Physiology of Aggressive Behavior

Aggressive behavior or the threat of aggression is accompanied by strong neuroendocrine and autonomic stress responses in the two participants of the social interaction. The magnitude and the nature of this response depend on the outcome of the aggressive interaction, that is, winning or losing. Because the formation and maintenance of social hierarchies is one of the most important functions of aggressive behavior, much of the stress of everyday life has its origin in this social structure.

The relationship between aggression and stress obviously relates to the physiology of aggression. Therefore, the most important physiological mechanisms underlying aggressive behavior are briefly summarized. A complicating factor is the fact that various forms of aggressive behavior have a different physiological basis. Moreover, the causal physiological mechanisms underlying aggression cannot always be distinguished from the physiological consequences of the aggressive interaction. These consequences are in turn dependent on the outcome of the aggressive interaction, that is, victory or defeat.

Neuroendocrine Factors. Traditionally, high levels of offensive aggressive behavior have been linked to high levels of plasma testosterone. However, the direct causal relationship between testosterone and the expression of offensive behavior is still being discussed. It seems that various kinds of aggressive behavior may be differentially dependent on testosterone, whereas experiential factors strongly interfere with the degree in which aggression depends on plasma testosterone levels.

Winning experience results in a temporary increase in plasma testosterone levels, whereas defeat results in a long-lasting decrease. At the level of the brain, testosterone is metabolized into estrogen and dihydrotestosterone. Evidence in rodents shows the existence of separate estrogen- dependent and androgen-dependent neuronal mechanisms of offense.

Due to its high emotional character and the high amount of physical activity, aggression is usually accompanied by a high activation of the pituitary adrenocortical system and the sympathetic adrenomedulary system. However, the reactivity of these neuroendocrine systems appears to differ as an important trait characteristic between highly aggressive and nonaggressive individuals. Aggressive males are characterized by a high reactivity of the sympathetic nervous system and the adrenal medulla, whereas nonaggressive males show a higher reactivity of the pituitary of the adrenocortical axis and the parasympathetic branch of the autonomic nervous system. Recently, hyporesponsiveness of the hypothalamic-pituitary- adrenocortical (HPA) axis has been associated with the development of extreme and presumably pathological levels of aggressive behavior in rats.

Genetic Factors. The role of genetic factors in aggression has long been recognized. Bidirectional selection in rodents usually leads to highly significant differences in aggressive behavior within three or four generations. Extensive studies in human twins confirm a considerable genetic contribution to the individual level of aggression and violence.

The initial studies in humans focused on the XYY syndrome in relation to criminal violence. Several studies in mice addressed the question of to what extent biological variation in aggressive behavior might be due to genetic variation at the Y chromosome. It appeared that the pairing region of the Y chromosome includes the steroid sulfatase gene and the sex-determining region, which might be responsible for at least some of the individual variation in aggression. Behavioral analyses of the rapidly increasing number of genetically manipulated mouse strains show the involvement of more than 50 other genes involved in elevated levels of aggression.

Some of these genes code for important components of the neurobiology of aggression such as serotonergic and monoaminergic neurotransmission and gonadal steroid receptors and metabolism. However, for most of these genes it is unknown how they relate to the existing knowledge of the physiology of aggression.

Studies aimed at genetic polymorphisms related to individual variation in aggression are mainly performed in humans. So far, the most consistent findings show polymorphism at the promoter regions of the genes coding for the serotonin transporter, for monoamine oxidase A, and for catechol-O-methyl- transferase. However, due to the involvement of these neurobiological systems in a wide variety of other behaviors, it is unlikely that this genetic variation is exclusively correlated with aggression per se.

Central nervous organization. There is a large body of literature on the central-nervous-system organization of aggressive behavior in animals. The specific involvement of various limbic and midbrain structures depends on the type of aggressive behavior. Offensive aggression involves specific hypothalamic, premamillary, and preoptic areas; the medial and central nuclei of the amygdala; and the prefrontal cortex. Defensive aggression involves the medial hypothalamus, the septal area, and the periaqueductal gray.

Evidence suggests that the neuronal systems involved in these types of aggressive behavior are remarkably similar across species and may be homologous to those in humans. High levels of aggression or violence are often associated with functional disturbances in one or more of these brain regions. In the human literature, much attention has been paid to the dyscontrol syndrome, or episodic rage, which is probably attributed to seizure activity in certain brain areas.

Brain imaging studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) in humans with a history of violence and antisocial behavior show a reduced blood flow and glucose utilization in temporal and prefrontal cortical regions.

The most consistent findings of central nervous system functioning in aggressive behavior in both animals and humans, however, involve serotonin (5-HT). Low concentrations of 5-hydroxyindole- acetic acid, a metabolite of serotonin, in the cerebrospinal fluid have been consistently found as a trait characteristic in highly violent, aggressive, or suicidal patients. These findings are supported by many animal studies showing the anti-aggressive effects of selective 5-HT1A or 5-HT1B receptor agonists.

Various other neurotransmitters including noradrenalin, dopamine, and γ-aminobutyric acid (GABA) and neuropeptides such as vasopressin are shown to be involved in the control of aggressive behavior in animals as well. However, their role in human aggression and violence is far from clear.