Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium.
University Department of Psychiatry, Campus Duffel, Antwerp, Belgium.
Front Immunol. 2020 Jan 17;10:2971. doi: 10.3389/fimmu.2019.02971. eCollection 2019.
Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology. Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1-2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers. Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5-17.5, all < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7-21.0, all < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers ( ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers ( ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms ( = 0.5, < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels ( = 0.5, < 0.010). The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness.
不同的免疫系统上调模式存在于精神病的急性与治疗后状态。我们探索了外周免疫系统和两种免疫相关神经内分泌途径（IDO 和 GTP-CH1 途径）中的状态和特质标志物在精神病患者的纵向样本中的存在情况。我们还评估了这些标志物与神经精神症状的相关性。 在一个包含 49 名急性精神病住院患者和 52 名匹配健康对照的跨诊断组中，测量了外周血标志物的血浆浓度。在入院后 48 小时内采集急性精神病发作患者的样本（在开始使用抗精神病药物之前），在 1-2 周后和 8 周治疗后再次采集样本。使用 HPLC 和 LC-MS/MS 分析测定犬尿氨酸、犬尿喹啉酸（KA）、3-羟基犬尿氨酸（3-HK）、喹啉酸（QA）、苯丙氨酸、酪氨酸、亚硝酸盐和新蝶呤的浓度。使用多重免疫测定法测定 CRP、CCL2（MCP1）和细胞因子的浓度。在基线和随访时进行 PANSS 访谈和认知测试。使用混合模型分析来确定特质和状态标志物。 患者在所有时间点的 CRP、CCL2、IL1RA 血浆浓度均显著升高，而 KA 和 KA/Kyn 浓度显著降低（F7.5-17.5，均 <0.001）。在急性精神病状态下发现了更高浓度的 IL6、IL8、IL1RA、TNFα 和 CCL2，以及更低浓度的 QA 和 3-HK（F8.7-21.0，均 <0.005），这些标志物在治疗后恢复正常。抗精神病药物治疗开始后，入院时的亚硝酸盐浓度急剧升高（F42.4，<0.001）。急性发作期间的 PANSS 阳性量表评分与促炎免疫标志物呈正相关（≥|0.5|），而阴性量表评分与 IDO 途径标志物呈负相关（≥|0.4|）。入院至随访期间 KA 和 3-HK 水平的正常化与阴性症状的较大改善相对应（=0.5，<0.030），而 SDST 评分的相对改善与 KA 水平的降低呈负相关（=0.5，<0.010）。 急性精神病状态的特征是免疫标志物的状态特异性增加和外周 IDO 途径标志物的减少。升高的 CRP、CCL2 和 IL1RA，以及降低的 KA 和 KA/Kyn 是精神病的特质标志物。
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