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Focusing on violence from assessment, through underlying neurobiology, to treatment and other recommendations for practice, this book will be of interest to forensic psychiatrists, general adult psychiatrists, psychiatric residents, psychologists, psychiatric social workers and rehabilitation therapists.
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A catalog record for this publication is available from the British Library
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Chapter 10 Aggression, DRD1 polymorphism, and lesion location in penetrating traumatic brain injury Matteo Pardini, Frank Krueger, Colin A. Hodgkinson, Vanessa Raymont, Maren Strenziok, Mario Amore, Eric M. Wassermann, David Goldman and Jordan H. Grafman
Pathological chronic aggressive behavior has been reported in up to 33% of patients with a traumatic brain injury (TBI) [ 1]. A number of different factors, including genetic predisposition, mono-aminergic system activity, and brain lesion location, are all thought to play a significant role in the development and maintenance of TBI-related aggression [ 2]. Regarding the symptomatic treatment options for aggression in TBI, to date most attention has been focused on the dopaminergic system [ 3].
Despite the widespread use of anti-dopaminergic drugs to treat aggression [ 4], converging evidence suggests that the relationship between dopamine and aggression is more complex than previously thought. In experimental models, for example, both D2 agonist and antagonists as well as D1 partial agonists and antagonists have been shown to reduce aggressive behaviors [ 5– 7], while the classic pro-dopaminergic amphetamine has been shown to increase, decrease, or fail to change aggressive behavior levels depending on various factors, such as context and type of aggression [ 8].
Moreover, in humans, despite the consensus on the role of antipsychotics to treat aggression, pro-dopaminergic stimulants drugs have also been proposed as a possible pharmacological treatment for aggressive behaviors in specific patient groups. In attention deficit hyperactivity disorder (ADHD) patients, for example, stimulants have been shown to reduce aggressive behavior by remodulating to prefrontal cortex (PFC) dopamine levels [ 9], while pro-dopaminergic compounds have been proposed as a possible treatment for aggressive behavior in different dementing illnesses, such as frontotemporal dementia (FTD) [ 10, 11].
Compared to the aforementioned clinical populations, the study of the biological basis of aggressive behavior in penetrating TBI (pTBI) presents another confounding factor, i.e., the presence of focal brain lesions, which could modulate the relationship between the dopaminergic system and aggression. Indeed, transcranial magnetic stimulation (TMS) experiments have shown that dorsolateral PFC inhibition reduces dopamine release in deep gray matter [ 12], while dorsolateral PFC stimulation increases striatal dopaminergic activity [ 13]. In animal models, medial frontal lesions have been found to increase deep gray matter dopaminergic activity [ 14], possibly through modulation of ventrotegmental area activity.
In this study, we explored the relationship between lesion location, pTBI-related aggressive behaviors, and dopaminergic tone. Based on the aforementioned literature and previous studies that have shown a significant role of PFC in aggressive behaviors [ 2], we hypothesized that PFC lesion location significantly impacts the interaction between dopaminergic activity and aggression in pTBI. Given the key nature of PFC territories in pTBI-related aggression, we predicted a significant modulatory effect on the dopaminergic system/aggression interaction only by PFC but not non-PFC damage, and potentially a regional specificity of lesion location inside the PFC.
To test our hypotheses, we investigated, in a group of Vietnam War Veterans, the interaction between long-term pathological aggression, lesion location, and interindividual differences in endogenous dopaminergic tone due to functional single nucleotide polymorphic (SNP) differences in the main components of the dopaminergic system [ 15, 16], i.e., the dopamine receptor D1 ( DRD1), the dopamine receptor D2 ( DRD2), and the dopamine-degrading enzyme catechol-O-methyltransferase (COMT).
We decided to focus on these components of the dopaminergic system, as DRD1 and DRD2 represent the prototypical members of the two groups of dopamine receptors (i.e., the DRD1-like and DRD2-like families) [ 15], while COMT is thought to represent the major dopamine-degrading enzyme in the synaptic cleft [ 16]. Evaluation of functional SNPs has been shown to be a useful tool to study the relationship between aggressive behaviors and mono-aminergic systems, both in healthy subjects and neuropsychiatric conditions [ 15, 16], as well as a proxy-marker of baseline dopaminergic tone in pharmacological challenges studies [ 17].
