Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury

Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke-NIH, Bethesda, MD, USA.
Neurology (Impact Factor: 8.29). 03/2011; 76(12):1038-45. DOI: 10.1212/WNL.0b013e318211c33e
Source: PubMed


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).
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).
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.
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.

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    • "However, the functional effect of a polymorphism following TBI may not be similar to the effects found among healthy populations. Some polymorphisms that have been shown to influence function within healthy populations may show little or no influence following TBI, particularly when TBI lesions occur in areas in which the polymorphism exerts its primary influence (Pardini et al. 2011). Other polymorphisms, which show little or no influence among healthy populations , may become important mediators of outcome when capacities are reduced by TBI (McAllister 2009). "
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    • "However, the presence of aggressive and violent behavior was not associated with lesion size or history of seizures. The genotyping that was carried out as part of PH3 demonstrated an association between prefrontal cortex lesions and MAO-A in modulating aggression (Pardini et al., in press). "
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