Characterizing Neurobehavioral Dysregulation Among Former American Football Players: Findings From the DIAGNOSE CTE Research Project

Surya V. Pulukuri, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Tessa R. Fagle, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Diana Trujillo-Rodriguez, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Suzan van Amerongen, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Charles Bernick, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Yonas E. Geda, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Jennifer V. Wethe, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Elaine R. Peskind, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Douglas I. Katz, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Michael L. Alosco, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Joseph N. Palmisano, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Yorghos Tripodis, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Charles H. Adler, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Laura J. Balcer, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Eric M. Reiman, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Martha E. Shenton, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Jeffrey L. Cummings, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).
Robert A. Stern, Chronic Traumatic Encephalopathy Center (Pulukuri, Fagle, Trujillo-Rodriguez, van Amerongen, Katz, Alosco, Tripodis, Stern), Graduate Program in Neuroscience (Trujillo-Rodriguez), Department of Neurology (Katz, Alosco, Stern), Alzheimer's Disease Research Center (Alosco, Tripodis, Stern), Department of Neurosurgery and Department of Anatomy and Neurobiology (Stern), Boston University Chobanian and Avedisian School of Medicine, Boston; Department of Neurology, Alzheimer Center Amsterdam, Vrije Universiteit (VU) Amsterdam, VU University Medical Center, and Department of Neurodegeneration, Amsterdam Neuroscience, Amsterdam (van Amerongen); Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas (Bernick); Department of Neurology and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix (Geda); Department of Psychiatry and Psychology (Wethe) and Department of Neurology (Adler), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Peskind); Brain Injury Program, Encompass Health Braintree Rehabilitation Hospital, Braintree, Mass. (Katz); Biostatistics and Epidemiology Data Analytics Center (Palmisano) and Department of Biostatistics (Tripodis), Boston University School of Public Health; Departments of Neurology, Population Health, and Ophthalmology, New York University Grossman School of Medicine, New York (Balcer); Banner Alzheimer's Institute, University of Arizona, Translational Genomics Research Institute, Arizona State University, and Arizona Alzheimer's Consortium, Phoenix (Reiman); Departments of Psychiatry and Radiology, Psychiatry Neuroimaging Laboratory, Harvard Medical School, Brigham and Women's Hospital, Boston (Shenton); Department of Brain Health, Chambers-Grundy Center for Transformative Neuroscience, School of Integrated Health Sciences, University of Nevada Las Vegas (Cummings).

Document Type

Article

Abstract

OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD.

Medical Subject Headings

Humans; Football (injuries); Male; Adult; Chronic Traumatic Encephalopathy (diagnosis, complications, physiopathology); Cluster Analysis; Factor Analysis, Statistical; Middle Aged; Athletes; Young Adult; Neuropsychological Tests; Athletic Injuries (complications)

Publication Date

1-1-2025

Publication Title

The Journal of neuropsychiatry and clinical neurosciences

E-ISSN

1545-7222

Volume

37

Issue

1

First Page

38

Last Page

46

PubMed ID

39034669

Digital Object Identifier (DOI)

10.1176/appi.neuropsych.20230133

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