Our main objectives are to study whether individual differences in dopamine synthesis capacity are related to individual differences in confidence estimations, and to assess the role of a symptom-related context (i.e. incentives) on confidence…
ID
Source
Brief title
Condition
- Psychiatric disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are: the confidence level in a confidence task,
cognitive flexibility in a reversal task, dopamine synthesis capacity and
neuromelanin contrast ratio on nMRI scan.
Secondary outcome
1. Age
2. Gender
3. Smoking status
4. IQ
5. Alcohol use
6. Depression symptoms
7. Impulsivity
8. Socioeconomic status
Background summary
Gambling disorder (GD) is a behavioral addiction classified in the DSM-5 and is
characterized by persistent and problematic gambling behavior despite negative
consequences and an impairment in decision-making, biased towards risky and
rewarding choices. The metacognitive construct of confidence estimation is
important for decision-making, and importantly, abnormal confidence judgments
could lead to pathological decision-making. Moreover, the role of cognitive
flexibility (i.e. change behavior according to a changing environment) is
disrupted in GD. Research suggests that dopaminergic neurotransmission plays an
important role in the pathology of GD, as well as in confidence estimation. In
this research we will study, for the first time, the link between individual
differences in confidence judgments, dopamine synthesis capacity and cognitive
flexibility.
In-vivo measures of neurotransmission via positron emission tomography (PET)
imaging can provide us with direct insight into individual variability in
dopaminergic neurotransmission. However, this method is not feasible for
routine screening, since it is costly, invasive, time consuming and leads to
radiation exposure. Neuromelanin MRI (nMRI) indirectly measures striatal
dopamine synthesis and therefore has great potential as alternate biomarker to
18F-DOPA PET imaging.
Leveraging 18F-DOPA PET imaging, alongside nMRI, we will test for the first
time the specific role of individual differences of the dopaminergic system in
abnormal confidence estimations within relevant contexts. This study is
expected to result in increased insight into clinically important individual
differences in (abnormal) dopaminergic functioning and its interplay with
confidence abnormalities within various disorder-relevant contexts.
Study objective
Our main objectives are to study whether individual differences in dopamine
synthesis capacity are related to individual differences in confidence
estimations, and to assess the role of a symptom-related context (i.e.
incentives) on confidence estimations. Moreover, our main objective is to
assess the relationship between individual differences in dopamine synthesis
capacity and cognitive flexibility and to assess whether nMRI is a suitable
alternative for the measurement of dopamine synthesis capacity. Our secondary
objective is to study group differences in baseline dopamine synthesis capacity
and nMRI signal.
Study design
We leverage a cross-sectional study design, testing behavioral outcome measures
using questionnaires and computerized tasks, as well as neuroimaging measures
using MRI and PET imaging in 30 GD patients and 30 healthy controls (HC)
Study burden and risks
This study is expected to result in increased insight in important,
clinically-relevant, individual differences in confidence abnormalities and
its* link to individual differences in the dopaminergic system and symptom
severity. This knowledge has the potential to contribute to the development of
treatment alternatives, tailored to the individual and their context. This is
important for the quality of life for the patients and their environment, since
existing therapies do not help all patients to reduce their symptoms.
This study is the first step in a series of studies that has the overall aim to
translate knowledge on neurobiological vulnerabilities in addiction from
preclinical to experimental clinical research, from clinical research to
routine clinical practice and vice versa.
Also, in order to validate the pathophysiological mechanism of nMRI for its
usage as a clinical screening tool to detect abnormalities in dopamine
functioning in the future, it is crucial to acquire 18F-DOPA PET scans for
comparison as a critical validation step. After this, in the future it may be
possible to utilize nMRI scans to screen or select patients for specific
treatment routes in the future, contributing to a more cost-effective, faster
and less invasive screening method.
The risks can be considered negligible: PET imaging contrast liquid has not
been reported to be harmful and MRI is a non-invasive imaging technique.
Therefore, no adverse events are expected. In case a subject feels
uncomfortable in the MRI or PET scanner, it is possible to terminate the
scanning session at any moment without any consequence for the participant. The
risks in our view outweigh the potential benefit for this group.
Meibergdreef 5
Amsterdam 1105 AZ
NL
Meibergdreef 5
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
GD group:
• DSM-5 diagnosis for Gambling Disorder
• No other psychiatric disorders
• Willingness and ability to give written informed consent and willingness and
ability to understand, to participate and to comply with the study requirements
• 20-55 years of age
• Male
HC group:
• No current psychiatric diagnosis or history of addictions
• Willingness and ability to give written informed consent and willingness and
ability to understand, to participate and to comply with the study requirements
• 20-55 years of age
• Male
Exclusion criteria
All groups:
• Current major depressive disorder, bipolar disorder, psychotic disorder,
alcohol or substance dependence, or any cognitive disorder as assessed with the
MINI neurological disorders section
• IQ below 80
• Insufficient command of the Dutch language
• MRI contraindications such as metal implants or claustrophobia
• Use of dopaminergic ADHD medication,
• Endocrinological disorders or regular use of corticosteroids
• History of neurological treatment
• History of epilepsy
• History of autonomic failure
• History of clinically significant hepatic, cardiac, obstructive respiratory,
renal, cerebrovascular, metabolic or pulmonary disease
• Claustrophobia
• Current treatment with tricyclic antidepressant or antipsychotic medication
• Use of other psychotropic medication, or of recreational drugs over a period
of 72 hours prior to each test session, and use of alcohol within the last 24
hours before measurement
• Irregular sleep/wake rhythms (e.g. regular nightshifts)
Exclusion criteria directly related to PET scanning for both groups:
• Participation in a scientific examination where radiation was used, in the
last year
• Positive urine drug screen on the day of the PET scan. Participants will be
tested on cannabis, amphetamine, XTC, cocaine and opiates. Only recent cannabis
use will be accepted
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 | NL72675.091.20 |