Mario Amore
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy
Allen Azizian
Coalinga State Hospital, Coalinga, and Department of Criminology, California State University, Fresno, California, USA
Shannon M. Bader
California Department of State Hospitals, and Patton State Hospital, California, USA
Michael W. Barsom
Department of State Hospitals (DSH) – Metropolitan, Norwalk, California, USA
Nicole R. Bartholomew
Psychology Services, Federal Bureau of Prisons, Big Spring, Texas, USA
Amlan Basu
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, and Institute of Psychiatry, King’s College, London, UK
Charles Broderick
California Department of State Hospitals, Sacramento, California, USA
Rosalie S. Brooman-White
Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxford, UK
Darcy Brown
The School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
Leslie Citrome
Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York, USA
Emil F. Coccaro
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry (MC#3077), Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
Michael A. Cummings
Department of State Hospitals–Patton, Department of Psychiatry, Patton, California, USA; Department of Psychiatry and Human Behavior, University of California, Irvine, Orange, California, USA
Stephen E. Cummings
Department of Psychiatry, San Mateo Medical Center, San Mateo, California, USA
Pál Czobor
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
Laura J. Dardashti
California Department of State Hospitals, and Metropolitan State Hospital, California, USA
Mrigendra Das
Broadmoor Hospital, West London Mental Health Trust, Berkshire, amd School of Psychiatry, Oxford Deanery, Oxford, UK
Darci Delgado
California Department of State Hospitals, and Vacaville Psychiatric Program, California, USA
Sean E. Evans
Psychology Department, Department of State Hospitals, Patton, California, and Psychology Department, La Sierra University, Riverside, California, USA
Thomas Fahy
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
Jennifer R. Fanning
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry (MC#3077), Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
Alan R. Felthous
Division of Forensic Psychiatry, Department of Neurology & Psychiatry, Saint Louis University School of Medicine, Saint Louis, Missouri, USA
E. Fuller Torrey
Department of Psychiatry, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USA; Stanley Medical Research Institute, Chevy Chase, Maryland, USA
David Goldman
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
Jordan H. Grafman
Rehabilitation Institute of Chicago, Chicago, Illinois, USA
Nitin Gupta
Department of Psychiatry, Government Medical College and Hospital, Chandigarh, India
Margaret Guyer
Central Office Research Review Committee, Massachusetts Department of Mental Health, Massachusetts Mental Health Center Division of Public Psychiatry, and Harvard Medical School/Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Colin A. Hodgkinson
Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
Brian J. Holoyda
Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California, USA
Matthew J. Hoptman
Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, Department of Psychiatry, New York, USA, and University School of Medicine, and Department of Psychology, City University of New York, New York, USA
Deborah Horowitz
Office of Training and Development, Massachusetts Department of Mental Health, Westborough, Massachusetts, USA
James E. Hotham
Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxford, UK
Sharon A. Humphreys
Broadmoor High Secure Hospital, West London Mental Health NHS Trust, London, UK
James L. Knoll IV
Division of Forensic Psychiatry, Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York, USA
Rebecca Kornbluh
California Department of State Hospitals, Sacramento, California, USA
Frank Krueger
Molecular Neuroscience Department, George Mason University, Fairfax, and Department of Psychology, George Mason University, Fairfax, Virginia, USA
Fintan Larkin
Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Royce Lee
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry (MC#3077), Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
K. Luan Phan
Department of Psychiatry, University of Illinois College of Medicine, Mental Health Service Line, Jesse Brown Veterans Administration Medical Center, and Departments of Psychology, and Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois, USA
Barbara E. McDermott
Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California, USA
Jonathan M. Meyer
