Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids

J Psychosom Res. 2013 Nov;75(5):475-83. doi: 10.1016/j.jpsychores.2013.07.012. Epub 2013 Jul 26.

Abstract

Objective: Anger worsens in some patients during interferon-alpha (IFN-α) therapy. Elevated anger has also been associated with lower long-chain omega-3 (LCn-3) fatty acid levels. We examined whether fatty acids could influence vulnerability to anger during IFN-α exposure.

Methods: Plasma arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were determined prior to IFN-α therapy by mass spectroscopy. Repeated-measure analyses examined the relationship between AA/EPA+DHA and the subsequent development of labile anger and irritability in 82 subjects who prospectively completed the Anger, Irritability, and Assault Questionnaire (AIAQ) during the first eight weeks of IFN-α therapy.

Results: Prior to IFN-α therapy, AA/EPA+DHA did not correlate with either labile anger or irritability. Pre-treatment AA/EPA+DHA did correlate with the subsequent maximal increase in labile anger during IFN-α therapy (r=0.33; p=0.005). Over time, labile anger increased more in subjects with above median AA/EPA+DHA ratios (p<0.05). Of the 17 subjects ultimately requiring psychiatric intervention for anger, 14/17 had above-median AA/EPA+DHA ratios (p=0.009). There was also an interaction with the tumor necrosis factor-alpha (TNF-α) promoter polymorphism (A-308G), such that only those with both elevated AA/EPA+DHA and the A allele had increased labile anger (p=0.001). In an additional 18 subjects, we conversely observed that selective serotonin reuptake inhibitor treatment was associated with increased irritability during IFN-α therapy.

Conclusion: LCn-3 fatty acid status may influence anger development during exposure to elevated inflammatory cytokines, and may interact with genetic risk for increased brain TNF-α. LCn-3 supplements may be one strategy for minimizing this adverse side effect of IFN-α.

Keywords: Aggression; Anger; Antidepressant, tumor necrosis factor; Cytokine; Fatty acid; Inflammation; Interferon; Irritability.

Publication types

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

MeSH terms

  • Adult
  • Anger*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Arachidonic Acid / blood*
  • Dietary Supplements
  • Docosahexaenoic Acids / blood*
  • Eicosapentaenoic Acid / blood*
  • Fatty Acids, Omega-3 / administration & dosage
  • Female
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Recombinant Proteins
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics
  • Young Adult

Substances

  • Antiviral Agents
  • Fatty Acids, Omega-3
  • Interferon-alpha
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Eicosapentaenoic Acid