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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.JP

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.

Authors+Show Affiliations

Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address: lotrichfe@upmc.edu.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24182638

Citation

Lotrich, Francis E., et al. "Anger Induced By Interferon-alpha Is Moderated By Ratio of Arachidonic Acid to Omega-3 Fatty Acids." Journal of Psychosomatic Research, vol. 75, no. 5, 2013, pp. 475-83.
Lotrich FE, Sears B, McNamara RK. Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids. J Psychosom Res. 2013;75(5):475-83.
Lotrich, F. E., Sears, B., & McNamara, R. K. (2013). Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids. Journal of Psychosomatic Research, 75(5), 475-83. https://doi.org/10.1016/j.jpsychores.2013.07.012
Lotrich FE, Sears B, McNamara RK. Anger Induced By Interferon-alpha Is Moderated By Ratio of Arachidonic Acid to Omega-3 Fatty Acids. J Psychosom Res. 2013;75(5):475-83. PubMed PMID: 24182638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to omega-3 fatty acids. AU - Lotrich,Francis E, AU - Sears,Barry, AU - McNamara,Robert K, Y1 - 2013/07/26/ PY - 2013/04/25/received PY - 2013/07/15/revised PY - 2013/07/17/accepted PY - 2013/11/5/entrez PY - 2013/11/5/pubmed PY - 2014/10/8/medline KW - Aggression KW - Anger KW - Antidepressant, tumor necrosis factor KW - Cytokine KW - Fatty acid KW - Inflammation KW - Interferon KW - Irritability SP - 475 EP - 83 JF - Journal of psychosomatic research JO - J Psychosom Res VL - 75 IS - 5 N2 - 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. SN - 1879-1360 UR - https://www.unboundmedicine.com/medline/citation/24182638/Anger_induced_by_interferon_alpha_is_moderated_by_ratio_of_arachidonic_acid_to_omega_3_fatty_acids_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3999(13)00296-1 DB - PRIME DP - Unbound Medicine ER -