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Updated: Jun 3, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury
M Pardini1, F Krueger, C Hodgkinson
1Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke-NIH, Bethesda, MD, USA.
Objective:
This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI).
Methods:
We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a).
Results:
Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group.
Conclusions:
Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI.
Insights
Brain lesion location and MAO-A genotype interact to influence aggression in penetrating traumatic brain injury (PTBI). Prefrontal cortex integrity is key for modulating aggression related to genetics and trauma.
Area of Science:
- Neuroscience
- Genetics
- Trauma Research
Background:
- Penetrating traumatic brain injury (PTBI) can lead to aggression.
- The role of genetic factors, like monoamine oxidase A (MAO-A) polymorphism, in aggression post-PTBI is not fully understood.
- Brain lesion location may influence the expression of genetic predispositions for aggression.
Purpose of the Study:
- To investigate the interaction between MAO-A genotype and lesion location in the development of aggression in PTBI patients.
- To determine if prefrontal cortex (PFC) integrity affects the relationship between MAO-A, trauma, and aggression.
Main Methods:
- 155 PTBI patients and 42 controls from the Vietnam Head Injury Study were analyzed.
- PTBI patients were categorized by lesion location (PFC vs. non-PFC).
- MAO-A genotype (low vs. high transcriptional activity) and aggression (Neuropsychiatric Inventory aggression subscale) were assessed.
Main Results:
- Aggression was higher in PTBI patients with PFC lesions.
- A significant interaction was found between MAO-A activity and lesion location impacting aggression.
- In non-PFC lesions, high MAO-A activity correlated with higher aggression, unlike in PFC lesions.
Conclusions:
- Lesion location and MAO-A genotype interact to mediate aggression in PTBI.
- PFC integrity is crucial for modulating aggression influenced by genetic and experiential factors.
- Combining lesion and genotype data may enable risk stratification and personalized treatments for PTBI-related aggression.
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