Depressive Disorder, Major
Conditions
Keywords
depression, inflammation, anhedonia, psychomotor retardation
Brief summary
A large body of evidence on depression heterogeneity point to an "immunometabolic" subtype characterized by the clustering of immunometabolic dysregulations with atypical behavioral symptoms related to energy homeostasis. Motivational and motor impairments reflected by symptoms of anhedonia and psychomotor retardation in major depression are closely related to alterations in energy homeostasis, are associated with increased inflammation, and may be a direct consequence of the impact of inflammatory cytokines on the dopamine system in the brain. In the proposed project, the investigators will examine the effect of dopamine stimulation on motivation and motor function in patients with major depression and healthy controls and the role of inflammation using a double-blind, randomized, placebo-controlled, cross-over design. If successful, this study would provide crucial evidence that pharmacologic strategies that increase dopamine may effectively treat inflammation-related symptoms of anhedonia and psychomotor retardation in major depression.
Interventions
DRUGL-dopa/Carbidopa
Patients and healthy controls will receive one time administration of L-dopa/Carbidopa (100/25 mg).
DRUGPlacebo
Patients and healthy controls will receive one time administration of Placebo.
Sponsors
Charite University, Berlin, Germany
Prof. Dr. Stefan M. Gold
Prof. Dr. Soyoung Q Park
Dr. Ulrike Grittner
Motognosis GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
For patients with major depressive disorder: * diagnosis of major depressive disorder according to DSM-5 * free of antidepressant medication For healthy participants: * C-reactive protein (CRP): ≤ 1 mg/l * free of antidepressant medication * free of any current psychiatric disorder
Exclusion criteria
* diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, dementia, and current/past alcohol or drug dependence * central nervous system diseases * neurological diseases * suspicious undiagnosed skin lesions or a history of melanoma * narrow-angle or wide-angle glaucoma * bronchial asthma * history of peptic ulcer disease * history of seizures * any severe somatic disease * current infections or chronic inflammatory diseases (e.g., rheumatic diseases, inflammatory bowel disease) * pregnancy / breast-feeding * class 3 obesity (body mass index of 40 or higher) * Use of medication containing reserpine (certain antihypertensive agents), tricyclic antidepressants, bon-selective monoamine oxidase (MAO) inhibitors, antiparkinsonian drugs, sympathomimetic drugs, tetrabenazine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in response bias (logb) after L-dopa/Carbidopa compared to placebo in the Probabilistic Reward Task (PRT). | All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo. | The PRT, which uses a signal detection paradigm, will be used to measure response bias, the propensity to select the more rewarded response ("rich"). |
| The change in mean gait speed [m/s] after L-dopa/Carbidopa compared to placebo in the dual task. | All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo. | The dual task mean gait speed will be measured with six wearable inertial measurement units. In this dual task, participants walk at their usual speed while naming as many animals as possible. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change in choice of the hard task after L-dopa/Carbidopa compared to placebo in the Effort Expenditure for Rewards Task (EEfRT). | All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo. | The EEfRT, a widely used, multi-trial task in which participants are given an opportunity on each trial to choose between two different task difficulty levels in order to obtain monetary rewards, will be used as an objective measure of reward motivation. The EEfRT is reported as the percent of high effort (hard) trials selected. A higher percentage reflects higher motivation for effort expenditure. |
| The change in movement time [ms] after L-dopa/Carbidopa compared to placebo in the Reaction Time Task (RTI). | All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo. | The RTI from the Cambridge Neuropsychological Test Automated Battery (CANTAB) will be used to assess movement time, which is the time taken to touch the stimulus on the computer screen after the press pad had been released. |
| The change in risk propensity after L-dopa/Carbidopa compared to placebo in the Risky Decision-Making Task. | All participants will be tested on two separate experimental sessions separated by an interval of 48 hours, after L-dopa/Carbidopa or placebo. | In the Risky Decision-Making Task, participants have to make choices between a risky option and a safe alternative. Risk Propensity, the proportion of risk-taking trials, will be a secondary outcome. |
| Response bias (logb) in the PRT | After administration of placebo on Day 2 or Day 3. | — |
| Mean gait speed [m/s] in the dual task | After administration of placebo on Day 2 or Day 3. | — |
| Choice of the hard task in the EEfRT | After administration of placebo on Day 2 or Day 3. | — |
| Movement time [ms] in the RTI | After administration of placebo on Day 2 or Day 3. | — |
Countries
Germany
Contacts
CONTACTWoo Ri Chae, MD MSc
PRINCIPAL_INVESTIGATORWoo Ri Chae, MD MSc
Charite University, Berlin, Germany
Outcome results
None listed