Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11–MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case–control design (sample 1: N = 120) as well as MDD patients with and without anxious depression (sample 2: N = 170). Additionally, in sample 1, KLF11 methylation was correlated with Beck Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.

恐慌症 (PD) 是最常见的焦虑症之一，通常与重度抑郁症 (MDD) 并存。单胺氧化酶 A ( MAOA ) 基因的甲基化改变与 PD 和 MDD 的病因有关。Krüppel 样因子 11（KLF11；别名 TIEG2）是一种MAOA基因的激活转录因子，已被发现在 MDD 中增加，但尚未在 PD 中进行研究。为了进一步描述 KLF11-MAOA 通路在焦虑和情感障碍中的作用，KLF11在病例对照设计（样本 1：N = 120）中，两个独立的 PD 患者样本（样本 1：N  = 120）以及患有和没有焦虑抑郁症（样本 2：N  = 170）。此外，在样本 1 中，KLF11甲基化与贝克抑郁量表 (BDI-II) 评分相关。未检测到KLF11启动子甲基化与 PD的总体关联。然而，与健康对照组 ( p  = 0.010) 和没有合并 MDD ( p  = 0.008) 的 PD 患者相比，合并 MDD 的 PD 患者显示出显着的低甲基化。此外，KLF11甲基化与 PD 患者的 BDI-II 评分呈负相关（p  = 0.013）。与患有焦虑抑郁症的 MDD 患者相比，没有焦虑特征的 MDD 患者的KLF11甲基化名义上降低（ p  = 0.052）。目前的结果表明，KLF11启动子低甲基化分别作为 PD 中 MDD 合并症或非焦虑性抑郁症的潜在表观遗传标志物，可能构成焦虑症和情绪障碍的不同病理机制。