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IntroductionSome ultra-high exposure boxers from the 20th century suffered from neurological problems characterized by slurred speech, personality changes (e.g., childishness or aggressiveness), and frank gait and coordination problems, with some noted to have progressive Parkinsonian-like signs. Varying degrees of cognitive impairment were also described, with some experiencing moderate to severe dementia. The onset of the neurological problems often began while they were young men and still actively fighting. More recently, traumatic encephalopathy syndrome (TES) has been proposed to be present in athletes who have a history of contact (e.g., soccer) and collision sport participation (e.g., American-style football). The characterization of TES has incorporated a much broader description than the neurological problems described in boxers from the 20th century. Some have considered TES to include depression, suicidality, anxiety, and substance abuse.PurposeWe carefully re-examined the published clinical literature of boxing cases from the 20th century to determine whether there is evidence to support conceptualizing psychiatric problems as being diagnostic clinical features of TES.MethodsWe reviewed clinical descriptions from 155 current and former boxers described in 21 articles published between 1928 and 1999.ResultsMore than one third of cases (34.8%) had a psychiatric, neuropsychiatric, or neurobehavioral problem described in their case histories. However, only 6.5% of the cases were described as primarily psychiatric or neuropsychiatric in nature. The percentages documented as having specific psychiatric problems were as follows: depression = 11.0%, suicidality = 0.6%, anxiety = 3.9%, anger control problems = 20.0%, paranoia/suspiciousness = 11.6%, and personality change = 25.2%.DiscussionWe conclude that depression, suicidality (i.e., suicidal ideation, intent, or planning), and anxiety were not considered to be clinical features of TES during the 20th century. The present review supports the decision of the consensus group to remove mood and anxiety disorders, and suicidality, from the new 2021 consensus core diagnostic criteria for TES. More research is needed to determine if anger dyscontrol is a core feature of TES with a clear clinicopathological association. The present findings, combined with a recently published large clinicopathological association study, suggest that mood and anxiety disorders are not characteristic of TES and they are not associated with chronic traumatic encephalopathy neuropathologic change.

IntroductionWe examined postmortem brain tissue from men, over the age of 50, for chronic traumatic encephalopathy neuropathologic change (CTE-NC). We hypothesized that (i) a small percentage would have CTE-NC, (ii) those who played American football during their youth would be more likely to have CTE-NC than those who did not play contact or collision sports, and (iii) there would be no association between CTE-NC and suicide as a manner of death.MethodsBrain tissue from 186 men and accompanying clinical information were obtained from the Lieber Institute for Brain Development. Manner of death was determined by a board-certified forensic pathologist. Information was obtained from next of kin telephone interviews, including medical, social, demographic, family, and psychiatric history. The 2016 and 2021 consensus definitions were used for CTE-NC. Two authors screened all cases, using liberal criteria for identifying “possible” CTE-NC, and five authors examined the 15 selected cases.ResultsThe median age at the time of death was 65 years (interquartile range = 57–75; range = 50–96). There were 25.8% with a history of playing American football and 36.0% who had suicide as their manner of death. No case was rated as definitively having “features” of CTE-NC by all five authors. Ten cases were rated as having features of CTE-NC by three or more authors (5.4% of the sample), including 8.3% of those with a personal history of playing American football and 3.9% of those who did not play contact or collision sports. Of those with mood disorders during life, 5.5% had features of CTE-NC compared to 6.0% of those who did not have a reported mood disorder. Of those with suicide as a manner of death, 6.0% had features of CTE-NC compared to 5.0% of those who did not have suicide as a manner of death.DiscussionWe did not identify a single definitive case of CTE-NC, from the perspective of all raters, and only 5.4% of cases were identified as having possible features of CTE-NC by some raters. CTE-NC was very uncommon in men who played amateur American football, those with mood disorders during life, and those with suicide as a manner of death.

IntroductionThis systematic review examined whether race or ethnicity are associated with clinical outcomes (e.g., time to return to school/sports, symptom duration, vestibular deficits, and neurocognitive functioning) following sport-related concussion among child, adolescent, or college-aged student athletes. Additionally, this review assessed whether the existing literature on this topic incorporated or included broader coverage of social determinants of health.MethodsThe online databases PubMed, MEDLINE®, PsycINFO®, CINAHL, Cochrane Library, EMBASE, SPORTDiscus, Scopus, and Web of Science were searched.ResultsA total of 5,118 abstracts were screened and 12 studies met inclusion criteria, including 2,887 youth and young adults. Among the included articles, only 3 studies (25%) examined whether race and ethnicity were associated with outcomes following concussion as a primary objective. None of the studies assessed the association between social determinants of health and outcomes following concussion as a primary objective, although 5 studies (41.7%) addressed a social determinant of health or closely related topic as a secondary objective.DiscussionOverall, the literature to date is extremely limited and insufficient for drawing conclusions about whether race or ethnicity are categorically associated with outcomes from sport-related concussion, or more specifically, whether there are socioeconomic, structural, or cultural differences or disparities that might be associated with clinical outcome.Systematic review registrationidentifier: PROSPERO, CRD42016041479, CRD42019128300.

BackgroundSerotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding.MethodsThis was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication.ResultsThe study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50–83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use.ConclusionSerotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.

