Behavioral Epidemiology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
Department of Psychology, Faculty of Life Sciences, Humboldt-Universität zu Berlin, Berlin, Germany.
Depress Anxiety. 2018 Nov;35(11):1104-1113. doi: 10.1002/da.22812. Epub 2018 Aug 14.
It remains unresolved whether childhood adversities interact with genetic variation in regulator of G-protein signaling 2 (RGS2) rs4606 in predicting various anxiety and depressive disorders and whether diagnostic specificity exists in these interactions.
The genotype of RGS2 rs4606 was determined for N = 2,263 adults with European ancestry from the Study of Health in Pomerania. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were assessed with the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ, when participants were aged 29-89).
Logistic regressions adjusted for sex and age revealed that rs4606 interacted with total childhood adversity in predicting each diagnostic outcome except for panic disorder and generalized anxiety disorder, uncorrected and corrected for multiple testing (odds ratio [OR] = 1.06-1.16). That is, carriers of the GG (vs. CC/CG) genotype were at decreased risk for anxiety and/or depression in the presence of low, but at increased risk in the presence of high total childhood adversity. Respective gene-environment (G × E) interactions were found for (a) comorbid anxiety and depressive disorders (OR = 1.13), but neither pure anxiety nor pure depressive disorders and (b) pure/temporally primary anxiety disorders (OR = 1.07), but not pure/temporally primary depressive disorders. The G × E interaction remained associated with depressive disorders after introducing pure/temporally primary anxiety disorders as additional predictor (OR = 1.09).
rs4606 alters the risk of developing a range of anxiety but also depressive disorders after childhood adversities. A complex risk pattern of genotype, environmental factors, and preexisting anxiety contributes to subsequent depression development.
目前尚不清楚童年逆境是否与 G 蛋白信号转导调节因子 2（RGS2）rs4606 的遗传变异相互作用，以预测各种焦虑和抑郁障碍，以及这些相互作用是否存在诊断特异性。
对来自波美拉尼亚健康研究的 2263 名具有欧洲血统的成年人进行了 RGS2 rs4606 的基因分型。根据《精神障碍诊断与统计手册》第四版，使用慕尼黑综合国际诊断访谈（DIA-X/M-CIDI）评估终生焦虑和抑郁障碍。使用儿童创伤问卷（CTQ，当参与者年龄在 29-89 岁时）评估童年逆境。
调整性别和年龄的逻辑回归显示，rs4606 与总童年逆境相互作用，预测除惊恐障碍和广泛性焦虑障碍外的每种诊断结果，未经校正和校正多重检验（比值比 [OR] = 1.06-1.16）。也就是说，在低水平总童年逆境存在的情况下，GG（与 CC/CG 基因型相比）携带者患焦虑和/或抑郁的风险较低，但在高水平总童年逆境存在的情况下，风险增加。分别发现了（a）共病焦虑和抑郁障碍（OR = 1.13）和（b）单纯/原发性焦虑障碍（OR = 1.07）的基因-环境（G×E）相互作用，但无单纯/原发性抑郁障碍。在引入单纯/原发性焦虑障碍作为附加预测因素后，G×E 相互作用仍然与抑郁障碍相关（OR = 1.09）。
rs4606 改变了经历童年逆境后发生一系列焦虑症和抑郁症的风险。基因型、环境因素和先前存在的焦虑症的复杂风险模式导致随后的抑郁发展。
