Pecsok Maggie K, Mordy Arianna, Cristancho Mario A, Oathes Desmond, Roalf David R
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA,
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Psychopathology. 2024 Jul 12:1-16. doi: 10.1159/000538690.
Repetitive transcranial magnetic stimulation (rTMS) alleviates symptoms of major depressive disorder, but its neurobiological mechanisms remain to be fully understood. Growing evidence from proton magnetic resonance spectroscopy (1HMRS) studies suggests that rTMS alters excitatory and inhibitory neurometabolites. This preliminary meta-analysis aims to quantify current trends in the literature and identify future directions for the field.
Ten eligible studies that quantified Glutamate (Glu), Glu+Glutamine (Glx), or GABA before and after an rTMS intervention in depressed samples were sourced from PubMed, MEDLINE, PsychInfo, Google Scholar, and primary literature following PRISMA guidelines. Data were pooled using a random-effects model, Cohen's d effect sizes were calculated, and moderators, such as neurometabolite and 1HMRS sequence, were assessed. It was hypothesized that rTMS would increase cortical neurometabolites.
Within-subjects data from 224 cases encompassing 31 neurometabolite effects (k) were analyzed. Active rTMS in clinical responders (n = 128; k = 22) nominally increased glutamatergic neurometabolites (d = 0.15 [95% CI: -0.01, 0.30], p = 0.06). No change was found in clinical nonresponders (p = 0.8) or sham rTMS participants (p = 0.4). A significant increase was identified in Glx (p = 0.01), but not Glu (p = 0.6). Importantly, effect size across conditions were associated with the number of rTMS pulses patients received (p = 0.05), suggesting dose dependence.
Clinical rTMS is associated with a nominal, dose-dependent increase in glutamatergic neurometabolites, suggesting rTMS may induce Glu-dependent neuroplasticity and upregulate neurometabolism. More, larger scale studies adhering to established acquisition and reporting standards are needed to further elucidate the neurometabolic mechanisms of rTMS.
重复经颅磁刺激（rTMS）可缓解重度抑郁症的症状，但其神经生物学机制仍有待充分了解。来自质子磁共振波谱（1HMRS）研究的越来越多的证据表明，rTMS会改变兴奋性和抑制性神经代谢物。这项初步的荟萃分析旨在量化文献中的当前趋势，并确定该领域未来的方向。
根据PRISMA指南，从PubMed、MEDLINE、PsychInfo、谷歌学术和原始文献中筛选出10项符合条件的研究，这些研究对抑郁症样本在rTMS干预前后的谷氨酸（Glu）、Glu+谷氨酰胺（Glx）或γ-氨基丁酸（GABA）进行了量化。使用随机效应模型汇总数据，计算科恩d效应量，并评估神经代谢物和1HMRS序列等调节因素。假设rTMS会增加皮质神经代谢物。
分析了来自224例病例的受试者内数据，包括31种神经代谢物效应（k）。临床有反应者（n = 128；k = 22）中的活性rTMS名义上增加了谷氨酸能神经代谢物（d = 0.15 [95% CI：-0.01，0.30]，p = 0.06）。临床无反应者（p = 0.8）或假rTMS参与者（p = 0.4）未发现变化。发现Glx有显著增加（p = 0.01），但Glu没有（p = 0.6）。重要的是，不同条件下的效应量与患者接受的rTMS脉冲数相关（p = 0.05），表明存在剂量依赖性。
临床rTMS与谷氨酸能神经代谢物的名义上的、剂量依赖性增加相关，表明rTMS可能诱导Glu依赖性神经可塑性并上调神经代谢。需要更多、更大规模的研究遵循既定的采集和报告标准，以进一步阐明rTMS的神经代谢机制。