Blood-based biomarkers have been increasingly studied for diagnostic and prognostic purposes in patients with mild traumatic brain injury (MTBI). Biomarker levels in blood have been shown to vary throughout age groups. Our aim was to study four blood biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (NF-L), and total tau (t-tau), in older adult patients with MTBI. The study sample was collected in the emergency department in Tampere University Hospital, Finland, between November 2015 and November 2016. All consecutive adult patients with head injury were eligible for inclusion. Serum samples were collected from the enrolled patients, which were frozen and later sent for biomarker analyses. Patients aged 60 years or older with MTBI, head computed tomography (CT) imaging, and available biomarker levels were eligible for this study. A total of 83 patients (mean age = 79.0, SD = 9.58, range = 60–100; 41.0% men) were included in the analysis. GFAP was the only biomarker to show statistically significant differentiation between patients with and without acute head CT abnormalities [U(83) = 280, p < 0.001, r = 0.44; area under the curve (AUC) = 0.79, 95% CI = 0.67–0.91]. The median UCH-L1 values were modestly greater in the abnormal head CT group vs. normal head CT group [U (83) = 492, p = 0.065, r = 0.20; AUC = 0.63, 95% CI = 0.49–0.77]. Older age was associated with biomarker levels in the normal head CT group, with the most prominent age associations being with NF-L (r = 0.56) and GFAP (r = 0.54). The results support the use of GFAP in detecting abnormal head CT findings in older adults with MTBIs. However, small sample sizes run the risk for producing non-replicable findings that may not generalize to the population and do not translate well to clinical use. Further studies should consider the potential effect of age on biomarker levels when establishing clinical cut-off values for detecting head CT abnormalities.

BackgroundIndividuals with migraine disorders may be affected differently by concussions compared to individuals without migraine disorders. Prior studies on this topic have had mixed results. The purpose of this study was to systematically examine clinical outcomes following a sport-related concussion in athletes who have a pre-injury history of migraines.MethodsAll studies published prior to 15 May 2021 that examined pre-injury migraines as a possible predictor of clinical recovery from concussion were included. The search included (i) sport/athlete-related terms, (ii) concussion-related terms, and (iii) diverse predictor/modifier terms. After removing duplicates, 5,118 abstracts were screened, 538 full-text articles were reviewed, and 27 articles were included for narrative synthesis without meta-analysis (n = 25 with unique samples). Risk of bias was assessed using the domain-based Quality In Prognosis Studies (QUIPS) tool.ResultsMost studies did not find pre-injury migraines to be associated with concussion outcome, but several of these studies had small or very small sample sizes, as well as other methodological weaknesses. Risk of bias varied greatly across studies. Some of the larger, better-designed studies suggested pre-injury migraines may be a risk factor for worse concussion outcome. Most articles examined pre-injury migraines as an exploratory/secondary predictor of concussion outcome; very few were designed to examine migraine as the primary focus of the study. Migraine history was predominantly based on self-report and studies included minimal information about migraine (e.g., age of onset, frequency/severity, past treatment). Effect sizes were usually not reported or able to be calculated from reported study data.ConclusionThere is some evidence to suggest that pre-injury migraines may be a vulnerability factor for a worse outcome following concussion, with studies having the lowest risk of bias reporting a positive association. Future studies should focus on improving methodological quality when assessing the relationship between pre-injury migraines and concussion outcome and better characterizing pre-injury migraine status.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128292, identifier: PROSPERO 2019 CRD42019128292.

ImportancePrior research has shown a statistically significant association between sustaining a concussion and suicidality in adolescents, but this prior research controlled for relatively few variables predictive of suicidality.ObjectiveTo examine whether sustaining a concussion remained a significant predictor of suicidality after controlling for relevant covariates (e.g., sexual abuse/assault, bullying, substance use, depression), hypothesizing that the relationship between concussion and suicidality would become non-significant after controlling for these variables.DesignThis study involved secondary data analysis of the 2019 Youth Risk Behavior Surveillance (YRBS) System, a national cross-sectional study of adolescents. Analyses were stratified by gender.SettingA national sampling of U.S. high school students.ParticipantsEleven thousand two hundred sixty-two students in the YRBS database, including 5,483 boys and 5,779 girls.Exposure(s)Participants included in the analyses reported whether, in the last year, they experienced a concussion and/or suicidality.Main Outcomes and MeasuresThe main outcome was suicidality (i.e., ideation, planning, attempt), which was predicted by concussion in an unadjusted analysis and by concussion along with other risk factors in a multivariable analysis.ResultsThe final sample included 11,262 participants with available data on concussion and suicidality in the last year (14–18 years-old; 51.3% girls; 49.0% White). Per unadjusted odds ratios with 95% confidence intervals, there was a relationship between concussion and suicidal ideation [girls: OR = 1.46 (1.24, 1.73); boys: OR = 1.69 (1.41, 2.03)], planning (girls: OR = 1.39 [1.16, 1.66]; boys: OR = 1.76 [1.44, 2.14]), and attempt [girls: OR = 1.70 (1.32, 2.19); boys: OR = 3.13, (2.37, 4.15)]. These relationships became mostly non-significant after controlling for relevant risk factors for suicidality. The adjusted odds ratios showed no relationship between concussion and suicidal ideation [girls: OR = 1.11 (0.86, 1.44); boys: OR = 1.24 (0.92, 1.69)] or planning (girls: OR = 1.07 [0.82, 1.40]; boys: OR = 1.12 [0.82, 1.55]); but a significant relationship with suicide attempts in boys [OR = 1.98 (1.28, 3.04)], but not girls [OR = 1.05 (0.74, 1.49)].Conclusions and RelevanceThere was an association between concussion and suicidality in U.S. high school students; however, after controlling for other variables (e.g., depression, sexual abuse/assault, illicit drug use), there was no association between concussion and suicidality aside from a significant relationship between concussion and attempts in boys.

