THE NEUROBIOLOGY OF IMPULSIVE AGGRESSION

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Aggression is a significant problem in our society, with social, psychological, and financial impacts that may be impossible to assess fully. Data from the Epidemiological Catchment Area study44 suggest that 3.7% of the population commit one or more acts of violence each year, and the lifetime prevalence of aggressive behavior may be about 24%.5

The environmental and psychological roots of aggressive behavior have been studied for several centuries, yet it is only in the past 25 years that we have explored in a systematic fashion possible biologic vulnerabilities to this behavior. In this short time, much has been learned about the role of endocrine and neurotransmitter systems as inhibitors and facilitators of aggressive behavior. For example, many studies in both animals and human beings suggest that serotonin plays a significant inhibitory role with respect to aggressive behavior. Reduced central serotonergic functioning may be correlated with an increased tendency toward impulsive aggressive behavior. Other studies suggest that abnormalities in norepinephrine function play a role in the vulnerability to aggressive episodes. Evidence also points to the sex steroids and vasopressin as having a role in the modulation of aggressive behavior.

Unfortunately, studies of biologic vulnerability to aggression are hampered by several factors. First, although biologic factors may play an important role in the development of these behaviors, overlooking the influence of environmental and learned factors in the genesis of aggression is impossible. Second, there are problems in defining aggression for purposes of investigating biologic predisposing factors. All human beings experience anger and may behave aggressively given enough provocation. In addition, aggressive behavior may have varying causes, for example, delusional thinking, cognitive impairment, depression, and so on. Finally, much of what we know concerning the neurobiology of aggression comes from animal study data, and extrapolating those results to human aggression may be difficult.

Given these caveats, this article attempts to examine possible neurobiologic factors that may modulate impulsive aggression in human beings. We have chosen to discuss impulsive aggression rather than premeditated aggression because the former correlates more clearly with biologic indices of neurotransmitter function. The article concludes with a discussion of the clinical implications of these findings and makes recommendations for future research.

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)

  • A.S. Scerbo et al.

    Salivary testosterone and cortisol in disruptive children: Relationship to aggressive, hyperactive, and internalizing behaviors

    J Am Acad Child Adolesc Psychiatry

    (1994)
  • S.E. Arnold

    Estrogen for refractory aggression after traumatic brain injury

    Am J Psychiatry

    (1993)
  • M. Asberg et al.

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

    Arch Gen Psychiatry

    (1976)
  • S.R. Beckett et al.

    Attenuation of chemically induced defense response by 5-HT1 receptor agonists administered into the periaqueductal gray

    Psychopharmacology

    (1992)
  • R. Bland et al.

    Family violence and psychiatric disorder

    Can J Psychiatry

    (1986)
  • H.G. Brunner et al.

    Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

    Science

    (1993)
  • B. Cai et al.

    Biphasic effects of typical antidepressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice

    Pharmacol Biochem Behav

    (1993)
  • E.F. Coccaro et al.

    Buspirone challenge: Preliminary evidence for a role for central 5HT-1A receptor function in impulsive aggressive behavior in humans

    Psychopharmacol Bull

    (1990)
  • E.F. Coccaro et al.

    Physiological responses to d-fenfluramine and ipsapirone challenge correlate with indices of aggression in males with personality disorder

    Int Clin Psychopharmacol

    (1995)
  • E.F. Coccaro et al.

    Impulsive aggression in personality disorder correlates with tritiated paroxetine binding in the platelet

    Arch Gen Psychiatry

    (1996)
  • E. Coccaro et al.

    Serotonergic studies in affective and personality disorder patients: Correlations with behavioral aggression and impulsivity

    Arch Gen Psychiatry

    (1989)
  • F.A. Elliott

    Neurological findings in adult minimal brain dysfunction and the dyscontrol syndrome

    J Nerv Ment Dis

    (1982)
  • J. Grafman et al.

    Frontal lobe injuries, violence, and aggression: A report of the Vietnam Head Injury Study

    Neurology

    (1996)
  • J.D. Higley et al.

    Cerebrospinal fluid monoamine and adrenal correlates of aggression in free-ranging rhesus monkeys

    Arch Gen Psychiatry

    (1992)
  • E. Hollander et al.

    Serotonergic sensitivity in borderline personality disorder: Preliminary findings

    Am J Psychiatry

    (1994)
  • R.J. Kavoussi et al.

    Sertraline in the treatment of impulsive aggression in personality disordered patients

    J Clin Psychiatry

    (1994)
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    Address reprint requests to Richard Kavoussi, MD, Allegheny University Hospitals, Eastern Pennsylvania Psychiatric Institute, 3200 Henry Avenue, Philadelphia, PA 19129

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    From the Clinical Neuroscience Research Unit, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania

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