Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
Department of Psychiatry, University of California, San Francisco, School of Medicine, San Francisco, CA, USA.
Mol Psychiatry. 2014 Aug;19(8):895-901. doi: 10.1038/mp.2013.151. Epub 2013 Nov 12.
Patients with major depressive disorder (MDD) have an increased onset risk of aging-related somatic diseases such as heart disease, diabetes, obesity and cancer. This suggests mechanisms of accelerated biological aging among the depressed, which can be indicated by a shorter length of telomeres. We examine whether MDD is associated with accelerated biological aging, and whether depression characteristics such as severity, duration, and psychoactive medication do further impact on biological aging. Data are from the Netherlands Study of Depression and Anxiety, including 1095 current MDD patients, 802 remitted MDD patients and 510 control subjects. Telomere length (TL) was assessed as the telomere sequence copy number (T) compared to a single-copy gene copy number (S) using quantitative polymerase chain reaction. This resulted in a T/S ratio and was converted to base pairs (bp). MDD diagnosis and MDD characteristics were determined by self-report questionnaires and structured psychiatric interviews. Compared with control subjects (mean bp=5541), sociodemographic-adjusted TL was shorter among remitted MDD patients (mean bp=5459; P=0.014) and current MDD patients (mean bp=5461; P=0.012). Adjustment for health and lifestyle variables did not reduce the associations. Within the current MDD patients, separate analyses showed that both higher depression severity (P<0.01) and longer symptom duration in the past 4 years (P=0.01) were associated with shorter TL. Our results demonstrate that depressed patients show accelerated cellular aging according to a 'dose-response' gradient: those with the most severe and chronic MDD showed the shortest TL. We also confirmed the imprint of past exposure to depression, as those with remitted MDD had shorter TL than controls.
患有重度抑郁症（MDD）的患者发生与衰老相关的躯体疾病（如心脏病、糖尿病、肥胖和癌症）的发病风险增加。这表明抑郁患者存在加速生物学衰老的机制，而端粒较短可以表明这种衰老。我们检验了 MDD 是否与加速生物学衰老有关，以及抑郁的严重程度、持续时间和精神活性药物等特征是否会进一步影响生物学衰老。该研究的数据来自荷兰抑郁和焦虑研究，共纳入了 1095 例当前 MDD 患者、802 例缓解 MDD 患者和 510 例对照。使用定量聚合酶链反应，通过将端粒序列拷贝数（T）与单拷贝基因拷贝数（S）进行比较来评估端粒长度（TL），这得到了 T/S 比值，并转换为碱基对（bp）。MDD 诊断和 MDD 特征通过自我报告问卷和结构化精神科访谈来确定。与对照组（平均 bp=5541）相比，缓解期 MDD 患者（平均 bp=5459；P=0.014）和当前 MDD 患者（平均 bp=5461；P=0.012）的端粒长度校正后的 TL 更短。调整健康和生活方式变量并不能降低这些关联。在当前 MDD 患者中，单独的分析表明，抑郁严重程度越高（P<0.01）以及过去 4 年内症状持续时间越长（P=0.01）与 TL 越短相关。我们的研究结果表明，根据“剂量-反应”梯度，抑郁患者表现出加速的细胞衰老：病情最严重和慢性 MDD 患者的 TL 最短。我们还证实了过去暴露于抑郁的影响，因为缓解期 MDD 患者的 TL 比对照组更短。
