Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK.
Section of Clinical Psychology, University of Edinburgh, Medical Quad, Teviot Place, Edinburgh EH8 9AG, UK.
Psychol Med. 2018 Aug;48(11):1890-1899. doi: 10.1017/S0033291717003415. Epub 2017 Nov 29.
Polygenic risk scores (PRS) for depression correlate with depression status and chronicity, and provide causal anchors to identify depressive mechanisms. Neuroticism is phenotypically and genetically positively associated with depression, whereas psychological resilience demonstrates negative phenotypic associations. Whether increased neuroticism and reduced resilience are downstream mediators of genetic risk for depression, and whether they contribute independently to risk remains unknown.
Moderating and mediating relationships between depression PRS, neuroticism, resilience and both clinical and self-reported depression were examined in a large, population-based cohort, Generation Scotland: Scottish Family Health Study (N = 4166), using linear regression and structural equation modelling. Neuroticism and resilience were measured by the Eysenck Personality Scale Short Form Revised and the Brief Resilience Scale, respectively.
PRS for depression was associated with increased likelihood of self-reported and clinical depression. No interaction was found between PRS and neuroticism, or between PRS and resilience. Neuroticism was associated with increased likelihood of self-reported and clinical depression, whereas resilience was associated with reduced risk. Structural equation modelling suggested the association between PRS and self-reported and clinical depression was mediated by neuroticism (43-57%), while resilience mediated the association in the opposite direction (37-40%). For both self-reported and clinical diagnoses, the genetic risk for depression was independently mediated by neuroticism and resilience.
Findings suggest polygenic risk for depression increases vulnerability for self-reported and clinical depression through independent effects on increased neuroticism and reduced psychological resilience. In addition, two partially independent mechanisms - neuroticism and resilience - may form part of the pathway of vulnerability to depression.
抑郁的多基因风险评分 (PRS) 与抑郁状态和慢性相关，并为识别抑郁机制提供因果关系的锚点。神经质在表型和遗传上与抑郁呈正相关，而心理弹性则表现出负相关。神经质增加和心理弹性降低是否是抑郁遗传风险的下游介质，以及它们是否独立增加风险仍不清楚。
使用线性回归和结构方程模型，在一个大型的基于人群的队列中，即苏格兰家族健康研究（Generation Scotland：Scottish Family Health Study，GS：SFHS）（N=4166）中，检查了抑郁 PRS、神经质、心理弹性以及临床和自我报告的抑郁之间的调节和中介关系。神经质和心理弹性分别用艾森克人格量表简式修订版和简短韧性量表测量。
抑郁 PRS 与自我报告和临床抑郁的可能性增加有关。PRS 与神经质或与心理弹性之间没有发现相互作用。神经质与自我报告和临床抑郁的可能性增加有关，而心理弹性与风险降低有关。结构方程模型表明，PRS 与自我报告和临床抑郁之间的关联是由神经质介导的（43-57%），而心理弹性则以相反的方向介导（37-40%）。对于自我报告和临床诊断，抑郁的遗传风险均由神经质和心理弹性独立介导。
研究结果表明，抑郁的多基因风险通过增加神经质和降低心理弹性对自我报告和临床抑郁的独立影响，增加了自我报告和临床抑郁的易感性。此外，神经质和心理弹性两个部分独立的机制可能是抑郁易感性的途径之一。
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