Wang Junjie, Wei Yanyan, Hu Qiang, Tang Yingying, Zhu Hongliang, Wang Jijun
Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu 215137, China.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai 200030,China.
Schizophr Res Cogn. 2024 Nov 29;39:100339. doi: 10.1016/j.scog.2024.100339. eCollection 2025 Mar.
The dorsolateral prefrontal cortex (DLPFC) - cerebellum circuit has been implicated in the pathogenesis of negative symptoms of schizophrenia (SZ). Both areas are considered separate targets for repetitive transcranial magnetic stimulation (rTMS) treatment, showing potential for improving negative symptoms. However, there is still a lack of research that targets both DLPFC and cerebellum simultaneously. In this study, we will explore the efficacy and safety of dual-target rTMS based on the DLPFC-cerebellum circuit in the treatment of negative symptoms in SZ.
The study is a multicenter randomized, double-blind, and sham-controlled trial. First-episode schizophrenia is treated with adjunctive 1 Hz rTMS to the right DLPFC and intermittent theta burst stimulation (iTBS) to the cerebellum delivered sequentially in 20 sessions (active group) or a sham condition (sham group) along with antipsychotics. Clinical symptoms are assessed using the Positive and Negative Symptom Scale (PANSS) at baseline (T0), at the middle of the TMS intervention (after 10 sessions, T1), at the end of the intervention (after 20 sessions, T2), and at a 4-week follow-up after the intervention concludes (T3). Subjects will undergo magnetic resonance imaging (MRI) scans twice: once at baseline (T0) and again at the end of TMS intervention (T2). Comparisons of improvements in negative symptoms are conducted between the active and sham groups. Alterations in functional connectivity (FC) are also compared between both groups. Pearson or Spearman correlation analysis is performed to estimate the relationship between FC alteration and clinical symptom remission (PANSS negative subscale reduction scores and response rates, etc) depending on whether the data follows a normal distribution. In addition, potential neuroimaging biomarkers based on MRI associated with TMS treatment will be explored.
Positive results from this double-blind, sham-controlled, randomized study may optimize the TMS treatment strategy for SZ, particularly in managing negative symptoms. Clinicians can select TMS with increased confidence as a safe adjunctive treatment option. Furthermore, the findings of this trial may offer preliminary insights into the potential neuroimaging therapeutic mechanisms of TMS interventions targeting the prefrontal-cerebellar circuit.Trial registration: ClinicalTrials.govNCT04853485Primary sponsor: Jijun WANG (J. Wang), Principal Investigator: jijunwang27@163.com.
背外侧前额叶皮质（DLPFC）-小脑环路与精神分裂症（SZ）阴性症状的发病机制有关。这两个区域均被视为重复经颅磁刺激（rTMS）治疗的独立靶点，显示出改善阴性症状的潜力。然而，目前仍缺乏同时针对DLPFC和小脑的研究。在本研究中，我们将探索基于DLPFC-小脑环路的双靶点rTMS治疗SZ阴性症状的疗效和安全性。
本研究为多中心随机、双盲、假对照试验。首发精神分裂症患者在接受抗精神病药物治疗的同时，接受辅助治疗，即对右侧DLPFC进行1Hz rTMS治疗，并对小脑进行间歇性theta爆发刺激（iTBS），分20次依次进行（治疗组）或假刺激（假刺激组）。在基线（T0）、TMS干预中期（10次治疗后，T1）、干预结束时（20次治疗后，T2）以及干预结束后4周随访（T3）时，使用阳性和阴性症状量表（PANSS）评估临床症状。受试者将接受两次磁共振成像（MRI）扫描：一次在基线（T0），另一次在TMS干预结束时（T2）。比较治疗组和假刺激组阴性症状改善情况。同时比较两组之间功能连接（FC）的变化。根据数据是否呈正态分布，进行Pearson或Spearman相关分析，以评估FC改变与临床症状缓解（PANSS阴性分量表减分及反应率等）之间的关系。此外，还将探索基于MRI的与TMS治疗相关的潜在神经影像学生物标志物。
这项双盲、假对照、随机研究的阳性结果可能会优化SZ的TMS治疗策略，尤其是在管理阴性症状方面。临床医生可以更有信心地选择TMS作为一种安全的辅助治疗选择。此外，本试验的结果可能会为针对前额叶-小脑环路的TMS干预的潜在神经影像学治疗机制提供初步见解。试验注册：ClinicalTrials.govNCT04853485主要资助者：王继军（J. Wang），主要研究者：jijunwang27@163.com。
