Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis
Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis
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DOI：
10.1093/schbul/sbv028
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发表时间：
2015-09-01
影响因子：
6.6
通讯作者：
Dazzan, Paola
中科院分区：
文献类型：
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作者：
Mondelli, Valeria;Ciufolini, Simone;Dazzan, Paola
背景：皮质醇和炎症标志物在精神病发作时异常的报道越来越多。我们研究的主要目的是调查这些生物标志物预测首次发作精神病12周随访治疗反应的能力。研究方法：在一项纵向研究中，我们收集了68名首发精神病患者（和57名对照组）基线时的唾液和血液样本，并评估了12周后对临床医生主导的抗精神病药物治疗的反应。此外，我们在评估反应的同时对39名患者进行了重复生物学测量。在一天中的多个时间点收集唾液样品以测量昼夜皮质醇水平和皮质醇觉醒反应（CAR）;从血清样品分析白细胞介素（IL）-1 β、IL-2、IL-4、IL-6、IL-8、IL-10、肿瘤坏死因子-α和干扰素-γ（IFN-γ）水平。根据精神分裂症工作组共识的缓解症状标准，将患者分为无应答者（n = 38）和应答者（n = 30）。结果如下：在首次发作时，与应答者相比，无应答者具有显著较低的CAR（d = 0.6，P = .03）和较高的IL-6和IFN-γ水平（分别为d = 1.0，P = .003和d = 0.9，P = .02）。12周后，与应答者相比，无应答者显示出持续较低的CAR（P = .01）和较高的IL-6（P = .04）和IFN-γ（P = .05）。与对照组相比，这些异常在两个患者组中均存在，但在无应答者中更为明显。结论：皮质醇和炎症生物标志物在精神病发作时应被视为治疗反应的可能预测因子，以及开发新的治疗药物的潜在目标。
Background: Cortisol and inflammatory markers have been increasingly reported as abnormal at psychosis onset. The main aim of our study was to investigate the ability of these biomarkers to predict treatment response at 12 weeks follow-up in first episode psychosis. Methods: In a longitudinal study, we collected saliva and blood samples in 68 first episode psychosis patients (and 57 controls) at baseline and assessed response to clinician-led antipsychotic treatment after 12 weeks. Moreover, we repeated biological measurements in 39 patients at the same time we assessed the response. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, and interferon-gamma (IFN-gamma) levels were analyzed from serum samples. Patients were divided into Non-Responders (n = 38) and Responders (n = 30) according to the Remission symptom criteria of the Schizophrenia Working Group Consensus. Results: At first onset, Non-Responders had markedly lower CAR (d = 0.6, P = .03) and higher IL-6 and IFN-gamma levels (respectively, d = 1.0, P = .003 and d = 0.9, P = .02) when compared with Responders. After 12 weeks, Non-Responders show persistent lower CAR (P = .01), and higher IL-6 (P = .04) and IFN-gamma (P = .05) when compared with Responders. Comparison with controls show that these abnormalities are present in both patients groups, but are more evident in Non-Responders. Conclusions: Cortisol and inflammatory biomarkers at the onset of psychosis should be considered as possible predictors of treatment response, as well as potential targets for the development of novel therapeutic agents.