Xie Cheng, Xue Chen, Li Yuxi, Liu Xiaobo, Zhong Donglin, Jin Qizu, Li Juan, Jin Rongjiang
School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
The Third Hospital of Mianyang, Sichuan Mental Health Center, China.
J Psychiatr Res. 2025 Jan;181:470-483. doi: 10.1016/j.jpsychires.2024.12.016. Epub 2024 Dec 6.
Previous studies have reported inconsistent findings regarding event-related potentials (ERPs) abnormalities in individuals with generalized anxiety disorder (GAD). This meta-analysis aimed to systematically review and synthesize the existing evidence on ERP alterations in individuals with GAD.
A comprehensive literature search was conducted in PubMed, the Cochrane Library, Excerpta Medica Database, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang database, and China Biology Medicine (CBM) databases from inception to November 11, 2024. Gray literature and reference lists were also manually searched. Studies investigating ERP component differences between individuals with GAD and healthy controls were included. Two independent reviewers conducted study selection, data extraction, and risk of bias assessment. Influence and sensitivity analyses were performed to assess the robustness of the pooled results. Effect sizes (SMD, Hedge's g) were calculated for latency and amplitude differences. Heterogeneity was assessed using the I statistic. Meta-regression and subgroup analyses were conducted to explore the source of heterogeneity. Trim-and-fill analyses were applied to assess potential publication bias. Data synthesis was performed using R (version 4.2.3) software.
A total of 37 studies involving 1086 individuals with GAD and 1315 healthy controls were included. The overall risk of bias was rated as low for 25 studies and moderate for 12 studies. Ten ERP components were included in the quantitative meta-analysis: P3, N2, N1, P2, Error Related Negativity (ERN), Correction Related Negativity (CRN), Mismatch Negativity (MMN), P1 (amplitude), Pe, and LPP. Pooled results indicated that individuals with GAD exhibited decreased P3 amplitude (g = -0.54, 95% CI: -0.70 to -0.38, I = 20%, P = 0.22) and increased ERN amplitude (g = -0.42, 95% CI: -0.72 to -0.12, I = 40%, P = 0.11) compared to healthy controls. In addition, delayed latency of P3 (g = 0.43, 95% CI: 0.09 to 0.78, I = 75%, P < 0.01), N2 (g = 0.36, 95% CI: 0.11 to 0.62, I = 30%, P = 0.20), and MMN (g = 0.63, 95% CI: 0.52 to 0.75, I = 0%, P < 0.0001) was observed in individuals with GAD. Due to the limited number of included studies, the results of N170, N1/P2, N270, N400, VPP, BAEP, P1 (latency), P50, EPN and Nf were summarized narratively. Individuals with GAD were reported to have increased N170, N400, and VPP amplitude and delayed P1 latency compared to healthy controls. Age, sex ratio, sample size, diagnostic criteria, task-related modality, and paradigm were identified as potential influencing factors of ERP characteristics.
Individuals with GAD exhibit increased ERN amplitude and decreased P3 amplitude in contrast with healthy controls. In addition, delayed latency of P3, N2, and MMN is detected in individuals with GAD. The identified ERP components in individuals with GAD are associated with attention, cognition, visual perception, error or conflict monitoring, semantic information integration, and auditory sensory memory processes. Due to the limited number of included studies and high heterogeneity, further studies with high quality are needed to confirm these findings.
先前的研究报告了广泛性焦虑症（GAD）患者事件相关电位（ERP）异常的不一致结果。本荟萃分析旨在系统回顾和综合关于GAD患者ERP改变的现有证据。
从数据库建库至2024年11月11日，在PubMed、Cochrane图书馆、医学文摘数据库、科学引文索引数据库、中国知网（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库和中国生物医学文献数据库（CBM）中进行了全面的文献检索。还手动检索了灰色文献和参考文献列表。纳入研究GAD患者与健康对照之间ERP成分差异的研究。两名独立的评审员进行研究选择、数据提取和偏倚风险评估。进行了影响和敏感性分析以评估合并结果的稳健性。计算了潜伏期和波幅差异的效应量（标准化均数差、Hedge's g）。使用I²统计量评估异质性。进行了元回归和亚组分析以探索异质性的来源。应用了剪补分析以评估潜在的发表偏倚。使用R（版本4.2.3）软件进行数据合成。
共纳入37项研究，涉及1086例GAD患者和1315例健康对照。25项研究的总体偏倚风险被评为低，12项研究为中等。定量荟萃分析纳入了10个ERP成分：P3、N2、N1、P2、错误相关负波（ERN）、校正相关负波（CRN）、失配负波（MMN）、P1（波幅）、Pe和晚期正电位（LPP）。合并结果表明，与健康对照相比，GAD患者的P3波幅降低（g = -0.54，95%CI：-0.70至-0.38，I² = 20%，P = 0.22），ERN波幅增加（g = -0.42，95%CI：-0.72至-0.12，I² = 40%，P = 0.11）。此外，GAD患者的P3潜伏期延迟（g = 0.43，95%CI：0.09至0.78，I² = 75%，P < 0.01）、N2潜伏期延迟（g = 0.36，95%CI：0.11至0.62，I² = 30%，P = 0.20）和MMN潜伏期延迟（g = 0.63，95%CI：0.52至0.75，I² = 0%，P < 0.0001）。由于纳入研究数量有限，对N170、N1/P2、N270、N400、视觉正电位（VPP）、脑干听觉诱发电位（BAEP）、P1（潜伏期）、P50、早期后部负波（EPN）和负失匹配（Nf）的结果进行了描述性总结。据报道，与健康对照相比，GAD患者的N170、N400和VPP波幅增加，P1潜伏期延迟。年龄、性别比例、样本量、诊断标准与任务相关的模态和范式被确定为ERP特征的潜在影响因素。
与健康对照相比，GAD患者的ERN波幅增加，P3波幅降低。此外，在GAD患者中检测到P3、N2和MMN潜伏期延迟。在GAD患者中识别出的ERP成分与注意力、认知、视觉感知、错误或冲突监测、语义信息整合和听觉感觉记忆过程相关。由于纳入研究数量有限且异质性高，需要进一步的高质量研究来证实这些发现。
