Premenstrual Syndromes : PMS and PMDD - Rutuja :: The site ...

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Premenstrual syndrome: a case
of serotonergic dysfunction?
Elias Eriksson
SHOULD PMS BE REGARDED AN
ENDOCRINE CONDITION OR AS
A BRAIN DISORDER?
Triggered by sex steroids produced by the ovaries, premenstrual
syndrome (PMS) and premenstrual dysphoric
disorder (PMDD) may be, and have often been, regarded
primarily as endocrine conditions. Attempts to explain,
in terms of differences with respect to hormone levels,
why certain women are afflicted by premenstrual symptoms,
while other women are spared from such complaints,
however, have consistently failed. Therefore, it is
nowadays generally agreed that women with premenstrual
complaints differ from controls not with respect
to ovarian function, but with respect to how responsive
the target organs are to the influence of gonadal steroids.
Supporting this view, administration of exogenous sexual
hormones following the suppression of the endogenous
gonadal steroid production elicits PMS-like complaints
in women with PMS but not in controls. 1
One important target organ for sex steroids is the
central nervous system. Receptors for sex hormones are
thus abundant in many brain regions including the
amygdala and the hypothalamus. Since mood and behavioral
symptoms are key features of PMS, the brain obviously
is where underlying processes at least partly must
be sought. Consequently, a better understanding of the
mechanisms underlying PMS clearly requires insight
into the neurochemical basis of the influence of sex
steroids in relation to mood and behavior and why
certain individuals are particularly sensitive to this
influence. Hence, studies of PMS have to deal with the
same difficulties, and apply the same methodological
approaches, as research on the pathophysiology of other
psychiatric disorders.
Two factors render studies on the mechanisms
underlying psychiatric illness more difficult than other
fields of medical research. First, the brain is much more
complex than any other organ; hence, our knowledge
of how it operates to produce consciousness, thoughts,
memories, executive functioning, and emotions is as yet
very limited. And secondly, it is – as compared to many
other organs – relatively inaccessible for exploration.
Because of these difficulties, it is as yet impossible
to measure to what extent a certain individual is
characterized – for example – by shortage or excess of
a certain brain transmitter.
Notwithstanding these problems, over the past
50 years, very reasonable hypotheses concerning the
involvement of specific brain transmitters in conditions
such as depression, anxiety, schizophrenia, and attention
deficit hyperactivity disorder have been formulated.
These hypotheses have, without exception, been based
primarily on pharmacological observations: whereas
certain drugs have been found, accidentally, to reduce
the symptoms of the condition in question, other compounds
have been found to aggravate them. And by
then analyzing how these different compounds influence
brain neurotransmitters, using animal experiments,
researchers have been able to draw tentative
conclusions regarding the pathophysiology underlying
the studied condition. 2 Subsequently, usually decades
later, it has often been possible to obtain at least partial
confirmation of these theories by means of other
methodological approaches, such as brain imaging 3,4
or genotyping. 5 But the foundation of theories linking
brain neurotransmitters to psychiatric disorders has
always been the presumed mechanism of action of
drugs.
With respect to the brain mechanisms underlying PMS,
one particular neurotransmitter, serotonin, has been
proposed to play a key role. As is the case for other theories
implicating specific transmitters in specific conditions,
also this hypothesis is first and foremost based on