title: Impact of Serum Cytokine Levels on EEG-Measured Arousal Regulation in Patients with Major Depressive Disorder and Healthy Controls.
abstract: BACKGROUND
  In major depressive disorder (MDD), findings include hyperstable regulation of brain arousal measured by electroencephalography (EEG) vigilance analysis and alterations in serum levels of cytokines. It is also known that cytokines affect sleep-wake regulation. This study investigated the relationship between cytokines and EEG vigilance in participants with MDD and nondepressed controls, and the influence of cytokines on differences in vigilance between the two groups.
  
  
  METHODS
  In 60 patients with MDD and 129 controls, 15-min resting-state EEG recordings were performed and vigilance was automatically assessed with the VIGALL 2.0 (Vigilance Algorithm Leipzig). Serum levels of the wakefulness-promoting cytokines interleukin (IL)-4, IL-10, IL-13 and somnogenic cytokines tumor necrosis factor-α, interferon-x03B3; and IL-2 were measured prior to the EEG.
  
  
  RESULTS
  Summed wakefulness-promoting cytokines, but not somnogenic cytokines, were significantly associated with the time course of EEG vigilance in the MDD group only. In both groups, IL-13 was significantly associated with the course of EEG vigilance. In MDD compared to controls, a hyperstable EEG vigilance regulation was found, significant for group and group × time course interaction. After controlling for wakefulness-promoting cytokines, differences in vigilance regulation between groups remained significant.
  
  
  CONCLUSIONS
  The present study demonstrated a relationship between wakefulness-promoting cytokines and objectively measured EEG vigilance as an indicator for brain arousal. Altered brain arousal regulation in MDD gives support for future evaluation of vigilance measures as a biomarker in MDD. Since interactions between cytokines and EEG vigilance only moderately differed between the groups and cytokine levels could not explain the group differences in EEG vigilance regulation, cytokines and brain arousal regulation are likely to be associated with MDD in independent ways.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Schmidt
authors.forename: Annika
authors.initials: A
authors.lastname: Pschiebl
authors.forename: Christian
authors.initials: C
authors.lastname: Sander
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Kirkby
authors.forename: Julia
authors.initials: J
authors.lastname: Thormann
authors.forename: Juliane
authors.initials: J
authors.lastname: Minkwitz
authors.forename: Tobias
authors.initials: T
authors.lastname: Chittka
authors.forename: Julia
authors.initials: J
authors.lastname: Weschenfelder
authors.forename: Lesca M
authors.initials: LM
authors.lastname: Holdt
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.forename: Hubertus
authors.initials: H
authors.lastname: Himmerich
mesh_terms: D000328:Adult; D001143:Arousal; D002540:Cerebral Cortex / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood*; D003865:Major Depressive Disorder / Q000097:blood* / Q000503:physiopathology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma