The association between C-reactive protein, mood disorder, and cognitive function in UK Biobank

Abstract

Background Systemic inflammation has been linked with mood disorder and cognitive impairment. The extent of this relationship remains uncertain, with the effects of serum inflammatory biomarkers compared to genetic predisposition toward inflammation yet to be clearly established. Methods We investigated the magnitude of associations between C-reactive protein (CRP) measures, lifetime history of bipolar disorder or major depression, and cognitive function (reaction time and visuospatial memory) in 84,268 UK Biobank participants. CRP was measured in serum and a polygenic risk score for CRP was calculated, based on a published genome-wide association study. Multiple regression models adjusted for sociodemographic and clinical confounders. Results Increased serum CRP was significantly associated with mood disorder history (Kruskal–Wallis H = 196.06, p < 0.001, η2 = 0.002) but increased polygenic risk for CRP was not (F = 0.668, p = 0.648, η2 < 0.001). Compared to the lowest quintile, the highest serum CRP quintile was significantly associated with both negative and positive differences in cognitive performance (fully adjusted models: reaction time B = −0.030, 95% CI = −0.052, −0.008; visuospatial memory B = 0.066, 95% CI = 0.042, 0.089). More severe mood disorder categories were significantly associated with worse cognitive performance and this was not moderated by serum or genetic CRP level. Conclusions In this large cohort study, we found that measured inflammation was associated with mood disorder history, but genetic predisposition to inflammation was not. The association between mood disorder and worse cognitive performance was very small and did not vary by CRP level. The inconsistent relationship between CRP measures and cognitive performance warrants further study.

The association of anxiety and stress-related disorders with C-reactive protein (CRP) within UK Biobank

“…The primary outcome variable was inflammation as measured by high-sensitivity C-reactive protein (CRP) collected via blood samples during the baseline data collection ( Fry et al., 2019 ; Milton et al., 2021 ). Circulating CRP levels were measured using high sensitivity assays of all participants at baseline.…”

Psychiatric symptoms and cognitive impairment in “Long COVID”: the relevance of immunopsychiatry

“…The COVID-19 pandemic also provides an excellent example of the power of embedding a highly simplified, randomized trial platform comparing available and licensed medicines in real world settings. The RECOVERY trial was rapidly designed and set up in March 2020 5 . It randomized over 35,000 patients by February 2021.…”

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Socially stratified DNA-methylation profiles are associated with disparities in child and adolescent mental health

“…While inflammation is an essential component of immunosurveillance and host defense, a chronic low-grade inflammatory state is a pathological feature of a wide range of chronic health conditions that is also known to affect brain and psychological development 9,10 . Second, we examined genetic profiles of inflammation (i.e., polygenic scores of CRP, PGS-CRP 11 ), because there are genetic correlations of CRP with mood disorders in adults, such as PTSD 12 and depressive symptoms 13 that may include causal effects of CRP on depression 14,15 . Third, we previously reported that socioeconomic disadvantage and Latinx compared to White identity is associated with the pace of multi-system biological aging, as indicated by DunedinPoAm 16 , in an earlier sub-sample of salivary DNA-methylation data from the Texas Twin Project (N=600) 17 .…”