Considerable evidence links monoamine oxidase (MAO)-A to traits of violent behavior. It remains to be determined which of the monoamines is primarily responsible for the effects of mutations or deletions of the gene for this enzyme or for the effects of its pharmacological inhibition. An early influential study illustrated how acts of violence by the male members of a Dutch family who were also mentally retarded, appears to be linked to a missense mutation in the gene for this enzyme on the X chromosome. In preclinical research, mice lacking this gene were found to initiate injurious aggressive behavior faster. Probably, the most significant findings link the allelic variant with low activity of MAO-A to the antisocial and violent behavior only in those adult males who were severely maltreated in childhood, whereas the allelic variant with high MAO-A activity or the absence of maltreatment had no such influence in adults. A variable-number tandem repeat polymorphisms of MAO-A may also be associated with the increased probability of a life history of aggressive behavior, particularly aggression involving dysre-gulated affect. However, there is also evidence that links lower MAO-A activity to aggressive tendencies independent from polymorphisms in MAO-A. While MAO-A is one of the leading candidates, a number of inconsistent findings obscure the causal relationship between the expression of the MAO-A gene, its interaction with early life experiences, and traits of hostile, antisocial, aggressive outbursts.

The differential expression of specific genes for MAO-A in aggressive and nonaggressive individuals is often associated with alterations in the brain serotonin system, based on additional pharmacological studies. A wide array of methodological approaches has implicated the serotonin system in aggressive traits, impulsivity, and also in the initiation and termination of certain types of aggressive behavior. A venerable hypothesis postulated a serotonin deficiency as the characteristic of the trait of ► impulsive aggression, receiving early support from the 5-HT assay data obtained from the hindbrain of isolated aggressive mice and CSF 5-HIAA samples of patients. The significance of CSF 5-HIAA measures is compromised by the uncertainty as to their precise anatomical origin. Direct challenges of brain 5-HT functions with either an agonist or a tryptophan-depleted diet demonstrated a blunted prolac-tin response in violent patients with various diagnoses, possibly due to actions on 5-HT1A and 5-HT2A receptors. Instead of relying on a single sample of CSF, a peripheral marker, or an endocrine response to a single pharmaco-challenge, in vivo microdialysis reveals no changes in cortical 5-HT during the phase of initiating an attack, but then 5-HT begins to decline once the fight is progressing and terminating. The termination of an anticipated aggressive confrontation is accompanied by a decrease in accumbal 5-HT suggesting a potentially significant role for 5-HT in the inhibition of aggressive behavior. Thus, the tonic levels of 5-HT activity have been linked to aggressive traits, and phasic changes in 5-HT may be relevant to the termination of an aggressive burst.

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Anxiety and Depression 101

Anxiety and Depression 101

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