ObjectiveA cavum septum pellucidum (CSP) has been reported as a visible brain anomaly in normal individuals as well in some former combat and collision sport athletes. The appearance of CSP with fenestrations and ventricular enlargement are considered associated features of the neuropathological diagnosis of chronic traumatic encephalopathy. The current study examined CSP anatomic features and lateral ventricle size in retired elite rugby league players and controls.MethodsForty-one retired rugby league players and 41 healthy community controls, similar in age and education, underwent structural MRI scans. CSP grade, CSP length, corpus callosum septal length, and Evans' ratio (for lateral ventricle size) were rated by two of the current study authors. All participants also self-reported concussion exposure histories, depressive symptoms, daytime sleepiness, and impulsivity. They completed a neuropsychological test battery assessing premorbid intellectual functioning, attention, processing speed, language, visuospatial skills, memory, and aspects of executive functioning.ResultsThe two raters had high agreement for CSP grade (Cohen's κ = 0.80), CSP length [intraclass correlation (ICC) = 0.99], corpus callosum septal length (ICC = 0.73), the CSP/septal ratio (ICC = 0.99), and the Evans' ratio (ICC = 0.75). Twenty-five retired players (61.0%) had an abnormal CSP compared to 17 controls [41.5%; χ(1, 82)2 = 3.12, p = 0.08, odds ratio = 2.21]. The CSP/septal ratio was larger for retired players than for the controls. The Evans' ratio did not differ between the two groups. In the retired rugby league players (n = 41), those with normal (n = 16) and abnormal (n = 25) CSP grades did not differ across age, age of first exposure to collision sport, years of sport exposure, concussion history, or 23 clinical and cognitive variables.ConclusionThis study revealed a difference in the size of the CSP between retired professional rugby league players and controls. There was no significant difference in the size of the ventricles between the two groups. There were no significant differences between those with vs. without an abnormal CSP on age of first exposure to rugby league, years of exposure to repetitive neurotrauma, number of lifetime concussions, depression, impulsivity, perceived cognitive decline, or on any neuropsychological test.

IntroductionPre-injury and post-injury anxiety are prevalent and important to consider in the medical management of concussions in youth. We examined the association between anxiety and other physical, cognitive, and emotional symptoms in injured adolescents and young adults undergoing an initial evaluation in a specialty concussion clinic.MethodsParticipants were 158 adolescents and young adults presenting to a multidisciplinary concussion clinic for evaluation and treatment (54.4% girls and women; mean age = 17.3 years; SD = 2.9). Their median days post injury was 29 (interquartile range = 14–49; range = 7–349). They were divided into binary groups based on whether they had a pre-injury history of anxiety diagnosis or treatment and whether they were experiencing current anxiety in the week prior to the evaluation, and then compared on the Post-Concussion Symptom Scale.ResultsYouth with a pre-injury history of anxiety reported greater post-concussion symptoms (Md total score = 36.0, IQR = 21.5–53.0) compared to youth with no pre-injury history of anxiety (Md total score = 20.5, IQR = 6.0–36.0; MW U = 1,520.00 p = 0.001, r = 0.26, small-medium effect size). They reported significantly worse headaches, nausea, balance difficulty, dizziness, vision problems, fatigue, concentration difficulty, irritability, nervousness, sadness, feeling more emotional, trouble falling asleep, and sleeping more than usual. Youth with high post-injury anxiety reported greater post-concussion symptoms (Md total score = 55.0, IQR = 33.0–62.5) compared to youth with low post-injury anxiety (Md total score = 19.0, IQR = 6.0–35.0; MW U = 681.00, p < 0.001, r = 0.49, large effect size). They reported significantly worse headaches, nausea, vomiting, dizziness, vision problems, fatigue, sensitivity to light, feeling mentally foggy, feeling slowed down, concentration difficulty, memory difficulty, irritability, sadness, feeling more emotional, drowsiness, trouble falling asleep, sleeping less than usual, and sleeping more than usual. Logistic regressions revealed that both pre-injury and post-injury anxiety were strong predictors of persistent post-concussion symptoms, with high post-injury anxiety presenting the strongest independent predictor, while attention-deficit hyperactivity disorder and pre-injury migraines were not significant predictors. Essentially all adolescents with high post-injury anxiety (97.1%) and nearly 9 of 10 adolescents with pre-injury treatment for anxiety (87.8%) met criteria for persistent post-concussion symptoms.DiscussionPre-injury and post-injury anxiety are important risk factors for greater post-concussion symptoms among adolescents and young adults. Elevated post-injury anxiety was the strongest predictor of persistent post-concussion symptoms. Assessment of anxiety is important among adolescents presenting for concussion care and delivery of evidence-supported treatments for anxiety are important considerations for treatment planning for these youth.

BackgroundThere is growing public concern regarding the potential long-term effects of playing football on brain health, specifically that playing football before and during high school might cause damage to the brain that manifests years or decades later as depression or suicidality. This study examined if playing high school football was associated with increased lifetime risk for depression, suicidality over the past year, or depressed mood in the past week in men aged between their middle 30 s to early 40 s.MethodsPublicly available data from the National Longitudinal Study of Adolescent to Adult Health were analyzed. This longitudinal, prospective cohort study sampled nationally representative U.S. youth starting in 1994–1995 (Wave I) and most recently in 2016–2018 (Wave V). A total of 3,147 boys participated in Wave I (median age = 15), of whom 1,805 were re-assessed during Wave V (median age = 38).ResultsOf the 1,762 men included in the study, 307 (17.4%) men reported being diagnosed with depression and 275 (15.6%) reported being diagnosed with an anxiety disorder or panic disorder at some point in their life. When comparing men who played high school football to those who did not, there were no differences in the proportions of the sample who had a lifetime diagnosis of depression, lifetime diagnosis of anxiety/panic disorders, suicidal ideation in the past year, psychological counseling in the past year, or current depressed mood. However, men who received psychological counseling and/or experienced suicidal ideation during adolescence were significantly more likely to report a lifetime history of depression, suicidal ideation in the past year, and current depressed mood.ConclusionIndividuals who reported playing football during adolescence did not have an increased risk of depression or suicidal ideation when they were in their middle 30 s to early 40 s, but mental health problems during adolescence were associated with an increased risk for psychological health difficulties more than 20 years later.

