Vincent John, Hovatta Iiris, Frissa Souci, Goodwin Laura, Hotopf Matthew, Hatch Stephani L, Breen Gerome, Powell Timothy R
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Department of Biosciences, University of Helsinki, Helsinki, Finland.
J Affect Disord. 2017 Apr 15;213:16-22. doi: 10.1016/j.jad.2017.01.031. Epub 2017 Feb 3.
Studies have provided evidence that both childhood maltreatment and depressive disorders are associated with shortened telomere lengths. However, as childhood maltreatment is a risk factor for depression, it remains unclear whether this may be driving shortened telomere lengths observed amongst depressed patients. Furthermore, it's unclear if the effects of maltreatment on telomere length shortening are more pervasive amongst depressed patients relative to controls, and consequently whether biological ageing may contribute to depression's pathophysiology. The current study assesses the effects of childhood maltreatment, depression case/control status, and the interactive effect of both childhood maltreatment and depression case/control status on relative telomere length (RTL).
DNA samples from 80 depressed subjects and 100 control subjects were utilized from a U.K. sample (ages 20-84), with childhood trauma questionnaire data available for all participants. RTL was quantified using quantitative polymerase chain reactions. Univariate linear regression analyses were used to assess the effects of depression status, childhood maltreatment and depression by childhood maltreatment interactions on RTL. The false discovery rate (q<0.05) was used for multiple testing correction.
Analysis of depression case/control status showed no significant main effect on RTL. Four subtypes of childhood maltreatment also demonstrated no significant main effect on RTL, however a history of physical neglect did significantly predict shorter RTL in adulthood (F(1, 174)=7.559, p=0.007, q=0.042, Variance Explained=4.2%), which was independent of case/control status. RTL was further predicted by severity of physical neglect, with the greatest differences observed in older maltreated individuals (>50 years old). There were no significant depression case/control status by childhood maltreatment interactions.
A relatively small sample limited our power to detect interaction effects, and we were unable to consider depression chronicity or recurrence.
Shortened RTL was specifically associated with childhood physical neglect, but not the other subtypes of maltreatment or depression case/control status. Our results suggest that the telomere-eroding effects of physical neglect may represent a biological mechanism important in increasing risk for ageing-related disorders. As physical neglect is more frequent amongst depressed cases generally, it may also represent a confounding factor driving previous associations between shorter RTL and depression case status.
研究表明,童年期受虐和抑郁症均与端粒长度缩短有关。然而,由于童年期受虐是抑郁症的一个风险因素,目前尚不清楚这是否会导致抑郁症患者端粒长度缩短。此外,尚不清楚相对于对照组,受虐对抑郁症患者端粒长度缩短的影响是否更为普遍,以及生物衰老是否会导致抑郁症的病理生理过程。本研究评估了童年期受虐、抑郁症病例/对照状态以及童年期受虐与抑郁症病例/对照状态的交互作用对相对端粒长度(RTL)的影响。
利用来自英国样本(年龄20-84岁)的80名抑郁症患者和100名对照者的DNA样本,所有参与者均有童年创伤问卷数据。使用定量聚合酶链反应对RTL进行定量。单变量线性回归分析用于评估抑郁症状态、童年期受虐以及童年期受虐与抑郁症的交互作用对RTL的影响。错误发现率(q<0.05)用于多重检验校正。
抑郁症病例/对照状态分析显示对RTL无显著主效应。童年期受虐的四种亚型对RTL也无显著主效应,然而,身体忽视史确实显著预测成年期RTL缩短(F(1, 174)=7.559,p=0.007,q=0.042,解释方差=4.2%),这与病例/对照状态无关。身体忽视的严重程度进一步预测了RTL,在受虐年龄较大的个体(>50岁)中观察到最大差异。童年期受虐与抑郁症病例/对照状态之间无显著交互作用。
样本量相对较小限制了我们检测交互作用的能力,并且我们无法考虑抑郁症的慢性或复发情况。
RTL缩短与童年期身体忽视密切相关,但与其他受虐亚型或抑郁症病例/对照状态无关。我们的结果表明,身体忽视对端粒的侵蚀作用可能是增加衰老相关疾病风险的重要生物学机制。由于身体忽视在抑郁症患者中通常更为常见,它也可能是导致先前RTL缩短与抑郁症病例状态之间关联的一个混杂因素。