To determine if dopaminergic dysfunction and neuroinflammation is increased in patients with TRD compared to patients who respond to antidepressant medication
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- VTA-related BOLD-signals and habenula-VTA connectivity coding for Temporal
Difference Errors in reward/punishment-related learning
- [18F]DPA-714 binding potential in the brain
Secondary outcome
- Changes in VTA-related BOLD-signals and habenula-VTA connectivity coding for
Temporal Difference Errors in reward/punishment-related learning after
treatments (SSRI/SNRI in non-TRD group; and ECT in TRD-group; distinction of
responders and non-responders)
- Serum markers indicative of inflammation and changes thereof after treatment
- Clinical symptoms (HDRS-17, IDS-SR, RRS, SHAPS and TEPS) and changes thereof
after treatment
- Additional MRI-scans (T1 structural, DTI, and resting state) and changes
thereof after treatment
Background summary
Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder with
a lifetime prevalence of 18.7% in the Dutch adult population. Approximately 35%
of MDD patients still do not achieve a response after two courses of adequate
treatment with antidepressant medication. MDD which does not respond to at
least two trials of antidepressant medication is referred to as Treatment
Resistant Depression (TRD). With this study we will investigate two
pathophysiologic mechanisms that could underly MDD and lead to TRD: dysfunction
of the dopaminergic system and neuroinflammation. Both dopaminergic and
anti-inflammatory medication (for example Pramipexole and Celecoxib) show
promising results in trials investigating efficacy of these medication in the
treatment of depressive symptoms. However, it is unknown which MDD patients
suffer from dopaminergic dysfunction and/or neuroinflammation and therefore it
is unknown which patients could benefit from these potential new treatments. We
will investigate dopamine dysfunction via dopamine neuron activity in the
habenula-Ventral Tegmental Area (VTA) network during a pavlovian
reward/punishment-related learning task before and after treatment in MDD
patient with and without TRD. In addition, we will investigate baseline
microglial activation (indicating neuroinflammation) by measuring [18F]DPA-714
binding, and pro- and anti-inflammatory cytokines in peripheral blood before
and after treatment.
Study objective
To determine if dopaminergic dysfunction and neuroinflammation is increased in
patients with TRD compared to patients who respond to antidepressant medication
Study design
A longitudinal case-control study comparing two cohorts: TRD patients versus
non-TRD MDD patients. Patients will receive treatment as usual during the whole
duration of the study. Patients will undergo (f)MRI before the start of
treatment and after discontinuation of ECT (TRD group) or after six weeks of
antidepressant medication (non-TRD MDD group). Both TRD as well as non-TRD
patients will additionally undergo a [18F]DPA-714 PET-scan (as an opt-in) at
baseline and two vena punctures. TRD-patients will be recruited for
MRI-assessments according to a previously approved protocol (NL 48067.901.14)
and are asked to participate with the additional measures of this study
([18F]DPA-714 PET-scan and assessment of inflammation markers)
Study burden and risks
The (f)MRI measurements will require approximately 60 minutes of the patients
time at two time points. The [18F]DPA-714 tracer used for PET/CT-scan has a
favourable safety profile and no observational pharmacological effect due to
the small dosage used in this study. Radiation during PET-scan is within safety
limits. The entire PET-scan procedure including preparation will take
approximately 120-150 minutes. At last blood samples will be drawn at two
timepoints. Risks associated with these measurements are negligible.
Reinier Postlaan 4
Nijmegen 6525GC
NL
Reinier Postlaan 4
Nijmegen 6525GC
NL
Listed location countries
Age
Inclusion criteria
- Males and females between 18-70 years of age
- First or recurrent episode of unipolar major depressive disorder
- Treatment resistance for at least two antidepressants for the TRD group
- Never or only once being treated with antidepressants without effect for the
non-TRD group
Exclusion criteria
- ECT within one year prior to the current course
- Current use of antidepressants, antipsychotics and mood stabilizers
- Use of benzodiazepines within 24 hours before ECT
- Use of anti-inflammatory drugs for more than a week in the past month (for
patients included for PET-scan only)
- Use of immune suppressants (for patients included for PET-scan only)
- Presence of current or past relevant somatic disorder
- Presence of comorbid bipolar disorder, schizophrenia or substance abuse
disorder
- MRI- or PET-related exclusion criteria
- ECT-related exclusion criteria(for TRD group only)
- Low-affinity binder for TSPO (for patients included for PET-scan only)
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 | NL78514.091.21 |