Abstract：
There is a paucity of biomarkers for the prediction of treatment response in schizophrenia. In this study, we aimed to investigate whether diminished antipsychotic treatment response in relapsed versus first-episode schizophrenia can be revealed and predicted by a panel of blood-based biomarkers. A cross-sectional cohort consisting of 655 schizophrenia patients at different episodes and 606 healthy controls, and a longitudinal cohort including 52 first-episode antipsychotic-naïve schizophrenia patients treated with the same antipsychotic drugs during the 5-year follow-up of their first three episodes were enrolled. Plasma biomarker changes and symptom improvement were compared between the drug-free phase of psychosis onset and after 4 weeks of atypical antipsychotic drug (AAPD) treatment. In response to treatment, the extent of changes in the biomarkers of bioenergetic, purinergic, phospholipid and neurosteroid metabolisms dwindled down as number of episode and illness duration increased in relapsed schizophrenia. The changes of creatine, inosine, progesterone, allopregnanolone, cortisol and PE(16:0/22:6) were significantly correlated with the improvement of symptomatology. Inosine and progesterone at baseline were shown to be strong predictive biomarkers of treatment response. The results suggest that AAPD treatment response is diminished in the context of relapse, and our findings open new avenues for understanding the pathophysiology of treatment-resistance schizophrenia.
摘要：
缺乏用于预测精神分裂症治疗反应的生物标志物。在这项研究中,我们的目的是研究一组基于血液的生物标志物是否可以揭示和预测复发性与首发精神分裂症患者抗精神病药物治疗反应的减弱.一个由655名不同发作的精神分裂症患者和606名健康对照组成的横断面队列，纳入了一项纵向队列,包括52例首发抗精神病药物初治精神分裂症患者,在前3次发作的5年随访期间接受相同抗精神病药物治疗.在精神病发作的无药阶段和非典型抗精神病药物（AAPD）治疗4周后，比较了血浆生物标志物的变化和症状的改善。为了应对治疗，生物能生物标志物的变化程度，嘌呤能,在复发性精神分裂症中,随着发作次数和病程的增加,磷脂和神经类固醇代谢下降.肌酸的变化，肌苷,黄体酮,别孕烯醇酮,皮质醇和PE（16：0/22：6）与症状学的改善显着相关。基线时的肌苷和孕酮被证明是治疗反应的强预测性生物标志物。结果表明，在复发的情况下，AAPD治疗反应减弱，我们的发现为理解治疗抗性精神分裂症的病理生理学开辟了新的途径.
