Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA.
J Psychiatr Res. 2013 Feb;47(2):233-9. doi: 10.1016/j.jpsychires.2012.10.009. Epub 2012 Nov 8.
BDNF Val66Met by chronic stress interaction has been studied using childhood stress as a moderator, but has not been widely studied using chronic stress in adulthood.
Two independent samples were used: Duke-CG (238 Caucasians) and MESA (5524 Caucasians, African Americans and Hispanics). Chronic stress in Duke-CG was operationalized as having primary caregiving responsibility for a spouse or relative with diagnosed Alzheimer's disease or other major dementia; chronic stress in MESA was defined using chronic burden score constructed from self-reported problems of health (self and someone close), job, finance and relationships. CES-D scale was the measure of depression in both samples. The BDNF Val66Met by adulthood chronic stress interaction predicting CES-D was examined using linear regression, adjusted for covariates.
The main effect of BDNF Val66Met genotype on CES-D scores was non-significant (ps > 0.607) but the adulthood chronic stress indicator was significant (ps < 0.001) in both samples. The BDNF Val66Met genotype by adulthood chronic stress interaction was also significant (ps < 0.039) in both samples. The impact of chronic stress in adulthood on CES-D scores was significantly larger in Val/Val genotype individuals than Met carriers.
We found in two independent samples that depression levels increased significantly more as a function of adulthood chronic stress Val/Val genotype carriers than Met carriers. Individuals with the Val/Val genotype and chronic stress exposure could be targeted for interventions designed to reduce risk of depression if this finding is confirmed in future studies.
已有研究采用童年期应激作为调节变量，探讨 BDNF Val66Met 与慢性应激的相互作用，但采用成年期慢性应激作为调节变量的研究并不多见。
本研究使用了两个独立的样本：杜克 CG （238 名白种人）和 MESA （5524 名白种人、非裔美国人和西班牙裔人）。杜克 CG 中的慢性应激通过主要照顾患有阿尔茨海默病或其他严重痴呆症的配偶或亲属来进行操作化定义；MESA 中的慢性应激则使用自我报告的健康问题（自身和亲近的人）、工作、财务和人际关系构建的慢性负担评分来定义。CES-D 量表是两个样本中抑郁的测量工具。采用线性回归，调整协变量后，检验 BDNF Val66Met 与成年期慢性应激相互作用对 CES-D 的预测作用。
BDNF Val66Met 基因型对 CES-D 评分的主效应不显著（p 值均大于 0.607），但成年期慢性应激指标在两个样本中均显著（p 值均小于 0.001）。BDNF Val66Met 基因型与成年期慢性应激的相互作用在两个样本中也具有统计学意义（p 值均小于 0.039）。成年期慢性应激对 CES-D 评分的影响在 Val/Val 基因型个体中显著大于 Met 携带者。
在两个独立的样本中，我们发现，随着 Val/Val 基因型个体成年期慢性应激的增加，抑郁水平显著升高，而 Met 携带者则不然。如果这一发现能在未来的研究中得到证实，那么具有 Val/Val 基因型且暴露于慢性应激下的个体可能会成为旨在降低抑郁风险的干预措施的目标人群。
