Metcalf Christina A, Johnson Rachel L, Duffy Korrina A, Freeman Ellen W, Sammel Mary D, Epperson C Neill
Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Department of Biostatistics & Informatics, Colorado School of Public Health, Aurora, Colorado, USA.
Stress Health. 2024 Apr;40(2):e3313. doi: 10.1002/smi.3313. Epub 2023 Sep 7.
To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1β), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1β, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.
为了确定在一个中年女性纵向社区队列中，不良童年经历和当前生活压力源的高暴露是否会调节炎症因子与具有临床意义的抑郁症状之间的关系。方法：宾夕法尼亚卵巢衰老研究社区队列中的参与者（基线年龄：M = 45.3 [标准差 = 3.8]），如果他们在至少一次就诊时采集了测量基础炎症标志物的血样，且同时评估了抑郁症状严重程度和当前应激性生活事件，则纳入分析（N = 142，每位参与者的平均就诊次数 = 1.75 [标准差 = 0.92]）。在16年的时间里，参与者大约每年使用流行病学研究中心抑郁量表（CESD）自我报告抑郁症状严重程度，提供月经日记以确定绝经阶段，并提供血样。对剩余血样检测白细胞介素（IL）-6、白细胞介素1-β（IL-1β）、肿瘤坏死因子α（TNF-α）和高敏C反应蛋白（hsCRP）。使用儿童期不良经历问卷对早年生活压力进行量化（低 [0 - 1次经历] 与高 [≥ 2次经历]）。使用结构化访谈评估当前应激性生活事件（低 [0 - 1个事件] 与高 [≥ 2个事件]）。使用广义估计方程模型对与感兴趣的结果——具有临床意义的抑郁症状（CESD≥16）——以及危险因素：炎症标志物水平（对数转换）、儿童期不良经历组和当前生活压力源组之间的关联进行建模。协变量包括绝经阶段、研究基线时的年龄、体重指数、种族和吸烟状况。在调整协变量后，我们发现hsCRP水平对数、儿童期不良经历组和当前生活压力源组之间在出现具有临床意义的抑郁症状可能性上存在显著的三向交互作用（比值比：4.33；95%置信区间：1.22，15.46；p = 0.024）。仅对于具有高儿童期不良经历和高当前生活压力源的女性，较高的hsCRP与具有临床意义的抑郁症状的较高几率相关（比值比：1.46；95%置信区间1.07，1.98；p = 0.016）。这种三向交互作用对于IL-6、IL-1β或TNF-α不显著。对于中年期暴露于高儿童期不良经历和多种当前生活压力源的女性，CRP水平升高与具有临床意义的抑郁症状独特相关。早年生活逆境和当前生活压力源是可识别的个体危险因素，其负面影响可能通过针对中年女性炎症的干预措施而减轻。
