title: Pro- and anti-inflammatory cytokine associations with major depression in cancer patients.
abstract: OBJECTIVE
  Cytokines may be linked to depression, although it has been challenging to demonstrate this association in cancer because of the overlap between depressive symptoms and other sickness behaviors. This study investigates the relationship between cytokines and depression in cancer patients, accounting for confounding clinical and methodological factors.
  
  
  METHODS
  The GRID Hamilton Rating Scale for Depression and Neurotoxicity Rating Scale (NRS) for cytokine-induced sickness behaviors were administered to 61 cancer patients and 38 healthy controls. The cancer group was of mixed type and largely of late stage, with a recruitment rate of 35% and completion rate of 47%. Major depression was diagnosed in 19 of 61 (31%) cancer patients. Multiplexed cytokine assays for inflammatory and anti-inflammatory cytokines were conducted in plasma samples using electrochemiluminescence.
  
  
  RESULTS
  All cancer patients had high NRS scores and elevated levels of most cytokines. Cancer patients with major depression had higher NRS scores than those without major depression. IL-1rα was positively associated with the GRID scores of depressive symptoms (regression coefficient, 3.52 ± 1.18; P = .004), but not with major depression. Major depression was negatively associated with the anti-inflammatory cytokine IL-4 (regression coefficient, -0.65 ± 0.26; P = .013), but not with IL-1rα.
  
  
  CONCLUSIONS
  Depressive symptoms in cancer patients may represent sickness behaviors, which may have distinct cytokine associations from major depression. Sickness behaviors may be associated with an increase in inflammatory cytokines, whereas major depression may be induced by a failure to adequately resolve inflammation. Our findings suggest that cytokine-mediated interventions may be of value to treat depression in this population.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Supportive Care, University Health Network, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Madeline
authors.initials: M
authors.lastname: Li
authors.affiliation: Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kouzmina
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Supportive Care, University Health Network, Toronto, Ontario, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: McCusker
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Supportive Care, University Health Network, Toronto, Ontario, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Rodin
authors.affiliation: Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.|Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Supportive Care, University Health Network, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Rodin
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D003863:Depression / Q000097:blood / Q000175:diagnosis* / Q000276:immunology* / Q000523:psychology; D005260:Female; D006801:Humans; D055809:Illness Behavior; D007249:Inflammation; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000523:psychology; D011795:Surveys and Questionnaires
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators
keywords: cancer; cytokines; depression; interleukin-4; oncology; sickness behaviour