Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University, Munich, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, Nußbaumstraße 7, 80336 Munich, Germany; Hochschule Fresenius, University of Applied Sciences, Munich, Germany.
ECT Service, Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Bipolar Disorder Research Program, Department and Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8;105:110119. doi: 10.1016/j.pnpbp.2020.110119. Epub 2020 Oct 4.
We investigated the role of peripheral biomarkers associated with neuroplasticity and immune-inflammatory processes on the effects of transcranial direct current stimulation (tDCS), a safe, affordable, and portable non-invasive neuromodulatory treatment, in bipolar depression.
This is an exploratory analysis using a dataset from the sham-controlled study the Bipolar Depression Electrical Treatment Trial (BETTER)(clinicaltrials.govNCT02152878). Participants were 52 adults with type I or II bipolar disorder in a moderate-to-severe depressive episode, randomized to 12 bifrontal active or sham tDCS sessions over a 6-week treatment course. Plasma levels of brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), interleukins (IL) 2, 4, 6, 8, 10, 18, 33, 1β, 12p70, 17a, interferon gamma (IFN), tumor necrosis factor alpha (TNF) and its soluble receptors 1 and 2, ST2, and KLOTHO were investigated at baseline and endpoint. We performed analyses unadjusted for multiple testing to evaluate whether baseline biomarkers were predictive for depression improvement and changed during treatment using linear regression models.
A time x group interaction (Cohen's d: -1.16, 95% CI = -1.96 to -0.3, p = .005) was found for IL-8, with greater reductions after active tDCS. Higher baseline IL-6 plasma levels was associated with symptomatic improvement after tDCS (F = 5.43; p = .025). Other associations were not significant.
Our exploratory findings suggested that IL-6 is a potential predictor of tDCS response and IL-8 might decrease after tDCS; although confirmatory studies are warranted due to the multiplicity of comparisons.
我们研究了与神经可塑性和免疫炎症过程相关的外周生物标志物在经颅直流电刺激（tDCS）中的作用，tDCS 是一种安全、经济实惠且便携的非侵入性神经调节治疗方法，用于治疗双相情感障碍抑郁。
这是一项使用双相情感障碍电疗试验（BETTER）（clinicaltrials.govNCT02152878）的假对照研究数据集进行的探索性分析。参与者为 52 名患有 I 型或 II 型双相情感障碍且处于中度至重度抑郁发作期的成年人，随机分为 12 组接受双侧额极活性或假 tDCS 治疗，疗程为 6 周。在基线和终点时检测了脑源性神经营养因子（BDNF）、胶质细胞源性神经营养因子（GDNF）、白细胞介素（IL）2、4、6、8、10、18、33、1β、12p70、17a、干扰素 γ（IFN）、肿瘤坏死因子 α（TNF）及其可溶性受体 1 和 2、ST2 和 KLOTHO 的血浆水平。我们进行了未调整多重检验的分析，以评估基线生物标志物是否可预测抑郁改善，并使用线性回归模型评估其在治疗过程中的变化。
发现时间 x 组交互作用（Cohen's d：-1.16，95%CI=-1.96 至-0.3，p=0.005）对 IL-8 有影响，活性 tDCS 后 IL-8 降低更明显。较高的基线 IL-6 血浆水平与 tDCS 后症状改善相关（F=5.43；p=0.025）。其他关联没有统计学意义。
我们的探索性发现表明，IL-6 可能是 tDCS 反应的潜在预测因子，并且 IL-8 在 tDCS 后可能会降低；由于比较的多重性，需要进行确认性研究。
