Steffens D C, Plassman B L, Helms M J, Welsh-Bohmer K A, Saunders A M, Breitner J C
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Biol Psychiatry. 1997 Apr 15;41(8):851-6. doi: 10.1016/S0006-3223(96)00247-8.
A prior history of depression and the epsilon 4 allele of apolipoprotein E (APOE) have each been associated with development of Alzheimer's disease (AD). In a sample of 142 elderly twins from a large study of dementia, we examined the relation of major depression, APOE genotype and AD using time-dependent proportional hazards models. Compared against the risk for AD with no history of depression and no epsilon 4 allele, the risk ratio for AD with two epsilon 4 alleles was 2.87 (C.I. = 1.56-5.28), with one epsilon 4 allele, 1.82 (C.I. = 1.09-3.04) and with late-onset depression and no epsilon 4 allele, 2.95 (C.I. = 1.55-5.62). There was no suggestion of an interaction between prior depression and APOE genotype in their effects on AD risk. Results were similar when the sample was stratified by twin pair, so that a single genetic marker is unlikely to explain the relation among depression, APOE, and dementia. Risk ratios declined substantially with increasing intervals between the onset of depression and AD. Thus, for many individuals, the association of depression and AD may reflect the occurrence of prodromal depressive symptoms rather than a true risk relationship.
抑郁症病史和载脂蛋白E（APOE）的ε4等位基因均与阿尔茨海默病（AD）的发生有关。在一项大型痴呆症研究中的142对老年双胞胎样本中，我们使用时间依赖性比例风险模型研究了重度抑郁症、APOE基因型与AD之间的关系。与无抑郁症病史且无ε4等位基因的AD风险相比，携带两个ε4等位基因的AD风险比为2.87（置信区间=1.56 - 5.28），携带一个ε4等位基因的为1.82（置信区间=1.09 - 3.04），而患有晚发性抑郁症且无ε4等位基因的为2.95（置信区间=1.55 - 5.62）。既往抑郁症和APOE基因型对AD风险的影响之间没有相互作用的迹象。当按双胞胎对分层样本时结果相似，因此单一遗传标记不太可能解释抑郁症、APOE和痴呆症之间的关系。随着抑郁症发作与AD之间间隔时间的增加，风险比大幅下降。因此，对于许多个体而言，抑郁症与AD之间的关联可能反映了前驱抑郁症状的出现，而非真正的风险关系。
