间歇性θ爆发刺激治疗精神分裂症持续性阴性症状的效果及其与外周炎症指标变化的关系

(1.Xuzhou Oriental Hospital of Xuzhou Medical University, Xuzhou? 221004, China;2.Xuzhou Medical University, Xuzhou? 221004, China;

中文关键词:  精神分裂症  持续性阴性症状  间歇性θ爆发刺激  炎症

英文关键词:schizophrenia, persistent negative symptoms, intermittent theta burst stimulation, inflammation[Funded by National Natural Science Foundation of China (82371510), Social Development Project of Jiangsu Province (BE2023668) Clinical trial registration number: ChiCTR2500101060]

中文摘要:

      背景 精神分裂症阴性症状给社会带来了沉重负担，且对现有抗精神病药物治疗反应欠佳。间歇性θ爆发式刺激（intermittent theta burst stimulation，iTBS）作为一种新型神经调控技术具有潜在治疗价值，但其疗效证据及相关免疫炎症变化仍需进一步明确。 目的 ?探讨靶向左侧背外侧前额叶皮质（left dorsolateral prefrontal cortex，L-DLPFC）的iTBS对精神分裂症持续性阴性症状的疗效，并分析其与外周炎症指标变化的关系，以期为iTBS治疗精神分裂症持续性阴性症状提供临床依据，并为其潜在生物学机制的进一步研究提供线索。方法 ?采用随机、双盲、伪刺激对照临床试验设计，连续筛选2024年2月20日—2025年5月10日在徐州东方人民医院住院治疗的精神分裂症患者，最终纳入符合《精神障碍诊断与统计手册》第5版（DSM-5）精神分裂症诊断标准、且符合持续性阴性症状判定标准的患者60例。，按1∶1比例随机分为真刺激组和伪刺激组，每组30例，分别接受为期4周的iTBS或伪刺激干预。于基线、治疗结束及治疗后3个月随访时采用阳性与阴性症状量表（Positive and Negative Syndrome Scale，PANSS）评估临床症状，并于基线及治疗结束时检测外周血炎症相关指标。 结果 ①PANSS阴性症状分量表评分的组别 × 时间交互效应具有统计学意义（F = 5.410,P＜0.05），治疗结束及3个月随访时真刺激组评分均低于伪刺激组；②治疗结束时，真刺激组中性粒细胞计数（Z = 2.262，P = 0.024）、中性粒细胞/淋巴细胞比值（NLR）（Z = 2.048，P = 0.041）、血小板/淋巴细胞比值（Z = 2.070，P = 0.038）的变化值与伪刺激组比较差异具有统计学意义；③在真刺激组内，阴性症状评分变化值与中性粒细胞计数变化值（r = 0.392，P = 0.032）及NLR变化值（r = 0.370，P = 0.044）呈正相关，且相关性具有统计学意义。 结论 本研究表明，靶向L-DLPFC的iTBS可改善精神分裂症持续性阴性症状，其临床疗效可能与部分外周炎症指标的变化相关。

英文摘要:

      Background Negative symptoms of schizophrenia impose a substantial social burden and respond poorly to current antipsychotic treatment. Intermittent theta burst stimulation (iTBS), as a novel neuromodulation technique, has potential therapeutic value; however, evidence regarding its efficacy and related immune-inflammatory changes remains to be further clarified. Objective To investigate the efficacy of iTBS targeting the left dorsolateral prefrontal cortex(L-DLPFC) in treating persistent negative symptoms in schizophrenia, and to analyze its association with changes in peripheral inflammatory markers, with the aim of providing clinical evidence for the application of iTBS in the treatment of persistent negative symptoms in schizophrenia and offering clues for further investigation of its potential biological mechanisms. Methods A randomized, double-blind, sham-controlled clinical trial was conducted. Patients with schizophrenia who were hospitalized at Xuzhou Oriental Hospital between February 20, 2024 and May 10, 2025 were consecutively screened. A total of 60 patients who met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5)and fulfilled the criteria for persistent negative symptoms were ultimately enrolled. Participants were randomly assigned in a 1:1 ratio to the active group or the sham group, with 30 patients in each group. They received 4 weeks of active iTBS or sham stimulation, respectively. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS)at baseline, at the end of treatment, and at the 3-month follow-up. Peripheral blood inflammation-related indicators were measured at baseline and at the end of treatment. Results① The group × time interaction effect for the PANSS negative symptom subscale score was statistically significant(F = 5.410, P＜0.05), and the scores in the active group were lower than those in the sham group at the end of treatment and at the 3-month follow-up.② At the end of treatment, the changes in neutrophil(Z = 2.262, P = 0.024), neutrophil-to-lymphocyte ratio(NLR)(Z = 2.048, P = 0.041), and platelet-to-lymphocyte ratio(Z = 2.070, P = 0.038) differed significantly between the active group and the sham group.③ Within the active stimulation group, changes in PANSS negative symptom scores were positively correlated with changes in neutrophil(r = 0.392, P = 0.032) and NLR(r = 0.370, P = 0.044), and these correlations were statistically significant. Conclusion This study indicates that iTBS targeting the L-DLPFC may improve persistent negative symptoms in patients with schizophrenia, and its clinical efficacy may be associated with changes in some peripheral inflammatory indicators.