title: Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address: lotrichfe@upmc.edu.
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.forename: Barry
authors.initials: B
authors.lastname: Sears
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
mesh_terms: D000328:Adult; D000786:Anger; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D016718:Arachidonic Acid / Q000097:blood*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011994:Recombinant Proteins; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015525:Fatty Acids, Omega-3; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid
keywords: Aggression; Anger; Antidepressant, tumor necrosis factor; Cytokine; Fatty acid; Inflammation; Interferon; Irritability