UC Riverside

BACKGROUND: Social connection is critical to both psychological well-being and optimal immune function. The present study tested whether a behavioral intervention to increase social connection (promoting extraverted behavior) might reduce a threat-related immunoregulatory gene expression program known as the Conserved Transcriptional Response to Adversity (CTRA). The CTRA is characterized by elevated inflammatory gene expression and reduced innate antiviral gene expression in response to beta adrenergic signaling and has been associated with adverse social conditions such as loneliness and ostracism. METHODS: In an 8-week intervention (with 6-week behavior change protocol), participants from a campus community (N = 119; 87 % undergraduate; 9 % graduate; 4 % staff) were randomized to act more extraverted (sociable; Extraversion condition) or track routine daily activities (Control condition). Participants reported on psychological outcomes and provided dried blood spots for RNA sampling at pre-test (Week 0), post-test (Week 8), and 1-month follow-up (Week 12). Multilevel models tested condition differences in CTRA expression over time and examined mediation via psychological outcomes. RESULTS: Pre-registered analyses of pre-specified CTRA indicator genes showed no significant effects. Secondary genome-wide bioinformatic analyses of NF-κB, IRF, and CREB transcription control pathways found significantly greater reductions in CTRA-characteristic gene regulation among the Extraversion group relative to controls. These effects were partially mediated by reductions in loneliness. However, the intervention effect on CTRA gene regulation was not sustained at 1-month follow-up. IMPLICATIONS: Extraverted behavior may improve immune regulation by enhancing perceived social connection. Further research should replicate these findings and enhance the durability of effects.