Mondelli Valeria, Ciufolini Simone, Belvederi Murri Martino, Bonaccorso Stefania, Di Forti Marta, Giordano Annalisa, Marques Tiago R, Zunszain Patricia A, Morgan Craig, Murray Robin M, Pariante Carmine M, Dazzan Paola
Department of Psychological Medicine, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK; National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK;
National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK; Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK;
Schizophr Bull. 2015 Sep;41(5):1162-70. doi: 10.1093/schbul/sbv028. Epub 2015 Mar 31.
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.
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)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ (IFN-γ) 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.
At first onset, Non-Responders had markedly lower CAR (d = 0.6, P = .03) and higher IL-6 and IFN-γ 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-γ (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.
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.
越来越多的报告称，在精神病发作时皮质醇和炎症标志物会出现异常。我们研究的主要目的是调查这些生物标志物在首发精神病患者12周随访期预测治疗反应的能力。
在一项纵向研究中，我们在基线时收集了68例首发精神病患者（以及57名对照者）的唾液和血液样本，并在12周后评估了对临床医生主导的抗精神病药物治疗的反应。此外，在评估反应的同时，我们对39例患者重复进行了生物学测量。在一天中的多个时间点收集唾液样本，以测量昼夜皮质醇水平和皮质醇觉醒反应（CAR）；从血清样本中分析白细胞介素（IL）-1β、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缓解症状标准，将患者分为无反应者（n = 38）和反应者（n = 30）。
在首次发病时，与反应者相比，无反应者的CAR明显更低（d = 0.6，P = 0.03），IL-6和IFN-γ水平更高（分别为d = 1.0，P = 0.003和d = 0.9，P = 0.02）。12周后，与反应者相比，无反应者的CAR持续较低（P = 0.01），IL-6（P = 0.04）和IFN-γ（P = 0.05）更高。与对照者比较表明，这些异常在两组患者中均存在，但在无反应者中更明显。
精神病发作时的皮质醇和炎症生物标志物应被视为治疗反应的可能预测指标，以及新型治疗药物开发的潜在靶点。
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