Department of Psychiatry, University of California–San Diego, San Diego, California Department of State Hospitals, and Patton State Hospital, California, USA
John Monahan
School of Law, University of Virginia, Charlottesville, Virginia, USA
Robert D. Morgan
Department of Psychological Sciences, Texas Tech University, Lubbock, Texas, USA
Debbi A. Morrissette
Neuroscience Education Institute, Carlsbad, California, Department of Biology, California State University, San Marcos, California, and Department of Biology, Palomar College, San Marcos, California, USA
Jennifer A. O’Day
California Department of State Hospitals, and Metropolitan State Hospital, California, USA
Mark E. Olver
Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Matteo Pardini
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, and Magnetic Resonance Research Centre on Nervous System Diseases, University of Genoa, Genoa, Italy
Debra A. Pinals
Law and Psychiatry Program, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, USA
George J. Proctor
California Department of State Hospitals, and Patton State Hospital, California, USA
Cameron D. Quanbeck
Department of Psychiatry, San Mateo Health System, San Mateo, California, USA
Vanessa Raymont
Department of Medicine, Imperial College London, London, UK
Phillip J. Resnick
Division of Forensic Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Jose L. Romero-Ureclay
Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Benjamin Rose
California Department of State Hospitals, and Napa State Hospital, California, USA
Daniel R. Rosell
Department of Psychiatry, Icahn Medical School, Mount Sinai, New York, and Special Evaluation Program of Mood and Personality Disorders, Icahn Medical School, Mount Sinai, New York, USA
Callum C. Ross
Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Kathy Sanders
Clinical and Professional Services, Massachusetts Department of Mental Health, and Harvard Medical School/Massachusetts General Hospital, Boston, Massachusetts, USA
Robert J. Schaufenbil
California Department of State Hospitals, Sacramento, California, USA
Marie Schur
California Department of State Hospitals, and Atascadero State Hospital, California, USA
Eric H. Schwartz
California Department of State Hospitals, and Vacaville Psychiatric Program, California, USA
Charles L. Scott
Division of Psychiatry and the Law, Department of Psychiatry and Behavioral Sciences, University of California–Davis School of Medicine, 5 Sacramento, California, USA
Samrat Sengupta
Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Larry J. Siever
Department of Psychiatry, and Special Evaluation Program of Mood and Personality Disorders, Icahn Medical School, Mount Sinai, New York, and Department of Psychiatry and the VISN3 Mental Illness Research, Education, and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, New York, USA
Patrick J. D. Simpson
Medical Sciences Division, John Radcliffe Hospital, University of Oxford, Oxford, UK
Jennifer L. Skeem
School of Social Welfare & Goldman School of Public Policy, University of California–Berkeley, Berkeley, California, USA
Stephen M. Stahl
California Department of State Hospitals, Sacramento, University of California San Diego, California, USA, and University of Cambridge, Cambridge, UK
Maren Strenziok
Department of Psychology, George Mason University, Fairfax, Virginia, USA
Katalin A. Szabo
Department of Psychiatry, San Mateo Health System, San Mateo, and Behavioral Health and Recovery Services, San Mateo, and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA
John Tully
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
Richard A. Van Dorn
Research Triangle Institute International, Research Triangle Park, Durham, North Carolina, USA
Susan Velasquez
California Department of State Hospitals, and Patton State Hospital, California, USA
Morris Vinestock
Broadmoor Hospital, West London Mental Health Trust, Berkshire, UK
Jan Volavka
Department of Psychiatry, New York University School of Medicine, New York, USA
Raziya S. Wang
Behavioral Health and Recovery Services, San Mateo, California, USA
Katherine D. Warburton
California Department of State Hospitals, Sacramento, and Division of Psychiatry and the Law, University of California, Davis, California, USA
Eric M. Wassermann
Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Christopher L. White
Department of Psychiatry, San Mateo Health System, San Mateo, and Behavioral Health and Recovery Services, San Mateo, California, USA
Stephen C. P. Wong
Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, School of Medicine, University of Nottingham, Nottingham, UK, and Centre for Forensic Behavioural Science, Swinburne University of Technology, Melbourne, Australia