Effects of Pharmacological Dopamine Modulation on Motivation and Motor Function in Major Depression Characterized by Low-grade Inflammation.
Overview
- Phase
- Not Applicable
- Intervention
- L-dopa/Carbidopa
- Conditions
- Depressive Disorder, Major
- Sponsor
- Charite University, Berlin, Germany
- Enrollment
- 165
- Locations
- 1
- Primary Endpoint
- The change in response bias (logb) after L-dopa/Carbidopa compared to placebo in the Probabilistic Reward Task (PRT).
- Status
- Recruiting
- Last Updated
- last month
Overview
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.
Investigators
Woo Ri Chae, MD
Principal Investigator
Charite University, Berlin, Germany
Eligibility Criteria
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)
Arms & Interventions
L-dopa/Carbidopa followed by placebo
Participants will receive first L-dopa/Carbidopa (100/25 mg), and then placebo.
Intervention: L-dopa/Carbidopa
L-dopa/Carbidopa followed by placebo
Participants will receive first L-dopa/Carbidopa (100/25 mg), and then placebo.
Intervention: Placebo
Placebo followed by L-dopa/Carbidopa
Participants will receive first placebo, and then L-dopa/Carbidopa (100/25 mg).
Intervention: L-dopa/Carbidopa
Placebo followed by L-dopa/Carbidopa
Participants will receive first placebo, and then L-dopa/Carbidopa (100/25 mg).
Intervention: Placebo
Outcomes
Primary Outcomes
The change in response bias (logb) after L-dopa/Carbidopa compared to placebo in the Probabilistic Reward Task (PRT).
Time Frame: 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.
Time Frame: 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 Outcomes
- 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.)
- Response bias (logb) in the PRT(After administration of placebo on Day 2 or Day 3.)
- 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 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.)
- Movement time [ms] in the RTI(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.)