Simon Naomi M, Walton Zandra E, Bui Eric, Prescott Jennifer, Hoge Elizabeth, Keshaviah Aparna, Schwarz Noah, Dryman Taylor, Ojserkis Rebecca A, Kovachy Benjamin, Mischoulon David, Worthington John, De Vivo Immaculata, Fava Maurizio, Wong Kwok-Kin
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
Dana-Farber Cancer Institute, Boston, MA, United States.
Psychoneuroendocrinology. 2015 Aug;58:9-22. doi: 10.1016/j.psyneuen.2015.04.004. Epub 2015 Apr 13.
Leukocyte telomere length (LTL) is a marker of cellular turnover and oxidative stress. Studies suggest major depressive disorder (MDD) is associated with oxidative stress, but examinations of MDD and LTL have yielded mixed results, likely because of differences in measurement methods and unmeasured confounding. This study examined LTL and telomerase activity in 166 individuals with MDD compared to 166 age- and gender-matched matched controls free of any psychiatric disorder, using well-validated assays and clinical assessment methods, and controlling for a range of potential confounders.
Subjects aged 18 to 70 were evaluated by trained raters and provided blood for LTL and telomerase activity measurement. LTL was assayed using Southern blot and replicated with qPCR, and telomerase activity was assayed with a repeat amplification protocol using a commercial kit.
There was no significant difference in telomere length for individuals with MDD [mean (SD)=9.1 (3.0)kbp] compared to controls [mean(SD)=8.9(2.5)kbp] measured by Southern blot (p=0.65) or by confirmatory qPCR (p=0.91) assays. Controlling for potential confounders did not alter the results. Telomerase activity did not differ by MDD diagnosis overall (p=0.40), but the effect of MDD was significantly modified by gender (t(299)=2.67, p=0.0079) even after controlling for potential confounders, with telomerase activity significantly greater only in males with MDD versus controls.
Our well-characterized, well-powered examination of concurrently assessed telomere length and telomerase activity in individuals with clinically significant, chronic MDD and matched controls failed to provide strong evidence of an association of MDD with shorter LTL, while telomerase activity was higher in men with MDD [corrected].
白细胞端粒长度(LTL)是细胞更新和氧化应激的标志物。研究表明,重度抑郁症(MDD)与氧化应激有关,但对MDD和LTL的研究结果不一,这可能是由于测量方法的差异和未测量的混杂因素所致。本研究使用经过充分验证的检测方法和临床评估方法,对166例MDD患者和166例年龄及性别匹配的无任何精神疾病的对照者进行了LTL和端粒酶活性检测,并对一系列潜在混杂因素进行了控制。
由经过培训的评估人员对年龄在18至70岁的受试者进行评估,并采集血液用于LTL和端粒酶活性检测。LTL采用Southern印迹法检测,并用qPCR进行重复检测,端粒酶活性采用商业试剂盒通过重复扩增协议进行检测。
通过Southern印迹法(p = 0.65)或验证性qPCR检测(p = 0.91),MDD患者的端粒长度[平均值(标准差)= 9.1(3.0)kbp]与对照组[平均值(标准差)= 8.9(2.5)kbp]相比无显著差异。控制潜在混杂因素并未改变结果。总体而言,MDD诊断对端粒酶活性无差异(p = 0.40),但即使在控制潜在混杂因素后,MDD的影响在性别上仍有显著改变(t(299)=2.67,p = 0.0079),仅MDD男性患者的端粒酶活性显著高于对照组。
我们对具有临床意义的慢性MDD患者和匹配对照者同时评估端粒长度和端粒酶活性进行了特征明确、样本量充足的研究,未能提供有力证据证明MDD与较短的LTL相关,而MDD男性患者的端粒酶活性较高[校正后]。