title: A pilot study investigating tumor necrosis factor-α as a potential intervening variable of atypical antipsychotic-associated metabolic syndrome in bipolar disorder.
abstract: BACKGROUND
  Strong associations exist between tumor necrosis factor-α (TNF-α) and metabolic syndrome (MetS). Although TNF-α is associated with bipolar depression (BD), its role in atypical antipsychotic (AAP)-associated MetS in BD is unclear. Here, we investigate the potential intervening role of TNF-α in the indirect relationship between AAP treatment and MetS in BD.
  
  
  METHODS
  Using a cross-sectional design, 99 euthymic BD volunteers were stratified by the presence or the absence of MetS (National Cholesterol Education Program Adult Treatment Panel III). Serum TNF-α concentration, determined via chemiluminescent immunometric assays, was compared between groups (ie, MetS or no MetS). We investigated the intervening effect of TNF-α on the relation between AAP treatment and MetS in BD using regression techniques.
  
  
  RESULTS
  Treatment with those antipsychotics believed associated with a higher risk for MetS (ie, AAPs: olanzapine, quetiapine, risperidone, paliperidone, clozapine) was found to be associated with significantly greater TNF-α (F 1,88 = 11.2, P = 0.001, mean difference of 1.7 ± 0.51) and a higher likelihood of MetS (F 1,88 = 4.5, P = 0.036) than in those not receiving treatment with an AAP. Additionally, TNF-α was greater (trending toward significance; T 52 = 2.0, P = 0.05) in BD volunteers with MetS and was found to have a statistically significant effect on the indirect relationship between AAP treatment and elevated waist circumference in these BD volunteers.
  
  
  CONCLUSIONS
  These results identify TNF-α as a potential intervening variable of AAP-associated MetS in BD, not previously identified in this population. Future prospective studies could assess the predictive potential of TNF-α in determining risk of AAP-associated MetS in BD. Given previous evidence relating TNF-α and mood state in BD, this study increases the importance in understanding the role of TNF-α in "mind-body" interactions and renews discussions of the utility of research into the clinical efficacy of TNF-α antagonist treatment in mood disorders.
authors.affiliation: Department of Psychiatry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. prossin@med.umich.edu
authors.forename: Alan R
authors.initials: AR
authors.lastname: Prossin
authors.forename: Steven S
authors.initials: SS
authors.lastname: Zalcman
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Evans
authors.forename: McInnis G
authors.initials: MG
authors.lastname: McInnis
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000175:diagnosis; D008875:Middle Aged; D010865:Pilot Projects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha