Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India.
Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India.
Schizophr Res. 2019 May;207:37-47. doi: 10.1016/j.schres.2018.10.027. Epub 2018 Nov 6.
Several lines of investigations converge upon aberrant synaptic plasticity as a potential pathophysiological characteristic of schizophrenia. In vivo experiments using neuromodulatory perturbation techniques like Transcranial Magnetic and Direct Current Stimulation (TMS & tDCS) have been increasingly used to measure 'motor cortical plasticity' in schizophrenia. A systematic quantification of cortical plasticity and its moderators in schizophrenia is however lacking.
The PubMed/MEDLINE database was searched for studies up to December 31st, 2017 that examined case-control experiments comparing neuromodulation following single-session of TMS or tDCS. The primary outcome was the standardized mean difference for differential changes in motor evoked potential (MEP) amplitudes measured with single-pulse TMS (MEP Δ) between patients and healthy subjects following TMS or tDCS. After examining heterogeneity, meta-analyses were performed using fixed effects models.
A total of 16 datasets comparing cortical plasticity (MEP Δ) between 189 schizophrenia patients and 187 healthy controls were included in the meta-analysis. Patients demonstrated diminished MEP Δ with effect sizes (Cohen's d) ranging from 0.66 (LTP-like plasticity) to 0.68 (LTD-like plasticity). Heterosynaptic plasticity studies demonstrated a greater effect size (0.79) compared to homosynaptic plasticity studies (0.62), though not significant (P = 0.43). Clinical, perturbation protocol- and measurement-related factors, and study quality did not significantly moderate the aberrant plasticity demonstrated in schizophrenia.
Schizophrenia patients demonstrate diminished LTP- and LTD-like motor cortical plasticity, which is not influenced by the various clinical and experimental protocol related confounders. These consistent findings should encourage the use of perturbation-based biomarkers to characterize illness trajectories and treatment response.
多项研究表明，突触可塑性异常是精神分裂症的潜在病理生理学特征。越来越多的研究采用神经调节干预技术，如经颅磁刺激（TMS）和经颅直流电刺激（tDCS），来测量精神分裂症患者的“运动皮质可塑性”。然而，目前尚缺乏对精神分裂症皮质可塑性及其调节因素的系统量化研究。
检索 PubMed/MEDLINE 数据库，截至 2017 年 12 月 31 日，纳入比较单次 TMS 或 tDCS 后神经调节作用的病例对照试验。主要结局指标是 TMS 或 tDCS 后患者和健康对照者单脉冲 TMS 测量的运动诱发电位（MEP）振幅的差异变化（MEPΔ）的标准化均数差。在检查异质性后，使用固定效应模型进行荟萃分析。
共纳入 16 项比较 189 例精神分裂症患者和 187 例健康对照者皮质可塑性（MEPΔ）的数据集进行荟萃分析。患者的 MEPΔ减小，效应量（Cohen's d）范围为 0.66（LTP 样可塑性）至 0.68（LTD 样可塑性）。与同突触可塑性研究（0.62）相比，异突触可塑性研究（0.79）显示出更大的效应量，但无统计学意义（P=0.43）。临床、神经调节方案和测量相关因素以及研究质量并未显著调节精神分裂症患者的异常可塑性。
精神分裂症患者表现出 LTP 和 LTD 样运动皮质可塑性降低，这不受各种临床和实验方案相关混杂因素的影响。这些一致的发现应鼓励使用基于干预的生物标志物来描述疾病轨迹和治疗反应。
