Recently research has been done on the role of protein
activity on schizophrenia. Protein molecules have been shown to play
a part in normal development of neurons in the brain by stimulating some
receptors on the surface of dividing cells. One type of stimulator
is a class of molecules called cytokines.
Several studies have been done on the effect of cytokines in schizophrenia,
but the researchers have come to rather different conclusions. Some
scientists have shown that the schizophrenic brain has a markedly lower
amount of neurons. They hypothesized that this was due to a lower amount
of cytokines which would limit neuron development (12). However,
this idea is contradicted rather conclusively by another study which seemed
to show that cytokines have a definite worsening effect on schizophrenia.
Researchers tested the brains of schizophrenics
for the cytokine Interleukin-2 while they were on neuroleptic
medication. They found that schizophrenics who had a relapse tended
to have significantly higher levels of Interleukin-2 than those who didn't
relapse. This suggested to the researcher that too many cytokines might
affect the normal regulation of dopamine
(6).
Although the exact mechanism by which the cytokines might worsen the
symptoms of schizophrenia is unknown, the fact that they are involved suggests
another possible avenue by which estrogen might inhibit dopamine and thus
schizophrenia. While no studies to our knowledge have been done on
estrogen and cytokines in the brain, they have been linked in another body
system: the skeleton.
Studies have shown that estrogen helps keep bones
strong and that lack of estrogen is one reason for osteoporosis.
We know that there are two major types of cells in bone, osteoblasts which
form bone and osteoclasts which break down bone. In a normal body
they are in an efficient balance of renewal. Cytokines in the bone
are the agents that start osteoclasts on their task of destruction by binding
to them (10).
Researchers have found that in the presence of estrogen,
the amount of signal proteins on the osteoclasts which draw cytokines is
lower and the number of fake, decoy proteins increase. This prevents
cytokines from binding and thus causes fewer osteoclasts and less bone
destruction. After menopause, the estrogen can no longer exert a
protective force and the cytokines flourish, causing bone destruction (10).
It seems very possible that the effect of estrogen
on cytokine production in the bone might also be replicated in a related
way in the brains of schizophrenics, given the cytokine-schizophrenia connection
established by McAllister and the beneficial effects of estrogen on schizophrenics.
One interesting note in the osteoporosis study was that estrogen had no
effect on the receptors in the beneficial bone forming osteoblast cells,
but seemed to selectively affect the osteoclasts. Perhaps estrogen
might work similarly in the brain, showing little effect on cytokines in
the normal brain but exerting a regulating effect when necessary in schizophrenic
brains. Estrogen might create decoy proteins in the brain as well,
to keep cytokines from binding to dopamine receptors and stimulating their
unchecked growth. However, this is just speculation. Research
in the future could try to determine if estrogen has an effect on the levels
of Interleukin-2 in the schizophrenic brain; if not, other possibilities
must be examined.