Child and adolescent student athletes with attention-deficit/hyperactivity disorder (ADHD) report a greater lifetime history of concussion than those without ADHD. This case-control study compared youth with and without ADHD presenting for care at a specialty concussion clinic on their lifetime history of concussion. We hypothesized that a greater proportion of youth with ADHD would report a history of prior concussion. Archival clinical data from patients presenting to a specialty concussion clinic in Montreal, Québec, Canada between September 2015 and August 2019 were analyzed. The sample included 2,418 children and adolescents (age: M = 13.6, SD = 2.7, range 5–18 years; 50.9% girls), including 294 (12.2%) with ADHD and 2,124 (87.8%) without ADHD. The proportion with prior concussion among youth with ADHD (43.9%) was significantly greater than youth without ADHD [37.5%, χ2 = 4.41, p = 0.04, OR = 1.30, 95% confidence interval (CI): 1.02–1.67]. A significantly higher proportion of boys with ADHD had a prior concussion history (48.1%) than boys without ADHD [38.4%, χ2 = 5.33, p = 0.02, OR = 1.48 (95% CI: 1.06–2.09)], but this difference was not observed for girls (χ2 = 0.31, p = 0.58). Youth with ADHD did not differ with regard to their estimated longest duration of symptoms from a prior concussion (Z = 1.52, p = 0.13) and the proportion who reported taking longer than 28 days to recover from a prior concussion did not differ between those with ADHD (15.3%) and without ADHD (12.2%), χ2 = 2.20, p = 0.14. Among youth presenting to a specialty clinic, ADHD was associated with greater lifetime history of concussion but not a greater duration of symptoms from a prior injury.

We examined the association between the severity of acute concussion symptoms and time to return to school and to sports in National Collegiate Athletic Association (NCAA) Division III collegiate athletes. We hypothesized that students with the lowest burden of acute symptoms, measured in the first 72 h, would have the fastest return to school and sports and those with the highest burden of symptoms would have the slowest return to school and sports. This injury surveillance cohort included 808 athletes from 11 NCAA Division III colleges who sustained a concussion between 2014 and 2019. Athletic trainers documented time to return to school and to sports. Kruskal-Wallis tests with post-hoc planned comparison Mann-Whitney U tests were used to assess whether athletes took longer to return based on their acute symptom burden (Low, Medium, or High). Survival analysis (Kaplan Meier with log rank tests) was used to compare the recovery times based on acute symptom burden (censored at 28 days). Chi-square tests compared the proportion of those who had not yet returned to school or sports at various recovery benchmarks (i.e., 1 week, 10 days, 2 weeks, 3 weeks, 4 weeks) based on acute symptom burden. Women (median = 5 days) took slightly longer than men (median = 4 days) to return to school (p = 0.001; r = −0.11, small effect). Women and men did not differ on time to return to sports (p = 0.32, r = −0.04). A greater proportion with high acute symptoms remained out of school at 5 (odds ratio, OR = 4.53), 7 (OR = 4.98), and 10 (OR = 4.80) days compared to those with low acute symptoms. A greater proportion with high acute symptoms remained out of sports at 10 (OR = 4.11), 14 (OR = 3.46), and 21 (OR = 3.01) days compared to those with low acute symptoms. This study shows a strong association between having a high burden of acute post-concussion symptoms and having a slower return to school and sports in Division III collegiate athletes. Moreover, it also illustrates the converse: that those athletes with a low burden of acute symptoms have a faster return to school and sports.

The objective of this study was to examine the incidence of concussion and risk factors for sustaining concussion among children from the United States general population. This prospective cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study®. Children were recruited from schools across the US, sampled to reflect the sociodemographic variation of the US population. The current sample includes 11,013 children aged 9 to 10 years old (47.6% girls; 65.5% White) who were prospectively followed for an average of 1 year (mean = 367.9 days, SD = 40.8, range 249–601). The primary outcome was caregiver-reported concussion during a 1 year follow-up period. Logistic regression was used to determine which potential clinical, health history, and behavioral characteristics (assessed at baseline) were prospectively associated with concussion. In the 1 year follow-up period between ages 10 and 11, 1 in 100 children (n = 123, 1.1%) sustained a concussion. In univariate models, three baseline predictors (ADHD, prior concussion, and accident proneness) were significantly associated with sustaining a concussion. In a multivariate model, controlling for all other predictors, only prior concussion remained significantly associated with the occurrence of a concussion during the observation period (Odds Ratio = 5.49, 95% CI: 3.40–8.87). The most robust and only independent prospective predictor of sustaining a concussion was history of a prior concussion. History of concussion is associated with 5.5 times greater odds of sustaining concussion between ages 10 and 11 among children from the general US population.

Introduction: It is reasonable to estimate that tens of millions of men in the United States played high school football. There is societal concern that participation in football confers risk for later-in-life mental health problems. The purpose of this study is to examine whether there is an association between a personal history of playing high school football and death by suicide.Methods: The subjects were obtained from the Lieber Institute for Brain Development (LIBD) brain donation program in collaboration with the Office of the Medical Examiner at Western Michigan University Homer Stryker MD School of Medicine. Donor history was documented via medical records, mental health records, and telephone interviews with the next-of-kin.Results: The sample included 198 men aged 50 or older (median = 65.0 years, interquartile range = 57–75). There were 34.8% who participated in contact sports during high school (including football), and 29.8% participated in high school football. Approximately one-third of the sample had suicide as their manner of death (34.8%). There was no statistically significant difference in the proportions of suicide as a manner of death among those men with a personal history of playing football compared to men who did not play football or who did not play sports (p = 0.070, Odds Ratio, OR = 0.537). Those who played football were significantly less likely to have a lifetime history of a suicide attempt (p = 0.012, OR = 0.352). Men with mood disorders (p < 0.001, OR = 10.712), substance use disorders (p < 0.020, OR = 2.075), and those with a history of suicide ideation (p < 0.001, OR = 8.038) or attempts (p < 0.001, OR = 40.634) were more likely to have suicide as a manner of death. Moreover, those men with a family history of suicide were more likely to have prior suicide attempts (p = 0.031, OR = 2.153) and to have completed suicide (p = 0.001, OR = 2.927).Discussion: Suicide was related to well-established risk factors such as a personal history of a mood disorder, substance abuse disorder, prior suicide ideation, suicide attempts, and a family history of suicide attempts. This study adds to a steadily growing body of evidence suggesting that playing high school football is not associated with increased risk for suicidality or suicide during adulthood.

