In a nested case-control study of TBI patients during the first three months following injury, we found that verbal aggression was quite prevalent but physical aggression was virtually absent. Aggression in the post-TBI period was associated with impaired post-TBI psychosocial functioning, new-onset major depression post-TBI, and increased dependence on activities of daily living. Interestingly enough, recurrence of pre-TBI major depression was not a predictor of aggression.
We report several significant negative findings. Only one of the 67 participants exhibited physical aggression, and this was in a milder form (aggression only toward objects). None exhibited physical aggression towards self or others. We observed no significant association between post-TBI aggression and several covariates reported in prior studies including childhood behavior problems, adult behavior problems, legal charges, pre or post-TBI substance abuse or dependence, neuropsychological tests or brain lesions.
The prevalence of aggression is similar to what is reported in the literature,2,8
as is the mix of TBI severity with approximately 60% having mild TBI.32
On reviewing the literature on the subtypes of aggression after brain injury, several studies have noted an association between brain injury and physical aggression.34-37
Only one person reported to history of physical aggression in our study. Our findings are consistent with anecdotal reports on the predominance of verbal aggression after TBI.38,39
Dyer et al.38
have also noted a higher prevalence of verbal aggression rather than physical aggression in a sample of TBI patients studied six months post-injury. This discrepancy in the literature could be due to differences in the definition of aggression, severity of TBI, and duration since TBI. Another possibility is that TBI aggression occurs in two forms: mild verbal aggression associated with mood disorder but not with pre-injury or post-injury behavior problems, and severe physical aggression which can be more complex and associated with significant behavior and legal problems.
We did however, observe that aggression was strongly associated with new-onset major depressive episodes which increased the risk of aggression by 8-fold, but not with recurrent major depression. Possibly new-onset depression after TBI is a phenotypic variant of idiopathic major depression with verbal aggression as a presenting symptom. Several other studies2,8
have also noted a significant association between depression and aggression but none of them have separated post-TBI depression as new-onset depression and recurrent depression. This is one of the strengths of our study.
Many researchers have also noted a relationship between aggression and pre-morbid characteristics such as childhood behavior problems,6
adult behavior difficulties, legal problems40
and substance abuse.2,41
However, we did not observe these associations in our cohort. All prior studies have examined global aggression combining both verbal and physical aggression. The lack of an association in our study could be because our study observed only verbal aggression, which is likely to reflect a milder form of aggression than physical aggression. Thus, it is possible that mild (verbal) aggression is associated with post-TBI depression, while more severe (physical) aggression may be associated with adult and childhood behavioral problems and substance abuse. Our finding of the relationship between female gender and aggression (that trended towards statistical significance) was unexpected but not surprising, given our findings of a positive relationship between aggression and depressive syndrome. It is well known that females are at higher risk of developing major depression,42
though this has not been established for TBI cohorts.
Our study also found a significant association between verbal aggression and post-TBI social impairment. Baguley et al.8
have also noted a significant association between poor satisfaction with life and aggression 6 and 24 months post-TBI. This is not surprising as one might well predict that aggression would be interfering with relationships and reintegration into the community. However, the increased risk of aggression in persons with poor social functioning is quite remarkable (62-fold increased), even higher than that of depression. This finding has significant therapeutic implications for the immediate post-TBI period, suggesting the particular importance of improving psychosocial support, strengthening social connections, and providing adequate resources via individual, group and family therapy in reducing aggression. Studies have shown that psychosocial support and positive interpersonal relationships play an important role in reducing aggression.43
An alternative explanation for our results is that early diagnosis and appropriate treatment of aggression might lead to better social and inter-personal functioning.
The significant association between aggression and increased dependence in activities of daily living has been reported before.44
One possibility is that persons with TBI are resistant to assistance provided by their caregiver, perceiving assistance as an invasion of personal space. It is also possible that aggression may be associated with lack of motivation in the context of post-TBI depression with concomitant lack of interest in self-care and help from care providers. Alternatively, aggression may only be a confounder as our results showed that those with body injuries were more likely to have increased dependency on activities of daily living.
The literature suggests potential brain mechanisms for post-TBI aggression. Tateno et al.2
found frontal lesions to be associated with aggression and suggest that frontal lobe injury can cause damage to the ascending serotonergic pathways, which can contribute to the pathophysiology of both depression and violent behavior. As systematic analysis of neuroimaging data was not part of our study, we are unable to comment on this possibility. However, we found no significant difference between those with and without aggression on CT head scans, performed as part of clinical work up. Similarly, we also did not find any group differences on neuropsychological tests, and more specifically, on tests particularly sensitive to frontal functioning system. Starkstein and Robinson45
have pointed out TBI aggression is probably secondary to loss of balance between inhibitory pathways in the prefrontal cortex and excitatory limbic structures that mediate mood. These mechanisms could explain our finding of an association between aggression and new-onset depression in the immediate post-TBI period. More sensitive neuroimaging tools such as functional MRI or diffusion tensor imaging scans may shed light on the brain mechanisms underlying TBI aggression.
Our findings do not prove that the aggression in the post-TBI period observed in our subjects was caused by the TBI, nor that any association was due to the biological effects of brain injury. For example, body injury was associated with increased dependence in ADLs which was further associated with aggression. It is possible that body injury could be an important mediator of aggression in the population, but the small sample size did not allow for systematic assessment of mediators and interactions. Similarly, the lack of association between TBI severity and aggression suggests the possibility that other factors than TBI are responsible for aggression; conversely, it could also suggest that TBI itself (rather than TBI severity) is an important risk factor for aggression. The lack of control groups with exposure to non-TBI bodily injuries and/or no injury is a limitation in addressing these issues. Other limitations of the study include the assessment of a narrowly defined cohort of TBI patients. Our study sample included only those with first time closed head injury, clear history of loss of consciousness, and those who were hospitalized. These strict inclusion/exclusion criteria may limit generalizability. Further, medication data was not available, precluding any study of the association between medications and aggression. Antipsychotics, benzodiazepines, antidepressants, and opioid analgesics are often used in the acute TBI period and might be effective treatments for severe agitation, which could account for the absence of physical aggression in our cohort. Systematic analysis of brain imaging data was also not performed, and thus we were unable to assess the association of exact lesion location and aggression. Finally, aggression was assessed only once in the acute TBI period by self-reports which is often associated with under-reporting and minimization of symptoms. However, whenever collateral informants were available, the subjects’ history was always corroborated.
To the best of our knowledge, this is the second published study examining aggression in non-delirious patients within the first three months of TBI. Our finding of a significant association between poor psychosocial functioning and verbal aggression underscores the point that psychosocial support is an important aspect of emotional recovery and therefore should be an integral part of rehabilitation. Our preliminary finding that incident new-onset major depression after TBI, but not recurrent major depression, is associated with post-TBI aggression is novel and may have substantial implications for the phenomenology and treatment of post-TBI aggression.