One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. Six visits will be scheduled within a year:~V0 (inclusion visit): verification of inclusion and exclusion criteria, information, and consent.~V1 (before randomization - baseline state):~Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.~Neuro-cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating. Part of the tests will be performed during the functional MRI session.~Structural (anatomical) and functional MRI, ASL.~Blood samples.~Randomization and introduction of the new antidepressant will occur immediately after V1. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the assigned treatment will not be changed for 4 weeks (until V3).~V2 (7 days after the beginning of the new antidepressant - 'early response visit'):~o Similar to V1.~V3 (28 days after the beginning of the new antidepressant - 'conventional response visit'):~Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.~Blood samples~V4 (6 months after the beginning of the new antidepressant - 'remission visit'):~Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.~Cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating.~Structural (anatomical) MRI, ASL~Blood samples~V5 (one year after the beginning of the new antidepressant - 'functional remission visit'):~Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.~36 healthy volunteers without a history of neurologic or psychiatric disorder, matched for age, gender, and education will be included. They will perform V0-V2 (without MRI and blood sample at V2). Healthy volunteers will not receive any treatment as part of the research.
This study aims to better understand the mechanisms of action of antidepressants, but also the neural correlates of motivation deficits. One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. The objective will be to predict the therapeutic response to two first-line antidepressants on the basis of an early neurocomputational assessment of motivation. Antidepressant treatment will be administered as monotherapy after randomization between two drugs: escitalopram and vortioxetine. Patients will undergo six visits and follow-up for one year. The investigators will combine computer modeling and functional MRI to identify motivational deficits and elucidate their brain correlates before initiation, after 7 days and after 6 months of treatment. 36 healthy volunteers will also be included to allow comparison with patients with depression. They will not receive any treatment.