title: Melancholic and atypical major depression--connection between cytokines, psychopathology and treatment.
abstract: OBJECTIVE
  Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment.
  
  
  METHODS
  We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS).
  
  
  RESULTS
  IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression.
  
  
  CONCLUSIONS
  Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.
authors.affiliation: Clinic of Psychiatry, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia. bojanadunjic1978@gmail.com
authors.forename: Bojana
authors.initials: B
authors.lastname: Dunjic-Kostic
authors.forename: Maja
authors.initials: M
authors.lastname: Ivkovic
authors.forename: Nevena V
authors.initials: NV
authors.lastname: Radonjic
authors.forename: Natasa D
authors.initials: ND
authors.lastname: Petronijevic
authors.forename: Maja
authors.initials: M
authors.lastname: Pantovic
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Damjanovic
authors.forename: Sanja Totic
authors.initials: ST
authors.lastname: Poznanovic
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Jovanovic
authors.forename: Tanja
authors.initials: T
authors.lastname: Nikolic
authors.forename: Miroslava
authors.initials: M
authors.lastname: Jasovic-Gasic
mesh_terms: D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000523:psychology / Q000628:therapy*; D018450:Disease Progression; D004522:Educational Status; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012907:Smoking / Q000009:adverse effects / Q000523:psychology; D012959:Socioeconomic Factors; D059020:Suicidal Ideation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha