Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 Aug 10:rs.3.rs-4379779.
doi: 10.21203/rs.3.rs-4379779/v1.

Role of Inflammation in Depressive and Anxiety Disorders, Affect, and Cognition: Genetic and Non-Genetic Findings in the Lifelines Cohort Study

Naoise Mac Giollabhui  1 , Chloe Slaney, Gibran Hemani, Eimear Foley  2 , Peter van der Most, Ilja Nolte  3 , Harold Snieder  4 , George Davey Smith  2 , Golam Khandaker  5 , Catharina Hartman
Affiliations

Role of Inflammation in Depressive and Anxiety Disorders, Affect, and Cognition: Genetic and Non-Genetic Findings in the Lifelines Cohort Study

Naoise Mac Giollabhui et al. Res Sq. .

Update in

Abstract

Inflammation is associated with a range of neuropsychiatric symptoms; however, the nature of the causal relationship is 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. 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 (Nmax=57,946), followed by MR analysis examining evidence of causality of CRP on outcomes (Nmax=23,268). In non-genetic analyses, higher CRP was associated with a depressive disorder, lower positive/higher negative affect, and worse executive function, attention, and psychomotor speed after adjusting for potential confounders. In genetic analyses, CRPgrs was associated with any anxiety disorder (β = 0.002, p = 0.037) whereas GlycAGRS was associated with major depressive disorder (β = 0.001, p = 0.036). Both CRPgrs (β = 0.006, p = 0.035) and GlycAGRS (β = 0.006, p = 0.049) were associated with greater negative affect. Inflammatory GRSs were not associated with cognition, except slL-6RGRS which was associated with poorer memory (β=-0.009, p = 0.018). There was weak evidence for a 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 dysregulated immune physiology may impact a broad range of trans-diagnostic affective symptoms.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest No conflicts of interest were reported.

Figures

Figure 1
Figure 1
Associations of genetic risk scores for inflammatory markers with mood, anxiety disorders and positive and negative affect scores.
Figure 2
Figure 2
Associations of genetic risk scores for inflammatory markers with cognitive task performance.
Figure 3
Figure 3
Visualisation of the overall pattern of results for CRP in the cohort and genetic analyses
See this image and copyright information in PMC

References

    1. Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet 2020; 396(10258): 1204–1222. - PMC - PubMed
    1. James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet 2018; 392(10159): 1789–1858. - PMC - PubMed
    1. Taylor CA, Bouldin ED, McGuire LC. Subjective Cognitive Decline Among Adults Aged ≥45 Years - United States, 2015–2016. MMWR Morb Mortal Wkly Rep 2018; 67(27): 753–757. - PMC - PubMed
    1. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry 2014; 26(1): 102–113. - PMC - PubMed
    1. Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun 2022; 101: 93–135. - PMC - PubMed

Publication types

LinkOut - more resources