Elsevier

Advances in Genetics

Volume 75, 2011, Pages 151-169
Advances in Genetics

Chapter 7 - The Neurochemistry of Human Aggression

https://doi.org/10.1016/B978-0-12-380858-5.00005-8Get rights and content

Abstract

Various data from scientific research studies conducted over the past three decades suggest that central neurotransmitters play a key role in the modulation of aggression in all mammalian species, including humans. Specific neurotransmitter systems involved in mammalian aggression include serotonin, dopamine, norepinephrine, GABA, and neuropeptides such as vasopressin and oxytocin. Neurotransmitters not only help to execute basic behavioral components but also serve to modulate these preexisting behavioral states by amplifying or reducing their effects. This chapter reviews the currently available data to present a contemporary view of how central neurotransmitters influence the vulnerability for aggressive behavior and/or initiation of aggressive behavior in social situations. Data reviewed in this chapter include emoiric information from neurochemical, pharmaco-challenge, molecular genetic and neuroimaging studies.

Introduction

Since the late 1970s, data from scientific research studies have suggested that endogenous brain chemicals called neurotransmitters play a key role in the modulation of aggression. Human aggression is a multidimensional behavior that is determined by an amalgamation of biological, genetic, environmental, and psychological factors. Neurotransmitters not only help to execute these basic behavioral components but also serve to modulate these preexisting behavioral states by amplifying or reducing their effects. Genetic abnormalities in a number of neurotransmitter pathways have been implicated in aggression-related disorders. Current and future research aims to understand how these neurotransmitters function both normally and abnormally to mediate aggression and other human behaviors. With the evolution of genetic testing and continued development of neuroimaging technologies such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) scanning, the ability of the scientific researcher to investigate the brain's constellation of synapses and neurotransmitters is growing ever more proficient. While it is clear from these studies that neurotransmitters contribute significantly to the predisposition of an individual toward aggressiveness, whether neurotransmitter dysfunction alone is sufficient to cause violent aggression remains unclear.

Aggression may be impulsive or premeditated in nature. In the former case, impulsivity defines, or describes, the aggression. That is, it is the aggression that is impulsive not that the person is aggressive and at other times impulsive, though that may be true as well. Diagnoses associated with impulsive aggression include Intermittent Explosive Disorder (IED) characterized by frequent and problematic impulsive aggressive outbursts, and Borderline Personality Disorder (BPD) characterized by instability in self-image, in interpersonal relationships as well as impulsivity and affect (including anger and aggression). In the latter case, the aggression is planned and carried out in order to achieve some tangible goal. Diagnoses associated with this type of aggression include Antisocial Personality Disorder (AsPD) which is characterized by a pattern of disregard for, and violation of, the rights of others. These types of aggression are not mutually exclusive, however, and some individuals display both types of aggression at different times.

Section snippets

Serotonin

Serotonin or 5-hydroxytryptamine (5-HT) is a multipurpose monoamine neurotransmitter derived from the amino acid, l-tryptophan, and has been implicated as an important regulator of mood (Kumar et al., 2010, Kunisato et al., 2010, Ruhé et al., 2007), appetite (Curzon, 1991, Dourish, 1995, Lam et al., 2010), gastrointestinal muscle contractility (Gershon, 2004, Xu et al., 2007), self-injurious behavior (Peddeer, 1992), and sleep (Monti, 2010, Monti and Jantos, 2008, Monti and Monti, 2000). With

Dopamine

Dopamine (DA) is a catecholamine neurotransmitter that acts both on the central and the sympathetic branch of the peripheral nervous systems. DA in the CNS has been linked to cognition (Browman et al., 2005, Heijtz et al., 2007), movement (Devos et al., 2003), sleep (Dzirasa et al., 2006, Lima et al., 2008), mood (Brown and Gershon, 1993, Diehl and Gershon, 1992), attention (Nieoullon, 2002), and learning and memory (Arias-Carrión and Pöppel, 2007, Denenberg et al., 2004). Additionally, DA has

