title: Mood disturbance during experimental endotoxemia: Predictors of state anxiety as a psychological component of sickness behavior.
abstract: Lipopolysaccharide (LPS) administration is a well-established model to assess afferent immune-to-brain communication and behavioral aspects of inflammation. Nevertheless, only few studies in comparatively small samples have assessed state anxiety as a psychological component of sickness behavior despite possible clinical implications for the pathophysiology of neuropsychiatric conditions. Thus, the goal of the present analyses carried out in a large, pooled dataset from two independent study sites was to analyze the state anxiety response to LPS administration and to investigate predictors (i.e., cytokine changes; pre-existing anxiety and depression symptoms assessed with the Hospital Anxiety and Depression Scale) of the LPS-induced state anxiety changes at different time points after LPS administration. Data from 186 healthy volunteers who participated in one of six randomized, placebo-controlled human studies involving intravenous administration of LPS at doses of 0.4-0.8ng/kg body weight were combined. State anxiety as well as circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 concentrations were significantly increased 2h and 3h after LPS administration, with a peak at 2h, and returned to baseline 6h after administration. Greater changes in IL-6 from baseline to 3h after LPS administration significantly and independently predicted a more pronounced LPS-induced state anxiety response. In addition, higher pre-existing subclinical anxiety symptoms significantly predicted a lower increase in state anxiety 3h and 6h after LPS-administration, which was mediated by TNF-α changes. In conclusion, our findings give additional support for a putative role of inflammatory mechanisms in the pathophysiology of stress-related and anxiety disorders and give new insight on the potential role of pre-existing subclinical affective symptoms.
authors.affiliation: Stockholm University, Stress Research Institute, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Neuroscience, Division of Psychology, Solna, Stockholm, Sweden; Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Julie
authors.initials: J
authors.lastname: Lasselin
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Elsenbruch
authors.affiliation: Stockholm University, Stress Research Institute, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Neuroscience, Division of Psychology, Solna, Stockholm, Sweden; Osher Center for Integrative Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lekander
authors.affiliation: Stockholm University, Stress Research Institute, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Neuroscience, Division of Psychology, Solna, Stockholm, Sweden; Osher Center for Integrative Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Axelsson
authors.affiliation: Stockholm University, Stress Research Institute, Stockholm, Sweden; Karolinska Institutet, Department of Clinical Neuroscience, Division of Psychology, Solna, Stockholm, Sweden.
authors.forename: Bianka
authors.initials: B
authors.lastname: Karshikoff
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany; Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Jan-Sebastian
authors.initials: JS
authors.lastname: Grigoleit
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Engler
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
authors.affiliation: Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Germany. Electronic address: sven.benson@uk-essen.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Benson
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D001007:Anxiety / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced; D005260:Female; D006801:Humans; D055809:Illness Behavior; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D055815:Young Adult
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides
keywords: Anxiety; Cytokines; HADS; Inflammation; Interleukin-6; Lipopolysaccharide; Predictor variables; Psychological condition; STAI; Sickness behavior