Prediction of the Therapeutic Response in Depression Based on Neuro-computational Modeling Assessment of Motivation

Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation

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.

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.

Patients with major depressive disorder

Inclusion Criteria:

• Meeting DSM-5 criteria for major depressive disorder (single or recurrent episodes)
• With a MADRS score >= 24
• For which a new line of treatment is needed
• No previous line of antidepressant for this episode or wash-out long-enough to avoid carry-over effects
• Valid health care insurance

Exclusion Criteria:

• Treatment-resistant depression (defined as insufficient response despite at least 2 trials of antidepressant prescribed at adequate dose and duration)
• Subjects with a trial of escitalopram and/or vortioxetine for the current episode, or with contra-indication to one of these two drugs
• Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
• Subject with a history of neurological disorder: parkinson's disease, dementia
• Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
• Pregnant or breastfeeding women
• involuntary hospitalisation and legal protection measures

Healthy volunteers

Inclusion Criteria:

- Valid health care insurance

Exclusion Criteria:

• Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
• Subject with a history of neurological disorder: parkinson's disease, dementia
• Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
• Pregnant or breastfeeding women