The present research proposal is a study of distribution and density of the sigma1-receptor in the brain. A PET-scan will be used to compare depressed patients to healthy controls. Our hypothesis is that receptor density will be increased in people…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome variables will be the distribution volume, the binding
potential and receptor density in the brain. Our hypothesis is that the number
of sigma-receptors will be increased in persons with a depressive disorder.
Secondary outcome
not applicable
Background summary
A depressive disorder is a serious illness that that causes much suffering and
frequently results in chronicity. The cause of a depression is mainly unknown,
it has a multifactorial etiology. It is assumed that both biological,
psychological and social factors play a role play in the etiology. With respect
to the biological factors it is kwnown that several chemical messengers, (or
neuro-transmitter systems) play a role. The scientific research of the last
decades has pointed in particular at the serotonergic system, the
noradrenergic system has received less attention. All available antidepressants
exert their effect through serotonergic or noradrenergic systems. Although it
has been known for some time that neurotransmitter systems are involved in the
pathophysiology of depression, it has hardly received attention. The
therapeutic possibilities for the depressive disorder are still far from
optimum. Although the currently available antidepressants have reasonable
effectivity, still a substantial part of the patients experiences unpleasant
sideeffects, frequently leading to noncompliance in the therapy. A subset of
patients experience no or a partial response to the prescibed antidepressive
drug. Sigma-receptor has already been discovered a number of decades ago.
Particularly the sigma1-receptor appears to play a role in many
neuropsychiatric disorders. It has not been cleared up yet which substance is
endogenous for the sigma-receptor. Substances that stimulate the
sigma1-receptor appear to have antidepressant effect. All antidepressives have
a moderate to high affinity for the sigma1-receptor. The antidepressant effect
is lost when a sigma1-blocking agent is added. Sigma1-receptor stimulating
agents may even exert a stronger antidepressant effect than the SSRI Prozac(R).
Because it is not known to what extent medication influences the
sigma1-receptors, only drug free subjects (patients and healthy volunteers)
will be included in the study.
Study objective
The present research proposal is a study of distribution and density of the
sigma1-receptor in the brain. A PET-scan will be used to compare depressed
patients to healthy controls. Our hypothesis is that receptor density will be
increased in people with a depressive disorder. An increase in sigma1-receptor
density (up-regulation) in depressive disorder is a further affirmation for a
role for the sigma1-receptor in depression, and brings new therapeutic
possibilities a step closer.
Study design
The study is observational, patients will be compared to healthy controls. It
is a pilot study, therefore the study groups will be kept small (10 versus 10).
Intervention
not applicable
Study burden and risks
The PET study will take approximately 2 hours for all subjects. Before,
participators have been taken a questionnaire (30 min.), and have had oral
information from the researcher (30 min.). Taking part in the study brings
along radiation burden, which amounts 1.26 mSv. This can be considered as
acceptable dose, it falls within the WHO range for medical and scientific
purposes. It is not expectable that this exposure will be disadvantageous in
any way for the study participators. The PET procedure takes two and a half
hour, of which 90 minutes is spent in the camera. Although people may
experience as a lenghty part, it is not considered as burdensome. Our
experience is that people often fall asleep in the PET scan. However, people
may feel burdened by the introduction and dwelling of the arterial canula, and
well as os teh venous infusion. Introduction of the arterial canula occurs
under local anaesthesia. In an earlier PET-study with depressive people we
found the load for participators to be acceptable. Patients and healthy
volunteers can make a well-considered choice for taking part in the study when
they have received good explanation about the procedure.
postbus 30001
9700 RB Gronigen
Nederland
postbus 30001
9700 RB Gronigen
Nederland
Listed location countries
Age
Inclusion criteria
Fulfilling the criteria for major depression according to DSM-IV-TR criteria
Informed consent.
Regarded by the treating physician to have competence of judgement
Age 18-50 years
Exclusion criteria
Current use of any medication (patients must be drug-free for three weeks) except use of benzodiazepines.
Drug or alcohol abuse in the past year
Prior cardiovascular disease, brain disease (including former traumatic contusion)
Evidence of any general medical disease, e.g. significant kidney or liver disease
Abnormalities at clinical neurological examination
Pregnancy ;(healthy controls): presence in the past of any psychiatric diagnosis, or the presence of a psychiatric disturbance in first-degree relatives of the subject, will be used as an exclusion criterion.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL11850.042.06 |