A pilot study investigating tumor necrosis factor-α as a potential intervening variable of atypical antipsychotic-associated metabolic syndrome in bipolar disorder

Ther Drug Monit. 2013 Apr;35(2):194-202. doi: 10.1097/FTD.0b013e31827e18d2.

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.

Materials and 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.

Discussion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Biomarkers / metabolism
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / epidemiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Metabolic Syndrome / chemically induced*
  • Metabolic Syndrome / diagnosis
  • Middle Aged
  • Pilot Projects
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / physiology
  • Young Adult

Substances

  • Antipsychotic Agents
  • Biomarkers
  • Tumor Necrosis Factor-alpha