The effect of Comorbidity with Alcohol use disorder on the Dopaminergic and Serotonergic system

Substance use disorders (SUD) cause long-term negative consequences for health,
social functioning, and society. However, current evidence-based treatments for
SUD are only moderately effective. This is, at least partly, due to the large
clinical heterogeneity related to frequent psychiatric comorbidities. A better
understanding of the differences and overlap in neurobiology of these
comorbidities is necessary, as this can provide markers for personalized
(pharmacological) treatment.

The main study objective is to investigate differences in the dopaminergic and
serotonergic systems between adults with alcohol use disorder (AUD) and
co-occurring internalizing (e.g. depression) or externalizing (e.g. ADHD)
mental disorders; and relate this to drug use motives.

Specifically, we will investigate differences between adults with AUD and
internalizing or externalizing mental disorders and healthy controls in:
- Brain activity and behavioural measurements during a reinforcement learning
task in the MRI scanner (serotoninergic and dopaminergic system proxies)
- Whole brain rsFC of the raphe nuclei (serotoninergic system proxy)
- Whole brain rsFC of the substantia nigra (dopaminergic system proxy)
- Clinical characteristics, such as drug use motives

The secondary study objectives are to investigate differences between adults
with AUD and internalizing or externalizing mental disorders and healthy
controls in:
- Brain anatomy and resting state brain activity.
o Whole brain analyses
o Region of interest approach for the dopaminergic and serotonergic related
brain areas (serotoninergic and dopaminergic system proxies)
- Symptom severity of AUD, internalizing and externalizing mental disorders on
the all brain imaging measurements
- Serotonin and testosterone hair concentrations and their relation to all
brain imaging measurements and symptom severity of AUD, internalizing and
externalizing mental disorders

2.2 Part 2 - Dopamine
The primary study objectives are to investigate differences between adults with
AUD and internalizing or externalizing mental disorders in:
- Dopamine transporter (DAT) availability measured with 18F-FE-PE2I

The secondary study objectives are to investigate the:
- DAT availability in relation to whole brain rsFC of the substantia nigra
(dopaminergic system proxy) measure as explained in part 1
- DAT availability in relation to symptom severity of AUD, internalizing and
externalizing mental disorders and drug use motives measures as explained in
part 1

This study will be a one-time assessment consisting 2 parts: (1) a multitude of
questionnaires, tasks, a single interview and magnetic resonance imaging (MRI),
and (2) dopamine transporter positron emission tomography (PET)

Participants have no direct benefit from partaking in this study. However, they
provide critical information about the pathophysiology in comorbid AUD, which
could lead to new insights for treatment options in the future. Additionally,
the diagnostic interview (MINI) can lead to new insights in the psychological
health of the participants, which may improve their treatment plan and health.

Possible sources of discomfort to participants include the time spent on the
study, the behavioural tasks, and neuroimaging (fMRI and PET). Psychiatric
assessments and questionnaires may cause some distress as participants are
asked to reflect on (presence of) psychiatric symptoms. However, the batteries
used is well-validated and often used to assess these outcomes (see chapter 8.3
for more details). To reduce the existing risks of the MRI measurement, we only
include participants for whom the risk is small (i.e. normal inclusion criteria
for MRI scanning; no metal in body, no medical devices, not pregnant). Please
note that this is NOT an intervention study. However, as we make us the
specific PET tracer 18F-FE-PE2I DAT PET for assessment purposes
(neuro-imaging), we carefully defined exclusion criteria to minimize risks.
Correspondence with the radiology department will happen in case of any
participant specific doubts. The nuclear radiation is of the same order of
magnitude as the annual background radiation in various parts of the world, see
also K6 radiation ethics form for more details.To administer the PET tracers, a
venous drip will be placed by trained personnel before scanning and will be
removed directly after PET imaging is completed. Participants are made aware of
this during recruitment.

Considering these exclusion criteria we do not expect (S)AE side effects. An
additional risk exists concerning incidental findings from MRI or PET.
Furthermore, special care is take when the participant is being made
comfortable on the scanner bed (MRI and PET) to evenly distribute support of
the head to avoid stiffness of local pressure, in order to avoid excessive
motion. In addition, it will be made clear to participants that they are able
to request a break at any time during the study