Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion.
An imbalance of neuroactive kynurenine pathway metabolites has been proposed as one mechanism behind the neuropsychiatric sequelae of certain neurological disorders. We hypothesized that concussed football players would have elevated plasma levels of neurotoxic kynurenine metabolites and reduced levels of neuroprotective metabolites relative to healthy football players and that altered kynurenine levels would correlate with post-concussion mood symptoms.



Mood scales and plasma concentrations of kynurenine metabolites were assessed in concussed (N=18; 1.61 days post-injury) and healthy football players (N=18). A subset of football players returned at 1-week (N=14; 9.29 days) and 1-month post-concussion (N=14, 30.93 days).



Concussed athletes had significantly elevated levels of quinolinic acid (QUIN) and significantly lower ratios of kynurenic acid (KYNA) to QUIN at all time points compared with healthy athletes (p's<0.05), with no longitudinal evidence of normalization of KYNA or KYNA/QUIN. At 1-day post-injury, concussed athletes with lower levels of the putatively neuroprotective KYNA/QUIN ratio reported significantly worse depressive symptoms (p=0.04), and a trend toward worse anxiety symptoms (p=0.06), while at 1-month higher QUIN levels were associated with worse mood symptoms (p's<0.01). Finally, concussed athletes with worse concussion outcome, defined as number of days until return-to-play, had higher QUIN and lower KYNA/QUIN at 1-month post-injury (p's<0.05).



These results converge with existing kynurenine literature on psychiatric patients and provide the first evidence of altered peripheral levels of kynurenine metabolites following sports-related concussion.
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
Rashmi
R
Singh
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA Faculty of Community Medicine, The University of Tulsa, Tulsa, Oklahoma, USA.
Jonathan
J
Savitz
Departments of Surgery and Psychiatry, University of Oklahoma College of Medicine, Tulsa, Oklahoma, USA Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, Oklahoma, USA Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, USA.
T Kent
TK
Teague
Department of Athletics, The University of Tulsa, Tulsa, Oklahoma, USA.
David W
DW
Polanski
The Mind Research Network/Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA Neurology Department, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA.
Andrew R
AR
Mayer
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Patrick S F
PS
Bellgowan
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA The Mind Research Network/Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Timothy B
TB
Meier
D001265:Athletic Injuries / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D001924:Brain Concussion / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D005500:Follow-Up Studies; D005538:Football / Q000293:injuries*; D006801:Humans; D007737:Kynurenine / Q000097:blood*; D008297:Male; D019964:Mood Disorders / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D009460:Neurologic Examination; D038223:Post-Concussion Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D012016:Reference Values; D013223:Statistics as Topic; D055815:Young Adult
D007737:Kynurenine