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

Published online by Cambridge University Press:  11 March 2014

Matteo Pardini ,
Frank Krueger ,
Colin A. Hodgkinson ,
Vanessa Raymont ,
Maren Strenziok ,
Mario Amore ,
Eric M. Wassermann ,
David Goldman  and
Jordan H. Grafman
Matteo Pardini
Affiliation:
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy
Frank Krueger
Affiliation:
Molecular Neuroscience Department, George Mason University, Fairfax, Virginia, USA Department of Psychology, George Mason University, Fairfax, Virginia, USA
Colin A. Hodgkinson
Affiliation:
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
Vanessa Raymont
Affiliation:
Department of Medicine, Imperial College London, London, UK
Maren Strenziok
Affiliation:
Department of Psychology, George Mason University, Fairfax, Virginia, USA
Mario Amore
Affiliation:
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy
Eric M. Wassermann
Affiliation:
Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
David Goldman
Affiliation:
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
Jordan H. Grafman*
Affiliation:
Rehabilitation Institute of Chicago, Chicago, Illinois, USA
*
*Address for correspondence: Jordan Grafman, PhD, Director, Brain Injury Research, Coleman Chair in Physical Medicine and Rehabilitation, Rehabilitation Institute of Chicago, 345 East Superior Street, Chicago, IL 60611, USA. (Email: jgrafman@northwestern.edu)
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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.

Keywords

Aggressionbehavioral neurologydopamineprefrontal cortextraumatic brain injury
Type
Original Research
Information
CNS Spectrums , Volume 19 , Issue 5 , October 2014 , pp. 382 - 390
Copyright
Copyright © Cambridge University Press 2014 

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Footnotes

The work was supported by the U.S. National Institute of Neurological Disorders and Stroke intramural research program and a project grant from the U.S. Army Medical Research and Material Command administrated by the Henry M Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year post-injury follow-up study). 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 U.S. Government. M.P., F.K., and J.G. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. M.P. thanks the nonprofit association AKWO, Lavagna (Genoa) Italy, for its unrestricted support.

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