McFarquhar Martyn, Elliott Rebecca, McKie Shane, Thomas Emma, Downey Darragh, Mekli Krisztina, Toth Zoltan G, Anderson Ian M, Deakin J F William, Juhasz Gabriella
Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Cathie Marsh Centre for Census and Survey Research, School of Social Sciences, Faculty of Humanities, University of Manchester, Manchester, UK.
Neuropsychopharmacology. 2014 Jun;39(7):1743-53. doi: 10.1038/npp.2014.22. Epub 2014 Jan 29.
Evidence suggests that depression is a risk factor for dementia; however, the relationship between the two conditions is not fully understood. A novel gene (TOMM40) has been consistently associated with Alzheimer's disease (AD), but has received no attention in depression. We conducted a three-level cross-sectional study to investigate the association of the TOMM40 rs2075650 SNP with depression. We recruited a community sample of 1220 participants (571 controls, 649 lifetime depression) to complete a psychiatric background questionnaire, the Brief Symptom Inventory, and Big Five Inventory at Level-1, 243 (102 controls, 97 remitted, 44 currently depressed) to complete a face-to-face clinical interview and neuropsychological testing at Level-2 and 58 (33 controls, 25 remitted) to complete an emotional face-processing task during fMRI at Level-3. Our results indicated that the TOMM40 rs2075650 G allele was a significant risk factor for lifetime depression (p = 0.00006) and, in depressed subjects, was a significant predictor of low extraversion (p = 0.009). Currently depressed risk allele carriers showed subtle executive dysfunction (p = 0.004) and decreased positive memory bias (p = 0.021) together with reduced activity in the posterior (p(FWE) = 0.045) and anterior (p(FWE) = 0.041) cingulate during sad face emotion processing. Our results suggest that TOMM40 rs2075650 may be a risk factor for the development of depression characterized by reduced extraversion, impaired executive function, and decreased positive emotional recall, and reduced top-down cortical control during sad emotion processing.
有证据表明，抑郁症是痴呆症的一个风险因素；然而，这两种病症之间的关系尚未完全明了。一种新基因（TOMM40）一直与阿尔茨海默病（AD）相关，但在抑郁症方面尚未受到关注。我们开展了一项三级横断面研究，以调查TOMM40 rs2075650单核苷酸多态性（SNP）与抑郁症的关联。我们招募了一个由1220名参与者组成的社区样本（571名对照者，649名终生患抑郁症者），在一级层面完成一份精神科背景问卷、简明症状量表和大五人格量表；243名参与者（102名对照者，97名缓解期患者，44名当前抑郁症患者）在二级层面完成面对面临床访谈和神经心理学测试；58名参与者（33名对照者，25名缓解期患者）在三级层面于功能磁共振成像（fMRI）期间完成一项情绪面孔加工任务。我们的结果表明，TOMM40 rs2075650 G等位基因是终生患抑郁症的一个显著风险因素（p = 0.00006），并且在抑郁症患者中，是外向性低的一个显著预测指标（p = 0.009）。当前患抑郁症的风险等位基因携带者表现出轻微的执行功能障碍（p = 0.004）和积极记忆偏差降低（p = 0.021），同时在悲伤面孔情绪加工期间，扣带回后部（p(FWE) = 0.045）和前部（p(FWE) = 0.041）的活动减少。我们的结果表明，TOMM40 rs2075650可能是抑郁症发生的一个风险因素，其特征为外向性降低、执行功能受损、积极情绪回忆减少，以及在悲伤情绪加工期间自上而下的皮层控制减弱。