Norepinephrine (Noradrenaline)

Synthesized from tyrosine-derived dopamine via dopamine decarboxylase and β-hydroxylase (Sofuoglu and Sewell, 2009), norepinephrine (NE) is both a catecholamine neurotransmitter and a stimulant stress hormone. As a stress hormone, NE primarily targets brain regions responsible for attention such as the amygdala and works in conjunction with epinephrine (adrenaline) to produce the “fight-or-flight” response (Tanaka et al., 2000). During times of high stress, this response increases heart rate,

GABA

While gamma-aminobutyric acid (GABA) has a critical and well-defined function in vertebrate neurological systems, its role in behavioral aggression is not as prominent as 5-HT, DA, and NE. GABA is a primary neurotransmitter in the CNS, and is known as chief inhibitory neurotransmitter (de Almeida et al., 2005). GABA-related activity and dysfunction has been associated with schizophrenia (Kantrowitz et al., 2009, Wassef et al., 1999), epilepsy (Snodgrass, 1992, Treiman, 2001), and pain and

Peptides

Limited published data suggest relationships between human aggression and central vasopressin, oxytocin, and opiates. (Coccaro et al., 1998b) first reported a positive correlation between CSF vasopressin concentration and life history of aggression in male and female subjects with personality disorders. This relationship was confined to males and remained even after the inverse correlation between CSF vasopressin and a collateral assessment of serotonin function (i.e., PRL response to FEN) was

Conclusion

The neurobiology of aggression is clearly complex. However, we now know more about the biological underpinnings of this behavior than ever before and this knowledge points the way to possible strategies for treatment. Many agents appear to have therapeutic efficacy but many only work on the brain 5-HT system. In the upcoming years, we look to the development of agents that work on non-5-HT systems (e.g., vasopressin, oxytocin, etc.) so that we may have a more varied toolbox with which to treat

References (130)

  • N.D. Daw et al.

    Opponent interactions between serotonin and dopamine

    Neural Netw.

    (2002)
  • R.M. de Almeida et al.

    Escalated aggressive behavior: Dopamine, serotonin and GABA

    Eur. J. Pharmacol.

    (2005)
  • M.G. De Simoni et al.

    Modulation of striatal dopamine metabolism by the activity of dorsal raphe serotonergic afferences

    Brain Res.

    (1987)
  • V.H. Denenberg et al.

    The role of dopamine in learning, memory, and performance of a water escape task

    Behav. Brain Res.

    (2004)
  • D. Devos et al.

    Effect of l-dopa on the pattern of movement-related (de)synchronisation in advanced Parkinson's disease

    Neurophysiol. Clin.

    (2003)
  • D.J. Diehl et al.

    The role of dopamine in mood disorders

    Compr. Psychiatry

    (1992)
  • S. Engelborghs et al.

    The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia

    Neurochem. Int.

    (2008)
  • S.J. Enna et al.

    The role of GABA in the mediation and perception of pain

    Adv. Pharmacol.

    (2006)
  • D.L. Gardner et al.

    CSF metabolites in borderline personality disorder compared with normal controls

    Biol. Psychiatry

    (1990)
  • R.D. Heijtz et al.

    Motor inhibitory role of dopamine D1 receptors: Implications for ADHD

    Physiol. Behav.

    (2007)
  • L. Hernandez et al.

    Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis

    Life Sci.

    (1988)
  • E.M. Hull et al.

    Copulation increases dopamine activity in the medial preoptic area of male rats

    Life Sci.

    (1993)
  • D.D. Lam et al.

    Brain serotonin system in the coordination of food intake and body weight

    Pharmacol. Biochem. Behav.

    (2010)
  • R. Lee et al.

    Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder

    Psychoneuroendocrinology

    (2009)
  • M.M. Lima et al.

