Jiang Rong, Babyak Michael A, Brummett Beverly H, Siegler Ilene C, Kuhn Cynthia M, Williams Redford B
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Psychoneuroendocrinology. 2017 May;79:13-19. doi: 10.1016/j.psyneuen.2017.02.005. Epub 2017 Feb 13.
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with cortisol responses to stress with gender differences reported, although the findings are not entirely consistent. To evaluate the role of Val66Met genotype and gender on cortisol responses to stress, we conducted a 45-min mental stress protocol including four tasks and four rest periods. Blood cortisol was collected for assay immediately before and after each task and rest period. A significant two-way interaction of Val66Met genotype×gender (P=0.022) was observed on the total area under the curve (AUC), a total cortisol response over time, such that the Val/Val genotype was associated with a larger cortisol response to stress as compared to the Met group in women but not in men. Further contrast analyses between the Val/Val and Met group for each stress task showed a similar increased cortisol pattern among women Val/Val genotype but not among men. The present findings indicate the gender differences in the effect of Val66Met genotype on the cortisol responses to stress protocol, and extend the evidence for the importance of gender and the role of Val66Met in the modulation of stress reactivity and subsequent depression prevalence. Further studies and the underlying mechanism need to be investigated, which may provide an insight for prevention, intervention, and treatment strategies that target those at high risk.
脑源性神经营养因子（BDNF）Val66Met多态性与对应激的皮质醇反应相关，且有性别差异的报道，尽管研究结果并不完全一致。为了评估Val66Met基因型和性别对应激时皮质醇反应的作用，我们实施了一项45分钟的心理应激方案，包括四项任务和四个休息时段。在每项任务和休息时段前后立即采集血样检测皮质醇。在曲线下总面积（AUC，即随时间变化的总皮质醇反应）上观察到Val66Met基因型×性别的显著双向交互作用（P = 0.022），即与Met组相比，Val/Val基因型在女性中对应激的皮质醇反应更大，而在男性中并非如此。对每个应激任务的Val/Val组和Met组进行进一步对比分析显示，Val/Val基因型女性的皮质醇模式有类似的增加，但男性中没有。本研究结果表明Val66Met基因型对应激方案皮质醇反应的影响存在性别差异，并进一步证明了性别在应激反应调节及后续抑郁症患病率中以及Val66Met的作用的重要性。需要进一步研究其潜在机制，这可能为针对高危人群的预防、干预和治疗策略提供见解。
