My theory suggests all tissues of the body depend on
the "melatonin-DHEA cycle." I think this cycle is
necessary for growth, development, and function
during childhood and adolescence and maintenance
and function of the adult. I look for disturbances of
this cycle to help explain pathology. Migraine
headaches and epilepsy may result from malfunctions
in melatonin (MLT) and DHEA. Prior to my
explanation, increased MLT in epilepsy and reduced
MLT in migraines has been discovered. However,
according to a medical literature search (medline), no
one has addressed any connection of DHEA with
migraines or epilepsy.
The main connection of low MLT in migraines is
found in the female cycle. MLT "increases
significantly from the follicular to the luteal phase" in
normal womens cycles (Cephalalgia 1995; 15: 136);
another study found that MLT is significantly
reduced throughout the cycle in women with
migraines. This second study also found that MLT is
decreased during headaches (Caphalalgia 1994; 14:
205). I have read anecdotal remarks on the internet
that some women have increased migraines during
the second part of their cycles (luteal phase). MLT
begins a steep decrease just prior to puberty, and
declines rapidly thereafter. Since, "migraine occurs
most commonly in men and women aged 25-55
years" (Neurology 1994; 34 Suppl. 2: 6), I suggest
that this is a time when MLT reaches critically low
levels in susceptible people. Low MLT is somehow
connected to migraines, but, I suggest, the levels of
DHEA have to be examined to fully explain it.
I suggest migraines result from low MLT and
increased DHEA. Women produce more DHEA
from birth than men. This extra DHEA should have
most effect on migraines prior to the onset of
interfering sex hormones, before puberty. It has been
found that "when the onset [of migraines] is below
the age of puberty there is a striking predominance of
women over men in a ratio of 3:1," (Headache 1994;
34: S8). It is part of my theory that the hormone,
testosterone, causes DHEA to be used for
"testosterone target tissues." This use of DHEA by
these tissues should reduce the availability of DHEA,
i.e., increased testosterone should decrease
migraines. This can be seen in the fact that,
following puberty, women still have more migraines
and that whites have more migraines than blacks.
Blacks produce more testosterone than whites. "In
women, migraine prevalence was significantly higher
in Caucasians (20.4%) than in African (16.2%)... A
similar pattern was observed among men (8.6%,
7.2%, ...)." (Neurology 1996; 47: 52). Interestingly,
my theory suggests that people of higher testosterone
congregate together, as in cities, and higher
DHEA/lower testosterone types tend to live apart
from cities. The prevalence of migraines also follows
this pattern. "Females, whites, and individuals
residing in rural counties were more likely to suffer
migraine headache than their respective comparison
groups." (Clinical Therapeutics 1994; 16: 855).
I have read that headaches occur when blood vessels
in the brain constrict. Since I have suggested
elsewhere that I think DHEA stimulates constriction
of blood vessels and increases blood pressure, I
suggest increased DHEA causes the constriction of
blood vessels in migraine headaches. Constricting
blood vessels and reduced blood flow is
characteristic in migraines. "The transient neuronal
excitatory wave is followed by a longer lasting
depressive wave, which involves a substantial
reduction in cortical blood flow (with an active
constriction of resistance vessels) and ionic changes
and transmitter release into the extracellular fluid
compartment." (Cephalalgia 1992; 12: 75).
I have produced a theory of sleep that explains the
connection of MLT and DHEA. It can be found in
detail at http://www.naples.net/~nfn03605 on the
internet. At its most basic, I suggest melatonin binds
to neurons and shut them down. The connection
with DHEA is that MLT shuts down the nerves that
release the hormone, prolactin (PRL). It is also
known that PRL specifically and powerfully
stimulates DHEA. When MLT shuts down PRL,
DHEA production is reduced and its stimulating
effects on the brain are reduced. This is sleep. Now,
to keep this from killing us, PRL is released in
rebound to the negative effects of MLT. This cycles
slowly until a large release of PRL occurs in the early
morning. This large release of PRL then starts a large
morning release of DHEA, which awakens us. In the
quotation just above, I suggest the "excitatory wave"
represents the effects of MLT, i.e., the shutdown of
MLT causes nerves to rebound in response. I
suggest the "depressive wave" represents the
restabilization caused by a subsequent response of
secreted DHEA. The increased DHEA causes the
blood vessel constriction that causes the migraine
headache.
With the foregoing in mind, it should be easier to
explain epilepsy with the MLT - DHEA cycle. MLT
is high in epileptic people. "Melatonin production in
untreated patients with active epilepsy is increased
and had a circadian pattern with a phase difference as
compared with that of normal subjects." (Epilepsia
1995; 36: 75). In the paragraph, just above, I
demonstrated how MLT can induce the production of
DHEA. During the day, my sleep mechanism
suggests that the larger production of DHEA is
involved in inhibiting synthesis of MLT from the
pineal gland (where MLT is made). This means that
once DHEA is "used up" during the day, there is not
enough DHEA to keep the pineal from making MLT.
When MLT production occurs, the shut down of PRL
occurs and DHEA is reduced to even lower levels.
This is how the sleep - wake cycle occurs.
Sleep deprivation keeps MLT from being released.
This has been determined. "It was found that the
melatonin levels were increased after sleep
deprivation..." (Sleep 1988; 11: 362). A much later
study found that MLT was not increased by sleep
deprivation, but that "Prolactin was higher on the
post-sleep deprivation and control nights but did not
rise on the deprivation night." (Journal of Pineal
Research 1996; 20: 7). Sleep deprivation increases
the build up of the thing that stimulates DHEA, i.e.,
prolactin. Since increased sleep is a consequence of
sleep deprivation, I suggest MLT increases. Since it
is the PRL that stimulates DHEA production, both of
these studies say, essentially, the same.
There is another way of seeing this. I have suggested
that DHEA stimulates the nerves that inhibit synthesis
of MLT. I suggest that electroconvulsive shock
exerts its effects by stimulating DHEA. In the
following quotation, I suggest the reduced production
of MLT is due to increased DHEA, inhibiting the
pineal gland. "In ECS [chronic elctroconvulsive
shock]-treated rats, both pineal and serum melatonin
levels after isoproterenol administration were
significantly lower than those in sham-treated animals
and in rats receiving subconvulsive shock."
(Psychiatry Research 1994: 53: 185).
I suggest that the opposite mechanism explains
epilepsy. I suggest the increased melatonin found in
untreated epileptics builds up and is released so that
nerves are shut down. Individuals susceptible to
epilepsy must have entire sections of the brain shut
down so much that they "rebound" and call up a
large response of DHEA. It is this rebound response
that is the large area of stimulated nerves that cause
the seizures. Once the brain has stimulated sufficient
DHEA, then the seizure stops.
James Howard