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

AbstractObjective 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. s 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. s 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. sion 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.