Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-05T00:44:31.509Z Has data issue: false hasContentIssue false
  • English
  • Français

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: [email protected])
Get access Rights & Permissions [Opens in a new window]

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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

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.

References

1. Tateno, A, Jorge, RE, Robinson, RG. Clinical correlates of aggressive behavior after traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2003; 15(2): 155–160.Google Scholar
2. Pardini, M, Krueger, F, Hodgkinson, C, etal. Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury. Neurology. 2011; 76(12): 1038–1045.CrossRefGoogle ScholarPubMed
3. Comai, S, Tau, M, Gobbi, G. The psychopharmacology of aggressive behavior: a translational approach: part 1: neurobiology. J Clin Psychopharmacol. 2012; 32(1): 83–94.Google Scholar
4. Goedhard, LE, Stolker, JJ, Heerdink, ER, etal. Pharmacotherapy for the treatment of aggressive behavior in general adult psychiatry: a systematic review. J Clin Psychiatry. 2006; 67(7): 1013–1024.Google Scholar
5. Tidey, JW, Miczek, KA. Effects of SKF 38393 and quinpirole on aggressive, motor and schedule-controlled behaviors in mice. Behav Pharmacol. 1992; 3(6): 553–565.CrossRefGoogle ScholarPubMed
6. Rodríguez-Arias, M, Miñarro, J, Aguilar, MA, Pinazo, J, Simón, VM. Effects of risperidone and SCH 23390 on isolation-induced aggression in male mice. Eur Neuropsychopharmacol. 1998; 8(2): 95–103.Google Scholar
7. Aguilar, MA, Miñarro, J, Pérez-Iranzo, N, Simón, VM. Behavioral profile of raclopride in agonistic encounters between male mice. Pharmacol Biochem Behav. 1994; 47(3): 753–756.Google Scholar
8. Miczek, KA, Tidey, JW. Amphetamines: aggressive and social behavior. In: Asghar K, De Souza E, eds. Pharmacology and Toxicology of Amphetamine and Related Designer Drugs. Washington, DC: National Institute on Drug Abuse; 1989: 68Y100.Google Scholar
9. Blader, JC, Pliszka, SR, Jensen, PS, Schooler, NR, Kafantaris, V. Stimulant-responsive and stimulant-refractory aggressive behavior among children with ADHD. Pediatrics. 2010; 126(4): 796–806.Google Scholar
10. Huey, ED, Putnam, KT, Grafman, J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology. 2006; 66(1): 17–22.Google Scholar
11. Huey, ED, Garcia, C, Wassermann, EM, Tierney, MC, Grafman, J. Stimulant treatment of frontotemporal dementia in 8 patients. J Clin Psychiatry. 2008; 69(12): 1981–1982.Google Scholar
12. Ko, JH, Monchi, O, Ptito, A, etal. Theta burst stimulation-induced inhibition of dorsolateral prefrontal cortex reveals hemispheric asymmetry in striatal dopamine release during a set-shifting task: a TMS-[(11)C]raclopride PET study. Eur J Neurosci. 2008; 28(10): 2147–2155.CrossRefGoogle ScholarPubMed
13. Strafella, AP, Paus, T, Barrett, J, Dagher, A. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001; 21(15): RC157.CrossRefGoogle ScholarPubMed
14. Jaskiw, GE, Karoum, FK, Weinberger, DR. Persistent elevations in dopamine and its metabolites in the nucleus accumbens after mild subchronic stress in rats with ibotenic acid lesions of the medial prefrontal cortex. Brain Res. 1990; 534(1–2): 321–323.Google Scholar
15. Seeman, P, Van Tol, HH. Dopamine receptor pharmacology. Trends Pharmacol Sci. 1994; 15(7): 264–270.CrossRefGoogle ScholarPubMed
16. Volavka, J, Bilder, R, Nolan, K. Catecholamines and aggression: the role of COMT and MAO polymorphisms. Ann N Y Acad Sci. 2004; 1036: 393–398.CrossRefGoogle ScholarPubMed
17. Cohen, MX, Krohn-Grimberghe, A, Elger, CE, Weber, B. Dopamine gene predicts the brain's response to dopaminergic drug. Eur J Neurosci. 2007; 26(12): 3652–3660.CrossRefGoogle ScholarPubMed
18. Raymont, V, Greathouse, A, Reding, K, etal. Demographic, structural and genetic predictors of late cognitive decline after penetrating head injury. Brain. 2008; 131(Pt 2): 543–558.Google Scholar
19. Cummings, JL, Mega, M, Gray, K, etal. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994; 44(12): 2308–2314.Google Scholar
20. Bremner, JD, Vermetten, E, Mazure, CM. Development and preliminary psychometric properties of an instrument for the measurement of childhood trauma: the Early Trauma Inventory. Depress Anxiety. 2000; 12(1): 1–12.Google Scholar
21. Solomon, J, Raymont, V, Braun, A, Butman, JA, Grafman, J. User-friendly software for the analysis of brain lesions (ABLe). Comput Methods Programs Biomed. 2007; 86(3): 245–254.CrossRefGoogle ScholarPubMed
22. Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, etal. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002; 15(1): 273–289.CrossRefGoogle ScholarPubMed
