Dopamine Modulation of Motivation and Motor Function in Major Depression & Inflammation

Effects of Pharmacological Dopamine Modulation on Motivation and Motor Function in Major Depression Characterized by Low-grade Inflammation.

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.

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.