Monoamine oxidase

Monoamine oxidases (singular abbreviation MAO) are enzymes that oxidize monoamine neurotransmitters and are the target of monoamine oxidase inhibitors. Recent PET research has shown that MAO is also heavily depleted by tobacco use.

External resources:

• http://alpha2.bmc.uu.se/gerard/mao
• http://www.eurekalert.org/pub_releases/2001-11/euhs-sdt_1112101.php
• http://alpha2.bmc.uu.se/gerard/research_mao
• Slides showing the effects of tobacco smoking on MAO (http://www.nida.nih.gov/meetsum/nicotine/slides/16Volkow/VolkowSlides)

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An interesting research finding about genetics and MAO:

An Abuse-Inducible Violence Gene?

One of the most interesting examples of a study of the relationships of genes and environment and violence was reported in August 2002 (Caspi et al., Science, vol. 297, p851). The conclusion of the study is that there is a genetic conditions with the following characteristics: IF a boy has a gene which causes low levels of activity of the enzyme mono-amine oxidase A (MAOA), AND that boy is subjected to maltreatment, THEN he will likely show conduct and antisocial personality disorders as a child and as an adult, and have a disposition towards violence, and increased incidence of conviction for violent offences.

This study was done by comparing a genetic difference in the promoter region of the gene for the enzyme. The observable DNA difference is known to be associated with (and is probably actually the cause of) the level of expression of the gene, and therefore the levels of enzymatic activity.

Exactly what is meant by childhood maltreatment is not explained in Caspi’s paper. The violent tendencies of the subjects of the study were quantified by various personality tests (which might, of course, be open to criticism), and by police records.

Those subjects in Caspi’s study with the low-activity MAOA allele who were not abused, did not have any more tendency towards violence than those with the high-activity MAOA who were also not abused. In fact, the graphs presented suggest that they actually had less violent tendencies than the high-activity MAOA subjects, although this is not actually mentioned in the text of the paper.

Conversely, in all cases, no matter what the MAOA activity, there was a correlation between childhood maltreatment and violent tendencies – just a lot more, in the case of the low MAOA subjects.

Caspi suggests that childhood maltreatment, specifically, may be the inducer of the effect, because in children, another enzyme – monoamine oxidase B – is not sufficiently active to take over the job of an insufficient MAOA. It is implied that this would be the case in adults.

A strong association between lack of MAO activity and criminality was previously reported in another study, of a family in which a null?activity MAOA gene was being transmitted (as opposed to the more common, merely low-activity allele, in Caspi’s study).

It is interesting to observe that one class of anti-depressant drugs acts by inhibiting monoamine oxidase.

MAOA converts the neurotransmitters adrenaline, nor-adrenaline, and serotonin, into inactive molecules. Removal of neurotransmitters (by chemical breakdown, as in this case, or by re-uptake), after they have done their job of passing on a nerve signal, is necessary for the correct functioning of nervous communication. If the enzyme that is supposed to break them down is inefficient, then they continue to ‘repeat the same message’.

The MAOA gene is located on the X chromosome. Therefore, it exists in single copy in males (XY), making Caspi’s study relatively easy do for boys. There are indications that similar conclusions will also apply to girls (XX), qualified by the following factors: 1) for those girls with a low-activity MAOA gene on one X-chromosome, and an high activity version on the other, which one is expressed (and in which cells of the body and brain) will be the outcome of the apparently random process of X inactivation, whereby one or other X chromosome in each cell of a female is genetically ‘switched off’; and 2) females are on average much less violent than males anyway, no matter what their environment and genotypes are.

The subjects of Caspi’s research are part of a ‘longitudinal study’ group (like in that TV program ‘7 Up’), who are now 26 years old, and have been bothered by researchers every few years since they were three. This kind of study would make an intriguing example in a discussion of the ethics of ‘informed consent’. It is not stated when or how the samples for DNA analysis were taken.

It may be interesting to speculate on the adaptive implications of the phenomenon observed by Caspi et al. There are advantages and disadvantages to violence, and these generally depend on social context. In a harmonic society, violence by an individual usually disadvantages that individual, as well as his immediate victims – conversely, in a violent, disharmonic, social context, you gotta be tough to survive. A mechanism which ‘assesses’ the ambient violence of the social setting, and adapts accordingly, might have better average survival value over the long term, than the survival value of mechanisms ‘set’ to relatively high, or relatively low, violence.

Another thing to consider about this report, is that the conclusion could be inverted, and still be valid: IF children (with the low-level MAOA gene) are treated nicely, THEN they grow up nice. There will probably be more examples of personality-related genes whose expression is influenced by early (or even adult) environment, and, as a precautionary principle, it is probably a good idea to be nice to people, and try and spread happiness.