Dopaminergic modulation of neuronal response to a stimulus-reward task in people with 22q11 deletion syndrome and healthy volunteers: a functional MRI study.

The neurobiological aspects of psychotic symptoms are still not fully
understood, but dopaminergic neurotransmission is thought to play an important
role. How dopaminergic disturbances can cause the experience of psychosis is
still a matter of study.
It is presumed that dopamine plays a central role in rewards, motivation and
the attribution of salience.
It is possible that a dysregulation in dopaminergic neurotransmission leads to
aberrant assignment of salience to external objects and internal
representations, which subsequently leads to psychotic symptoms. In previous
imaging studies looking at neuroanatomical substrates of rewards, e.g by drugs
or financial rewards, it was found that mainly brain areas rich in dopamine
were involved, like the orbitofrontal cortex (OFC) and the ventral striatum. In
this study we want to investigate if dopaminergic modulation during a
reward-task leads to changes in these and/or other areas.
People with velo-cardio-facial syndrome are, by carrying a deletion on
chromosome 22q11, at greater risk for the development of a psychotic
disorder.
In a recent study of our research group, we have found a disturbed dopaminergic
neurotransmission in non-psychotic individuals with VCFS. VCFS is therefore a
unique research model to investigate psychosis, and the role of dopamine in
abberant assigment of salience and the experience of rewards in the general
population. Therefore, we also want to look at differences in brain activity
after dopaminergic modulation between healthy indiviuals and people with VCFS.

Main goal is to gain more insight in the role of dopaminergic neurotransmission
in rewards, motivation and the attribution of salience in the etiology of
psychosis.
Primary question is whether a change in blood oxygation level dependent (BOLD)
fMRI activity is being measured after temporary acute dopamine depletion with
alpha-metyrosine (AMPT) during a stimulus-reward task in healthy volunteers and
people with VCFS.

A stimulus-reward task is being carried out within an MRI-scanner, one time
with baseline conditions and one time after temporary dopamine depletion with
AMPT. This will take place in two seperate sessions, with an interval of two
weeks and in randomized order.

Temporary acute dopamine depletion with alpha-metyrosine (AMPT).

Possible side effects are stiffness (extrapyramidal symptoms), dysphoria,
transitory anxiety, tiredness, sedation and sleeping problems. In a previous
study of our research group with 24 comparable individuals, in reaction to the
proposed dose of AMPT only sleepiness was reported. There have not been any
reports of longer lasting side effects, which would also not be expected
farmacologically, because of the de half-life of 3.4-3.7 hours. In addition,
there is a burden in time of 1 day and 1 daily period.