Research Department of Behavioural Science and Health, Institute of Epidemiology and Healthcare, University College London, London, UK.
Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Psychol Med. 2023 Mar;53(4):1426-1436. doi: 10.1017/S0033291721003007. Epub 2021 Aug 5.
Adverse childhood experiences (ACEs) and genetic liability are important risk factors for depression and inflammation. However, little is known about the gene-environment (G × E) mechanisms underlying their aetiology. For the first time, we tested the independent and interactive associations of ACEs and polygenic scores of major depressive disorder (MDD-PGS) and C-reactive protein (CRP-PGS) with longitudinal trajectories of depression and chronic inflammation in older adults.
Data were drawn from the English longitudinal study of ageing (~3400). Retrospective information on ACEs was collected in wave3 (2006/07). We calculated a cumulative risk score of ACEs and also assessed distinct dimensions separately. Depressive symptoms were ascertained on eight occasions, from wave1 (2002/03) to wave8 (2016/17). CRP was measured in wave2 (2004/05), wave4 (2008/09), and wave6 (2012/13). The associations of the risk factors with group-based depressive-symptom trajectories and repeated exposure to high CRP (i.e. ⩾3 mg/L) were tested using multinomial and ordinal logistic regression.
All types of ACEs were independently associated with high depressive-symptom trajectories (OR 1.44, 95% CI 1.30-1.60) and inflammation (OR 1.08, 95% CI 1.07-1.09). The risk of high depressive-symptom trajectories (OR 1.47, 95% CI 1.28-1.70) and inflammation (OR 1.03, 95% CI 1.01-1.04) was also higher for participants with higher MDD-PGS. G×E analyses revealed that the associations between ACEs and depressive symptoms were larger among participants with higher MDD-PGS (OR 1.13, 95% CI 1.04-1.23). ACEs were also more strongly related to inflammation in participants with higher CRP-PGS (OR 1.02, 95% CI 1.01-1.03).
ACEs and polygenic susceptibility were independently and interactively associated with elevated depressive symptoms and chronic inflammation, highlighting the clinical importance of assessing both ACEs and genetic risk factors to design more targeted interventions.
不良的童年经历（ACEs）和遗传易感性是抑郁和炎症的重要危险因素。然而，对于它们发病机制的基因-环境（G×E）机制知之甚少。我们首次测试了 ACEs 与大抑郁症多基因评分（MDD-PGS）和 C 反应蛋白多基因评分（CRP-PGS）的独立和交互关联，以及它们与老年人抑郁和慢性炎症的纵向轨迹。
数据来自英国老年人纵向研究（约 3400 人）。在第 3 波（2006/07 年）中收集 ACEs 的回顾性信息。我们计算了 ACEs 的累积风险评分，并分别评估了不同的维度。从第 1 波（2002/03 年）到第 8 波（2016/17 年），我们确定了抑郁症状。第 2 波（2004/05 年）、第 4 波（2008/09 年）和第 6 波（2012/13 年）测量了 CRP。使用多项和有序逻辑回归测试危险因素与基于群组的抑郁症状轨迹和反复暴露于高 CRP（即 ⩾3 mg/L）之间的关联。
所有类型的 ACEs 均与高抑郁症状轨迹（OR 1.44，95%CI 1.30-1.60）和炎症（OR 1.08，95%CI 1.07-1.09）独立相关。具有较高 MDD-PGS 的参与者患高抑郁症状轨迹（OR 1.47，95%CI 1.28-1.70）和炎症（OR 1.03，95%CI 1.01-1.04）的风险也更高。G×E 分析表明，在具有较高 MDD-PGS 的参与者中，ACEs 与抑郁症状之间的关联更大（OR 1.13，95%CI 1.04-1.23）。ACEs 与 CRP-PGS 较高的参与者的炎症也有更强的相关性（OR 1.02，95%CI 1.01-1.03）。
ACEs 和多基因易感性与升高的抑郁症状和慢性炎症独立且相互关联，突出了评估 ACEs 和遗传危险因素以设计更有针对性的干预措施的临床重要性。