23. Koenigs, M, Huey, ED, Calamia, M, Raymont, V, Tranel, D, Grafman, J. Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression. J Neurosci. 2008; 28(47): 12341–12348.Google Scholar
24. Hodgkinson, CA, Yuan, Q, Xu, K, etal. Addictions biology: haplotype-based analysis for 130 candidate genes on a single array. Alcohol Alcohol. 2008; 43(5): 505–515.CrossRefGoogle ScholarPubMed
25. Huang, W, Ma, JZ, Payne, TJ, etal. Significant association of DRD1 with nicotine dependence. Hum Genet. 2008; 123(2): 133–140.CrossRefGoogle ScholarPubMed
26. Fukui, N, Suzuki, Y, Sugai, T, etal. Exploring functional polymorphisms in the dopamine receptor D2 gene using prolactin concentration in healthy subjects. Mol Psychiatry. 2010; 16(4): 356–358.Google Scholar
27. Hamidovic, A, Dlugos, A, Skol, A, Palmer, AA, de Wit, H. Evaluation of genetic variability in the dopamine receptor D2 in relation to behavioral inhibition and impulsivity/sensation seeking: an exploratory study with d-amphetamine in healthy participants. Exp Clin Psychopharmacol. 2009; 17(6): 374–383.Google Scholar
28. Shih, JC, Chen, K, Ridd, MJ. Monoamine oxidase: from genes to behavior. Annu Rev Neurosci. 1999; 22(1): 197–217.CrossRefGoogle Scholar
29. Vijayraghavan, S, Wang, M, Birnbaum, SG, Williams, GV, Arnsten, AF. Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci. 2007; 10(3): 376–384.CrossRefGoogle ScholarPubMed
30. Floresco, SB. Prefrontal dopamine and behavioral flexibility: shifting from an “inverted-U” toward a family of functions. Front Neurosci. 2013; 7: 62.Google Scholar
31. Cools, R, Frank, MJ, Gibbs, SE, etal. Striatal dopamine predicts outcome-specific reversal learning and its sensitivity to dopaminergic drug administration. J Neurosci. 2009; 29(5): 1538–1543.Google Scholar
32. Knutson, B, Gibbs, SE. Linking nucleus accumbens dopamine and blood oxygenation. Psychopharmacology (Berl). 2007; 191(3): 813–822.Google Scholar
33. Scheres, A, Milham, MP, Knutson, B, Castellanos, FX. Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2007; 61(5): 720–724.Google Scholar
34. Couppis, MH, Kennedy, CH. The rewarding effect of aggression is reduced by nucleus accumbens dopamine receptor antagonism in mice. Psychopharmacology (Berl). 2008; 197(3): 449–456.Google Scholar
35. Zamboni, G, Huey, ED, Krueger, F, Nichelli, PF, Grafman, J. Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology. 2008; 71(10): 736–742.CrossRefGoogle ScholarPubMed
36. Takahata, R, Moghaddam, B. Target-specific glutamatergic regulation of dopamine neurons in the ventral tegmental area. J Neurochem. 2000; 75(4): 1775–1778.CrossRefGoogle ScholarPubMed
37. Diekhof, EK, Nerenberg, L, Falkai, P, etal. Impulsive personality and the ability to resist immediate reward: an fMRI study examining interindividual differences in the neural mechanisms underlying self-control. Hum Brain Mapp. 2012; 33(12): 2768–2784.CrossRefGoogle ScholarPubMed
38. Buckholtz, JW, Treadway, MT, Cowan, RL, etal. Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci. 2010; 13(4): 419–421.Google Scholar
39. Plichta, MM, Scheres, A. Ventral-striatal responsiveness during reward anticipation in ADHD and its relation to trait impulsivity in the healthy population: a meta-analytic review of the fMRI literature. Neurosci Biobehav Rev. 2014; 38: 125–134.Google Scholar
40. Wong, TM. Brain injury and aggression: can we get some help? Neurology. 2011; 76(12): 1032–1033.CrossRefGoogle ScholarPubMed
41. Fowler, SB, Hertzog, J, Wagner, BK. Pharmacological interventions for agitation in head-injured patients in the acute care setting. J Neurosci Nurs. 1995; 27(2): 119–123.Google Scholar
42. Kline, AE, Massucci, JL, Zafonte, RD, etal. Differential effects of single versus multiple administrations of haloperidol and risperidone on functional outcome after experimental brain trauma. Crit Care Med. 2007; 35(3): 919–924.CrossRefGoogle ScholarPubMed
43. Hoffman, AN, Cheng, JP, Zafonte, RD, Kline, AE. Administration of haloperidol and risperidone after neurobehavioral testing hinders the recovery of traumatic brain injury-induced deficits. Life Sci. 2008; 83(17–18): 602–607.Google Scholar
44. de Almeida, J, Palacios, JM, Mengod, G. Distribution of 5-HT and DA receptors in primate prefrontal cortex: implications for pathophysiology and treatment. Prog Brain Res. 2008; 172: 101–115.Google Scholar
45. DeYoung, CG, Peterson, JB, Séguin, JR, etal. The dopamine D4 receptor gene and moderation of the association between externalizing behavior and IQ. Arch Gen Psychiatry. 2006; 63(12): 1410–1416.Google Scholar
46. Bakermans-Kranenburg, MJ, van Ijzendoorn, MH, Caspers, K, Philibert, R. DRD4 genotype moderates the impact of parental problems on unresolved loss or trauma. Attach Hum Dev. 2011; 13(3): 253–269.Google Scholar