MAO A gene interacts with testosterone to predict sociopathy

Genetic studies of our population estimate that about 50 percent of the differences in trait sociopathy between individuals are due to small differences in our genes. These small individual differences in our genes are called polymorphisms (poly=many, morph=forms), for many forms of the same gene. It is clear that polymorphisms interact with environmental factors during childhood and adolescence to produce sociopathy. It is also clear that the set of traits that we call sociopathy involves many polymorphisms.

There is accumulating evidence that a functional VNTR polymorphism in the promoter region of the monoamine oxidase A (MAO A) gene may give some men a predisposition to sociopathy. Four independent studies have found that this polymorphism interacts with childhood stress to predict sociopathy. VNTR stands for variable number of tandem repeats (the differences between us are due to differences in the numbers of these tandem repeats), the promoter is the part of the gene that regulates its activity. The mutation related to sociopathy makes it less likely that the MAO A gene will be expressed, resulting in lower levels of MAO A. MAO A is an enzyme that breaks down dopamine and other monoamine neurotransmitters such as serotonin and norepinephrine that are critical in emotional responses and impulse control.

There is one Dutch family where a rare MAO A stop-codon polymorphism leads to very low levels of MAO A. All the affected men in this family suffer from mild intellectual impairment and sociopathy. They have very poor impulse control, having committed rape, extreme violence and arson. Follow this link to page 1035 of the article to read the details of their poor impulse control and aggression.

Scientists have used genetic engineering to produce mice that lack the MAO A gene. These mice exhibit increased aggression. High testosterone also increases aggression in male mice.

Previously in “Would somebody please tell me why he did this!”, I discussed the observation that many studies have found testosterone levels to be higher in sociopaths. Increased testosterone levels have also been observed in teens and children at risk for sociopathy. In males, stress can actually increase testosterone levels. This may be one pathway whereby childhood stress leads to antisocial personality disorder (ASPD).

Dr. Rickard Sjoberg from Uppsala University in Sweden, in collaboration with NIH researchers, published a paper in April that is the first to tie together genes and testosterone in the development of sociopathy. Their paper A Non-Additive Interaction of a Functional MAO-A VNTR and Testosterone Predicts Antisocial Behavior (Neuropsychopharmacology, 2007), describes research on 140 Finnish unrelated male criminal alcoholics and controls. In this group of men, high testosterone levels were related to the diagnosis of ASPD, and to aggression, replicating other work.

They also examined low and high expressing MAO A genotypes in their subjects. The low expressing genotype was found in 19/45 controls and 32/95 criminals. Thus, many controls and not all criminals had the low expressing MAO A genotype. However, when they re-examined the relationship between testosterone and aggression and testosterone and ASPD, they found that high testosterone levels were only associated with ASPD and aggression in individuals with the low expressing MAO A genotype.

High testosterone levels in those with the low expressing MAO A genotype were also associated with low levels of MHPG, a byproduct of the breakdown of norepinephrine. These authors also mention that smoking decreases MHPG levels and they factored that in when they did their statistics. This is very interesting given that prenatal smoking increases the risk of sociopathy.

The low expressing MAO A genotype is generally found in about 30 percent of men and so is common. Interestingly, it is found in only 9 percent of women. Also of importance to gender differences in the rate of sociopathy is that this gene is found on the X chromosome. Women have two X chromosomes and men only have one. Therefore, men are more likely to be affected by mutations in genes that are found on the X chromosome. Interestingly, there are studies suggesting that the genetic transmission of ASPD is highest when the affected biologic parent is the mother. This is consistent with the idea that mothers who have two low expressing MAO A genes are passing them on to all of their sons.

Fathers do not contribute an X chromosome to their son’s genetic make-up. Therefore, this particular polymorphism cannot be responsible for the genetic transmission of sociopathy or alcoholism from father to son.

There are other genetic polymorphisms that have been found in higher frequency in sociopaths. Until now I have not been convinced enough of their importance to share the findings with you. The take home message is that the gene-environment interactions that produce sociopathy occur on multiple levels and are very complex. In any case, children who may carry genetic risk require special parenting and protection from the stress caused by a sociopathic and/or addicted parent.