From the Boston University Alzheimer's Disease Research Center and Chronic Traumatic Encephalopathy Center (M.U., E.N., S.D., B.A., N.S., A.S., J.P., J.D.C., D.D., B.D., L.G., B.H., D.K., N.K., R.C.C., V.E.A., R.A.S., T.D.S., Y.T., A.C.M., M.L.A., J.M.), Framingham Heart Study (R.B., A.C.M.), Departments of Pathology and Laboratory Medicine (J.D.C., T.D.S., A.C.M.), Neurology (B.D., B.H., D.K., R.C.C., R.A.S., A.C.M., M.L.A., J.M.), Psychiatry (L.G.), Radiology (L.G.), Ophthalmology (L.G.), and Biomedical Engineering (L.G.), Boston University Chobanian & Avedisian School of Medicine; Departments of Applied Social Sciences (S.W.C., D.R.) and Biomedical Engineering (L.G.), Boston University; Department of Biostatistics (F.T.-Z., Z.B., B.M., J.P., Y.T.), Boston University School of Public Health; Spaulding Rehabilitation Hospital (D.D.), Charlestown; Braintree Rehabilitation Hospital (B.D., D.K.); Department of Rehabilitation and Human Performance (K.D.-O.C.), Brain Injury Research Center, Department of Pathology (J.C.), Department of Artificial Intelligence & Human Health, Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease, Friedman Brain Institute, and Neuropathology Brain Bank & Research CoRE, Icahn School of Medicine at Mount Sinai, New York, NY; VA Boston Healthcare System (B.H., N.K., V.E.A., T.D.S., A.C.M.); Department of Neurosurgery (R.C.C.), Emerson Hospital, Concord; and VA Bedford Healthcare System (V.E.A., T.D.S., A.C.M.), MA.
Neurology. 2024 Dec 24;103(12):e210056. doi: 10.1212/WNL.0000000000210056. Epub 2024 Nov 27.
Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with exposure to repetitive head impacts, including from contact sports and military service. Although CTE case reports have commonly described aggression during midlife, recent studies failed to show associations between CTE tau burden and aggression. First-degree family history of mental illness (1°FHMI) is a well-established risk factor of aggression. We tested the hypothesis that CTE pathology moderates the association between 1°FHMI and aggression, providing an explanation for the lack of association previously observed.
This was a retrospective examination of consecutive, deceased, male brain donors with repetitive head impact exposure from the Understanding Neurologic Injury and Traumatic Encephalopathy Study at Boston University from 2014 to 2021. Neuropathologists diagnosed CTE using established National Institute of Neurological Disorders and Stroke criteria. Informants were administered the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA) and were queried regarding 1°FHMI. Exploratory factor analysis evaluated BGLHA factor structure. Stratified by CTE status, linear regression analyses examined relationships between 1°FHMI and standardized adult BGLHA scores and factor scores. Models were adjusted for race, age at death, education, years of contact sport play, military history, substance use treatment history, psychologically traumatic event history, and BGLHA childhood score.
Among 845 brain donors, the mean age at death was 60.3 (SD = 19.6) years. 589 donors (69.7%) had CTE, and 383 donors (45.3%) had a 1°FHMI. 1°FHMI was significantly associated with standardized adult BGLHA scores in those with CTE, but not in those without CTE (CTE present: β = 0.16, 95% CI 0.02-0.29; CTE absent: β = 0.10, 95% CI -0.12 to 0.32). The largest effects were observed among those with CTE, aged 40-59 years (CTE present: β = 0.64, 95% CI 0.32-0.96; CTE absent: β = 0.05, 95% CI -0.44 to 0.54), particularly for BGLHA factors of emotional dysregulation/impulsiveness (CTE present: β = 1.68, 95% CI 0.78-2.58; CTE absent: β = 0.09, 95% CI -1.20 to 1.37) and antisocial behavior (CTE present: β = 1.56, 95% CI 0.64-2.47; CTE absent: β = 0.10, 95% CI -1.19 to 1.40).
Among brain donors exposed to repetitive head impacts, CTE pathology moderated the effect of 1°FHMI on BGLHA scores, with the largest effects in midlife. Predisposition to mental illness and CTE pathology may increase risk of aggression beyond each risk factor's additive effects. Prospective studies are needed to confirm these results.
慢性创伤性脑病（CTE）是一种与反复头部撞击有关的神经退行性 tau 病，包括接触性运动和兵役。尽管 CTE 病例报告通常描述了中年时期的攻击性，但最近的研究未能显示 CTE tau 负担与攻击性之间存在关联。一级亲属精神病史（1°FHMI）是攻击性的一个既定风险因素。我们检验了 CTE 病理学是否调节了 1°FHMI 与攻击性之间的关联，为以前观察到的缺乏关联提供了一个解释。
这是一项对来自波士顿大学的理解神经损伤和创伤性脑病研究中连续的、已故的、有重复头部撞击暴露的男性脑捐献者的回顾性检查，时间从 2014 年到 2021 年。神经病理学家使用国家神经疾病和中风研究所的既定标准诊断 CTE。知情人接受了 Brown-Goodwin 终生攻击性评估（BGLHA），并被询问一级亲属精神病史。探索性因素分析评估了 BGLHA 因子结构。根据 CTE 状态进行分层，线性回归分析检查了 1°FHMI 与标准化成人 BGLHA 评分和因子评分之间的关系。模型调整了种族、死亡时的年龄、教育程度、接触性运动年限、兵役史、物质使用治疗史、心理创伤事件史和 BGLHA 儿童评分。
在 845 名脑捐献者中，死亡时的平均年龄为 60.3（SD=19.6）岁。589 名捐献者（69.7%）有 CTE，383 名捐献者（45.3%）有一级亲属精神病史。在有 CTE 的捐献者中，一级亲属精神病史与标准化成人 BGLHA 评分显著相关，但在没有 CTE 的捐献者中则不相关（CTE 存在：β=0.16，95%CI 0.02-0.29；CTE 不存在：β=0.10，95%CI -0.12 至 0.32）。在年龄为 40-59 岁的有 CTE 的捐献者中观察到最大的影响（CTE 存在：β=0.64，95%CI 0.32-0.96；CTE 不存在：β=0.05，95%CI -0.44 至 0.54），特别是在 BGLHA 的情绪失调/冲动性（CTE 存在：β=1.68，95%CI 0.78-2.58；CTE 不存在：β=0.09，95%CI -1.20 至 1.37）和反社会行为（CTE 存在：β=1.56，95%CI 0.64-2.47；CTE 不存在：β=0.10，95%CI -1.19 至 1.40）方面。
在暴露于反复头部撞击的脑捐献者中，CTE 病理学调节了一级亲属精神病史对 BGLHA 评分的影响，在中年时期的影响最大。精神病史和 CTE 病理学的易感性可能会增加攻击性的风险，超过每个风险因素的累加效应。需要前瞻性研究来证实这些结果。
