title: Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression.
abstract: BACKGROUND
  Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms.
  
  
  METHODS
  We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.
  
  
  RESULTS
  Serum neopterin was significantly higher in depressed patients and in particular in those with melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα.
  
  
  CONCLUSIONS
  Depression and melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression.
authors.affiliation: Maes Clinics @ TRIA, Bangkok, Thailand. dr.michaelmaes@hotmail.com
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.forename: Ivana
authors.initials: I
authors.lastname: Mihaylova
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
authors.forename: Karl
authors.initials: K
authors.lastname: Ringel
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016000:Cluster Analysis; D003866:Depressive Disorder / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D005221:Fatigue / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology*; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha