Neurobehavioral dysregulation, depressive symptoms, and cognition in former American football players
18 affiliations
- 1Department of Epidemiology and Biostatistics, School of Public Health, University of Nevada, Las Vegas
- 2Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas
- 3Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas
- 4Department of Neurology, Boston University Chobanian & Avedisian School of Medicine
- 5Boston University Alzheimer’s Disease Research Center
- 6BU CTE Center, Boston University
- 7Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine
- 8Department of Neurology, Boston Medical Center
- 9Department of Psychiatry and Psychology, Mayo Clinic School of Medicine and Science
- 10Department of Neurosciences, University of California San Diego School of Medicine
- 11Department of Psychiatry, University of California San Diego School of Medicine
- 12Department of Neurology, Mayo Clinic School of Medicine and Science
- 13Encompass Health Rehabilitation Hospital
- 14Department of Neurology, Grossman School of Medicine, New York University
- 15Center for Health Data Science, Boston University School of Public Health
- 16Cleveland Clinic Lou Ruvo Center for Brain Health
- 17Banner Alzheimer’s Institute
- 18Department of Psychiatry, University of Arizona College of Medicine—Phoenix
Abstract
Neurobehavioral dysregulation (NBD) is a core clinical feature of traumatic encephalopathy syndrome (TES), but its relationships with repetitive head impact (RHI) exposure, cognitive performance, and depressive symptoms remain unclear. This study examined clinical factors associated with NBD among former American football players with substantial RHI exposure. Cross-sectional baseline data were analyzed from 179 former American football players enrolled in the DIAGNOSE CTE Research Project, including 119 former professional and 60 former college players. NBD was assessed using measures of impulsivity, behavioral regulation, hostility, and emotional lability. Multivariate regression models evaluated associations of continuous NBD scores with depressive symptom dimensions, cognitive performance, playing level, and years of football participation, adjusting for demographic and clinical covariates. Secondary analyses evaluated dichotomized NBD outcomes using study-specific thresholds. Bonferroni-adjusted p -values were reported for multiple comparisons. Depressive symptoms demonstrated the most consistent associations with NBD. Greater neurovegetative depressive symptom burden was associated with greater impulsivity (estimate = 6.84; 95% CI = 4.45, 9.23; p -value < 0.0001), behavioral dysregulation (estimate = 11.63; 95% CI = 8.50, 14.76; p -value < 0.0001), hostility (estimate = 5.07; 95% CI = 2.32, 7.81; p -value = 0.0004), and emotional lability (estimate = 1.16; 95% CI = 0.12, 2.20; p -value = 0.0284). Greater agitated/reactive depressive symptom burden was associated with greater impulsivity (estimate = 3.42; 95% CI = 1.44, 5.41; p -value = 0.0008) and hostility (estimate = 5.11; 95% CI = 2.89, 7.32; p -value < 0.0001), while greater affective depressive symptom burden was associated with greater behavioral dysregulation (estimate = 3.09; 95% CI = 0.01, 6.18; p -value = 0.0494). Better verbal memory was associated with lower impulsivity (estimate = −2.02; 95% CI = -3.65, −0.40; p -value = 0.0149) and behavioral dysregulation (estimate = −2.64; 95% CI = −4.76, −0.52; p -value = 0.0150), while better executive speed was associated with lower behavioral dysregulation (estimate = −3.10; 95% CI = −5.11, −1.09; p -value = 0.0027). Years of football exposure was not independently associated with NBD outcomes. Among former American football players with substantial RHI exposure, depressive symptom burden was more consistently associated with NBD than football participation characteristics or cognitive performance. These findings support a heterogeneous clinical phenotype and underscore the importance of evaluating depressive symptoms when interpreting NBD in the context of TES.
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BibTeX
@article{kleven2026neurobehavioral,
title = {{Neurobehavioral dysregulation, depressive symptoms, and cognition in former American football players}},
author = {Brooke D. Conway Kleven and Michael L. Alosco and Jennifer V. Wethe and Sarah J. Banks and Charles H. Adler and Douglas I. Katz and Robert C. Cantu and Laura J. Balcer and Yorghos Tripodis and Jesse Mez and Charles Bernick and Eric M. Reiman and Robert A. Stern and Jeffrey L. Cummings},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1952836},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1952836/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neurobehavioral dysregulation, depressive symptoms, and cognition in former American football players
AU - Brooke D. Conway Kleven
AU - Michael L. Alosco
AU - Jennifer V. Wethe
AU - Sarah J. Banks
AU - Charles H. Adler
AU - Douglas I. Katz
AU - Robert C. Cantu
AU - Laura J. Balcer
AU - Yorghos Tripodis
AU - Jesse Mez
AU - Charles Bernick
AU - Eric M. Reiman
AU - Robert A. Stern
AU - Jeffrey L. Cummings
PY - 2026
DA - 2026/10/13
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1952836
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1952836/full
AB - Neurobehavioral dysregulation (NBD) is a core clinical feature of traumatic encephalopathy syndrome (TES), but its relationships with repetitive head impact (RHI) exposure, cognitive performance, and depressive symptoms remain unclear. This study examined clinical factors associated with NBD among former American football players with substantial RHI exposure. Cross-sectional baseline data were analyzed from 179 former American football players enrolled in the DIAGNOSE CTE Research Project, including 119 former professional and 60 former college players. NBD was assessed using measures of impulsivity, behavioral regulation, hostility, and emotional lability. Multivariate regression models evaluated associations of continuous NBD scores with depressive symptom dimensions, cognitive performance, playing level, and years of football participation, adjusting for demographic and clinical covariates. Secondary analyses evaluated dichotomized NBD outcomes using study-specific thresholds. Bonferroni-adjusted p -values were reported for multiple comparisons. Depressive symptoms demonstrated the most consistent associations with NBD. Greater neurovegetative depressive symptom burden was associated with greater impulsivity (estimate = 6.84; 95% CI = 4.45, 9.23; p -value < 0.0001), behavioral dysregulation (estimate = 11.63; 95% CI = 8.50, 14.76; p -value < 0.0001), hostility (estimate = 5.07; 95% CI = 2.32, 7.81; p -value = 0.0004), and emotional lability (estimate = 1.16; 95% CI = 0.12, 2.20; p -value = 0.0284). Greater agitated/reactive depressive symptom burden was associated with greater impulsivity (estimate = 3.42; 95% CI = 1.44, 5.41; p -value = 0.0008) and hostility (estimate = 5.11; 95% CI = 2.89, 7.32; p -value < 0.0001), while greater affective depressive symptom burden was associated with greater behavioral dysregulation (estimate = 3.09; 95% CI = 0.01, 6.18; p -value = 0.0494). Better verbal memory was associated with lower impulsivity (estimate = −2.02; 95% CI = -3.65, −0.40; p -value = 0.0149) and behavioral dysregulation (estimate = −2.64; 95% CI = −4.76, −0.52; p -value = 0.0150), while better executive speed was associated with lower behavioral dysregulation (estimate = −3.10; 95% CI = −5.11, −1.09; p -value = 0.0027). Years of football exposure was not independently associated with NBD outcomes. Among former American football players with substantial RHI exposure, depressive symptom burden was more consistently associated with NBD than football participation characteristics or cognitive performance. These findings support a heterogeneous clinical phenotype and underscore the importance of evaluating depressive symptoms when interpreting NBD in the context of TES.
SN - 1664-2295
ER -