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

Neurology. 2011 Mar 22;76(12):1038-45. doi: 10.1212/WNL.0b013e318211c33e.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aggression / physiology*
  • Alleles
  • Brain Injuries / complications
  • Brain Injuries / genetics
  • Brain Injuries / pathology
  • Brain Injuries / psychology*
  • Brain Mapping / methods
  • Genotype
  • Head Injuries, Penetrating / complications
  • Head Injuries, Penetrating / genetics
  • Head Injuries, Penetrating / pathology
  • Head Injuries, Penetrating / psychology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Monoamine Oxidase / genetics*
  • Polymorphism, Genetic
  • Prefrontal Cortex / injuries*
  • Prefrontal Cortex / pathology
  • Psychiatric Status Rating Scales
  • Stress Disorders, Post-Traumatic / complications
  • Stress Disorders, Post-Traumatic / diagnosis

Substances

  • Monoamine Oxidase