The relation between free serotonin in plasma, serotonin in trombocytes and the genotype of the serotonin transporter in carcinoid patients, patients on selective serotonin reuptake inhibitors and healthy controls.

Serotonin (5-hydroxytryptamine), a neurotransmitter, is involved in many
physiological processes in the body, such as muscle contraction, regulation of
blood pressure, and neurotransmission in the periphery abd the central nervous
system. The serotonin transporter (SERT) is the most important regulator of the
biologically active free serotonin in the circulatio. It takes care of
extracellulair free serotonin transport over the celmembrane into the
trombocytes, neurons and enterochromaffin cells, where storage and metabolism
take place. Pathophysiologically, serotonine plays a role in a.o. depression.
Excessive periphere serotonine synthesis, storage, excretion and metabolism is
the most important characteristic of carcinoid patients.
To investigate the correlation between plasma free serotonin and its actions on
the cardiovasculair system, the gastro-intestinal and the respirative tract,
the free fraction need to be measured. So far, no methods or machinery were
available to analyze this fraction in a relaibale way, and therefore only the
platelet stored serotonin concentrations (present in higher amoubts) were
measured.

To determine the influence of the serotonin transporter activity on the plasma
free serotonin and dopamine amount and the stored amount (in trombocytes) in
three different populations (healthy controls, carcinoid patients and patients
on medication altering the serotonin availability (SSRIs in depressive patients
and patients with an anxiety disorder).

Primary research question
Is there a difference in the amounts of free serotonin and dopamine and
trombocytes-stored serotonin and dopamine between healthy controls,
serotonin-producing carcinoid patients and patients on medication altering the
serotonin availability (SSRIs in depressive patients and patients with an
anxiety disorder)?

Secundary research question
Is the serotonin transporter activity responsible for the amount of free
serotonin in plasma and the stored amount in trombocytes and is there a
difference between the three groups?

Carcinoid patients (30), patients on SSRI-medication (70) and healthy controls
(5) participate in the study. Blood is collected for the analysis of plasma
free serotonine and dopamine, in trombocytes stored serotonin and dopamine and
genotyping of the serotonin transporter present on the trombocytes.
There are no risks attached to participation. Venapunction is the only burden.
To quantify serotonin and dopamine isotope-dilution mass spectrometry is used.
Real-time polymerase chain reaction is applied
to genotype the sertonine transporter.

Blood will be sampled once by venapuncture (21 mL). Medical risks due to
participation in the study is minimal.