Peer victimization in adolescence alters gene expression and cytokine profiles during transition to adulthood

Abstract

Social adversity downregulates antiviral genes and upregulates inflammatory genes, altering cytokine levels. We investigated how peer victimization during adolescence affects gene expression, cytokine levels, and cellular dynamics in young adulthood. Using data from the Zurich Brain and Immune Gene Study (z-GIG, n=200; 47% female), we assessed peer victimization between ages 11 and 20 and analyzed mRNA abundance and plasma cytokine profiles from 144 participants at age 21. Employing a counterfactual design with genetically-informed inverse-probability weighting, we adjusted for baseline confounders in individual and environmental characteristics, enhancing causal inferences regarding peer victimization and health outcomes. In silico deconvolution displayed that victims exhibited altered leukocyte composition, including reduced MΦ1- and elevated MΦ2-like monocytes, compared to non- victimized peers. They also had higher proportions of activated dendritic cells and regulatory T cells, along with changes in various immune cell ratios. Differential expression of genes was overrepresented in immunomodulatory Reactome pathways, such as Immune system, Cytokine signaling in immune system, Interferon signaling, and Signaling by interleukins. Exploratory analysis revealed additional downregulated Reactome pathways of interest. Victims showed elevated levels of pro- inflammatory cytokines, including CCL5, CCL11, and IL-16 compared with controls. Transcription factors STAT2 and IRF1 were identified as key drivers, with numerous matches in overrepresented Reactome pathways. Findings suggest that adolescent peer victimization can lead to changes in gene regulatory activity and cytokine levels, potentially altering the immune profile in young adulthood. These results underscore the importance of health policies aimed at preventing peer victimization, building resilience, and mitigating its long-term effects.