Peer Victimization Affects Gene Expression Profiles during Adolescence

• In Event: Pathways to Adolescent Physical Health Outcomes: Unpacking the Power of Peers

Abstract

Adolescents who are exposed to peer victimization are at increased risk for developing a wide range of mental health problems as well as poor physical health, such as sleep disturbances, high BMI, and elevated biomarkers of cardiovascular risk. Mounting evidence suggests that these health consequences may also persist until adulthood, several years after exposure to victimization. These findings raise the possibility that the pervasive and long-lasting effects of victimization are the result of processes of biological embedding. Yet, little work has directly examined the extent to which peer victimization is associated with molecular processes that may be involved in disease risk.

This study aimed to address this research gap by investigating the extent to which a history of peer victimization is associated with an altered gene expression profile characterized by increased pro-inflammatory activity and decreased antiviral and antibody-related activity. This profile, referred to as Conserved Transcriptional Response to Adversity (CTRA), has been previously observed among adults with a history of adversity and is suggested to have major implications for health.

Participants were 172 Dutch adolescents (44.2% girls; Mage = 12.66 years, SD = 0.52 at baseline) followed over four time points, during the first two years of secondary school. Adolescents’ self-reported peer victimization was assessed at each time point and genome-wide transcriptional profiling of RNA was assayed from dried blood spot samples collected at Time 4. First, using a Confirmatory Factor Analysis, a latent variable representing adolescents’ history of peer victimization across Time 1-4 was computed with the peer victimization scores at the four time points as manifested indicators. Subsequently, an approach that combined hypothesis-free and hypothesis-driven analyses was employed to examine the link between the latent variable of peer victimization and the CTRA gene expression profile, adjusting for a set of a priori covariates (i.e., sex, race, age, BMI, smoking, heavy alcohol consumption, and current illness symptoms).

Genome-wide transcriptional analyses (hypothesis-free analyses) showed a total of 361 gene transcripts to be up-regulated as a function of peer victimization and 299 gene transcripts were found to be down-regulated. Consistent with the CTRA profile, hypotheses-driven bioinformatics analyses of transcription factors regulating those genes (TELiS analyses) indicated reduced activity of Interferon Response Factors in adolescents experiencing high levels of peer victimization. However, contrary to the CTRA hypothesis, results also indicated reduced pro-inflammatory gene regulation (i.e., NF-kB, AP-1) in peer victimized adolescents. Follow-up analyses distinguishing between occasional peer victimization (scores >0.75 SD from the mean on 1 assessment only) and chronic peer victimization (>0.75 SD from the mean on at least 2 assessments) found reduced pro-inflammatory activity (NF-kB and AP-1) only among chronically victimized adolescents, whereas occasionally victimized adolescents showed the CTRA-typical enhanced NF-kB activity, as compared to non-victimized adolescents.

These results reveal a distinct set of transcriptional alterations associated with chronic vs. occasional peer victimization, with the typical CTRA profile emerging in those experiencing occasional victimization and a distinct, more globally immunosuppressed profile emerging in those experiencing chronic victimization. Ongoing analyses seek to characterize the psychological and neuroendocrine mechanisms of both profiles.

Authors

• Matteo Giletta, Ghent University
  Presenting Author

• Steve W Cole, University of California, Los Angeles
  Non-Presenting Author