Meet Val and Met, anxiety genes!

Suppose you had an awful experience, something traumatic which shook you up and upset you deeply.  What would the effects of that be? How would you cope? Would you be able to deal with your memories, or would you have flashbacks, panic attacks, feel unable to get on with your life?

Researchers in Germany and the USA have been studying why some people develop PTSD (post-traumatic stress disorder) but others, in the same traumatic circumstances, don’t get the disorder and manage to cope with just bad memories.

The answer appears to be nature, not nurture, and is linked to one of the permissive amines, dopamine. People who carry a fairly common variation of a dopamine gene known as COMT show an exaggerated “startle” reflex when they view unpleasant scenes or pictures, and this makes it harder for them to control or regulate their emotional response or arousal.  This variant increases the sensitivity of these individuals, and with other genetic and environmental factors involved these people are more prone to develop anxiety disorders such as PTSD.

COMT codes for an enzyme which breaks down dopamine, which means that the enzyme damps down the dopamine’s effect.  There are two variants or alleles of this gene, Val158 and Met158. Approximately half the population carries one of each, they are heterozygous. The other half are homozygous; about a quarter have two Vals, and a quarter have two Mets.

The sample was a group of 96 young women, average age 22 years. They were shown some happy pictures, animals or babies; neutral pictures, household items; and upsetting pictures such as weapons or injured crime victims. There were 12 pictures of each type, each with a 6 second duration. At random intervals a loud noise sounded as a startle probe, and the startle response to this was measured from contractions of the eye-blink muscles.

The two-Met women showed a significantly stronger startle reflex to the noise and more general anxiety than the Val-Met or two-Val women. This suggests that the Met alleles code for less dopamine-destroying enzyme and so in these individuals their dopamine levels are higher and could last longer than in the other two types. More dopamine in the pre-frontal cortex and limbic system (areas associated with emotional arousal, memory and attention) could cause these people to focus on emotionally arousing stimuli,and be unable to tear their eyes or attention away. This could lead to greater upset and a more serious anxiety, or even an anxiety disorder.

This conclusion is only a suggestion, it is a hypothetical construct. But it is interesting that only humans amongst the primates have these alleles. The other primates, such as chimpanzees, have just the two-Val combination, so this indicates the Met allele is a relatively recent – in evolutionary terms – mutation.

Now why might it have been adaptive, beneficial, for our ancient ancestors to have this extra allele, so that it is was passed down the generations? Why might being two-Met have helped survival?

Montag, C., Buckholtz, J.W., Hartmann, P., Merz, M., Burk, C., Hennig, J. and Reuter, M. (2008) COMT Genetic Variation Affects Fear Processing: Psychophysiological Evidence,  Behavioral Neuroscience, Vol 122, No. 4

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