Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects.
Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects.
Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States. Electronic address: ecoccaro@bsd.uchicago.edu.
Emil F
EF
Coccaro
Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States.
Royce
R
Lee
Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States.
Jennifer R
JR
Fanning
Division of Biological Chemistry, Biocenter, Medical University, Innsbruck, Austria.
Dietmar
D
Fuchs
Department of Physiology & Pharmacology, Karolinska Institute, Stockholm, Sweden.
Michel
M
Goiny
Department of Physiology & Pharmacology, Karolinska Institute, Stockholm, Sweden.
Sophie
S
Erhardt
Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, United States; Laboratory of Behavioral Medicine, Van Andel Research Institute, Grand Rapids, MI, United States.
Kyle
K
Christensen
Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, United States; Laboratory of Behavioral Medicine, Van Andel Research Institute, Grand Rapids, MI, United States.
Lena
L
Brundin
Department of Psychology, University of Colorado, Colorado Springs, CO, United States.
Mary
M
Coussons-Read
D000328:Adult; D000374:Aggression / Q000502:physiology* / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6; D007736:Kynurenic Acid / Q000097:blood / Q000378:metabolism; D007737:Kynurenine / Q000097:blood / Q000378:metabolism*; D008297:Male; D010848:Picolinic Acids / Q000097:blood / Q000378:metabolism; D017378:Quinolinic Acid / Q000097:blood / Q000378:metabolism; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D010848:Picolinic Acids; D007737:Kynurenine; D014364:Tryptophan; D002097:C-Reactive Protein; D017378:Quinolinic Acid; D007736:Kynurenic Acid; C030614:picolinic acid
Aggression; CRP; IL-6; Kynurenine pathway; Plasma; sIL-1RII