ImportanceBrain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior.ObjectiveTo examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation.Design, Setting, and ParticipantsData for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan.ExposuresAll participants underwent positron emission tomography imaging of TSPO binding with 11C-ER176 and concurrent arterial blood sampling.Main Outcome and MeasuresA weighted average of 11C-ER176 total distribution volume (VT) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors.ResultsIn the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11C-ER176 VT was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, −0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, −0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11C-ER176 VT (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11C-ER176 VT was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P < .001, respectively).Conclusion and RelevanceTSPO binding in individuals with depression may be a marker of vulnerability to acute stress-related increases in suicidal ideation and negative affect. Continued study is needed to determine the causal direction of TSPO binding and stress-related suicidal ideation or negative affect and whether targeting neuroinflammation may improve resilience to life stress in patients with depression.

中文翻译：

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抑郁症中的神经炎症、与压力相关的自杀意念和消极情绪


重要性脑转运蛋白 18k Da （TSPO） 结合是神经炎症过程（如神经胶质增生）的推定标志物，与压力相关，在抑郁和自杀人群中升高。然而，目前尚不清楚神经炎症是否能缓和日常生活压力对自杀意念和负面影响的影响，从而增加自杀行为的风险。目的探讨抑郁症参与者 TSPO 结合与真实世界日常急性应激相关自杀意念和负面影响的关联，以及自杀行为史和临床医生评定的自杀意念。设计、设置和参与者本横断面研究的数据是从 2019 年 6 月到 2023 年 7 月收集的。手术在纽约州纽约市的一家医院研究中心进行。参与者是通过临床推荐、哥伦比亚大学研究主题门户网站和对互联网广告的回应招募的。在签署研究方案知情同意书的 148 名参与者中，53 名年龄在 18 至 60 岁之间且符合当前重度抑郁症诊断标准的成年人使用批准的数据完成了程序并被纳入。参与者在扫描时没有精神分裂症谱系障碍、活动性身体疾病、认知障碍和物质中毒或戒断。暴露所有参与者都接受了 TSPO 与 11C-ER176 结合的正电子发射断层扫描成像，并同时进行了动脉血采样。主要结局和测量计算 11 个先验脑区 11C-ER176 总分布体积 （VT） 的加权平均值，并构成主要结局指标。 临床医生评定的自杀意念是通过贝克自杀意念量表 （BSS） 测量的。一部分参与者 （n = 21） 完成了 7 天的生态瞬时评估 （EMA），每天报告自杀意念、负面影响和压力源。结果在 53 名参与者 （平均 [SD] 年龄，29.5 [9.8] 岁;37 [69.8%] 女性和 16 [30.2%] 男性）的总体样本中，11C-ER176 VT 在趋势水平上与临床医生评定的自杀意念严重程度相关 （β，0.19;95% CI，-0.03 至 0.39;P = .09），并且没有自杀未遂史差异 （n = 15;β，0.18;95% CI，-0.04 至 0.37;P = .11）。探索性分析表明，存在自杀意念（BSS 或 EMA）与较高的 11C-ER176 VT 相关 （β，0.21;95% CI，0.01 至 0.98;P = .045）。在完成 EMA 的 21 名参与者中，与非应激期相比，11C-ER176 VT 与压力源 EMA 期间更大的自杀意念和负面影响相关 （β，0.12;东南， 0.06;95% CI，0.01 至 0.23;P = .03 和 β，0.19;东南， 0.06;95% CI，0.08 至 0.30;P < .001）。结论和相关性 抑郁症个体的 TSPO 结合可能是易受急性压力相关自杀意念和负面影响增加影响的标志。需要继续研究以确定 TSPO 结合和与压力相关的自杀意念或负面影响的因果方向，以及靶向神经炎症是否可以提高抑郁症患者对生活压力的恢复力。