THE NEUROBIOLOGY OF IMPULSIVE AGGRESSION
Section snippets
BRAIN LESIONS
The study of patients who suffer brain injuries can provide important clues to the neurobiology of impulsive aggressive behavior. As many as 70% of patients with brain injuries secondary to blunt trauma exhibit irritability and aggression.31 In addition, many patients with histories of uncontrolled rage have a history of head trauma.17 Head injury is significantly more common in male spouse batterers than in nonviolent men.37
Although there is a correlation between aggressive behavior and brain
SEX STEROIDS
In human beings, androgens appear to play a role in the regulation of aggressive behavior, but the nature of that role is unclear.38 Violent offenders appear to have higher testosterone levels than criminals who commit nonviolent crimes (burglary, theft, drug dealing), and those with high testosterone levels also are more aggressive in prison settings.16 In violent alcoholic offenders, high free testosterone concentration in cerebrospinal fluid (CSF) is associated with increased aggressiveness
SEROTONIN
The connection between serotonin (5-HT) and aggression has been established with the repeated observation that abnormalities in central 5-HT function correlate with impulsive aggression. For example, many studies show that the major metabolite of serotonin, 5-hydroxyindolacetic acid (5-HIAA), is reduced in the CSF of subjects with a history of aggression (violence toward others and violent suicide attempts) compared with those with no such history. It was in 1976 that Asberg and associates2
DOPAMINE AND NOREPINEPHRINE
The brain's dopaminergic and noradrenergic systems also appear to play a role in the genesis of impulsive aggressive behavior. Animal studies suggest that increasing brain dopamine activity creates a state in which animals are more prepared to respond impulsively and aggressively to stimuli in the environment.4 Antidepressant medications that inhibit noradrenergic uptake or stimulate noradrenergic output increase aggressive behavior in isolated mice,10 and this effect can be blocked by
OTHER NEUROBIOLOGIC FACTORS
Other brain systems have been implicated to play a role in the vulnerability to aggressive behavior. For example, central effects of arginine vasopressin (AVP) may influence aggressive behavior. Micro-injection of AVP-receptor blockers into the anterior hypothalamus of a hamster has been found to decrease aggression, whereas injection of AVP into the ventrolateral hypothalamus leads to offensiveaggression.18
Nitric oxide (NO) is a neurotransmitter found in high densities in emotion-regulating
INTERACTIONS BETWEEN SYSTEMS
Hypothesizing that only one neurobiologic system influences aggressive behavior would be naive. Unfortunately, there have been few studies on the interaction between the different brain systems that may contribute to the regulation of aggressive behavior. Studies conducted suggest intriguing possibilities. For example, when rats that had become dominant following administration of testosterone received serotonin agonists, a dose-dependent decrease in aggression was displayed.6 These data
SUMMARY
As noted previously, it is likely that the tendency to lash out verbally or physically at others is influenced by an interaction among multiple complex biologic factors. We need to investigate how these systems interact with each other to develop a more thorough understanding of the brain's influence over aggressive behavior.
We are at a very early stage in our understanding of the neurobiology of aggression. There are no simple tools for studying the complex neurophysiology of the human brain.
References (52)
- et al.
Dopamine functions in appetitive and defensive behaviors
Prog Neurobiol
(1992) - et al.
Serotonergic control of androgen-induced dominance
Pharmacol Biochem Behav
(1994) - et al.
Blood platelet uptake of serotonin in episodic aggression
Psychiatr Res
(1989) - et al.
Aggression in humans correlates with cerebrospinal fluid metabolite
Psychiatry Res
(1979) - et al.
Growth hormone responses to intravenous clonidine challenge correlate with behavioral irritability in psychiatric patients and healthy volunteers
Psychiatry Res
(1991) - et al.
Testosterone, crime, and misbehavior among 692 male prison inmates
Personality and Individual Differences
(1995) - et al.
Vasopressin and serotonin interactions in the control of agonistic behavior
Psychoneuroendocrinology
(1994) - et al.
Aggression and brain serotonergic responsivity: Response to slides in male macaques
Physiol Behav
(1995) - et al.
Low cerebrospinal fluid 5 hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior
Life Sci
(1983) - et al.
