Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head trauma, common in contact sports and military service. Although commonly associated with aggression in middle age, recent studies have shown that this relationship depends on other factors. A new study found that CTE amplifies the effects of a family history of mental illness (FHMI) on aggression, especially in individuals aged 40 to 59.
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with the abnormal accumulation of a protein called tau in the brain. This accumulation is often linked to repetitive head impacts, such as those experienced in contact sports (e.g., football, boxing) or during military service.
CTE is part of a group of diseases called tauopathies, which include other neurodegenerative conditions, but is distinct because it is directly related to repeated trauma.
Although reports frequently associate CTE with aggressive behavior, especially during middle age, more recent studies have found inconsistencies in this relationship. In other words, the presence of CTE alone does not explain aggression in all individuals diagnosed.
However, a family history of first-degree mental illness (i.e., close relatives with mental disorders) is known to be a recognized risk factor for aggressive behavior. This raises the possibility that CTE may intensify the effects of a genetic predisposition to aggression.
To explore this relationship, researchers at Boston University analyzed data from 845 deceased brain donors who had been exposed to repetitive head impacts. The study was conducted between 2014 and 2021 and is part of a larger study called the Understanding Neurologic Injury and Traumatic Encephalopathy Study.
The brains were evaluated by neuropathologists to confirm the presence of CTE using criteria established by the National Institute of Neurological Disorders and Stroke (NINDS). In addition, family members or close associates of the donors completed detailed questionnaires about the deceased’s lifetime behavior, including a history of aggression, using a tool called the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA).
They also provided information about the presence of a first-degree family history of mental illness (1st FHMI).
The image shows a coronal section of the brains of normal individuals (left) and those with advanced CTE (right).
The researchers divided the donor data into two main groups: those diagnosed with CTE and those without the pathology. They then performed statistical analyses to investigate how family history of mental illness influenced aggression in both groups.
They took into account several factors, such as age, race, educational level, military history, experience with contact sports, psychological trauma and even substance use. The goal was to isolate the impact of CTE and the 1st FHMI on aggression.
Among the 845 brain donors, the average age at death was approximately 60 years. Of these, 69.7% were diagnosed with CTE, and 45.3% had a first-degree family history of mental illness.
The results revealed that a family history of mental illness was significantly associated with aggressive behavior in adulthood only among those with CTE.
In the CTE group, the impact of 1°FHMI was moderate but statistically significant (β = 0.16, indicating a positive association). In the non-CTE group, this association was not significant.
Also, the relationship between CTE, 1°FHMI, and aggression was most pronounced in the 40–59 age group. Individuals with CTE in this age group and with 1°FHMI had significantly higher levels of aggression than those without CTE or outside this age group.
When the researchers looked at specific factors of aggression, the greatest effects of CTE and 1°FHMI were seen in areas such as emotional dysregulation/impulsivity and antisocial behavior. These behaviors were significantly more pronounced in the CTE group.
The study suggests that CTE may amplify the effects of a genetic predisposition to aggressive behavior, especially in middle age.
This means that in people with CTE, a family history of mental illness may exacerbate aggressive behavior, creating a greater risk than the sum of the individual factors. These findings help explain why some previous studies have failed to identify a clear link between CTE and aggression.
The results point to the need for prospective studies that can confirm these associations more robustly. Furthermore, understanding the interaction between genetic predisposition and CTE pathology may pave the way for more targeted interventions, either to treat aggressive behavior in at-risk individuals or to identify those most vulnerable to CTE early.
This research also reinforces the importance of addressing the cumulative impacts of contact sports and head injuries over the lifespan.
READ MORE:
Chronic Traumatic Encephalopathy, Family History of Mental Illness, and Aggression in Brain Donors With Repetitive Head Impact Exposure
Madeline Uretsky, Evan Nair, Rebecca Burton, Shea W Cronin, Danielle Rousseau, Fatima Tuz-Zahra, Shruti Durape, Bobak Abdolmohammadi, Zachary Baucom, Nicole Saltiel, Arsal Shah, Brett Martin, Joseph Palmisano, Jonathan D Cherry, Daniel Daneshvar, Brigid Dwyer, Kristen Dams-O'Connor, John Crary, Lee Goldstein, Bertrand Huber, Douglas Katz, Neil Kowall, Robert C Cantu, Victor E Alvarez, Robert A Stern, Thor D Stein, Yorghos Tripodis, Ann C McKee, Michael L Alosco, Jesse Mez
Neurology. 2024 Dec 24;103(12):e210056.
doi: 10.1212/WNL.0000000000210056.
Abstract:
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 for 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 sports 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 the risk of aggression beyond each risk factor's additive effects. Prospective studies are needed to confirm these results.
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