Wu Huiqin, Zhong Yuan, Xu Huazhen, Ding Huachen, Yuan Shiting, Wu Yun, Liu Gang, Liu Na, Wang Chun
Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China.
School of Psychology, Nanjing Normal University, Nanjing, China.
Front Psychiatry. 2022 May 24;13:853613. doi: 10.3389/fpsyt.2022.853613. eCollection 2022.
This study aimed to test the hypothesis that the relationship between glutamic acid decarboxylase (GAD) 1 gene methylation and severity of clinical symptoms of panic disorder (PD) is mediated by the effect of GAD1 gene methylation on gray matter volume (GMV) and the effect of GMV on PD.
Panic disorder ( = 24) patients were recruited consecutively from the Affiliated Brain Hospital of Nanjing Medical University through outpatient and public advertising, eligible healthy controls (HCs) ( = 22) were recruited from public advertising. We compared GMV and GAD1 gene methylation in PD and HCs to estimate the differences, and on the basis of the relationship between gray matter volumes and GAD1 gene methylation in PD patients was evaluated, the role of GMV as a mediator of GAD1 gene methylation and PD clinical symptoms was analyzed.
Panic disorder patients had significantly lower methylation in the GAD1 promoter region on Cytosine-phosphate-guanine (CPG) 7 than HCs ( = 2.380, = 0.021). Pearson correlation analysis found a significant negative association between cg171674146 (cg12) site and clinical severity ( = 24, = -0.456, = 0.025). Compared to HCs, patients with PD had decreased gray matter volumes in several brain regions, which were also associated with PD severity. Left postcentral gyrus (PoCG) GMV mediated the association between cg12 methylation and PD severity, and there was a significant mediation effect of right angular gyrus (ANG) gray matter volumes on the relationship between cg12 methylation and PD severity.
No direct results can be derived for methylation patterns in different brain regions; the study is cross-sectional; relatively small size.
本研究旨在检验以下假设，即谷氨酸脱羧酶（GAD）1基因甲基化与惊恐障碍（PD）临床症状严重程度之间的关系是由GAD1基因甲基化对灰质体积（GMV）的影响以及GMV对PD的影响所介导的。
通过门诊和公开招募，从南京医科大学附属脑科医院连续招募惊恐障碍患者（n = 24），从公开招募中选取符合条件的健康对照（HCs）（n = 22）。我们比较了PD患者和HCs的GMV和GAD1基因甲基化情况以评估差异，并在评估PD患者灰质体积与GAD1基因甲基化之间关系的基础上，分析GMV作为GAD1基因甲基化与PD临床症状之间介导因素的作用。
惊恐障碍患者在胞嘧啶-磷酸-鸟嘌呤（CPG）7位点的GAD1启动子区域甲基化水平显著低于HCs（t = 2.380，P = 0.021）。Pearson相关分析发现，cg171674146（cg12）位点与临床严重程度之间存在显著负相关（n = 24，r = -0.456，P = 0.025）。与HCs相比，PD患者在几个脑区的灰质体积减少，这些脑区也与PD严重程度相关。左侧中央后回（PoCG）的GMV介导了cg12甲基化与PD严重程度之间的关联，并且右侧角回（ANG）灰质体积对cg12甲基化与PD严重程度之间的关系有显著的中介作用。
无法直接得出不同脑区甲基化模式的结果；本研究为横断面研究；样本量相对较小。
