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. This study investigated the effects of peer victimization (PV) during adolescence on gene expression, cellular dynamics, and cytokine profiles in young adulthood. Data from the Zurich Brain and Immune Gene Study (z-GIG, n = 200; 47% female) captured PV between ages 11 and 20, with mRNA and plasma cytokines analyzed in 144 participants at age 22. A counterfactual design with genetically informed inverse probability weighting adjusted for baseline confounders in individual and environmental characteristics. In silico deconvolution revealed altered leukocyte composition in victims, including an M2-like monocyte-skewed profile. Differentially expressed genes in victims were enriched in preselected Reactome pathways, including Interferon signaling, Metabolism and Signal transduction. Exploratory Reactome-wide queries confirmed pathways in the Immune System and Metabolism, highlighted their downregulation, and identified additional pathways, such as those involved in Chromatin organization and Metabolism of proteins. Transcription factors STAT2, IRF2, and NF-{kappa}B emerged as key regulators in victims, with target genes prominently mapped to Interferon signaling and Chromatin organization pathways. Victims exhibited altered cytokine levels, including pro-inflammatory CCL4, TNF, CXCL9, and CXCL10. These findings suggest that adolescent PV can lead to changes in gene regulation and cytokine levels, potentially altering the immune profile into young adulthood. The results underscore the importance of health policies aimed at prevention, building resilience, and mitigating the long-term effects of PV.