Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion.

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.

Recovery of cerebral blood flow following sports-related concussion.

IMPORTANCE: Animal models suggest that reduced cerebral blood flow (CBF) is one of the most enduring physiological deficits following concussion. Despite this, longitudinal studies documenting serial changes in regional CBF following human concussion have yet to be performed. OBJECTIVE: To longitudinally assess the recovery of CBF in a carefully selected sample of collegiate athletes and compare time course of CBF recovery with that of cognitive and behavioral symptoms. DESIGN, SETTING, AND PARTICIPANTS: A cohort of collegiate football athletes (N = 44) participated in this mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging between March 2012 and December 2013. Serial imaging occurred approximately 1 day, 1 week, and 1 month postconcussion for a subset of participants (n = 17). All athletes reported no premorbid mood disorders, anxiety disorders, substance abuse, or alcohol abuse. MAIN OUTCOMES AND MEASURES: Arterial spin labeling magnetic resonance imaging was used to collect voxelwise relative CBF at each visit. Neuropsychiatric evaluations and a brief cognitive screen were also performed at all 3 points. Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome (ie, number of days withheld from competition). RESULTS: The results indicated both cognitive (simple reaction time) and neuropsychiatric symptoms at 1 day postinjury that resolved at either 1 week (cognitive; P < .005) or 1 month (neuropsychiatric; P < .005) postinjury. Imaging data suggested both cross-sectional (ie, healthy vs concussed athletes; P < .05) and longitudinal (1 day and 1 week vs 1 month postinjury; P < .001) evidence of CBF recovery in the right insular and superior temporal cortex. Importantly, CBF in the dorsal midinsular cortex was both decreased at 1 month postconcussion in slower-to-recover athletes (t11 = 3.45; P = .005) and was inversely related to the magnitude of initial psychiatric symptoms (Hamilton Depression Scale: r = -0.64, P = .02; Hamilton Anxiety Scale: r = -0.56, P = .046), suggesting a potential prognostic indication for CBF as a biomarker. CONCLUSIONS AND RELEVANCE: To our knowledge, these results provide the first prospective evidence of reduced CBF in human concussion and subsequent recovery. The resolution of CBF abnormalities closely mirrors previous reports from the animal literature and show real-world validity for predicting outcome following concussion.

The underreporting of self-reported symptoms following sports-related concussion.

OBJECTIVES: This cohort study was conducted to examine patterns of symptom reporting in concussed athletes in two different testing environments. DESIGN: A prospective cohort study was conducted with repeated measures. METHODS: Self-reported symptoms collected by team athletic trainers using the ImPACT Post-Concussion Scale (PCS) were compared to symptoms collected in a confidential setting using structured interviews for depression and anxiety. Ratings were scaled to match scoring of the PCS and categorized into symptom-domains. Scores collected 2 days post-concussion were compared across different rating scales. Confidential self-report scores approximately 9 days post-concussion in cleared athletes were compared to PCS scores collected during return-to-play decisions. Finally, confidential self-report scores collected 9 days post-concussion were compared between cleared and not cleared athletes. RESULTS: Athletes self-reported significantly fewer symptoms to team athletic trainers using the ImPACT test compared to self-reported symptoms collected in a confidential setting during the acute phase of concussion using standard psychiatric interviews. Athletes cleared to play continued to underreport symptoms 9 days post-concussion, particularly psychiatric symptoms. Finally, cleared athletes self-reported similar magnitude of symptoms than non-cleared athletes 9 days post-concussion in confidential research setting. CONCLUSIONS: The systematic underreporting of post-concussion symptoms may represent motivated behavior or differences in self-reporting data acquisition. By underreporting symptoms, many cleared athletes are still symptomatic over 1-week post-concussion. This study highlights the need for objective measures for somatic and psychiatric symptoms.

Relationship of collegiate football experience and concussion with hippocampal volume and cognitive outcomes.

IMPORTANCE: Concussion and subconcussive impacts have been associated with short-term disrupted cognitive performance in collegiate athletes, but there are limited data on their long-term neuroanatomic and cognitive consequences. OBJECTIVE: To assess the relationships of concussion history and years of football experience with hippocampal volume and cognitive performance in collegiate football athletes. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study conducted between June 2011 and August 2013 at a US psychiatric research institute specializing in neuroimaging among collegiate football players with a history of clinician-diagnosed concussion (n = 25), collegiate football players without a history of concussion (n = 25), and non-football-playing, age-, sex-, and education-matched healthy controls (n = 25). EXPOSURES: History of clinician-diagnosed concussion and years of football experience. MAIN OUTCOMES AND MEASURES: High-resolution anatomical magnetic resonance imaging was used to quantify brain volumes. Baseline scores on a computerized concussion-related cognitive battery were used for cognitive assessment in athletes. RESULTS: Players with and without a history of concussion had smaller hippocampal volumes relative to healthy control participants (with concussion: t48 = 7.58; P < .001; mean difference, 1788 µL; 95% CI, 1317-2258 µL; without concussion: t48 = 4.35; P < .001, mean difference, 1027 µL; 95% CI, 556-1498 µL). Players with a history of concussion had smaller hippocampal volumes than players without concussion (t48 = 3.15; P < .001; mean difference, 761 µL; 95% CI, 280-1242 µL). In both athlete groups, there was a statistically significant inverse relationship between left hippocampal volume and number of years of football played (t46 = -3.62; P < .001; coefficient = -43.54; 95% CI, -67.66 to -19.41). Behavioral testing demonstrated no differences between athletes with and without a concussion history on 5 cognitive measures but did show an inverse correlation between years of playing football and reaction time (ρ42 = -0.43; 95% CI, -0.46 to -0.40; P = .005). CONCLUSIONS AND RELEVANCE: Among a group of collegiate football athletes, there was a significant inverse relationship of concussion and years of football played with hippocampal volume. Years of football experience also correlated with slower reaction time. Further research is needed to determine the temporal relationships of these findings.

Leg and calf press training modes and their impact on jump performance adaptations.

To examine the effects of resistance exercise (REX) mode on jump performance, subjects were assigned to one of three groups over a 6-week period with no cross-over. Subjects were assigned to leg and calf press REX on either a standard (n = 10) or ergometer (n = 9) device while a third group (n = 9) served as controls (CTRL). REX subjects worked out twice per week, which consisted of a three-set, 10-repetition paradigm for leg and calf press exercises. Immediately before and after the 6-week period, subjects performed tests that assessed jump (standing vertical jump, four-jump test protocol, depth jump) ability, while a fourth estimated knee extensor fast-twitch percentage (FT%) from fatigue incurred through a 50-repetition isokinetic protocol. Data analyses utilized 3 x 2 (group x time) repeated-measures ANCOVAs. Several dependent variables showed effects by group (standard REX, ergometer REX > CTRL) and time (post > pre). An interaction occurred for explosive leg power factor, a four-jump test variable, with standard REX post-test values as the interaction source. A trend for an interaction occurred for depth jump hang time, as ergometer REX values improved over time. Results suggest that mode-specific adaptations occur with REX training. Thus, athletes are best served with the selection of a REX device that is most specific to the demands of their jump performance task.