A study of a Dutch family with X-linked borderline retardation and behavior disorders

A point mutation was localized on exon 8 of the gene encoding MAO-A. The mutation changed a codon for the addition of the amino acid glutamine to a stop codon (a sequence of three base that codes for termination of mRNA translation into protein - enzyme). This means that during protein synthesis the proccess gets interrupted prematurely, and MAO-A is never completely contsructed, making it totally inaffective at its normal catalytic activites.

It shouldn't be a surprise that levels of seratonin, norepinephrine, dopamine, and other MAO-A substrates were at elevated levels for affected males compared to carriers and control subjects. Of course, MAO-A product levels for VMA, HVA, and 5-HIAA were substantially lower than both carrier and control groups. Levels for the substrates and products of MAO-B fell within normal ranges. This means that the behavioral problems of the affected males are most likely a result of their lack of MAO-A activity.

All of the affected males in the family have had very strange behavioral histories. The 8 affected males all have experienced repeated episodes of overly aggressive behavior, usually brought out by extreme anger out of proportion to the provocation. These aggresive periods usually lasted 1-3 days. During these periods, the men would sleep very little any have frequent night terrors. One male was convicted of the rape of his sister, and later stabbed a warden in the chest with a pitchfork after being told to get on with his work. Another male, when told that his work was substandard, attempted to run of his boss with a car. Another affected male would force his sister to undress in front of him, threatening them with a knife. In addition, two of the affected males were known arsons. Some of the affective males have had episodes of voyeurism, exhibitionism, and sudden grasping or holding of female relatives.

What this study offers us is the possible relationship between the MAO-A gene and the underlying systems of aggression and emotional response. The elimination of MAO-A activity by the gene mutation seems to be strongly correlated with inappropriate emotional responses, usually resulting in aggression that is out of proportion to the cause. It is truly fascinating that a change of less than 3 base-pairs in these males MAO-A gene can cause such complex behavioral consequenses. The connection between the MAO-A gene and aggression is further strengthened by studies involving mice lacking the MAO-A gene.