Aggressive behavior: A comprehensive review of its neurochemical mechanisms and management
Highlights
► Aggressive acts cause harm to another organism. ► Serotonin is the major neurochemical basis of aggression. ► Subsets of 5-HT receptors are more relevant in aggression. ► The usefulness of antipsychotics in aggression is limited by catalepsy. ► Serenics have selective antiaggressive effects.
Introduction
Aggression is a deliberate series of actions that lead to harm, injury, or destruction of another organism and is the most common factor promoting violent crimes. Beyond being the immediate cause of physical injury, aggressive behavior also produces profound long term emotional disabilities in its victims (Weinshenker & Siegel, 2002). When outburst of aggression is comorbid with DSM-IV-defined neuropsychiatric disorders, the offenders are usually given psychiatric care, but when they appear normal or healthy, their most likely fate is punishment by law (Weinshenker & Siegel, 2002). However, this punitive approach often increases aggression, thereby promoting the propensity for violent crimes.
Although aggression is detrimental to the society, it also serves as a useful defensive purpose for obtaining the desired goal of self-preservation in life threatening events (Moffitt et al., 2008, Moyer, 1968, Siegel and Victoroff, 2009). Mental illness, prolonged stress, poverty, and drug abuse are common factors that contribute to the higher rate of violence or aggressive outbursts (Gowin et al., 2010, Moffitt et al., 2008, Moss et al., 1990, Siegel and Victoroff, 2009, Weinshenker and Siegel, 2002). In vulnerable individuals, stress in particular, can lead to a subtype of depression characterized by anger, anxiety, and aggression (Barnett et al., 1991, Weinshenker and Siegel, 2002). Stress might be a strong factor that can precipitate aggression and predicts the severity of developing violence behavior (Barnett et al., 1991).
The major limitation in the study of aggression is the lack of suitable animal models with predictive validity of human aggression that can provide insight into the neural mechanisms underlying the disorder, as well as new targets of therapeutic intervention (Blanchard and Blanchard, 2003, Gowin et al., 2010, Moffitt et al., 2008, Miczek et al., 2002, Miczek et al., 1994). The use of antipsychotics in the treatment of aggression is limited by serious adverse effects, which necessitate the search for agents that can selectively reduce aggression without affecting other behaviors or causing any serious unwanted side effects. Current research is now focused on the development of serenics (compounds with selective anti-aggressive activity) that stimulate specific subsets of 5-HT receptors that are critically involved in the initiation and execution of aggressive acts (Miczek et al., 2002, Moffitt et al., 2008). However, the complex neural mechanisms and lack of a unified classification scheme for the categorization of human aggression has contributed greatly to the slow pace in the development of specific anti-aggressive agents (Weinshenker & Siegel, 2002). The aim of this review is to discuss the types, neurochemical bases, and animal models of aggression, with an appraisal of the pharmacological approach to the treatment of the disorder.
Section snippets
Types of aggression
The lack of a unified classification scheme for the categorization of human aggression has contributed greatly to the slow pace in the development of new medicines with specific anti-aggressive properties (Weinshenker & Siegel, 2002). Various types of aggression have been described in literature based on the factors that trigger it. Moyer (1968) classified aggression into the seven different categories: (1) Fear induced-aggression: This occurs when the animal is placed in a position where
Neurochemical basis of aggressive behaviors
The neural mechanism that mediates aggression is still poorly understood even though several neurochemicals are implicated in the pathogenesis of this behavioral trait. Serotonin, or 5-hydroxytryptamine (5-HT), is the major neurochemical implicated in aggression and violent crimes. It has been shown to play a key role in the initiation, execution and treatment of aggressive acts (Berman et al., 1997, Gowin et al., 2010). Several studies have confirmed a negative correlation between serotonin
Animal models of offensive aggression
The development of animal models that mimic specific aggressive disorders could lead to additional insights into the mechanisms that underlie aggression and treatment options. There are two major types of animal models of aggression: offensive and defensive aggressive paradigms (Adams, 1979, Malone et al., 1998, Weinshenker and Siegel, 2002). Models of offensive aggression include isolation-induced aggression, resident–intruder paradigm, and maternal aggression (Adams, 1979, Malick, 1979,
Animal models of defensive behaviors
Defensive behaviors are forms of agonistic behavior, which are characterized by submission, flight, and similar reactive behaviors. Fighting, when it occurs in a defensive animal, is merely a reaction to an attack. The defensive behaviors such as flight or submission are apparently intended to escape from or prevent further agonistic interactions (Koolhaas et al., 1980). Some of the drugs such as the neuroleptics with anti-offensive activity are known to impair the defensive and flight
Limits to animal models
Although the use of animal models has shed some light on behavioral and neurobiological mechanisms of aggression, it is still difficult to relate these mechanisms to human violence. Fighting in animals, for example, consists of combinations of biting, wrestling and chasing, whereas aggression in humans can take both physical and verbal forms (Nelson & Trainor, 2007). Thus, this diversity tends to limit direct comparisons between species in components of aggression. Another major problem with
Pharmacological treatment of aggression
The major goal of aggression research is to develop pharmacotherapeutic agents that can be used to control human aggression and violence without impairing other behaviors. These research efforts are yet to yield specific compounds that can selectively reduce aggression in humans. The first attempt toward the treatment of aggressive behavior began in the mid-1970s with the use of lithium carbonate in prison inmates (Dostal and Zvolsky, 1970, Sheard et al., 1976). Lithium carbonate was shown to
Conclusion and challenges for future research
Although several mechanisms are involved in the expression of aggression, it is imperative that the precise neurochemical vulnerabilities be clearly defined and understood. It is a challenge for future research to elucidate how precisely these mechanisms interact to contribute to aggressive behavior. Further, animal studies of aggression typically measure aggressive behavior under a controlled single set of environmental conditions. However, expression of aggression in humans is subject to
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