Role of the kynurenine pathway and the endocannabinoid system as modulators of inflammation and personality traits

• Published in: Psychoneuroendocrinology Vol. 110; p. 104434
• Main Authors: Heilman, Patrick, Hill, Matthew N., Coussons-Read, Mary, Brundin, Lena, Coccaro, Emil F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2019
• Subjects: 2-Arachidonoylglycerol; Adult; Anxiety Disorders - blood; Anxiety Disorders - epidemiology; Anxiety Disorders - etiology; Arachidonic Acids - blood; Cohort Studies; Endocannabinoids - blood; Endocannabinoids - metabolism; Endocannabinoids - physiology; Female; Glycerides - blood; Humans; Inflammation - epidemiology; Inflammation - etiology; Inflammation - metabolism; Interleukin-6; Interleukin-6 - blood; Kynurenine - metabolism; Kynurenine - physiology; Male; Middle Aged; Neuroticism; Personality - physiology; Personality Disorders - blood; Personality Disorders - epidemiology; Personality Disorders - etiology; Picolinic acid; Picolinic Acids - blood; Receptors, Cannabinoid - metabolism; Receptors, Cannabinoid - physiology; Reward dependence; Signal Transduction - physiology; Neuroticism; Reward dependence; Picolinic acid; 2-Arachidonoylglycerol; Interleukin-6
• ISSN: 0306-4530; 1873-3360; 1873-3360
• DOI: 10.1016/j.psyneuen.2019.104434

•IL-6, 2-AG, and KP metabolites in people with/without mood, anxiety, and personality disorder were correlated with measures of personality.•IL-6 levels were significantly associated with plasma 2-AG levels and plasma picolinic acid levels which correlated inversely with 2-AG levels across all subjects, independent of IL-6.•We also identified associations between IL-6 and novelty seeking, and between PIC and neuroticism.•These data provide evidence of a link between IL-6, endocannabinoids, and KP metabolites and suggest that these factors influence personality traits. Kynurenine pathway metabolites and endocannabinoids both exert potent regulatory effects on the immune system, but the relationship between these molecules is unknown. The role of these immunobiological mediators in emotionality and personality traits is not previously characterized. Interleukin-6 (IL-6), 2-arachidonoylglycerol (2-AG) and picolinic acid (PIC) were measured in the plasma of physically healthy individuals who had history of mood, anxiety, and personality disorders (n = 96) or who had no history of any psychiatric disorder (n = 56) by DSM-5 Criteria. Dimensional assessments of personality were performed using the Eysenck Personality Questionnaire (EPQ) and the Tridimensional Personality Questionnaire (TPQ). Plasma IL-6 levels were significantly associated with plasma 2-AG levels and plasma PIC levels across all subjects. PIC levels were also negatively associated with 2-AG levels across all subjects, independent of IL-6 levels. In our analysis of the biological determinants of personality factors, we identified significant associations between IL-6 and novelty seeking assessment, and between PIC and neuroticism assessment. These data provide evidence of a biological link between metabolites of the kynurenine pathway, the endocannabinoid system and IL-6 and suggest that these factors may influence personality traits.