Psychobiology of AnxietyAnxiety 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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