title: Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury.
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.
authors.affiliation: Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke-NIH, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pardini
authors.forename: F
authors.initials: F
authors.lastname: Krueger
authors.forename: C
authors.initials: C
authors.lastname: Hodgkinson
authors.forename: V
authors.initials: V
authors.lastname: Raymont
authors.forename: C
authors.initials: C
authors.lastname: Ferrier
authors.forename: D
authors.initials: D
authors.lastname: Goldman
authors.forename: M
authors.initials: M
authors.lastname: Strenziok
authors.forename: S
authors.initials: S
authors.lastname: Guida
authors.forename: J
authors.initials: J
authors.lastname: Grafman
mesh_terms: D000374:Aggression / Q000502:physiology*; D000483:Alleles; D001930:Brain Injuries / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D001931:Brain Mapping / Q000379:methods; D005838:Genotype; D020197:Head Injuries, Penetrating / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000293:injuries* / Q000473:pathology; D011569:Psychiatric Status Rating Scales; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000175:diagnosis
chemical_list: D008995:Monoamine Oxidase