title: Clinical response augments NK cell activity independent of treatment modality: a randomized double-blind placebo controlled antidepressant trial.
abstract: BACKGROUND
  Major depressive disorder (MDD) has been associated with alterations in immune function. Suppression of natural killer (NK) cell activity (NKCA) reliably characterizes immunological alterations observed in MDD. Antidepressant pharmacotherapy has been associated with modulation of NKCA. Previous investigations into antidepressant modulation of NKCA have not employed randomized double-blind placebo controlled designs. Thus, it is unknown whether treatment-associated changes in immune function are due to drug, placebo, or spontaneous remission effects. The present investigation examined the effect of antidepressant treatment on NKCA utilizing a randomized double-blind placebo controlled experimental design.
  
  
  METHODS
  Patients (N = 16) met DSM-IV criteria for MDD and were randomly assigned to drug (N = 8; citalopram, 20 mg/day) or placebo (N = 8) under double-blind conditions. Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS). NK cell function was measured using a standard chromium-release assay and NK cell number assessed by flow cytometry. HDRS scores, NK cell function, and NK cell numbers were collected at 0, 1, 2 and 4 weeks of treatment.
  
  
  RESULTS
  Clinical response was associated with augmented NKCA independent of treatment condition. Failure to respond to treatment resulted in significantly reduced NKCA over treatment interval.
  
  
  CONCLUSIONS
  The present results suggest that alterations in the depressive syndrome, regardless of therapeutic modality, may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA. matt.frank@uchsc.edu
authors.forename: M G
authors.initials: MG
authors.lastname: Frank
authors.forename: S E
authors.initials: SE
authors.lastname: Hendricks
authors.forename: W J
authors.initials: WJ
authors.lastname: Burke
authors.forename: D R
authors.initials: DR
authors.lastname: Johnson
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use*; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram