Francis E Lotrich1, Barry Sears, Robert K McNamara. 1. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address: lotrichfe@upmc.edu.
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.
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.
Authors: E F Coccaro; P D Harvey; E Kupsaw-Lawrence; J L Herbert; D P Bernstein Journal: J Neuropsychiatry Clin Neurosci Date: 1991 Impact factor: 2.198
Authors: Vilma Gabbay; Rachel D Freed; Carmen M Alonso; Stefanie Senger; Jill Stadterman; Beth A Davison; Rachel G Klein Journal: J Clin Psychiatry Date: 2018-06-26 Impact factor: 4.384
Authors: Marissa J Luft; Martine Lamy; Melissa P DelBello; Robert K McNamara; Jeffrey R Strawn Journal: Curr Probl Pediatr Adolesc Health Care Date: 2018-01-19
Authors: Anne Mette Beier; Lotte Lauritzen; Hanga C Galfalvy; Thomas B Cooper; Maria A Oquendo; Michael F Grunebaum; J John Mann; M Elizabeth Sublette Journal: J Psychiatr Res Date: 2014-06-26 Impact factor: 4.791
Authors: Philip R Szeszko; Robert K McNamara; Juan A Gallego; Anil K Malhotra; Usha Govindarajulu; Bart D Peters; Delbert G Robinson Journal: Schizophr Res Date: 2021-01-11 Impact factor: 4.939