Chapter 7 - The Neurochemistry of Human Aggression
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
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