Research Reports - Aggression, DRD1 polymorphism, and lesion location in penetrating traumatic brain injury

CNS Spectr. 2014 Oct;19(5):382-90

Pardini M(1), Krueger F(2), Hodgkinson CA(3), Raymont V(4), Strenziok M(5), Amore M(1), Wassermann EM(6), Goldman D(3), Grafman JH(7)

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
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.

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