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

Inflammation has been linked to various neuropsychiatric symptoms, though the direction of this relationship is still uncertain. To explore whether inflammation influences mood disorders, anxiety, and cognitive performance, Mac Giollabhui et al. (2025) employed a combination of non-genetic methods, genetic risk scores (GRS), and Mendelian randomization (MR) analyses. They studied data from approximately 55,098 individuals (59% women) in the Dutch Lifelines cohort, examining both current and future associations between C-reactive protein (CRP) levels and emotional as well as cognitive outcomes. These included depression, anxiety, positive and negative affect, and cognitive functions like attention, psychomotor speed, memory, and executive skills, assessed initially and again after an average of 3.91 years. Additionally, the study assessed how genetic predispositions for inflammation—measured by GRSs for CRP, interleukin-6 (IL-6), IL-6 receptor (IL-6R and soluble IL-6R), and glycoprotein acetyls (GlycA)—related to these outcomes in up to nearly 58,000 participants. Findings from non-genetic analysis showed that higher CRP levels were linked to depression, increased negative affect, decreased positive affect, and impairments in executive function, attention, and psychomotor speed—even after adjusting for other factors. Genetically, the CRP GRS was related to anxiety disorders, and the GlycA GRS was tied to major depression. Both CRP and GlycA GRSs were also associated with more negative affect. Most inflammatory GRSs did not show associations with cognition, except for the soluble IL-6R GRS, which was linked to poorer memory. Although the MR analysis did not find strong evidence for CRP causing anxiety, results across methods consistently indicated a relationship between inflammation and negative emotional states. Overall, these findings suggest that inflammation may play a role in a wide range of emotional symptoms across different psychiatric conditions. [NPID: Inflammation, C-reactive protein, genetic risk scores, negative affect, depression, anxiety, cognition, lifelines cohort, interleukin-6]

Year: 2025

Reference: Mac Giollabhui, N., Slaney, C., Hemani, G., Foley, É. M., van der Most, P. J., Nolte, I. M., Snieder, H., Davey Smith, G., Khandaker, G. M., & Hartman, C. A. (2025). Role of inflammation in depressive and anxiety disorders, affect, and cognition: genetic and non-genetic findings in the lifelines cohort study. Translational Psychiatry, 15(1), 164. https://doi.org/10.1038/s41398-025-03372-w

Related Studies

Dietary fiber and its associations with depression and inflammation

Action of dietary fibers on inflammation and depression This review explored the action of dietary fibers on inflammation and depression, and the poorly understood mechanism between the two. This included looking at microbiota-driven modification of gene expression and increased neurotransmitter production as possibilities. Swann et al. (2020) identified a possible mediatory effect of inflammation on […]

Diet quality, dietary inflammatory index and body mass index as predictors of response to adjunctive N-acetylcysteine and mitochondrial agents in adults with bipolar disorder: A sub-study of a randomised placebo-controlled trial

Ashton et al. (2020) examined a randomized controlled trial on the impact of several nutraceutical treatments on patients with bipolar depression. The 133 participants received 16 weeks adjunctive treatment of either placebo or N-acetylcysteine (alone or combined with mitochondrial-enhancing nutraceuticals). Four weeks after stopping the treatment, the subjects were assessed on diet (quality, inflammatory potential), […]