First aim is to quantify DA function of meso-limbic/cortical DA pathways (measured with 18F-FE-PE2I Position Emission Tomography (PET) in PD-depression with or without anhedonia (vs. non-depressed PD). Second aim is to associate these DAT findings…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Differences between (anhedonic and non-anhedonic) depressed PD patients and
non-depressed PD patients in: (1) Baseline DAT-availability measured with PET;
(2) Functional connectivity from seeds with aberrant DAT-availability compared
to non-depressed PD.
Secondary outcome
Differences between (anhedonic and non-anhedonic) depressed PD patients and
non-depressed PD patients in effort-reward weighting on an
effort-reward-choice-task (ERCT), fMRI-based BOLD signal when performing the
ERCT during the decisional phase, fMRI-based BOLD signal when performing a
reinforcement learning task, neuromelanin, and subjective self-report
measurements assessing depression, anhedonia, apathy and anxiety.
Background summary
Parkinson*s Disease (PD) is the second most prevalent neurodegenerative brain
disease, characterized by degeneration of dopaminergic (DA) neurons. In PD,
depression is very common (35%) with a high disease burden. Although the
etiology of PD-depression is likely multifactorial, specific brain regions and
neurotransmitters have been implicated, including dopamine. Despite increasing
interest in identifying underlying mechanisms of depression in PD, we still
lack insight needed to tailor individual treatments. Moreover, studies in
(non-PD) depression indicate the need to distinguish psychiatric phenotypes of
depression. The anhedonic subtype is of particular interest in PD. Anhedonia is
defined as a decreased motivation for and sensitivity to rewarding experiences
and is linked to aberrant DA neurotransmission. Prior clinical research in
PD-depression was hampered by three limitations: psychiatric assessment was not
performed according to the state of the art, clinical heterogeneity was not
considered, and radiotracers not selective for dopamine transporter (DAT) were
used. In the present study, we explicitly focus on clinically carefully defined
subgroups, anhedonic vs. non-anhedonic depression, and use a selective DAT
tracer.
Study objective
First aim is to quantify DA function of meso-limbic/cortical DA pathways
(measured with 18F-FE-PE2I Position Emission Tomography (PET) in PD-depression
with or without anhedonia (vs. non-depressed PD). Second aim is to associate
these DAT findings with differences in functional connectivity (measured by
resting state functional Magnetic Resonance Imaging (fMRI) (vs. non-depressed
PD) in these networks.
Study design
This observational cross-sectional multimodal neuroimaging study combines fMRI
with a novel, highly selective DAT PET tracer (18F-FE-PE2I) in a comparison of
three groups of PD-patients.
Study burden and risks
Participants will attend screening session with a psychiatric interview of
approximately 90 minutes, followed by two study days of approximately 5-6 hours
each; entailing two assessments with fMRI, questionnaires and behavior tasks
and one PET-session. At least 12 hours preceding one of the two fMRI sessions,
participants will have to refrain from dopaminergic medication, and as such,
patients will arrive in a practically defined OFF state. At the end of the
measurement, they will resume their normal medication regime.
The load on participants consists of the time spent on this project,
potentially a temporary worsening of symptoms caused by withholding medication,
and the low-dose nuclear radiation due to the PET session (of the same order of
magnitude as the annual background radiation in various parts of the world.).
Individual participants do not directly benefit from participation. We expect
that this study will improve our knowledge about the cerebral mechanisms
underlying (anhedonic versus non-anhedonic) depression in PD, which may lead to
new ways of treating depression in PD, a disease with high burden on patients
and their relatives.
Reinier Postlaan 10
Nijmegen 6525CG
NL
Reinier Postlaan 10
Nijmegen 6525CG
NL
Listed location countries
Age
Inclusion criteria
For the present study, we will select patients from the PPP and PRIME cohorts
and from clinical samples from neurologists embedded in Parkinsonnet and/or in
the service area of the RadboudUMC. The PPP study is a pro-spective,
longitudinal, single-center cohort study of the Radboudumc in the Netherlands
which started in October 2017. Enrollment period will take 2 years, in which a
total of 650 adult patients diagnosed with PD with <=5 years duration will be
included. PRIME is a prospective longitudinal study of the RadboudUMC of the
Netherlands which started in 2019 and enrolls 1200 patients with either
clinically diagnosed PD or parkinsonism.
ParkinsonNet is an innovative health care concept that consists of 70
professional networks for PD covering all of the Netherlands
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
• A diagnosis of PD with <=10 years duration, defined as time since diagnosis
made by a neurologist.
• Subject can read and understand Dutch.
• Subject is willing, competent, and able to comply with all aspects of the
protocol
• meeting DSM-criteria for a depression including the criterium of a sad mood
(depressed PD group)
• in the 5 past years and/or currently not meeting DSM-criteria for a
depression (non-depressed PD control group)
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
Exclusion criteria:
• Contraindications for MRI, e.g., claustrophobia, presence of an active
implant, pacemaker, insulin pump, neurostimulator, ossicle prosthesis,
pregnancy, and/or other medical device or other non-removable metal part
incompatible with MRI.
• Contraindications for PET e.g., inability to lie flat or lie still for the
duration of the scan, claustrophobia (occasionally).
• Use of medication or drugs with evident DAT-binding like methylphenidate,
buproprion, amphetamines, cocaine that cannot be discontinued according to the
PET-protocol. Note that we allow use of anti-depressants with the exception of
those antidepressants with a high DAT binding defined as a relatively low Ki of
<1000 (, i.e. for the Netherlands buproprion, duloxetine and sertraline).
Moreover, we will exclude patients using antidepressants at higher than minimal
effective dosages used for antidepressive effects when the Ki is <10000 (i.e.
for the Netherlands amitryptiline, clomipramine, maprotiline, nortriptyline,
fluoxetine, paroxetine).
• Being diagnosed with dementia (defined as a Montreal Cognitive Assessment
(MoCA) <21/30 (Dalymple-Alford 2010), assessed ON Parkinson medication).
• Psychiatric diagnosis of bipolar disorder.
• Presence of current psychotic symptoms.
Design
Recruitment
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 | NL74241.091.20 |
| Other | NL8664 |