Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts.
Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts.
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DOI：
10.1038/s41380-021-01188-w
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发表时间：
2021-12
影响因子：
11
通讯作者：
Khandaker GM
中科院分区：
文献类型：
--
作者：
Milaneschi Y;Kappelmann N;Ye Z;Lamers F;Moser S;Jones PB;Burgess S;Penninx BWJH;Khandaker GM
我们研究了炎症是否与所有抑郁和焦虑症状一致相关，以及这些相关性是否具有潜在的因果关系。数据来自英国生物银行（UKB）的147，478人和荷兰抑郁和焦虑研究（NESDA）的2，905人。在两个队列中测量循环C反应蛋白（CRP），在NESDA中测量白细胞介素-6（IL-6）。这些蛋白质的遗传工具从已发表的GWAS和UKB获得。抑郁和焦虑症状进行了评估与自我报告问卷。在NESDA中，神经植物性（食欲，睡眠，精神）症状被分解为增加与减少。在联合分析中，较高的CRP与抑郁情绪的抑郁症状相关，（OR = 1.06，95%CI = 1.05-1.08），食欲改变（OR = 1.25，95%CI = 1.23-1.28），睡眠问题（OR = 1.05，95%CI = 1.04-1.06），疲劳（OR = 1.12，95% CI = 1.11-1.14）、焦虑易怒症状（OR = 1.06，95% CI = 1.05-1.08）、控制感担忧症状（OR = 1.03，95% CI = 1.02-1.04）。在NESDA中，较高的IL-6还与快感缺乏相关（OR = 1.30，95%CI = 1.12-1.52）。CRP（OR = 1.27，95%CI = 1.13-1.43）和IL-6（OR = 1.26，95%CI = 1.07-1.49）水平升高与睡眠增加相关。CRP升高与食欲增加相关（OR = 1.21，95% CI = 1.08-1.35），IL-6升高与食欲下降相关（OR = 1.45，95% CI = 1.18-1.79）。在孟德尔随机化分析中，遗传预测的较高IL-6活性与疲劳（估计值= 0.25，SE = 0.08）和睡眠问题（估计值= 0.19，SE = 0.07）的风险增加相关。炎症与情绪低落和快感缺乏的核心抑郁症状以及疲劳、睡眠改变和食欲变化的躯体/神经植物性症状相关。与焦虑的关联性不太一致。IL-6/IL-6 R通路可能与抑郁症有因果关系。实验研究需要进一步评估因果关系，机制和抑郁症的免疫治疗的有用性。
We examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05–1.08), altered appetite (OR = 1.25, 95%CI = 1.23–1.28), sleep problems (OR = 1.05, 95%CI = 1.04–1.06), and fatigue (OR = 1.12, 95% CI = 1.11–1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05–1.08) and worrying control (OR = 1.03, 95% CI = 1.02–1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12–1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13–1.43) and IL-6 (OR = 1.26, 95% CI = 1.07–1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08–1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18–1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms.
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DOI：
10.1016/j.bbi.2015.06.001
发表时间：
2015-10
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Haapakoski R;Mathieu J;Ebmeier KP;Alenius H;Kivimäki M
通讯作者：
Kivimäki M
影响因子：
25.8
作者：
Khandaker GM;Pearson RM;Zammit S;Lewis G;Jones PB
通讯作者：
Jones PB
影响因子：
2.5
作者：
Fourrier C;Sampson E;Mills NT;Baune BT
通讯作者：
Baune BT
影响因子：
11
作者：
Khandaker, Golam M.;Zuber, Verena;Burgess, Stephen
通讯作者：
Burgess, Stephen
影响因子：
6.9
作者：
Badini I;Coleman JRI;Hagenaars SP;Hotopf M;Breen G;Lewis CM;Fabbri C
通讯作者：
Fabbri C