Mac Giollabhui Naoise, Slaney Chloe, Hemani Gibran, Foley Éimear M, van der Most Peter J, Nolte Ilja M, Snieder Harold, Davey Smith George, Khandaker Golam M, Hartman Catharina A
Depression Clinical & Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, USA.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
Transl Psychiatry. 2025 May 10;15(1):164. doi: 10.1038/s41398-025-03372-w.
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 = 35,300; N = 57,946), followed by MR analysis examining evidence of causality of CRP on outcomes (N=22,154; N = 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 was associated with any anxiety disorder (β = 0.002, p = 0.037) whereas GlycA was associated with major depressive disorder (β = 0.001, p = 0.036). Both CRP (β = 0.006, p = 0.035) and GlycA (β = 0.006, p = 0.049) were associated with greater negative affect. Inflammatory GRSs were not associated with cognition, except sIL-6R 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.
炎症与一系列神经精神症状相关，但因果关系问题仍不明确。我们使用了互补的非基因、遗传风险评分（GRS）和孟德尔随机化（MR）分析，以研究炎症标志物是否与情感、抑郁和焦虑障碍以及认知相关。我们在来自荷兰生命线队列的约55,098名个体（59%为女性）中进行测试，检验了C反应蛋白（CRP）与以下各项的同时性/前瞻性关联：抑郁和焦虑障碍；积极/消极情感；以及在基线时和3.91年后（标准差 = 1.21）进行的随访评估中的注意力、心理运动速度、情景记忆和执行功能。此外，我们研究了炎症GRS（CRP、白细胞介素6 [IL-6]、IL-6受体[IL-6R和可溶性IL-6R（sIL-6R）]、糖蛋白乙酰化物[GlycA]）与这些相同结果之间的关联（N = 35,300；N = 57,946），随后进行MR分析以检验CRP对结果的因果关系证据（N = 22,154；N = 23,268）。在非基因分析中，在调整潜在混杂因素后，较高的CRP与抑郁症、较低的积极/较高的消极情感以及较差的执行功能、注意力和心理运动速度相关。在基因分析中，CRP与任何焦虑障碍相关（β = 0.002，p = 0.037），而GlycA与重度抑郁症相关（β = 0.001，p = 0.036）。CRP（β = 0.006，p = 0.035）和GlycA（β = 0.006，p = 0.049）均与更大的消极情感相关。炎症GRS与认知无关，除了sIL-6R与较差的记忆相关（β = -0.009，p = 0.018）。使用MR分析时，CRP与焦虑之间的关联不显著（β = 0.12；p = 0.054）。基因和非基因分析为CRP与消极情感之间的关联提供了一致的证据。这些结果表明，炎症可能会影响广泛的跨诊断情感症状。
