Dopaminergic neurotransmission and cognitive decline in velocardiofacial syndrome

Most patients with VCFS function intellectual on a borderline or mild disabled
level. Many (± 30%) develop psychotic disorders and schizophrenia. For that
reason it can give insight in pathophysiology of psychosis. Within the 22q11.
region there are several candidate genes of schizophrenia. The gene coding for
catechol-O-methyl-transferase (COMT) lies in this region and is one of the most
serious candidate gene for schizophrenia and other psychiatric disorders. It is
responsible for katabolism of the catecholamines. A deletion of 22q11.2 results
most of the time in a haplo-insufficiency of the COMT gene which can result in
increase of dopamine brain concentration and a risk in developing a psychosis.
In our population, non-psychotic VCFS patients, we recently found a disturbed
dopaminergic neurotransmission. A subcategory VCFS patients, suffering from
severe psychosis, develop a severe cognitive decline. Also some patients
function on a lower intellectual level (without a decline) as described in
literature. Is unclear until now if these phenomenon*s can be attributed to
disfunctioning of the catecholaminergic neurotransmitter system compared to
patients with VCFS that function better. Also we wonder if AMPT intervention
could be of any benefit in mentioned subpopulation as described before.

1. How functions the dopaminergic neurotransmission in adult patients with VCFS
who are functioning on an intellectual level of moderate to severe impairment
(IQ < 55) by a) a strong cognitive decline or b) a premorbid level of
functioning.
2. Is it possible after the one time gift (challenge) to forsee the effects of
the trial?
3. How will these patients react on a trial of four weeks AMPT (1 g daily)
intervention.
4. Is there a connection between a low active COMT gene, the length of the
deletion or other genotypes or haplo-insufficiencies?
5. Describe the behavioural phenotype of patients with VFS and an IQ below 55.

Administering AMPT in a fixed once only dose of 1,5 gram and a short trial of 4
weeks twice daily 0,5 gram AMPT

Once only administration (orally) of 1,5 gram AMPT (challenge). In advance en
afterwards determination of parameters in blood and urine.
4 week AMPT trial of twice daily administration of 0,5 gram AMPT

Participants can feel sedated and slight dejected. Eventually one may
experience extrapyramidal side effects. Also restlessness is described.
Eventually benzodiazepines can be administered to give some relieve.