The characteristics of event-related potentials in generalized anxiety disorder: A systematic review and meta-analysis

Abstract

Objectives: 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.

Methods: 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 I² 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.

Results: 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, I² = 20%, P = 0.22) and increased ERN amplitude (g = -0.42, 95% CI: -0.72 to -0.12, I² = 40%, P = 0.11) compared to healthy controls. In addition, delayed latency of P3 (g = 0.43, 95% CI: 0.09 to 0.78, I² = 75%, P < 0.01), N2 (g = 0.36, 95% CI: 0.11 to 0.62, I² = 30%, P = 0.20), and MMN (g = 0.63, 95% CI: 0.52 to 0.75, I² = 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.

Conclusions: 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.

Keywords: Event-related potentials; Generalized anxiety disorder; Meta-analysis; Systematic review.