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

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.
Competing Interests: Dr. Bernick has received research support from Haymon Boxing, Top Rank Promotions, and the Ultimate Fighting Championship. Dr. Geda has received funding from the Barrow Neurological Foundation, NIH (grant R01 AG057708), and Roche; and he has served on the advisory board of Lundbeck. Dr. Wethe is a cocreator of Mayo Clinic Concussion Check, which incorporates the King-Devick Test, in association with the Mayo Clinic. Dr. Katz has received royalties from Springer/Demos Publishing for a textbook on brain injury, he has served as an expert witness in legal cases involving brain injury and concussion, he has received a stipend from Encompass Health as program medical director for brain injury and chair of the annual Neurorehabilitation Conference, and he has received honoraria for a keynote address for the annual medical directors meeting of HealthSouth. Dr. Alosco has received research support from Life Molecular Imaging and the Rainwater Charitable Foundation, he has received a single-time honorarium from the Michael J. Fox Foundation, and he has received royalties from Oxford University Press. Dr. Tripodis has received financial support from the American Medical Association. Dr. Adler has served as a consultant for Avion, CND Life Sciences, Jazz, and PreCon Health. Dr. Balcer has served as editor-in-chief of the Journal of Neuro-Ophthalmology, and her spouse co-owns a patent on an N-methyl-d-aspartate receptor antibody assay. Dr. Reiman has been a compensated scientific adviser to Alkahest, Alzheon, Aural Analytics, Cognition Therapeutics Denali, Enigma, Green Valley, Retromer Therapeutics, and Vaxxinity; and he is a cofounder of, shareholder with, and adviser to ALZPath. Dr. Cummings has served as a consultant to Acadia, Actinogen, Acumen, AlphaCognition, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, Bristol-Myers Squib, Cassava, Cerecin, Diadem, EIP Pharma, Eisai, GAP Innovations, GemVax, Genentech, Janssen, Jocasta, Karuna, Lighthouse, Lilly, LSP/EQT, Lundbeck, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, Ono, Optoceutics, Otsuka, Oxford Brain Diagnostics, PRODEO, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, Sinaptica, Suven, SynapseBio, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies; he has been supported by the Alzheimer’s Disease Drug Discovery Foundation, the Joy Chambers-Grundy Endowment, NIH (grants P20GM109025, U01NS093334, R01AG053798, P30AG072959, R35AG71476, R25AG083721), and the Ted and Maria Quirk Endowment; he owns the copyright of the Neuropsychiatric Inventory; and he is a shareholder with Acumen, Alzheon, Artery, Behrens, MedAvante-Prophase, and Vaxxinity. Dr. Stern has been a member of the Board of Directors of King-Devick Technologies, and he has received royalties for published neuropsychological tests from Psychological Assessment Resources. The other authors report no financial relationships with commercial interests.