Department of Neurobiology and Affiliated Mental Health Center, Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, Zhejiang, China.
Curr Neuropharmacol. 2024;22(1):159-167. doi: 10.2174/1570159X21666230104090046.
Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study.
Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response.
At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly ( < 0.05). Lower baseline TWBCc predicted greater reductions in Positive and Negative Syndrome Scale (PANSS) total and negative scores over time ( < 0.05). We found significant mediation of TWBCc for effects of waist circumference, fasting low-density lipoprotein cholesterol, and glucose on reductions in PANSS total scores and PANSS negative subscale scores ( < 0.05).
TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.
全白细胞计数(TWBCc)是慢性和低度炎症的指标,与精神分裂症患者的临床症状和代谢改变有关。抗精神病药对 TWBCc 的影响、TWBCc 对药物反应的预测价值以及代谢改变的作用需要进一步研究。
精神分裂症患者随机分为利培酮、奥氮平、喹硫平、阿立哌唑、齐拉西酮、奋乃静和氟哌啶醇单药治疗 6 周的药物试验。我们反复测量了临床症状、TWBCc 和代谢指标(体重指数、血压、腰围、空腹血脂和血糖)。我们使用混合效应线性回归模型来测试 TWBCc 是否可以预测药物反应。采用中介分析来探讨代谢改变对药物反应的影响。
在基线时,先前接受治疗的患者 TWBCc 较高。利培酮、奥氮平、喹硫平、奋乃静和氟哌啶醇治疗后,TWBCc 显著降低(<0.05)。较低的基线 TWBCc 预测 PANSS 总分和阴性评分随时间的变化更大(<0.05)。我们发现 TWBCc 对腰围、空腹低密度脂蛋白胆固醇和血糖对 PANSS 总分和 PANSS 阴性子量表评分降低的影响具有显著的中介作用(<0.05)。
TWBCc 受精神分裂症患者中某些抗精神病药的影响,短期治疗后降低,长期治疗后升高。TWBCc 可预测药物反应,TWBCc 较低预示着对抗精神病药的反应更好。它还介导了某些代谢指标对阴性症状改善的影响。这表明代谢状态可能通过炎症影响临床表现。