Objective: Rugby league is an international full-contact sport, with frequent concussive injuries. Participation in other full-contact sports such as American football has been considered to be a risk factor for neuropsychiatric sequelae later-in-life, but little research has addressed the mental and cognitive health of retired professional rugby league players. We examined predictors and correlates of perceived (self-reported) cognitive decline in retired National Rugby League (NRL) players.Methods: Participants were 133 retired male elite level rugby league players in Australia. Participants completed clinical interviews, neuropsychological testing, and self-report measures. The Informant Questionnaire on Cognitive Decline in the Elderly, self-report (IQCODE-Self), measured perceived cognitive decline.Results: The median age of the sample was 55.0 (M = 53.1, SD = 13.9, range = 30–89) and the median years of education completed was 12.0 (M = 11.9, SD = 2.6, range = 7–18). The retired players reported a median of 15.0 total lifetime concussions (M = 28.0, SD = 36.6, range = 0–200). The mean IQCODE-Self score was 3.2 (SD = 0.5; Range = 1.3–5.0); 10/133 (7.5%) and 38/133 (28.6%) scored above conservative and liberal cutoffs for cognitive decline on the IQCODE-Self, respectively. Perceived cognitive decline was positively correlated with current depressive symptoms, negatively correlated with years of professional sport exposure and resilience, and unrelated to objective cognition and number of self-reported concussions. A multiple regression model with perceived cognitive decline regressed on age, concussion history, professional rugby league exposure, depression, resilience, objective cognitive functioning, daytime sleepiness, and pain severity showed depression as the only significant predictor.Conclusion: This is the first large study examining subjectively experienced cognitive decline in retired professional rugby league players. Similar to studies from the general population and specialty clinics, no relationship was found between objective cognitive test performance and perceived cognitive decline. Depressive symptoms emerged as the strongest predictor of perceived cognitive decline, suggesting that subjective reports of worsening cognition in retired elite rugby league players might reflect psychological distress rather than current cognitive impairment.

Background: Serotonergic antidepressants may predispose to bleeding but the effect on traumatic intracranial bleeding is unknown.Methods: The rate of intracranial bleeding in patients with antidepressant medication was compared to patients not antidepressants in a cohort of patients with acute head injury. This association was examined by using a consecutive cohort of head trauma patients from a Finnish tertiary center emergency department (Tampere University Hospital, Tampere, Finland). All consecutive (2010–2012) adult patients (n = 2,890; median age = 58; male = 56%, CT-positive = 22%, antithrombotic medication users = 25%, antidepressant users = 10%) who underwent head CT due to head trauma in the emergency department were included.Results: Male gender, GCS

A controversial theory proposes that playing tackle football before the age of 12 causes later in life brain health problems. This theory arose from a small study of 42 retired National Football League (NFL) players, which reported that those who started playing tackle football at a younger age performed worse on selected neuropsychological tests and a word reading test. The authors concluded that these differences were likely due to greater exposure to repetitive neurotrauma during a developmentally sensitive maturational period in their lives. Several subsequent studies of current high school and collegiate contact/collision sports athletes, and former high school, collegiate, and professional tackle football players have not replicated these findings. This narrative review aims to (i) discuss the fundamental concepts, issues, and controversies surrounding existing research on age of first exposure (AFE) to contact/collision sport, and (ii) provide a balanced interpretation, including risk of bias assessment findings, of this body of evidence. Among 21 studies, 11 studies examined former athletes, 8 studies examined current athletes, and 2 studies examined both former and current athletes. Although the literature on whether younger AFE to tackle football is associated with later in life cognitive, neurobehavioral, or mental health problems in former NFL players is mixed, the largest study of retired NFL players (N = 3,506) suggested there was not a significant association between earlier AFE to organized tackle football and worse subjectively experienced cognitive functioning, depression, or anxiety. Furthermore, no published studies of current athletes show a significant association between playing tackle football (or other contact/collision sports) before the age of 12 and cognitive, neurobehavioral, or mental health problems. It is important to note that all studies were judged to be at high overall risk of bias, indicating that more methodologically rigorous research is needed to understand whether there is an association between AFE to contact/collision sports and later in life brain health. The accumulated research to date suggests that earlier AFE to contact/collision sports is not associated with worse cognitive functioning or mental health in (i) current high school athletes, (ii) current collegiate athletes, or (iii) middle-aged men who played high school football. The literature on former NFL players is mixed and does not, at present, clearly support the theory that exposure to tackle football before age 12 is associated with later in life cognitive impairment or mental health problems.

Background: The purpose of this study was to determine if earlier age of first exposure to football is associated with worse brain health in middle-aged and older adult men who played high school football.Methods: Men from the United States, aged 35 and older, who reported playing high school football, completed a customized, online health survey via the Amazon Mechanical Turk (mTurk) platform. Survey items included physical, psychological, and cognitive symptoms over the past week and over the past year, sports participation history (including age of first exposure to football), medical history, and concussion history. Participants also completed the Patient Health Questionnaire-8 (PHQ-8) and the British Columbia Post-Concussion Symptom Inventory (BC-PSI).Results: There were 186 men (age M = 51.78, SD = 10.93) who participated in high school football, and 87 (46.8%) reported football participation starting before the age of 12 and 99 (53.2%) reported football participation at or after the age of 12. Those who started playing football at an earlier age reported a greater number of lifetime concussions (M = 1.95, SD = 1.79) compared to those who started playing at age 12 or later (M = 1.28, SD = 1.52; U = 3,257.5, p = 0.003). A similar proportion of men who played football before vs. after the age of 12 reported a lifetime history of being prescribed medications for depression, anxiety, chronic pain, headaches, or memory problems. When comparing men who played football before vs. after the age of 12, the groups did not differ significantly in their ratings of depression, anger, anxiety, headaches, migraines, neck or back pain, chronic pain, concentration problems, or memory problems over the past week or the past year. The two groups did not differ significantly in their ratings of current symptoms of depression (PHQ-8; U = 4,187.0, p = 0.74) or post-concussion-like symptoms (BC-PSI; U = 3,944.0, p = 0.53). Furthermore, there were no statistically significant correlations between the age of first exposure to football, as a continuous variable, and PHQ-8 or BC-PSI scores.Conclusion: This study adds to a rapidly growing body of literature suggesting that earlier age of first exposure to football is not associated with later-in-life brain health.

Background: There is considerable interest in determining whether later-in-life depression is associated with lifetime history of concussions or the duration of a career in professional contact and collision sports. Rugby league is a high-intensity collision sport involving a large number of tackles per game and a high rate of concussions. We examined predictors and correlates of depression in retired elite level rugby league players in Australia.Methods: Retired elite level rugby league players (N = 141, age: M = 52.6, SD = 13.8; Range = 30–89 years) completed the Depression, Anxiety, and Stress Scale (DASS), Brief Pain Inventory, Connor-Davidson Resilience Scale (CD-RISC), and Epworth Sleepiness Scale; they also reported on lifetime history of concussions. The DASS depression score was regressed on age, total number of self-reported concussions, years played professionally, CD-RISC score, BPI pain interference score, and ESS score.Results: The retired players reported a median of 15 total lifetime concussions [interquartile range (IQR) = 6–30], and a median of 8 years playing professional sports (IQR = 3.5–11). The proportion of the sample endorsing at least mild current depression was 29%. The DASS depression score was positively correlated with the DASS anxiety (r = 0.54) and DASS stress scores (r = 0.58). The CD-RISC score was negatively correlated with the depression score (r = −0.53). Depression scores were not significantly correlated with pain severity (r = 0.14), and were weakly correlated with life interference due to pain (r = 0.20) and years playing professional sports (r = −0.17). Depression scores were not significantly correlated with lifetime history of concussions (r = 0.14). A multiple regression model, with age, total number of self-reported concussions, years played professionally, the CD-RISC, Brief Pain Inventory-pain interference score, and Epworth Sleepiness Scale score as predictors was significant, with 35% of the variance in DASS depression accounted for. The two significant independent predictors of depression were lower resilience and greater life interference due to pain.Conclusions: This is the first large study of depression in retired rugby league players. Depression in these retired players was not meaningfully associated with lifetime history of concussions or number of years playing elite level collision sport. Depression was associated with current anxiety, stress, resilience, and life interference due to chronic pain.

Objective: There are no validated or agreed upon diagnostic clinical criteria for chronic traumatic encephalopathy or traumatic encephalopathy syndrome. This study examines the leading research criteria for traumatic encephalopathy syndrome (TES) in middle-aged men in the general population.Method: Participants were 409 men between the ages of 35 and 55 recruited through an online crowdsourcing platform. Participants provided demographic information, medication history, concussion history, contact sport history, current medication use, and current symptoms. Research criteria for TES were applied to the sample.Results: Over half of the total sample met TES symptom criteria (56.2%), without applying the neurotrauma exposure criteria. Those with 4+ prior concussions had higher rates of meeting TES criteria compared to those with 0–3 prior concussions, but the results were not statistically significant (69.8 vs. 54.6%; χ2 = 3.58, p = 0.06). Exposure to contact sports was not related to higher rates of TES (ps ≥ 0.55). In a binary logistic regression predicting the presence of mild or greater TES, significant predictors were sleep difficulties [Odds ratio (OR) = 6.68], chronic pain (OR = 3.29), and age (OR = 1.04). Neurotrauma exposure was not a significant predictor (p = 0.66). When analyzing those with no prior concussions or contact sport histories (n = 126), 45.2% met symptom criteria for mild or greater TES; chronic pain and sleep difficulties were associated with a higher prevalence of meeting criteria for TES in this subgroup (ps < 0.001).Conclusions: Men who participated in contact sports in high school or college were not more likely to meet criteria for TES than men who participated in non-contact sports or no sports. In a multivariable model, sleep problems and chronic pain were predictive of meeting the symptom criteria for TES, but the repetitive neurotrauma exposure criterion was not a significant predictor of meeting the TES symptom criteria.

Objective: To examine the relationship between video-identified onfield motor incoordination, the acute assessment of concussion, and recovery time during three seasons of National Rugby League (NRL) play.Methods: Blows to the head (“head impact events”) were recorded by sideline video operators and medical staff. Any player with a suspected concussion underwent a Head Injury Assessment in which he was taken off the field and medically evaluated, including the administration of the Sports Concussion Assessment Tool, 5th Edition (SCAT5). Video footage was later examined to determine the presence or absence of onfield motor incoordination following the head impact event.Results: Motor incoordination was identified in 100/1,706 head impact events (5.9%); 65 of the 100 instances of motor incoordination (65.0%) were ultimately medically diagnosed with a concussion. In 646 athletes for whom SCAT5 data were available, those with motor incoordination were more likely to report both dizziness and balance problems than those without motor incoordination, but there were no group differences on an objective balance test. Additionally, there was no relationship between presence/absence of motor incoordination and number of games missed or time to medical clearance for match play.Conclusion: In NRL players, motor incoordination is a readily observable onfield sign that is strongly associated with a medical diagnosis of concussion and with self-reported dizziness/balance problems. However, onfield motor incoordination is not associated with objective balance performance and it is not predictive of time to recover following concussion.

