MAOA gene

MAOA activity have been implicated in a wide range of psychiatric disorders. Deficiency in MAOA enzyme activity due to a hemizygous chain termination mutation of the MAOA gene has recently been shown to be associated with impulsive aggression and hypersexual behavior in affected males from a single extended pedigree (Brunner syndrome) (Brunner et al. 1993). 

Vanyukov, Michael M., Howard B. Moss, Ling M. Yu, Ralph E. Tarter, and Ran-Jan Deka. 1995a. "Preliminary Evidence for an Association of a Dinucleotide Repeat Polymorphism at the MAOA Gene with Early Onset Alcoholism/ Substance Abuse." American journal of Medical Genetics 60 122-26. 

Genetic factors are clearly involved. The MAOA gene, located on the X chromosome, is involved in the metabolism of dopamine, noradrenaline, and serotonin. Low MAO activity behavior was the first gene strongly linked to violence and antisocial behavior. 

In 2002,Avshalom Caspi,and a colleagues at the Institute of Psychiatry in London found that maltreated boys producing a variant of the MAOA gene were more likely to develop antisocial problems than were maltreated boys who had a variant producing high MAOA activity. Debra Foley, Ph.D., of Virginia Commonwealth University and coworkers reproduced these finding in 2004 (Caspi, 2004). 

Kent Nilsson and his group at Uppsala University in Sweden have come up with the same finding, but with a twist. When adverse psychosocial conditions were taken into consideration, the short MAOA gene variant no longer produced antisocial behavior. Thus, the short gene variant affects antisocial behavior only under adverse psychosocial conditions. 

The discovery that MAO has two isoenzymes with different distributions, substrate specificity and inhibitor sensitivity has helped to rehabilitate the MAOIs to some extent. These isoenzymes are the products of different genes on the X-chromosome and share about 70% sequence homology. Whereas noradrenaline and 5-HT are metabolised preferentially by MAOa, tyramine and dopamine can be metabolised by either isoenzyme. Selective inhibitors of MAOa (e-g- moclobemide Da Prada et al. 1989) should therefore be safe and effective antidepressants whereas the selective MAOb inhibitor, selegiline, should not have any appreciable antidepressant activity (Table 20.5). 

Experiments using both knock-out and pharmacological approaches have demonstrated that serotonin plays a role in modulating synaptogenesis in rodents. Monoamine oxidase (MAO) is an enzyme which degrades neurotransmitters such as noradrenaline, dopamine, and serotonin. There are two distinct forms of the enzyme, A and B, which are encoded by two separate genes, both with 15 exons and lying adjacent to each other on human Xpl 1.23-11.4 [77]. Both MAO A and B deaminate dopamine but have some different characteristics with respect to time of expression and other enzymatic activities MAOA preferentially deaminates serotonin and noradrenaline and its maximal activity appears in the fetal brain. MAOB mainly deaminates neurotransmitters... 

Monoamine oxidase A (MAOA) seems to be the principal serotonin degrading enzyme. The gene is located on chromosome Xpll [77]. Recent reports have shown that a low activity genetic variant of monoamine oxidase A (MAOA) is likely to be related to aggressive behavior, but only when paired with abusive experience in childhood. It also has been found that the low activity form of MAOA was associated with more adult symptoms of antisocial alcoholism than the high activity variant [113]. No studies related to autism have been carried out with this polymorphism (for more details see section 5 in Serotonergic innervations). 

Fig. 6.6 (a) Section of the double helix of the gene expressing the enzyme MAOA. (b) C-t 1 corgyllne PEf scan showing the regional distribution In the brain of the MAOA enzyme, (c) Aggressive subject, (d) Aggressive behavior. 

The gene that expresses the MAOA enzyme is located on the X chromosome, and it is involved in the control of mood, aggression, and pleasure. Subjects with low MAOA activity react much more strongly to stress than those with high activity. 

Brunner et al. (1993) found that aggressive behavior was associated with a mutation of the gene for the enzyme MAOA (Science 262 578-580,1993). In men with borderline mental retardation and aggressive tendencies, they found greatiy reduced MAO activity. Mutations of the C936T gene were related to criminal/antisocial behavior. 

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