Variations in the enzyme Monoamine Oxidase-A (which breaks down neurotransmitters such as serotonin) have been previously found to affect whether abuse as a child causes greater tendency toward anti-social behavior and violence. Now some researchers have looked at brains with the two different MAO-A variations and found that people with the short variation of MAO-A have less brain gray matter in an area that regulates mood.
The gene is one of two common versions that code for the enzyme monoamine oxydase-A (MAO-A), which breaks down key mood-regulating chemical messengers, most notably serotonin. The previously identified violence-related, or L, version, contains a different number of repeating sequences in its genetic code than the other version (H), likely resulting in lower enzyme activity and hence higher levels of serotonin. These, in turn, influence how the brain gets wired during development. The variations may have more impact on males because they have only one copy of this X-chromosomal gene, while females have two copies, one of which will be of the H variant in most cases.
Several previous studies had linked increased serotonin during development with violence and the L version of MAO-A. For example, a 2002 study* by NIMH-funded researchers discovered that the gene’s effects depend on interactions with environmental hard knocks: men with L were more prone to impulsive violence, but only if they were abused as children. Meyer-Lindenberg and colleagues set out to discover how this works at the level of brain circuitry.
Using structural MRI in 97 subjects, they found that those with L showed reductions in gray matter (neurons and their connections) of about 8 percent in brain structures of a mood-regulating circuit (cingulate cortex, amygdala) among other areas. Volume of an area important for motivation and impulse regulation (orbital frontal cortex) was increased by 14 percent in men only. Although the reasons are unknown, this could reflect deficient pruning — the withering of unused neuronal connections as the brain matures and becomes more efficient, speculates Meyer-Lindenberg.
The researchers then looked at effects on brain activity using functional MRI (fMRI) scans. While performing a task matching emotionally evocative pictures — angry and fearful faces — subjects with L showed higher activity in the fear hub (amygdala). At the same time, decreased activity was observed in higher brain areas that regulate the fear hub (cingulate, orbital frontal, and insular cortices) — essentially the same circuit that was changed in volume.
While these changes were found in both men and women, two other experiments revealed gene-related changes in men only. In a task which required remembering emotionally negative information, men, but not women, with L had increased reactivity in the fear (amygdala) and memory (hippocampus) hubs. Men with L were also deficient during a task requiring them to inhibit a simple motor response; they failed to activate a part of the brain (cingulate cortex) important for inhibiting such behavioral impulses. This region was, conspicuously, the cortex area that was most reduced in volume.
The findings echo those of a 2005 NIMH study** showing how another serotonin-related gene variant shapes the same mood-regulating circuit. In this study also, the gene version that boosts serotonin levels resulted in impaired emotion-related lower brain structures, increased fear hub activation and a weaker response of its regulatory circuits. Yet, the effects of the L version of MAO-A were more extensive, perhaps reflecting the fact that it also impacts another key mood-regulating neurotransmitter, norepinephrine.
The weakened regulatory circuits in men with L are compounded by intrinsically weaker connections between the orbital frontal cortex and amygdala in all men, say the researchers.
Next time someone tries to punch you out in a bar just calmly explain to him that he's only trying to beat you up because he doesn't have enough gray matter in his cingulate cortex and amygdala.
Do you believe in free will? I'm sure that there's some set of genetic variations that cause you to think such a thought.
|Share |||Randall Parker, 2006 March 26 10:41 PM Brain Genetics|