Stress-related gene regulation: Do isolated and connected individuals differ?

Yvonne S. Yang, Jonathan K. Wynn, Steve Cole, Michael F. Green

Research output: Contribution to journalArticlepeer-review


Background: Social isolation and loneliness (known as social disconnection, collectively) lead to serious downstream health effects, including shortening of lifespan and higher risk for cardiac disease. We must better understand how isolation and loneliness lead to these negative health outcomes. Previous literature has demonstrated that social motivation and social ability are contributors to the likelihood of social isolation and loneliness. We examined the effect of the above social factors on immune gene expression in socially-connected and −isolated individuals. Methods: Recruitment occurred via two online advertisements, one for socially isolated individuals and another for general research participants. Participants (n = 102) were separated into groups (isolated versus connected) based on which ad they responded to, and provided data on isolation, loneliness, social motivation, and social ability. The Conserved Transcriptional Response to Adversity (CTRA) stress gene regulation program was assessed with genome-wide transcriptional profiling. Results: CTRA gene expression patterns were reversed between connected and isolated groups across several variables. Social isolation was associated with higher CTRA levels in the connected group, but lower levels in the isolated group. Social approach was associated with lower CTRA levels in the connected group, but higher in the isolated group, and the converse was true for social avoidance. CTRA levels were minimally affected by social ability measures. Conclusion: Prior work on social isolation and loneliness has focused on loneliness and has identified many negative downstream health effects. In this study we demonstrate that objective social isolation may not be associated with the same negative downstream health effects, and in fact, social interaction may be more stressful than social isolation for some socially-isolated individuals.

Original languageEnglish
Pages (from-to)372-378
Number of pages7
JournalBrain, Behavior, and Immunity
StatePublished - Aug 2024
Externally publishedYes

Bibliographical note

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© 2024


  • Brain immune connection
  • Conserved transcriptional response to adversity
  • Loneliness
  • Social isolation
  • Stress


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