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...

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Veröffentlicht in:Translational psychiatry Jg. 15; H. 1; S. 164 - 14
Hauptverfasser: 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.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 10.05.2025
Nature Publishing Group
Schlagworte:
13/21
631/208/2489
631/477/2811
Adult
Affect
Anxiety disorders
Anxiety Disorders - blood
Anxiety Disorders - genetics
Anxiety Disorders - psychology
Attention
Behavioral Sciences
Biological Psychology
Biomarkers - blood
C-Reactive Protein - metabolism
Cognition
Cognition & reasoning
Cohort analysis
Cohort Studies
Depressive Disorder - blood
Depressive Disorder - genetics
Episodic memory
Executive Function
Female
Humans
Inflammation
Inflammation - blood
Inflammation - genetics
Inflammation - psychology
Interleukin-6 - blood
Male
Medicine
Medicine & Public Health
Memory, Episodic
Mendelian Randomization Analysis
Middle Aged
Netherlands
Neurosciences
Pharmacotherapy
Prospective Studies
Psychiatry
Receptors, Interleukin-6 - blood
Receptors, Interleukin-6 - genetics
Netherlands
ISSN:2158-3188, 2158-3188
Online-Zugang:Volltext
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Zusammenfassung: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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ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-025-03372-w