PMID- 24182638
OWN - NLM
STAT- MEDLINE
DCOM- 20141007
LR  - 20220316
IS  - 1879-1360 (Electronic)
IS  - 0022-3999 (Print)
IS  - 0022-3999 (Linking)
VI  - 75
IP  - 5
DP  - 2013 Nov
TI  - Anger induced by interferon-alpha is moderated by ratio of arachidonic acid to 
      omega-3 fatty acids.
PG  - 475-83
LID - S0022-3999(13)00296-1 [pii]
LID - 10.1016/j.jpsychores.2013.07.012 [doi]
AB  - OBJECTIVE: Anger worsens in some patients during interferon-alpha (IFN-alpha) 
      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-alpha exposure. METHODS: Plasma arachidonic acid 
      (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were 
      determined prior to IFN-alpha 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-alpha therapy. RESULTS: Prior to IFN-alpha 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-alpha 
      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-alpha) 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-alpha 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-alpha. LCn-3 supplements may be one 
      strategy for minimizing this adverse side effect of IFN-alpha.
CI  - (c) 2013.
FAU - Lotrich, Francis E
AU  - Lotrich FE
AD  - Department of Psychiatry, Western Psychiatric Institute and Clinic, University of 
      Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address: 
      lotrichfe@upmc.edu.
FAU - Sears, Barry
AU  - Sears B
FAU - McNamara, Robert K
AU  - McNamara RK
LA  - eng
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - R34 MH083924/MH/NIMH NIH HHS/United States
GR  - MH083924/MH/NIMH NIH HHS/United States
GR  - R01 MH090250/MH/NIMH NIH HHS/United States
GR  - R01MH020950/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130726
PL  - England
TA  - J Psychosom Res
JT  - Journal of psychosomatic research
JID - 0376333
RN  - 0 (Antiviral Agents)
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
SB  - IM
MH  - Adult
MH  - *Anger
MH  - Antiviral Agents/administration & dosage/adverse effects
MH  - Arachidonic Acid/*blood
MH  - Dietary Supplements
MH  - Docosahexaenoic Acids/*blood
MH  - Eicosapentaenoic Acid/*blood
MH  - Fatty Acids, Omega-3/administration & dosage
MH  - Female
MH  - Humans
MH  - Interferon-alpha/*administration & dosage/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Prospective Studies
MH  - Recombinant Proteins
MH  - Risk Factors
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Young Adult
PMC - PMC3817416
MID - NIHMS510537
OTO - NOTNLM
OT  - Aggression
OT  - Anger
OT  - Antidepressant, tumor necrosis factor
OT  - Cytokine
OT  - Fatty acid
OT  - Inflammation
OT  - Interferon
OT  - Irritability
EDAT- 2013/11/05 06:00
MHDA- 2014/10/08 06:00
PMCR- 2014/11/01
CRDT- 2013/11/05 06:00
PHST- 2013/04/25 00:00 [received]
PHST- 2013/07/15 00:00 [revised]
PHST- 2013/07/17 00:00 [accepted]
PHST- 2013/11/05 06:00 [entrez]
PHST- 2013/11/05 06:00 [pubmed]
PHST- 2014/10/08 06:00 [medline]
PHST- 2014/11/01 00:00 [pmc-release]
AID - S0022-3999(13)00296-1 [pii]
AID - 10.1016/j.jpsychores.2013.07.012 [doi]
PST - ppublish
SO  - J Psychosom Res. 2013 Nov;75(5):475-83. doi: 10.1016/j.jpsychores.2013.07.012. 
      Epub 2013 Jul 26.