Family history of mental illness tied to aggression in chronic traumatic encephalopathy

Key takeaways:

• CTE pathology moderated the association between family history of mental illness and aggression.
• The largest effects were observed in middle-aged male brain donors with CTE.

First-degree family history of mental illness was associated with aggression among male brain donors with chronic traumatic encephalopathy who were exposed to repetitive head impacts, according to a study published in Neurology.

“Although chronic traumatic encephalopathy (CTE) case reports have commonly described aggression during midlife, recent studies failed to show associations between CTE tau burden and aggression,” Madeline Uretsky, MS, research program manager at the Boston University Alzheimer’s Disease Research Center, and colleagues wrote. “First-degree family history of mental illness is a well-established risk factor of aggression. We tested the hypothesis that CTE pathology moderates the association between first-degree family history of mental illness and aggression, providing an explanation for the lack of association previously observed.”

Uretsky and colleagues retrospectively examined data from 845 deceased male brain donors aged 18 years or older (mean age at death, 60.3 years; 83.3% white) who were contact sport athletes or combat military veterans and/or had prolonged exposure to physical violence. The brain donations occurred from 2014 to 2021 to the Understanding Neurologic Injury and Traumatic Encephalopathy Brain Bank at Boston University.

A trained research assistant administered the 11-item version of the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA) to informants for the donor — such as their parent, spouse or adult child — through structured retrospective telephone interviews.

Additionally, informants were questioned about donors’ first-degree family history of mental illness.

The researchers categorized the donors into four groups, according to whether they had:

• CTE and a first-degree family history of mental illness (n = 256; 30.3%);
• CTE alone (n = 333; 39.4%);
• a first-degree family history of mental illness without CTE (n =127; 15%); and
• neither CTE nor a first-degree family history of mental illness (n = 129; 15.3%).

Among the 589 donors with CTE, 203 (34.5%) had a family history of mood disorders and 106 (18%) had a family history of other psychiatric disorders.

The researchers found a significant, positive association between having a first-degree family history of mental illness and the BGLHA score (P = .02), where donors with CTE who had such family history scored 0.16 standard deviation higher on the BGLHA compared with donors without family history (B = 0.16; 95% CI, 0.02-0.29). Conversely, where was no significant association between CTE and BGLHA score among those without a first-degree family history of mental illness (B = 0.1; 95% CI, –0.12 to 0.32).

They observed the largest effects of this association among those with CTE aged 40 to 59 years (B = 0.64; 95% CI, 0.32-0.96).

Next, researchers looked at whether certain aspects of aggression were greater predictors in an exploratory factor analysis of four BGLHA factors: emotional dysregulation and impulsivity, interpersonal relations, antisocial behavior, and physical manifestation of anger.

According to the researchers, emotional dysregulation and impulsivity (B = 0.4; 95% CI, 0.03-0.77) and antisocial behavior (B = 0.37; 95% CI, 0.02-0.73) were significantly associated with first-degree family history of mental illness among donors with CTE.

“The link between a family history of mental illness and aggression may be through a shared genetic background and also through shared environment and common behaviors, such as childhood experiences with family members,” Jesse Mez, MD, MS, of Boston University’s Chobanian & Avedisian School of Medicine, said in an American Academy of Neurology press release related to the study. “Identifying people who are more likely to show symptoms of aggression based on family history of mental illness would give us a way to predict the consequences of CTE and identify who may benefit most from treatment options.”

In a related editorial, Melissa Shuman Paretsky, PhD, of MSP Psychology PLLC, and David Q. Beversdorf, MD, of the University of Missouri, wrote that the study has many strengths, including its large sample size and retrospective examination of deceased male brain donors exposed to repetitive head impacts.

However, they acknowledged that the study also has several limitations, including its reliance on retrospective informant reports, which subjected the data “to recall bias and limited inferences regarding causality.” They also noted that most brain donors from the Understanding Neurologic Injury and Traumatic Encephalopathy Brain Bank were white, older men who had been professional football players, which may limit generalizability.

“Future studies must focus on younger players because CTE can emerge at younger ages, and on female athletes because they are increasingly participating in sports that may place them at risk,” Paretsky and Beversdorf wrote.

References:

• For those with CTE, family history of mental illness tied to aggression in middle age. https://www.aan.com/PressRoom/Home/PressRelease/5216. Published Nov. 27, 2024. Accessed Dec. 5, 2024.
• Paretsky MS, et al. Neurology. 2024;doi:10.1212/WNL.0000000000210201.