %CI: 1.04-1.61, p = 0.018), a trend towards higher IFN-γ (MD: 1.26, 95 %CI: 0.99-1.59, p = 0.056), and lower IL-16 (MD: 0.83, 95 %CI: 0.74-0.94, p = 0.004) than healthy controls, though not significant after correction for multiple testing. IL-8 and IL-16 were found positively associated with CSF white blood cells and CSF/serum albumin ratio. The study was limited by 77.9 % of the patients being on antipsychotic treatment at time of intervention, and that levels of nine of the 26 cytokines were below lower limit of detection (LLOD) in >50 % of samples; however, for the primary outcomes IL-6 and IL-8 more than 99.5 % of the samples were above LLOD and for IL-8 all samples exceeded the lower limit of quantification (LLOQ).
We found no evidence of increased IL-6 and IL-8 in patients with recent-onset psychotic disorders in contrary to previous findings in meta-analyses of CSF cytokines. Secondary analyses found indication of higher IL-4, decreased IL-16, and borderline increased IFN-γ in patients, neither of which have previously been reported on in CSF analyses of individuals with psychotic disorders.
Patients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22-29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria\'s except for the psychiatric diagnoses. All participants were aged 18-50 years and individuals with neurological or immunological disorders were excluded. CSF cytokines were analyzed with MesoScale V-PLEX neuroinflammation panel. Co-primary outcomes were CSF interleukin-6 (IL-6) and IL-8.
We included 104 patients and 104 healthy controls, matching on age, sex and BMI. No significant differences were found for the primary outcomes IL-6 (relative mean difference (MD): 0.97, 95 %CI: 0.84-1.11, p = 0.637) or IL-8 (MD: 1.01, 95 %CI: 0.93-1.09, p = 0.895). Secondary analyses found patients to have higher IL-4 (MD: 1.30, 95 %CI: 1.04-1.61, p = 0.018), a trend towards higher IFN-γ (MD: 1.26, 95 %CI: 0.99-1.59, p = 0.056), and lower IL-16 (MD: 0.83, 95 %CI: 0.74-0.94, p = 0.004) than healthy controls, though not significant after correction for multiple testing. IL-8 and IL-16 were found positively associated with CSF white blood cells and CSF/serum albumin ratio. The study was limited by 77.9 % of the patients being on antipsychotic treatment at time of intervention, and that levels of nine of the 26 cytokines were below lower limit of detection (LLOD) in >50 % of samples; however, for the primary outcomes IL-6 and IL-8 more than 99.5 % of the samples were above LLOD and for IL-8 all samples exceeded the lower limit of quantification (LLOQ).
We found no evidence of increased IL-6 and IL-8 in patients with recent-onset psychotic disorders in contrary to previous findings in meta-analyses of CSF cytokines. Secondary analyses found indication of higher IL-4, decreased IL-16, and borderline increased IFN-γ in patients, neither of which have previously been reported on in CSF analyses of individuals with psychotic disorders.
摘要：
背景：在精神病患者中观察到外周细胞因子水平升高；然而，对于精神病患者的脑脊液(CSF)中的细胞因子,缺乏针对个体匹配健康对照的大型高质量研究.
方法：诊断为非器质性，纳入前一年内的非情感性精神障碍(ICD-10:F20/22-29)和年龄和性别匹配的健康对照均按照相同的纳入和排除标准纳入,但精神病学诊断除外.所有参与者年龄为18-50岁，排除患有神经或免疫疾病的个体。用MesoScalV-PLEX神经炎症小组分析CSF细胞因子。共同的主要结果是CSF白介素-6（IL-6）和IL-8。
结果：我们包括104名患者和104名健康对照，年龄匹配，性别和BMI。主要结果IL-6（相对平均差（MD）：0.97，95CI：0.84-1.11，p=0.637）或IL-8（MD：1.01，95CI：0.93-1.09，p=0.895）没有发现显着差异。次要分析发现患者具有较高的IL-4（MD：1.30，95CI：1.04-1.61，p=0.018），IFN-γ升高的趋势（MD：1.26，95CI：0.99-1.59，p=0.056），与健康对照组相比，IL-16较低（MD：0.83，95CI：0.74-0.94，p=0.004），虽然在多次测试校正后并不显著。发现IL-8和IL-16与CSF白细胞和CSF/血清白蛋白比率呈正相关。这项研究的局限性在于，77.9％的患者在干预时接受了抗精神病药物治疗，在>50%的样本中，26种细胞因子中的9种水平低于检测下限(LLOD)；然而，对于主要结局,超过99.5%的样本IL-6和IL-8高于LLOD,对于IL-8,所有样本均超过定量下限(LLOQ).
结论：我们没有发现新发作的精神病患者IL-6和IL-8增加的证据，这与先前在CSF细胞因子的荟萃分析中的发现相反。二次分析发现患者IL-4升高，IL-16降低和IFN-γ临界增加的迹象，以前在对精神病患者的CSF分析中都没有报道过这两种情况。
方法：诊断为非器质性，纳入前一年内的非情感性精神障碍(ICD-10:F20/22-29)和年龄和性别匹配的健康对照均按照相同的纳入和排除标准纳入,但精神病学诊断除外.所有参与者年龄为18-50岁，排除患有神经或免疫疾病的个体。用MesoScalV-PLEX神经炎症小组分析CSF细胞因子。共同的主要结果是CSF白介素-6（IL-6）和IL-8。
结果：我们包括104名患者和104名健康对照，年龄匹配，性别和BMI。主要结果IL-6（相对平均差（MD）：0.97，95CI：0.84-1.11，p=0.637）或IL-8（MD：1.01，95CI：0.93-1.09，p=0.895）没有发现显着差异。次要分析发现患者具有较高的IL-4（MD：1.30，95CI：1.04-1.61，p=0.018），IFN-γ升高的趋势（MD：1.26，95CI：0.99-1.59，p=0.056），与健康对照组相比，IL-16较低（MD：0.83，95CI：0.74-0.94，p=0.004），虽然在多次测试校正后并不显著。发现IL-8和IL-16与CSF白细胞和CSF/血清白蛋白比率呈正相关。这项研究的局限性在于，77.9％的患者在干预时接受了抗精神病药物治疗，在>50%的样本中，26种细胞因子中的9种水平低于检测下限(LLOD)；然而，对于主要结局,超过99.5%的样本IL-6和IL-8高于LLOD,对于IL-8,所有样本均超过定量下限(LLOQ).
结论：我们没有发现新发作的精神病患者IL-6和IL-8增加的证据，这与先前在CSF细胞因子的荟萃分析中的发现相反。二次分析发现患者IL-4升高，IL-16降低和IFN-γ临界增加的迹象，以前在对精神病患者的CSF分析中都没有报道过这两种情况。