    Blockage of dopaminergic D(2) receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation

    Behav. Brain Res.

    (2008)
  • M. Linnoila et al.

    Low cerebrospinal fluid 5-hydroxylndolacetic acid concentration differentiates impulsive from nonimpulsive violent behavior

    Life Sci.

    (1983)
  • J.M. Monti

    The role of dorsal raphe nucleus serotonergic and non-serotonergic neurons, and of their receptors, in regulating waking and rapid eye movement (REM) sleep

    Sleep Med. Rev.

    (2010)
  • J.M. Monti et al.

    The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking

    Prog. Brain Res.

    (2008)
  • J.M. Monti et al.

    Role of dorsal raphe nucleus serotonin 5-HT1A receptor in the regulation of REM sleep

    Life Sci.

    (2000)
  • M.R. Munafò et al.

    Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: Meta-analysis and new data

    Biol. Psychiatry

    (2008)
  • A. Nieoullon

    Dopamine and the regulation of cognition and attention

    Prog. Neurobiol.

    (2002)
  • J.N. Oak et al.

    The dopamine D(4) receptor: One decade of research

    Eur. J. Pharmacol.

    (2000)
  • R.V. Parsey et al.

    Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor-binding potential measured by PET using [C-11]WAY-100635

    Brain Res.

    (2002)
  • H.O. Pettit et al.

    Effect of dose on cocaine self-administration behavior and dopamine levels in the nucleus accumbens

    Brain Res.

    (1991)
  • J.G. Pfaus et al.

    Sexual behavior enhances central dopamine transmission in the male rat

    Brain Res.

    (1990)
  • O. Pucilowski et al.

    Effect of 6-OHDA injected into the locus coeruleus on apomorphine-induced aggression

    Pharmacol. Biochem. Behav.

    (1986)
  • O. Pucilowski et al.

    Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala

    Pharmacol. Biochem. Behav.

    (1987)
  • L.A. Ricci et al.

    Serotonin-1A receptor activity and expression modulate adolescent anabolic/androgenic steroid-induced aggression in hamsters

    Pharmacol. Biochem. Behav.

    (2006)
  • L.A. Ricci et al.

    Alterations in the anterior hypothalamic dopamine system in aggressive adolescent AAS-treated hamsters

    Horm. Behav.

    (2009)
  • D.R. Rosell et al.

    Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients

    Biol. Psychiatry

    (2010)
  • J. Sawynok

    GABAergic mechanisms in antinociception

    Prog. Neuropsychopharmacol. Biol. Psychiatry

    (1984)
  • N. Alia-Klein et al.

    Brain monoamine oxidase. A activity predicts trait aggression

    J. Neurosci.

    (2008)
  • O. Arias-Carrión et al.

    Dopamine, learning and reward-seeking behavior

    Act. Neurobiol. Exp.

    (2007)
  • M. Asberg et al.

    5-HIAA in the cerebrospinal fluid: A biochemical suicide predictor

    Arch. Gen. Psychiatry

    (1976)
  • A.S. Brown et al.

    Dopamine and depression

    J. Neural Transm. Gen. Sect.

    (1993)
  • G.L. Brown et al.

    Aggression, suicide, and serotonin: Relationships to CSF amine metabolites

    Am. J. Psychiatry

    (1982)
  • M.C. Cervantes et al.

    Serotonin 5-HT1A and 5-HT3 receptors in an impulsive-aggressive phenotype

    Behav. Neurosci.

    (2009)
  • M.C. Cervantes et al.

    Differential responses to serotonin receptor ligands in an impulsive-aggressive phenotype

    Behav. Neurosci.

    (2010)
  • E.F. Coccaro

    Central neurotransmitter function in human aggression and impulsivity

  • E.F. Coccaro et al.

    The neuropsychopharmacologic challenge in biological psychiatry

    Clin. Chem.

    (1994)
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