Chen Stephen H, Epel Elissa S, Mellon Synthia H, Lin Jue, Reus Victor I, Rosser Rebecca, Kupferman Eve, Burke Heather, Mahan Laura, Blackburn Elizabeth H, Wolkowitz Owen M
Department of Psychology, Wellesley College, Wellesley, MA, USA.
Department of Psychiatry, University of California, San Francisco (UCSF), School of Medicine, 401 Parnassus Avenue, San Francisco, CA 94143, USA.
J Affect Disord. 2014 Dec;169:86-90. doi: 10.1016/j.jad.2014.07.035. Epub 2014 Aug 5.
Adverse childhood experiences (ACEs) are associated with poor physical and mental health outcomes in adulthood. Adverse childhood experiences are also associated with shortened leukocyte telomere length (LTL) in adults, suggesting accelerated cell aging. No studies have yet assessed the relationship of ACEs to LTL in individuals with major depressive disorder (MDD), despite the high incidence of antecedent ACEs in individuals with MDD. Further, no studies in any population have assessed the relationship of ACEs to the activity of telomerase, the major enzyme responsible for maintaining LTL, or the relationship between telomerase and LTL in individuals with ACEs.
Twenty healthy, unmedicated adults with MDD and 20 healthy age-, sex- and ethnicity-matched controls had ACEs assessed and had blood drawn for LTL and peripheral blood mononuclear cell (PBMC) resting telomerase activity.
In healthy controls, greater ACE exposure was associated with shorter LTL (p<.05) but was unassociated with telomerase activity. In MDD, however, the opposite pattern was seen: greater ACE exposure was unrelated to LTL but was associated with increased telomerase activity (p<.05) and with a higher telomerase:LTL ratio (p=.022).
Study limitations include the small sample size, a single timepoint assessment of telomerase activity, and the use of retrospective self-report to assess ACEs.
These results replicate prior findings of shortened LTL in healthy adults with histories of multiple ACEs. However, in MDD, this relationship was substantially altered, raising the possibility that activation of telomerase in ACE-exposed individuals with MDD could represent a compensatory response to endangered telomeres.
童年不良经历(ACEs)与成年后的身心健康不良后果相关。童年不良经历还与成年人白细胞端粒长度(LTL)缩短有关,提示细胞衰老加速。尽管患有重度抑郁症(MDD)的个体中ACEs的发生率很高,但尚无研究评估ACEs与MDD患者LTL之间的关系。此外,在任何人群中,都没有研究评估ACEs与端粒酶活性(维持LTL的主要酶)之间的关系,也没有研究评估ACEs个体中端粒酶与LTL之间的关系。
20名患有MDD的健康、未用药成年人以及20名年龄、性别和种族匹配的健康对照者接受了ACEs评估,并抽取血液检测LTL和外周血单核细胞(PBMC)静息端粒酶活性。
在健康对照者中,ACE暴露程度越高,LTL越短(p<0.05),但与端粒酶活性无关。然而,在MDD患者中,观察到相反的模式:ACE暴露程度越高,与LTL无关,但与端粒酶活性增加有关(p<0.05),且端粒酶:LTL比值更高(p=0.022)。
研究局限性包括样本量小、端粒酶活性的单时间点评估以及使用回顾性自我报告来评估ACEs。
这些结果重复了先前关于有多次ACEs病史的健康成年人LTL缩短的研究结果。然而,在MDD患者中,这种关系发生了实质性改变,这增加了一种可能性,即ACE暴露的MDD患者中端粒酶的激活可能代表对濒危端粒的一种代偿反应。