title: Trait sensitivity to social disconnection enhances pro-inflammatory responses to a randomized controlled trial of endotoxin.
abstract: One proposed mechanism for the association between social isolation and poor health outcomes is inflammation. Lonely or socially disconnected individuals show greater inflammatory responses, including up-regulation of pro-inflammatory gene expression, and people who are sensitive to cues of social disconnection (e.g., high levels of anxious attachment) exhibit greater inflammation in response to psychological stress. However, no studies have examined how sensitivity to social disconnection may influence pro-inflammatory responses to an inflammatory challenge. In the present study, we investigated the impact of sensitivity to social disconnection (a composite score comprised of loneliness, anxious attachment, fear of negative evaluation, and rejection sensitivity) on pro-inflammatory cytokines and gene expression in response to endotoxin, an inflammatory challenge, vs. placebo in a sample of one hundred and fifteen (n=115) healthy participants. Results showed that those who are more sensitive to social disconnection show increased pro-inflammatory responses (i.e., increased levels of tumor necrosis factor-alpha and interleukin-6) to endotoxin, as well as up-regulation of multiple genes related to inflammation. Furthermore, bioinformatics analyses revealed that those in the endotoxin group who are more sensitive to social disconnection exhibited a conserved transcriptional response to adversity (CTRA) regulatory profile, involving up-regulation of beta-adrenergic and pro-inflammatory transcription control pathways and down-regulation of antiviral transcription factors in response to endotoxin. These results may ultimately have implications for understanding the links between social isolation, inflammation, and health.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01671150.
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Mona
authors.initials: M
authors.lastname: Moieni
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Irwin
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jevtic
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Breen
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Hyong Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, United States.
authors.forename: Jesusa M G
authors.initials: JM
authors.lastname: Arevalo
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, and Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095, United States. Electronic address: steve.cole@ucla.edu.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095, United States. Electronic address: neisenbe@ucla.edu.
authors.forename: Naomi I
authors.initials: NI
authors.lastname: Eisenberger
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000523:psychology; D015850:Interleukin-6 / Q000097:blood*; D008132:Loneliness / Q000523:psychology; D008297:Male; D010551:Personality; D012934:Social Isolation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
chemical_list: D004731:Endotoxins; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Cytokines; Endotoxin; Inflammation; Loneliness; Rejection sensitivity; Social genomics