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

Abstract

Adolescents who experience peer victimization (PV) often report psychosomatic complaints; however, little is known about possible underlying molecular effects. Social adversity has already been shown to downregulate immune genes and upregulate inflammatory genes. This study investigated PV for potentially enduring molecular effects, in terms of gene expression, leukocyte composition, and cytokine levels in young adulthood. Participants (n = 144; 47% female) were drawn from the Zurich Brain and Immune Gene Study (z-GIG). PV was studied from age 11 to 20, and molecular data were collected at age 22. A counterfactual framework with genetically informed inverse probability weighting was applied to account for individual and environmental confounders. Compared to non-PV controls, victims showed extensive immune changes. In silico deconvolution revealed shifts in leukocyte composition, including an M2-like monocyte–skewed profile. Differentially expressed genes were enriched in several Reactome pathways, including Interferon signaling, Metabolism, Signal transduction, Chromatin Organization, and Metabolism of Proteins. Transcription factors STAT2 and IRF2 emerged as key regulators, with target genes primarily in the Interferon Signaling and Chromatin Organization pathways. Cytokine levels also differed, including elevated pro-inflammatory markers such as CCL4, TNF, CXCL9, and CXCL10. The findings provide preliminary evidence of the immunomodulatory potential of PV and highlight the importance of public health strategies aimed at prevention, building resilience, and mitigating long-term effects.