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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.
Footnotes
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Study funding: Supported by the US National Institute of Neurological Disorders and Stroke intramural research program and a project grant from the US Army Medical Research and Material Command administered by the Henry M. Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year postinjury follow-up study).
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- AFQT
- Armed Forces Qualification Test
- ANCOVA
- analysis of covariance
- BDI
- Beck Depression Inventory
- CAPS
- Clinician-Administered PTSD Scale
- DSM-IV-TR
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision
- ETI
- Early Trauma Inventory
- MAO-A
- monoamine oxidase A
- NPI-a
- aggression/agitation subscale of the Neuropsychiatric Inventory
- PFC
- prefrontal cortex
- PTBI
- penetrating traumatic brain injury
- PTSD
- posttraumatic stress disorder
- VHIS
- Vietnam Head Injury Study
- VNTR
- variable number tandem repeat.
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Editorial, page 1032
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Supplemental data at www.neurology.org
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The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, or the US Government.
- Received May 28, 2010.
- Accepted November 9, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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