Study of the Neural Circuits Underlying the Negative Emotional Bias of Depressive Disorders and Their Response to Ketamine

Comparison of the negative emotional bias measured by an image perception task (valence) before vs. after esketamine treatment [Baseline/1 month of treatment].

The blood oxygenation level is measured thanks to the blood-oxygen-level dependent (BOLD) signal obtained at the fMRI task. This signal will be recorded in depressed patients and control subjects at baseline (Day 0) and at the end-of-study visit (6 weeks after Day 0) only for patients.

The basolateral amygdala/ventral hippocampus and basolateral amygdala/nucleus accumbens (BLA/vHPC, and BLA/Nac) functional connectivity obtained at the resting-state fMRI will be recorded in depressed patients and control subjects at baseline (Day 0) and at the end-of-study visit (6 weeks) only for patients

The gray matter integrity obtained at the T1 (longitudinal relaxation time) MRI will be recorded in depressed patients and control subjects at baseline (Day 0) and at the end-of-study visit (6 weeks) only for patients

The white matter integrity obtained at the diffusion imaging will be recorded in depressed patients and control subjects at baseline (Day 0) and at the end-of-study visit (6 weeks) only for patients.

The depression severity will be assessed by the investigator with the Montgomery-Åsberg Depression Rating Scale (MADRS). The depression severity score will be then calculated. Score range (min - max): 0 - 60. Higher score relates to high depression severity. The questionnaire will be realized in depressed patients and control subjects at baseline (day 0) and throughout the study only for patients.

The task used to calculate the emotional bias score involves presenting images to patients and control subjects, each of which has normative ratings for valence and arousal. The objective is to present ten images per block (9 blocks repeated 3 times) allowing for an evaluation of high, neutral or low emotional valence as well as high, low or medium arousal levels. The results for each participant will be summarized in a contingency table. The total emotional bias score (accuracy score) will be calculated at baseline (Day 0) for patients and control subjects and at the end-of-study (Week 6) only for patients.

The suicidality will be assessed by the investigator with the Columbia-Suicide Severity Rating Scale. The suicidality score will be then calculated. The suicidal ideation section is rated on a scale from 1 to 5, with increasing severity from passive thoughts of death to active suicidal intent with a plan. The Suicidal Behavior section assesses past suicide attempts or preparation, with a focus on the presence and severity of suicidal actions. There is no overall score in C-SSRS but the investigator will evaluate the individual's risk level at baseline (Day 0) and at the and-of-study visit (Week 6) in depressed patients.

The Snaith-Hamilton Pleasure Scale (SHAPS) is used to measure the anhedonia. The total score ranges from 0 to 14 and is proportional to the degree of anhedonia. The questionnaire will be realized in depressed patients at baseline (day 0) and at the end-of-study visit in depressed patients.

The Beck anxiety scale consists of 21 self-reported items used to assess the intensity of physical and cognitive anxiety symptoms during the past week. The total score ranges from 0 to 63: minimal anxiety levels (0-7), mild anxiety (8-15), moderate anxiety (16-25), and severe anxiety (26-63). The questionnaire will be realized in depressed patients at baseline (day 0) and at the end-of-study visit in depressed patients.

The MAThyS is a visual analogic scale consisting of 20 items. Score is determined line-by-line and varies from 0 to 10 for each line (centimeters). A score of 0 indicates an inhibition of the state evaluated by the item. A score of 5 indicates no change from the patient's usual state. A score of 10 corresponds to excitation for the evaluated state. An overall score between 0 and 200 is thus obtained. The questionnaire will be realized in depressed patients and control subjects at baseline (day 0) and throughout the study only for patients.

The Young Mania Rating Scale (YMRS) has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. The total score ranges from 0 to 44 and is proportional to the degree of mania. The questionnaire will be assessed by the investigator at baseline (Day 0) in patients and control subjects as well as throughout the study for patients.

The Clinical Global Impression scale (CGI) will be used by the physician to assess, with a 7-point scale, the depression severity of the patient's clinical condition, as well as, the improvement in the patient's clinical condition following treatment. Each of these scales is rated from 0 to 7. A score of 7 indicates the maximum level of severity of the patient's depressive state, and in the other case, a score of 7 indicates the maximum worsening of the patient's condition. The questionnaire will be assessed by the physician at baseline (Day 0) in patients and control subjects as well as throughout the study for patients.

Patients complete the Psychological and Physical Pain Visual Analog Scale (PPP-VAS) at baseline (Day 0) and at the end-of-study visit (Week 6). The PPP-VAS consists of six dimensions presented as paper-based visual analog scales, which patients must annotate from 0 to 10, measuring current, mean and worst pain over the last 15 days, for physical then psychological pain (0 corresponding to no pain and 10 corresponding to the maximum imaginable pain).

The Clinician Administered Dissociative States Scale (CADSS) is administered by a physician to patients at Day 7, Week 2, Week 3, Week 4 and Week 5. This scale consists of 23 items, each rated from 0 to 4, with 0 indicating the absence of symptoms and 4 indicating the maximum severity of the symptom. The total score ranges from 0 (complete absence of dissociative symptoms) to a maximum score of 92 (highest level of dissociation).

The cognitive complaints in Bipolar disorder Rating Assessment (COBRA) consists of 16 items that are rated using a 4-point scale, 0 = never, 1 = sometimes, 2 = often, and 3 = always. The COBRA total score is obtained when the scores of each item are added up (min-max score range: 0 - 48). The higher the score, the more subjective complaints. The COBRA is a self-questionnaire. Patients and control subjects will complete this questionnaire at baseline (Day 0) and patients will also complete it at the end-of-study visit (Week 6).

The Starkstein Apathy Scale is a self-questionnaire that consists of 14 items that are rated using a 4-point scale (from 0 to 3). The total score is is obtained when scores of each item are added up (min-max score range: 0 - 42). The highest score is associated with the most significant apathy. Patients included in the current study will complete this questionnaire at baseline (Day 0) and at the end-of-study visit (Week 6).

Blood samples are collected from patients at baseline (Day 0), at the second week and at the end-of-study visit (Week 6), as well as from healthy subjects at baseline (Day 0). These blood samples will allow for the analysis of immune-inflammatory markers as well as the analysis of RNA editing markers.