title: Aggression, DRD1 polymorphism, and lesion location in penetrating traumatic brain injury.
abstract: OBJECTIVE
  This study evaluated whether structural brain lesions modulate the relationship between pathological aggression and the dopaminergic system in traumatic brain injury (TBI). While converging evidence suggests that different areas of the prefrontal cortex modulate dopaminergic activity, to date no evidence exists of a modulation of endogenous dopaminergic tone by lesion localization in penetrating TBI (pTBI).
  
  
  METHODS
  This study included 141 male Caucasian veterans who suffered penetrating pTBI during their service in Vietnam and 29 healthy male Caucasian Vietnam veterans. Participants were genotyped for 3 functional single nucleotide polymorphisms (SNPs): dopamine receptor D1 (DRD1) rs686, dopamine receptor D2 (DRD2) rs4648317, and catechol-O-methyltransferase (COMT) Val158Met. Patients underwent brain CT scans and were divided into medial prefrontal cortex, lateral prefrontal cortex, and posterior cortex lesion groups. Long-term aggression levels were evaluated with the agitation/aggression subscale of the Neuropsychiatric Inventory.
  
  
  RESULTS
  Our data showed that carriers of more transcriptionally active DRD1 alleles compared to noncarriers demonstrated greater aggression levels due to medial prefrontal cortex lesions but reduced aggression levels due to lateral prefrontal cortex lesions independently of DRD2 rs4648317 or COMT Val158Met genotypes.
  
  
  CONCLUSIONS
  Our results suggest that the relationship between pTBI-related aggression and the dopaminergic system is modulated by lesion location. Potentially lesion location could represent an easy-to-use, widely available, para-clinical marker to help in the development of an individualized therapeutic approach to pTBI-related pathological aggression.
authors.affiliation: 1Department of Neurosciences,Rehabilitation,Ophthalmology,Genetics and Maternal and Child Health,University of Genoa,Genoa,Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pardini
authors.affiliation: 3Molecular Neuroscience Department,George Mason University,Fairfax,Virginia,USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Krueger
authors.affiliation: 5Laboratory of Neurogenetics,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.affiliation: 6Department of Medicine,Imperial College London,London,UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Raymont
authors.affiliation: 4Department of Psychology,George Mason University,Fairfax,Virginia,USA.
authors.forename: Maren
authors.initials: M
authors.lastname: Strenziok
authors.affiliation: 1Department of Neurosciences,Rehabilitation,Ophthalmology,Genetics and Maternal and Child Health,University of Genoa,Genoa,Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Amore
authors.affiliation: 7Behavioral Neurology Unit,National Institute of Neurological Disorders and Stroke,National Institutes of Health,Bethesda,Maryland,USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wassermann
authors.affiliation: 5Laboratory of Neurogenetics,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.affiliation: 8Rehabilitation Institute of Chicago,Chicago,Illinois,USA.
authors.forename: Jordan H
authors.initials: JH
authors.lastname: Grafman
mesh_terms: D000374:Aggression / Q000502:physiology / Q000523:psychology*; D001930:Brain Injuries / Q000503:physiopathology / Q000523:psychology*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000293:injuries*; D005838:Genotype; D020197:Head Injuries, Penetrating / Q000503:physiopathology / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000293:injuries*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D014057:Tomography, X-Ray Computed; D014728:Veterans; D047829:Vietnam Conflict
chemical_list: C583260:DRD1 protein, human; C581293:DRD2 protein, human; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase