This study aims to (i) compare baseline NM-MRI signal between CHR-P individuals and healthy controls (HCs) and (ii) evaluate whether baseline NM-MRI signal can differentiate those CHR-P individuals who progress to psychosis within three years of…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
(1) Nigrostriatal dopaminergic functioning, as assessed with the NM-MRI
contrast-to-noise ratio (CNR) in the substantia nigra (SN). These outcomes will
be compared between CHR-P and HCs.
(2) The relationship between baseline NM-MRI CNR and three-year conversion to a
psychotic disorder in CHR-P individuals. The development of a (diagnosed)
psychotic disorder will be evaluated through a follow-up clinical evaluation of
the participant (in-person or by telephone; this is the preferred method) or by
consulting their treating mental healthcare professional or general
practitioner and/or through data linkage with health records provided by
Statistics Netherlands.
Secondary outcome
Supplementary NM-MRI data from FEP patients and HCs:
ANOVA will be used to examine the difference in NM-MRI CNR in the SN between
CHR-P individuals, FEP, and HCs. For this analysis, FEP and additional HC data
will be obtained from previous NM-MRI studies conducted at the Amsterdam UMC.
In these supplementary analyses, we will also explore the relationship between
NM-MRI signal and age, sex, drug/medication use, and psychosis symptom
severity, if sufficient information on these variables is available. Finally,
exploratory voxel-wise analysis of NM-MRI data will be conducted in addition to
the main region of interest analysis.
Background summary
Dopaminergic dysregulation, particularly of the nigrostriatal pathway, is a key
feature of psychotic disorders. Positron emission tomography (PET) studies have
consistently shown elevated striatal dopamine levels, not only in patients with
psychotic disorders but also in individuals at clinical high-risk for psychosis
(CHR-P), especially among those who later develop a psychotic disorder. These
findings suggest that striatal dopamine activity may serve as a predictive
biomarker for identifying CHR-P individuals at greatest risk of transitioning
to psychosis. However, the clinical utility of PET is hindered by its high
cost, lengthy scanning procedures, and reliance on radiotracers.
Neuromelanin-sensitive MRI (NM-MRI) can be used to image neuromelanin deposits
in the substantia nigra (SN), which serve as a proxy for striatal dopamine
activity. NM-MRI offers a non-invasive, rapid, and cost-effective alternative
for assessing dopaminergic dysfunction.
Study objective
This study aims to (i) compare baseline NM-MRI signal between CHR-P individuals
and healthy controls (HCs) and (ii) evaluate whether baseline NM-MRI signal can
differentiate those CHR-P individuals who progress to psychosis within three
years of follow-up from those who do not.
We hypothesize that (Hypothesis 1) at the overall group-level, without
considering which individuals later develop a psychotic disorder, baseline
NM-MRI SN signal will not significantly differ between CHR-P individuals and
HCs. However, we expect that (Hypothesis 2) baseline NM-MRI SN signal will be
elevated in CHR-P individuals who develop a psychotic disorder within three
years, compared to both CHR-P individuals who do not transition to psychosis
and HCs.
Study design
A prospective cohort study. After a baseline assessment, participants are
followed-up after three years through diagnostic assessment (in-person or by
telephone; this is the preferred method) and/or evaluation of medical health
records by contacting the participant*s mental healthcare provider or general
practitioner and/or through data linkage with health records provided by
Statistics Netherlands.
Study burden and risks
The burden associated with this study is moderate, consisting of participants*
time investment, (psychological) interviews and questionnaires, and an
MRI-scan. The risk is negligible.
Subjects complete a baseline screening, which takes approximately 3 hours. The
screening day takes place at the Amsterdam UMC. Eligible participants
subsequently make another visit to the Amsterdam UMC for an MRI-scan.
The MRI-scan is short (max. scanning time 30 min.). We have used the
MRI-scanning sequence in previous research at the Amsterdam UMC with vulnerable
patients like individuals with psychotic disorder and Parkinson*s disease, who
generally tolerate this well.
CHR-P individuals are included in this study due to their elevated risk of
developing a psychotic disorder within a relatively short timeframe, allowing
for a relatively brief follow-up period of three years during which
psychosis-conversion can still be reasonably expected. This would not be
possible in unselected samples, as the large number of participants and long
follow-up required would make the research impractical. Moreover, previously
conducted PET studies with CHR-P individuals support our hypothesis that we
will observe NM-MRI-measured nigrostriatal dopaminergic alterations in those
later transitioning to psychosis.
To assess whether CHR-P participants develop a psychotic disorder, they will
have the option of completing an additional diagnostic evaluation in-person or
via telephone after three years. Alternatively, participants can permit the
research team to access their healthcare information by contacting their mental
health professionals or general practitioner and/or through data linkage with
health records provided by Statistics Netherlands, thus reducing the burden of
follow-up.
The inclusion of HCs is essential for establishing a normative baseline against
which NM-MRI signal in CHR-P individuals can be compared. For our primary
research question, we will recruit HCs who will undergo the same study protocol
as the CHR-P participants. Additionally, we plan to use existing datasets of
HCs for secondary analyses. However, a limitation of this secondary,
supplementary analysis is that these datasets were collected using different
study protocols, which may introduce potential confounding factors. Therefore,
it is crucial to also include a newly recruited sample of HCs to ensure
consistency and reliability in the findings.
Participants may decide to stop participating in the study at any point in
time. They may also decide to withdraw their approval for a subsequent
follow-up assessment or for the consultation of their medical health records at
any point after baseline data collection and prior to data extraction.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Age 16-30 years old.
2. Dutch-speaking.
3. CHR-P only: Meets CHR-P classification criteria (i.e., the presence of
attenuated psychotic symptoms and a reduction in social functioning). Of note,
a CHR-P classification can also be made if a participant has a first-degree
relative with a psychotic disorder, but we will only include CHR-P individuals
if they themselves have experienced (attenuated) psychotic symptoms.
Exclusion criteria
All participants:
1. Current or past (suspected) presence of a psychotic disorder, such as
schizophrenia or other psychotic disorder, bipolar disorder, depressive
disorder with psychotic features.
2. Current or past (suspected) presence of a neurological disorder (e.g.,
Parkinson*s disease, epilepsy), evidence of brain damage, and/or other medical
illness (e.g., diabetes mellitus) that may affect brain function.
3. Intellectual disability (IQ<85).
4. (Non-removable) metal objects in or around the body.
5. In women: pregnancy and/or lactation.
HCs only:
6. HC: Ever in their lifetime met CHR-P criteria or was suspected to have a
psychotic disorder.
7. HC: Has a first-degree relative with a previous or current suspected or
diagnosed psychotic disorder.
8. HC: Current or past (in the past five years) (suspected) presence of any
psychiatric condition, like a major depressive episode, eating disorder,
personality disorder, autism, ADHD, or substance use disorder.
9. HC: Current use of psychotropic drugs. Individuals who have stopped using
the drugs for at least 3 months can participate in the study.
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 | NL88200.018.24 |