Lieberman Richard, Armeli Stephen, Scott Denise M, Kranzler Henry R, Tennen Howard, Covault Jonathan
Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut.
Department of Neuroscience, University of Connecticut Health Center, University of Connecticut School of Medicine, Farmington, Connecticut.
Am J Med Genet B Neuropsychiatr Genet. 2016 Sep;171(6):879-87. doi: 10.1002/ajmg.b.32460. Epub 2016 May 19.
Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780T-allele carriers, rs1360780C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc.
酒精使用障碍（AUD）具有致残性且代价高昂。识别并更好地理解影响AUD发展的风险因素仍是研究重点。尽管早年经历创伤会增加成年期精神障碍（包括AUD）的风险，但许多经历过早年创伤的个体并未出现精神病理学症状。潜在的遗传因素可能导致对童年经历创伤的敏感性差异。下丘脑 - 垂体 - 肾上腺（HPA）轴在童年创伤后功能易发生持久变化。FKBP5是一种编码HPA轴功能调节因子的基因，其功能遗传变异与成年期精神症状的发展相关，尤其是在早年经历创伤的个体中。在本研究中，我们在来自两所大学的1845名大学生样本中，考察了自我报告的早年创伤、过去一年的生活压力、过去一年的创伤以及FKBP5中的一个单核苷酸多态性（rs1360780）之间的相互作用对大量饮酒的影响。尽管我们发现早年创伤对rs1360780T等位基因携带者的大量饮酒没有影响，但与未经历早年创伤的rs1360780C纯合子相比，经历早年创伤的rs1360780*C纯合子大量饮酒的可能性较低（P < 0.01）。当前生活压力或过去一年的创伤与FKBP5基因型在大量饮酒方面不存在相互作用，这表明存在一个由FKBP5基因型调节的对应激敏感的发育时期。这些发现表明早年创伤和FKBP5基因变异对大量饮酒具有交互作用。© 2016威利期刊公司
