Gene polymorphisms and susceptibility to psychopathology in patients with metastatic carcinoid disease

Carcinoïd tumours are slowly growing malignant neuro-endocrine tumours
secreting various factors, of which serotonin is the most prominent one. The
production of serotonin in the carcinoid can increase so dramatically, that a
major fraction of whole body tryptophan is peripherally converted to serotonin.
Serotonin is not able to pass the blood brain barrier, thus the cerebral
synthesis of serotonin is highly dependent on the availability of tryptophan in
the blood circulation. Consequently, carcinoid tumor can lead to cerebral
depletion of serotonin. Previously was found that tryptophan depletion can lead
to increased irritability and aggression in humans with a carcinoid tumor and
animals. The relationship between serotonin and the presence of symptoms is not
always consistent and not all patients develop these symptoms. Apparently, some
individuals are more vulnerable for the consequences of tryptophan depletion
than others. This could be because of different gene polymorphisms in genes
that code for serotonin metabolism and/or noradrenergic function. Recently a
number of gene polymorphisms that affect serotonergic and noradrenergic
activity have been described. Of interest are polymorfisms of monoamine
oxidase-A, the serorotonin transporter, tryptophan hydroxylase and
catecholamine-O-methyltransferase.

In this study will be examined whether the polymorphisms of above mentioned
genes are related to the occurrence and extent of psychiatric symptoms in
patients suffering from carcinoid tumors. Since serotonin metabolism depends
also on the tumor activity, the relationship clinical symptoms and biochemical
parameters will be studied as well.

The design of this study is prospective. Polymorphism for 5-HTT, MOA-A and COMT
will bedetermined.
Psychopathology will be assessed by using the Symptom Checklist-90 (SCL-90) and
the Buss-Durkee Hostility Inventory (BDHI) three self-rating scales, in the
home situation. The SCL-90 is used to assess general mental health, because it
evaluates a broad range of psychological problems and symptoms of
psychopathology. Russo et. al. found that the main problems that occur in
carcinoid patients are irritability and disturbed impulse control. We*ll use
the BIS and BDHI to assess these symptoms. The BHDI are among the oldest and
widely used self-administered impulsivity tests. Total time investment for
patients and their partners will be about 60 minutes.

Questionnaires (appr. 60 minutes)
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