Researchers operationalize persistent post-concussion symptoms in children and adolescents using varied definitions. Many pre-existing conditions, personal characteristics, and current health issues can affect symptom endorsement rates in the absence of, or in combination with, a recent concussion, and the use of varied definitions can lead to differences in conclusions about persistent symptoms and recovery across studies. This study examined how endorsement rates varied by 14 different operational definitions of persistent post-concussion symptoms for uninjured boys and girls with and without pre-existing or current health problems. This cross-sectional study included a large sample (age range: 11–18) of girls (n = 21,923) and boys (n = 26,556) without a recent concussion who completed the Post-Concussion Symptom Scale at preseason baseline. Endorsements rates varied substantially by definition, health history, and current health issues. The most lenient definition (i.e., a single mild symptom) was endorsed by most participants (54.5% of boys/65.3% of girls). A large portion of participants with pre-existing mental health problems (42.7% of boys/51.5% of girls), current moderate psychological distress (70.9% of boys/72.4% of girls), and insufficient sleep prior to testing (33.4% of boys/47.6% of girls) endorsed symptoms consistent with mild ICD-10 postconcussional syndrome; whereas participants with no current or prior health problems rarely met this definition (1.6% of boys/1.6% of girls). The results illustrate the tremendous variability in the case definitions of persistent symptoms and the importance of harmonizing definitions across future studies.

Objective: Seven candidate cognition composite scores have been developed and evaluated as part of a research program designed to validate a cognition endpoint for traumatic brain injury (TBI) research and clinical trials, but these composites have yet to be examined longitudinally. This study examined test-retest reliability and methods for determining reliable change for these seven candidate composite scores, using the neuropsychological test battery from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI).Methods: Participants (18–59 years-old) with mild TBI (n = 124), orthopedic trauma without head injury (n = 67), and healthy community controls (n = 63) from the Trondheim MTBI follow-up study completed the CENTER-TBI neuropsychological test battery at 2 weeks and 3 months after injury. The battery included both traditional paper-and-pencil tests and computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Seven composite scores were calculated for the paper-and-pencil tests, the CANTAB tests, and all tests combined (i.e., 21 composites in total on each assessment): the overall test battery mean (OTBM); global deficit score (GDS); neuropsychological deficit score-weighted (NDS-W); low score composite (LSC); and the number of scores ≤5th percentile, ≤16th percentile, or

Objective: Identification and validation of blood-based biomarkers for the diagnosis and prognosis of mild traumatic brain injury (mTBI) is of critical importance. There have been calls for more research on mTBI in older adults. We compared blood-based protein marker glial fibrillary acidic protein (GFAP) concentrations in serum and in plasma within the same cohort of older adults and assessed their ability to discriminate between individuals based on intracranial abnormalities and functional outcome following mTBI.Methods: A sample of 121 older adults [≥50 years old with head computed tomography (CT), n = 92] seeking medical care for a head injury [Glasgow Coma Scale scores of 14 (n = 6; 5.0%) or 15 (n = 115; 95.0%)] were enrolled from the emergency department (ED). The mean time between injury and blood sampling was 3.4 h (SD = 2.1; range = 0.5–11.7). Serum GFAP concentration was measured first using the Human Neurology 4-Plex Assay, while plasma GFAP concentration was later measured using the GFAP Discovery Kit, both on an HD-1 Single molecule array (Simoa) instrument. Glasgow Outcome Scale-Extended was assessed 1 week after injury.Results: Both serum and plasma GFAP levels were significantly higher in those with abnormal CT scans compared to those with normal head CT scans (plasma: U = 1,198, p < 0.001; serum: U = 1,253, p < 0.001). The ability to discriminate those with and without intracranial abnormalities was comparable between serum (AUC = 0.814) and plasma (AUC = 0.778). In the total sample, GFAP concentrations were considerably higher in plasma than in serum (Wilcoxon signed-rank test z = 0.42, p < 0.001, r = 0.42). Serum and plasma GFAP levels were highly correlated in the total sample and within all subgroups (Spearman's rho range: 0.826–0.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum: U = 1,625, p = 0.002; plasma: U = 1,539, p = 0.013). Neither plasma (AUC = 0.653) nor serum (AUC = 0.690) GFAP were adequate predictors of functional outcome 1 week after injury.Conclusions: Despite differences in concentration, serum and plasma GFAP levels were highly correlated and had similar discriminability between those with and without intracranial abnormalities on head CT following an mTBI. Neither serum nor plasma GFAP had adequate discriminability to identify patients who would have poor functional outcome.

Background: Measuring cognitive functioning is common in traumatic brain injury (TBI) research, but no universally accepted method for combining several neuropsychological test scores into composite, or summary, scores exists. This study examined several possible composite scores for the test battery used in the large-scale study Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI).Methods: Participants with mild traumatic brain injury (MTBI; n = 140), orthopedic trauma (n = 72), and healthy community controls (n = 70) from the Trondheim MTBI follow-up study completed the CENTER-TBI test battery at 2 weeks after injury, which includes both traditional paper-and-pencil tests and tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Seven composite scores were calculated for the paper and pencil tests, the CANTAB tests, and all tests combined (i.e., 21 composites): the overall test battery mean (OTBM); global deficit score (GDS); neuropsychological deficit score-weighted (NDS-W); low score composite (LSC); and the number of scores ≤5th percentile, ≤16th percentile, or

Background: There are no validated or agreed upon criteria for diagnosing chronic traumatic encephalopathy (CTE) in a living person. In recent years, it has been proposed that anger dyscontrol represents a behavioral clinical phenotype of CTE. This is the first study to examine the specificity of the diagnostic research criteria for traumatic encephalopathy syndrome (TES, the clinical condition proposed to be CTE) in men from the US general population who have anger dyscontrol problems. It was hypothesized that a substantial percentage of these men would meet the research criteria for TES.Methods: Data from 4,139 men who participated in the National Comorbidity Survey Replication, an in-person survey that examined the prevalence and correlates of mental disorders in the United States, were included in this study. Men who were diagnosed with intermittent explosive disorder in the past year were the clinical sample of interest (n = 206; 5.0% of all men in the database), and the remaining men were used as a comparison sample. They were classified as meeting the research criteria for TES if they presented with the purported supportive clinical features of CTE (e.g., impulsivity/substance abuse, anxiety, apathy, suicidality, headache).Results: In this sample of men from the general population with intermittent explosive disorder, 27.3% met a conservative definition of the proposed research criteria for CTE (i.e., traumatic encephalopathy syndrome). If one assumes the delayed-onset criterion is present, meaning that the men in the sample are compared to former athletes or military veterans presenting with mental health problems years after retirement, then 65.0% of this sample would meet the research criteria for TES.Conclusions: These results have important implications. Using conservative criteria, at least one in four men from the general population, who have serious anger control problems, will meet the symptom criteria for TES. If one considers former athletes and military veterans with anger control problems who present many years after retirement and who experienced a documented decline in their mental health, nearly two-thirds will meet these research criteria. More research is needed to examine risks for misdiagnosing TES and to determine whether anger dyscontrol is a clinical phenotype of CTE.

