Psychobiology of Anxiety

Anxiety has its detrimental affects primarily through activation and maintenance of the flight-or-fight response, our emergency response system designed to get us out of dangerous situations. Fear or anxiety is primarily controlled through the amygdala, deep in the interior of the brain, and part of the limbic system. Below we review some of the psychobiological aspects.

Flight-or-fright activation

You can read a lot more about this system on the flight-or-fight webpage.

As stated above this response, kicked on by the Sympathetic Nervous System, is an emergency response system. It was designed by Mother Nature for when we are faced with danger, real or perceived. It dumps a lot of adrenalin and cortisols into our blood system, redistributes blood flow, depresses the immune system, and much more. It was never designed to be on for prolonged periods.

Fear genes?

Do some people have genes that make them more prone to high anxiety? The answer is, yes!

The geneticists that study this sort of thing call the characteristic, harm avoidance. Harm avoidance is associated not only with high anxiety, but also with other traits, including shyness and depression. Harm avoidance includes loss. Anxiety and depression? Yes. Both are affected or controlled by levels of serotonin (see Depression and Neurotransmitters (coming soon)). Anxiety can be thought of as the anticipation of harm or loss whereas depression derives from the experience of loss or harm.

Geneticists had known for some time that there was a strong genetic component to anxiety (and depression). Heritability studies with twins had shown 50% of anxiety was due to genetics (see studies in Living with Our Genes: Why They Matter More Than You Think, pp 54-86). The question was, what exact genes were involved?

Serotonin transporter gene

The gene that was identified was a serotonin transporter gene. This gene is responsible for producing the protein that reuptakes serotonin that has been released from neurons that secrete it. When serotonin is released from the neurons, it is secreted outside the cell. From there two things can happen. It can bind to serotonin receptor sites (proteins) on receiving cell membranes. In which case it causes specific biochemical reactions to take place within the receiving cell. Or, it can be reabsorbed by the the serotonin secreting neuron. This is the job of the serotonin transporter protein encoded by the serotonin transporter gene.

This protein is the site of the antidepressant, Prozac and its related derivatives. Prozac is a serotonin reuptake inhibiter (SRI). It interfers with the reuptake of serotonin, thus increasing the amount of serotonin that is available out side the neuron.

This "gene" and its two forms (alleles) is actually in the promoter region of the gene. Promoters control how much of the protein is produced (see Gene Regulation, coming soon, I hope.)

People with one form of the gene/promoter have higher anxiety (or higher harm avoidance). Those with the other form have lower anxiety.

Natural Selection and the anxiety genes

Now why would Mother Nature, a.k.a., natural selection let such a high anxiety gene stay around? I mean after all, it seems on the surface that it would be "good" to have the low anxiety allele, in that anxiety in general is not good for you, especially, high anxiety.

Well, as it turns out, people with the high anxiety version have more sex! More sex equals more offspring or at least the higher probability of more offspring. And in biology and evolution, he (or she) with the most offsprings, win! So natural selection would favor the high anxiety allele from this standpoint. This allele increases the fitness of its carriers through increasing the fertility or reproductive component.

Also, this allele would or should increase the viability component because its carriers take less chances, that is have higher harm avoidance. Thus, there viability component of fitness should also be increased.

The counter balance to this would be too much anxiety. The low anxiety gene would be favored by natural selection because the high anxiety carriers would be hiding back in their caves instead of getting out and doing things. (Of course, they may be hiding out, having a good time, reproducing. Sorry, I digress.)

Balancing selection for both alleles

My suspicion is that natural selection favors both genes. The heterozygote may have higher fitness than either homozygote. This is a form of balancing selection, well known by population geneticists (like myself in an earlier life).

Recall that we get one allele from our mom and one from our dad for each gene. Thus we carry two copies of each gene. If we get the same gene from both parents, then we are referred to as homozygous for that allele. If we get different alleles for that gene, then we are referred to as heterozygous.

When the heterozygote has higher fitness, or "higher" for any trait being measured, this is referred to as overdominance. Overdominane means heterozygote superiority. The best known case of balancing selection and overdominance in humans is for sickle cell anemia.

Sickle cell anemia

 There are two alleles for the alpha-hemoglobin allele, the normal allele, we can designate s+ and the sickle allele, s. In malaria infested environments, the s allele prevents the malaria from being able to survive inside the red blood cells. These blood cells are sickled (half-moon shaped), hence the name, sickle. They actually look like that in the microscope. So the  s allele gives higher fitness (viability) to the people who have it in this environment.

The down side is that in the homozygous condition (s/s) where the individual is carrying two sickle alleles, it is lethal. s/s individuals do not usually survive for very long.

So the most fit individuals are heterozygotes, s+/s. They are resistant to malaria yet can survive OK otherwise.

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