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Research paper
Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion
  1. Rashmi Singh1,
  2. Jonathan Savitz1,2,
  3. T Kent Teague3,4,5,
  4. David W Polanski6,
  5. Andrew R Mayer7,8,9,
  6. Patrick S F Bellgowan10,
  7. Timothy B Meier1,7
  1. 1Laureate Institute for Brain Research, Tulsa, Oklahoma, USA
  2. 2Faculty of Community Medicine, The University of Tulsa, Tulsa, Oklahoma, USA
  3. 3Departments of Surgery and Psychiatry, University of Oklahoma College of Medicine, Tulsa, Oklahoma, USA
  4. 4Department of Pharmaceutical Sciences, University of Oklahoma College of Pharmacy, Tulsa, Oklahoma, USA
  5. 5Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, USA
  6. 6Department of Athletics, The University of Tulsa, Tulsa, Oklahoma, USA
  7. 7The Mind Research Network/Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA
  8. 8Neurology Department, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
  9. 9Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA
  10. 10National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Timothy B Meier, The Mind Research Network/Lovelace Biomedical and Environmental Research Institute, Pete & Nancy Domenici Hall, 1101 Yale Blvd. NE, Albuquerque, NM 87106, USA; timothybmeier{at}gmail.com

Abstract

Objective 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.

Methods 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).

Results 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).

Conclusions 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.

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