Noradrenergic denervation attenuates desipramine enhancement of aggressive behavior in isolated mice
Pharmacol Biochem Behav
(1995)
Salivary testosterone and cortisol in disruptive children: Relationship to aggressive, hyperactive, and internalizing behaviors
J Am Acad Child Adolesc Psychiatry
Estrogen for refractory aggression after traumatic brain injury
Am J Psychiatry
5 HIAA in the cerebrospinal fluid: A biochemical suicide predictor?
Arch Gen Psychiatry
Attenuation of chemically induced defense response by 5-HT1 receptor agonists administered into the periaqueductal gray
Psychopharmacology
Family violence and psychiatric disorder
Can J Psychiatry
Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A
Science
Biphasic effects of typical antidepressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice
Pharmacol Biochem Behav
Buspirone challenge: Preliminary evidence for a role for central 5HT-1A receptor function in impulsive aggressive behavior in humans
Psychopharmacol Bull
Physiological responses to d-fenfluramine and ipsapirone challenge correlate with indices of aggression in males with personality disorder
Int Clin Psychopharmacol
Impulsive aggression in personality disorder correlates with tritiated paroxetine binding in the platelet
Arch Gen Psychiatry
Serotonergic studies in affective and personality disorder patients: Correlations with behavioral aggression and impulsivity
Arch Gen Psychiatry
Neurological findings in adult minimal brain dysfunction and the dyscontrol syndrome
J Nerv Ment Dis
Frontal lobe injuries, violence, and aggression: A report of the Vietnam Head Injury Study
Neurology
Cerebrospinal fluid monoamine and adrenal correlates of aggression in free-ranging rhesus monkeys
Arch Gen Psychiatry
Serotonergic sensitivity in borderline personality disorder: Preliminary findings
Am J Psychiatry
Sertraline in the treatment of impulsive aggression in personality disordered patients
J Clin Psychiatry
Cited by (125)
Serotonin and aggression—an update
2020, Handbook of Behavioral NeuroscienceCitation Excerpt :Here we will discuss chiefly the data implicating 5-HT1 and 5-HT2 receptors in aggressive behaviors since abundant data are available on these receptors. Clinically, the 5-HT1A receptor partial agonist buspirone reduces aggressive behavior in mentally retarded patients (Kavoussi, Armstead, & Coccaro, 1997; Ratey, Sovner, Parks, & Rogentine, 1991). Preclinically, systemic injections of 5-HT1A receptor agonists reduce aggressive behavior across several species, including fish, amphibian, birds, rodents, guinea pigs, and nonhuman primates (Bell & Hobson, 1994; Blanchard, Rodgers, Hendrie, & Hori, 1988; Clotfelter, O'Hare, McNitt, Carpenter, & Summers, 2007; de Boer et al., 1999, 2000; de Boer & Koolhaas, 2005; Dompert, Glaser, & Traber, 1985; Haug, Wallian, & Brain, 1990; Joppa, Rowe, & Meisel, 1997; Lindgren & Kantak, 1987; McMillen, DaVanzo, Scott, & Song, 1988; Miczek, Hussain, & Faccidomo, 1998; Muehlenkamp, Lucion, & Vogel, 1995; Nikulina, Avgustinovich, & Popova, 1992; Olivier & Mos, 1992; Sanchez, Arnt, Hyttel, & Moltzen, 1993; Sperry, Thompson, & Wingfield, 2003; Ten Eyck, 2008; Tompkins, Clemento, Taylor, & Perhach, 1980).
Serotonin and aggression
2019, The Serotonin System: History, Neuropharmacology, and PathologyNuclear medicine for the investigation of canine behavioral disorders
2016, Journal of Veterinary Behavior: Clinical Applications and ResearchMetabotropic glutamate receptor and fragile x signaling in a female model of escalated aggression
2016, Biological PsychiatrySerotonergic pharmacology in animal models: From behavioral disorders to dyskinesia
2014, NeuropharmacologyCitation Excerpt :The determination of whether the anti-aggressive effect occurs via pre- or post-synaptic sites had been extensively addressed using various approaches (lesion, microdialysis, pharmacological). Indeed, by acting on presynaptic sites, 5-HT1A/1B agonists very effectively inhibit 5-HT neurotransmission whereas by acting on post-synaptic receptors, they mimic the effect of 5-HT released, enhancing 5-HT signaling (De Boer and Koolhaas, 2005; Kavoussi et al., 1997). To further understand the involvement of 5-HT1A and 5-HT1B receptor in aggressive behavior, agonists were also administered to SERT deficient mice which exhibit a decreased aggressive behavior.
Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds
2013, Journal of Veterinary Behavior: Clinical Applications and ResearchCitation Excerpt :Therefore, it would be useful to analyze whether the serotonin levels of ECSs change during their development. Low levels of serotonin are correlated with impulsive aggression (Soubrié, 1986; Virkkunen and Linnoila, 1993; Mehlman et al., 1994; Higley et al., 1996; Kavoussi et al., 1997; Peremans et al., 2003). Studies in human and nonhuman primates show that low levels of serotonin are correlated with impulsive aggression rather than with overall aggression (Coccaro, 1989; Virkkunen and Linnoila, 1993; Higley, 2003).
Address reprint requests to Richard Kavoussi, MD, Allegheny University Hospitals, Eastern Pennsylvania Psychiatric Institute, 3200 Henry Avenue, Philadelphia, PA 19129
- *
From the Clinical Neuroscience Research Unit, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania