Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH 45237, United States; Cincinnati Children's Hospital Medical Center, Department of Psychiatry, Cincinnati, OH 45219, United States.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, Cincinnati, OH 45237, United States.
Brain Behav Immun. 2018 Jan;67:36-41. doi: 10.1016/j.bbi.2017.07.014. Epub 2017 Jul 20.
While disruption of acid-base homeostasis has been pathoetiologically implicated in panic disorder (PD), the mechanism by which pH imbalance is translated to panic pathophysiology is poorly understood. Recently, in a translational rodent model of PD, we reported a role of microglial acid sensing G-protein coupled receptor, T cell death associated gene-8 (TDAG8) in panic-associated behavior and physiology. However, the clinical validity of the TDAG8 receptor has not been investigated.
To assess TDAG8 in PD, we evaluated TDAG8 receptor expression in adolescents and young adults with PD and healthy comparison subjects.
Relative expression of TDAG8 mRNA was determined in peripheral blood mononuclear cells from patients with PD, and compared to expression in healthy subjects. Linear models were utilized to evaluate the relationship between TDAG8 expression and panic disorder symptom severity scale (PDSS) score as well as other potential explanatory variables (e.g., CRP, body mass index, sex, age). Models were refined based on the estimated parameter significance, evidence of omitted variable bias and Bayesian/Akaike information criteria.
Relative to healthy comparison subjects (n=17), expression of TDAG8 mRNA was significantly increased in patients with PD (n=15) (1.60±0.65 vs. 1.01±0.50, p=0.008). TDAG8 mRNA expression predicted PD symptom severity in a fixed effect model incorporating age and sex (p=0.003).
Collectively, our results suggest greater TDAG8 expression in patients with PD compared to healthy subjects, and directly link TDAG8 expression and the severity of the PD symptoms. Further investigation of the TDAG8 receptor in panic pathophysiology is warranted.
尽管酸碱平衡紊乱与惊恐障碍（PD）的病理生理学有关，但 pH 值失衡如何转化为惊恐病理生理学的机制尚不清楚。最近，在 PD 的转化啮齿动物模型中，我们报告了小胶质细胞酸感应 G 蛋白偶联受体 T 细胞死亡相关基因-8（TDAG8）在与惊恐相关的行为和生理学中的作用。然而，TDAG8 受体的临床有效性尚未得到研究。
为了评估 TDAG8 在 PD 中的作用，我们评估了 PD 患者和健康对照者外周血单个核细胞中 TDAG8 受体的表达。
测定 PD 患者和健康对照者外周血单个核细胞中 TDAG8 mRNA 的相对表达，并与健康对照者进行比较。利用线性模型评估 TDAG8 表达与惊恐障碍症状严重程度量表（PDSS）评分以及其他潜在解释变量（如 CRP、体重指数、性别、年龄）之间的关系。根据估计参数的显著性、遗漏变量偏差的证据和贝叶斯/赤池信息量标准，对模型进行了优化。
与健康对照组（n=17）相比，PD 患者（n=15）的 TDAG8 mRNA 表达显著增加（1.60±0.65 比 1.01±0.50，p=0.008）。在纳入年龄和性别的固定效应模型中，TDAG8 mRNA 表达可预测 PD 症状严重程度（p=0.003）。
总的来说，我们的研究结果表明，与健康对照者相比，PD 患者的 TDAG8 表达更高，并直接将 TDAG8 表达与 PD 症状的严重程度联系起来。进一步研究 TDAG8 受体在惊恐病理生理学中的作用是有必要的。