Objective: Pre-injury mental health problems are associated with greater symptom reporting following sport-related concussion. We applied a statistical and psychometric approach known as network analysis to examine the interrelationships among symptoms at baseline in adolescent student athletes with a history of mental health problems.Design: Cross-sectional study.Setting: High schools in Maine, USA.Participants: A cohort of 44,527 adolescent student athletes completed baseline preseason testing with ImPACT® between 2009 and 2015, and those with a history of mental health problems reporting at least one symptom were included (N = 2,412; 14–18 years-old, 60.1% girls).Independent Variables: Self-reported history of treatment for a psychiatric condition.Main Outcome Measures: Physical, cognitive, and emotional symptoms from the Post-Concussion Symptom Scale.Results: Student athletes reported high frequencies of emotional symptoms (nervousness: boys = 46.6%, girls = 58.3%; irritability: boys = 37.9%, girls = 46.9%; sadness: boys = 38.7%, girls = 53.2%), sleep/arousal-related symptoms (trouble falling asleep: boys = 50.4%, girls = 55.1%; sleeping less than usual: boys = 43.8%, girls = 45.2%; and fatigue: boys = 40.3%, girls = 45.2%), headaches (boys = 27.5%, girls = 41.8%), and inattention (boys = 47.8%, girls = 46.9%) before the start of the season. Although uncommonly endorsed, dizziness was the most central symptom (i.e., the symptom with the highest aggregate connectedness with different symptoms in the network), followed by feeling more emotional and feeling slowed down. Dizziness was related to physical and somatic symptoms (e.g., balance, headache, nausea, numbness/tingling) whereas increased emotionality was related to sadness, nervousness, and irritability. Feeling slowed down was connected to cognitive (e.g., fogginess, forgetfulness), and sensory symptoms (e.g., numbness/tingling, light sensitivity). There were no gender differences in the symptom network structure.Conclusions: We examined the interconnections between symptoms reported by student athletes with mental health problems at preseason baseline, identifying how physical, cognitive, and emotional symptoms interact and potentially reinforce each other in the absence of injury. These findings are a step toward informing more precise interventions for this subgroup of athletes if they are slow to recover following concussion.

Some people experience persistent symptoms following a mild traumatic brain injury (MTBI), and the etiology of those symptoms has been debated for generations. Post-concussion-like symptoms are caused by many factors both before and after MTBI, and this non-specificity is the bedrock of the conundrum regarding the existence of the post-concussion syndrome. A latent model or common cause theory for the syndrome is inconsistent with the prevailing biopsychosocial conceptualization. It is the thesis of this paper that adopting a network perspective for persistent symptoms following MTBI, including the post-concussion syndrome, could lead to new insights and targeted treatment and rehabilitation strategies. The network perspective posits that symptoms co-occur because they are strongly inter-related, activating, amplifying, and mutually reinforcing, not because they arise from a common latent disease entity. This approach requires a conceptual shift away from thinking that symptoms reflect an underlying disease or disorder toward viewing inter-related symptoms as constituting the syndrome or disorder. The symptoms do not arise from an underlying syndrome—the symptoms are the syndrome. A network analysis approach allows us to embrace heterogeneity and comorbidity, and it might lead to the identification of new approaches to sequenced care. The promise of precision rehabilitation requires us to better understand the interconnections among symptoms and problems so that we can produce more individualized and effective treatment and rehabilitation.

BackgroundThe extensive use of computed tomography (CT) after acute head injury is costly and carries potential iatrogenic risk. This systematic review examined the usefulness of blood-based glial fibrillary acidic protein (GFAP) for predicting acute trauma-related CT-positive intracranial lesions following head trauma. The main objective was to summarize the current evidence on blood-based GFAP as a potential screening test for acute CT-positive intracranial lesions following head trauma.MethodsWe screened MEDLINE, EMBASE, PsychInfo, CINAHL, Web of Science, the Cochrane Database, Scopus, Clinical Trials, OpenGrey, ResearchGate, and the reference lists of eligible publications for original contributions published between January 1980 and January 2017. Eligibility criteria included: (i) population: human head and brain injuries of all severities and ages; (ii) intervention: blood-based GFAP measurement ≤24 h post-injury; and (iii) outcome: acute traumatic lesion on non-contrast head CT ≤24 h post-injury. Three authors completed the publication screening, data extraction, and quality assessment of eligible articles.ResultsThe initial search identified 4,706 articles, with 51 eligible for subsequent full-text assessment. Twenty-seven articles were ultimately included. Twenty-four (89%) studies reported a positive association between GFAP level and acute trauma-related intracranial lesions on head CT. The area under the receiver operating characteristic curve for GFAP prediction of intracranial pathology ranged from 0.74 to 0.98 indicating good to excellent discrimination. GFAP seemed to discriminate mass lesions and diffuse injury, with mass lesions having significantly higher GFAP levels. There was considerable variability between the measured GFAP averages between studies and assays. No well-designed diagnostic studies with specific GFAP cutoff values predictive of acute traumatic intracranial lesions have been published.ConclusionIntracranial CT-positive trauma lesions were associated with elevated GFAP levels in the majority of studies. Methodological heterogeneity in GFAP assessments and the lack of well-designed diagnostic studies with commercially validated GFAP platforms hinder the level of evidence, and variability in levels of GFAP with no clearly established cutoff for abnormality limit the clinical usefulness of the biomarker. However, blood-based GFAP holds promise as a means of screening for acute traumatic CT-positive lesion following head trauma.