炎症在抑郁和焦虑障碍、情绪和认知中的作用：生命线队列研究中的遗传和非遗传发现。

IF 5.8 1区医学 Q1 PSYCHIATRY

Translational Psychiatry Pub Date : 2025-05-10 DOI:10.1038/s41398-025-03372-w

Naoise Mac Giollabhui, Chloe Slaney, Gibran Hemani, Éimear M Foley, Peter J van der Most, Ilja M Nolte, Harold Snieder, George Davey Smith, Golam M Khandaker, Catharina A Hartman

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引用次数: 0

摘要

炎症与一系列神经精神症状有关，但其因果关系尚不清楚。我们使用互补的非遗传、遗传风险评分（GRS）和孟德尔随机化（MR）分析来检查炎症标志物是否与情绪、抑郁和焦虑障碍以及认知相关。我们对来自荷兰生命线队列的约55,098名个体（59%为女性）进行了c -反应蛋白（CRP）与抑郁和焦虑障碍的并发/前瞻性关联测试；积极/消极的影响;注意力、精神运动速度、情景记忆和执行功能的基线和3.91年后的随访评估（SD = 1.21）。此外，我们研究了炎症GRSs （CRP、白细胞介素-6 [IL-6]、IL-6受体[IL-6R和可溶性IL-6R (sIL-6R)]、糖蛋白乙酰[GlycA]）与这些相同结果的关系(Nmin = 35300；Nmax = 57,946)，然后进行MR分析，检验CRP对结果的因果关系证据(Nmin= 22154；Nmax = 23,268)。在非遗传分析中，较高的CRP与抑郁症、较低的积极/较高的消极影响、较差的执行功能、注意力和精神运动速度相关，在调整潜在的混杂因素后。在遗传分析中，CRPGRS与任何焦虑症相关（β = 0.002, p = 0.037），而GlycAGRS与重度抑郁症相关（β = 0.001, p = 0.036）。CRPGRS （β = 0.006, p = 0.035）和GlycAGRS （β = 0.006, p = 0.049）与更大的负面情绪相关。炎性grs与认知无关，但sIL-6RGRS与较差的记忆相关（β = -0.009, p = 0.018）。MR结果显示crp -焦虑无显著相关性(β = 0.12；p = 0.054)。遗传和非遗传分析为CRP和负面影响之间的关联提供了一致的证据。这些结果表明，炎症可能影响广泛的跨诊断情感症状。

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Role of inflammation in depressive and anxiety disorders, affect, and cognition: genetic and non-genetic findings in the lifelines cohort study.

Inflammation is associated with a range of neuropsychiatric symptoms, but the issue of causality remains unclear. We used complementary non-genetic, genetic risk score (GRS), and Mendelian randomization (MR) analyses to examine whether inflammatory markers are associated with affect, depressive and anxiety disorders, and cognition. We tested in ≈55,098 (59% female) individuals from the Dutch Lifelines cohort the concurrent/prospective associations of C-reactive protein (CRP) with: depressive and anxiety disorders; positive/negative affect; and attention, psychomotor speed, episodic memory, and executive functioning at baseline and a follow-up assessment occurring 3.91 years later (SD = 1.21). Additionally, we examined the association between inflammatory GRSs (CRP, interleukin-6 [IL-6], IL-6 receptor [IL-6R and soluble IL-6R (sIL-6R)], glycoprotein acetyls [GlycA]) on these same outcomes (N_min = 35,300; N_max = 57,946), followed by MR analysis examining evidence of causality of CRP on outcomes (N_min=22,154; N_max = 23,268). In non-genetic analyses, higher CRP was associated with depressive disorder, lower positive/higher negative affect, and worse executive function, attention, and psychomotor speed after adjusting for potential confounders. In genetic analyses, CRP_GRS was associated with any anxiety disorder (β = 0.002, p = 0.037) whereas GlycA_GRS was associated with major depressive disorder (β = 0.001, p = 0.036). Both CRP_GRS (β = 0.006, p = 0.035) and GlycA_GRS (β = 0.006, p = 0.049) were associated with greater negative affect. Inflammatory GRSs were not associated with cognition, except sIL-6R_GRS which was associated with poorer memory (β = -0.009, p = 0.018). There was a non-significant CRP-anxiety association using MR (β = 0.12; p = 0.054). Genetic and non-genetic analyses provide consistent evidence for an association between CRP and negative affect. These results suggest that inflammation may impact a broad range of trans-diagnostic affective symptoms.

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来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.