Regarding our main objectives, we hypothesize that patients with a gambling disorder show an increase in dopamine synthesis capacity. Moreover, we hypothesize a positive relationship between individual differences in dopamine synthesis capacity and…
ID
Bron
Verkorte titel
Aandoening
Gambling Disorder
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Dopamine synthesis capacity (Ki values)
Achtergrond van het onderzoek
Rationale: 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, cognitive flexibility (i.e. the ability to modify 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 and cognitive flexibility within various disorder-relevant contexts.
Objective:
Our main objectives are to study group differences in baseline dopamine synthesis capacity, and whether individual differences in dopamine synthesis capacity are related to individual differences in confidence estimations and cognitive flexibility, and to assess the role of a symptom-related context (i.e. incentives) on confidence estimations. Moreover, we will assess the relationship between individual differences in dopamine synthesis capacity and cognitive flexibility and test whether nMRI is a suitable alternative for the measurement of dopamine synthesis capacity.
Doel van het onderzoek
Regarding our main objectives, we hypothesize that patients with a gambling disorder show an increase in dopamine synthesis capacity. Moreover, we hypothesize a positive relationship between individual differences in dopamine synthesis capacity and confidence levels, where people with gambling disorder compared to controls show an increase in dopamine synthesis capacity levels as well as higher confidence levels. Furthermore, we expect that confidence abnormalities (i.e. overconfidence) are aggravated in a symptom-related (i.e. high incentive) context in people with gambling disorder. Therefore, we expect an interaction effect between group and context on confidence. Moreover, we expect a negative relationship between dopamine synthesis capacity and cognitive flexibility in both groups, where gamblers show an increase in dopamine synthesis capacity levels and a decrease in cognitive flexibility compared to healthy control subjects. Lastly, we hypothesize that the nMRI signal in the substantia nigra correlates positively with striatal dopamine synthesis capacity on 18F-DOPA PET, making nMRI a suitable alternative to 18-FDOPA PET imaging.
Onderzoeksopzet
One time point (all subjects have one visit only)
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
GD group:
1. DSM-5 diagnosis for Gambling Disorder (To ensure that we are including people who exhibit pathological gambling behaviour, also considered compulsive gambling, we decided to include people who actually received this diagnosis and will by definition exhibit abnormal behaviour).
2. No other psychiatric disorders
3. Willingness and ability to give written informed consent and willingness and ability to understand, to participate and to comply with the study requirements
4. 20-55 years of age
5. Male
HC group:
6. No current psychiatric diagnosis or history of addictions
7. Willingness and ability to give written informed consent and willingness and ability to understand, to participate and to comply with the study requirements
8. 20-55 years of age
9. Male
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
A potential subject who meets any of the following criteria will be excluded from participation in this study:
All groups:
1. Current major depressive disorder, bipolar disorder, psychotic disorder, alcohol or substance dependence, or any cognitive disorder as assessed with the MINI neurological disorders section
2. IQ below 80
3. Insufficient command of the Dutch language
4. MRI contraindications such as metal implants or claustrophobia
5. Use of dopaminergic ADHD medication,
6. Endocrinological disorders or regular use of corticosteroids
7. History of neurological treatment
8. History of epilepsy
9. History of autonomic failure
10. History of clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic or pulmonary disease
11. Claustrophobia
12. 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
13. Irregular sleep/wake rhythms (e.g. regular nightshifts)
14. Use of MAO inhibitor, anaesthetic, anti-depressant or anti-psychotic drugs within the week prior to the start of the study
15. History of prescribed medication within the last month prior to the start of the study
Exclusion criteria directly related to PET scanning for both groups:
1. Participation in a scientific examination where radiation was used, in the last year
2. 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
3. Lactose intolerance (entacapone and carbidopa capsules contain lactose)
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL9359 |
| Ander register | METC Nijmegen Arnhem : 2020-6798 |