Clinical trial NCT06630065: Study of the Neural Circuits Underlying the Negative Emotional Bias of Depressive Disorders and Their Response to Ketamine
Official title: Translational Study of the Neural Circuits Underlying the Negative Emotional Bias of Depressive Disorders and Their Response to Ketamine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Depressive Disorder
Lead sponsor: Centre Hospitalier St Anne
Sponsor class: OTHER
First posted: 2024-10-08
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Major depressive disorder is the leading cause of disability worldwide, affecting up to 300 million people each year, and one in five people will experience depression at least once in their lives. Emotional bias is an essential component of characterized depressive episodes, leading depressed patients to attribute a more negative valence to emotional stimuli.

On the basis of recent and robust neuroscientific data revisiting the role of the cerebral amygdala as an essential essential structure for encoding the negative and positive valences and of emotional stimuli, the team has shown in mice that a depressive phenotype induced by a chronic administration of corticosterone, a well-known model of depression, is associated with a change in hedonic value allocation, i.e. pleasant odors become less pleasant, and aversive odors become even more unpleasant, mimicking what happens in humans (identical data in humans).

It assumes that:

1. There is a negative emotional bias in depressed patients compared with control subjects, evidenced by the assignment of more negative valences when viewing images.
2. In depressed subjects, compared with controls subjects, there is greater activation of the basolateral amygdala/ventral hippocampus pathway (the level of imaging resolution of imaging does not allow to study the basolateral amygdala/central amygdala pathway in humans) and less of the basolateral amygdala/nucleus accumbens pathway.
3. In depressed subjects, improvement in negative emotional bias correlated with a good response after after 4 weeks of treatment with esketamine (Spravato) measured by a 50% reduction in the Montgomery-Åsberg Depression Rating Scale.
4. In depressed patients, early improvement of emotional bias (after a single administration) is predictive of response to treatment at 4 weeks.
5. In depressed patients with a good response to a single 4-weeks course of esketamine (Spravato), a normalization of activation of basolateral amygdala/ventral hippocampus and basolateral amygdala/nucleus accumbens pathways is observed.
6. Depressed subjects have different immunoinflammatory and RNA editing patterns different from control subjects.
7. In depressed patients, clinical improvement correlates with normalization of patients; inflammatory profile and certain mRNA editing
8. Some clinical features of major depressive disorder are associated with greater negative emotional bias significant


Eligibility criteria: Inclusion Criteria:

Patient inclusion criteria :

* Age over 18
* Patient hospitalized or consulting at GHU Paris Psychiatrie et Neurosciences
* Patient with EDC (unipolar or bipolar) diagnosed according to the DSM-5 CRITERIA
* With MADRS score \> 20
* For whom a course of esketamine has been decided by the psychiatrist of the patient
* Patient having given written informed consent
* Patient covered by a social security plan

Inclusion criteria for control subjects :

* Over 18 years old
* No EDC assessed by MADRS \< 8

Exclusion Criteria:

Patient non-inclusion criteria:

* Psychiatric comorbidities: schizophrenic disorder or schizoaffective disorder, history of recreational use of ketamine
* Protected adults, persons under legal protection
* Contraindications to MRI, including refusal to be informed of the discovery of a clinically significant abnormality on MRI
* Pregnant or breast-feeding women
* Usual contraindications to esketamine :

  * Neurological comorbidity: epilepsy, neurodegenerative disease, cerebrovascular disease with recent history (\< 3 months) of stroke or ischemic attack or transient ischemic attack
  * Cardiological co-morbidity: vascular aneurysm, ischemic heart disease with acute elements or stent within the previous 12 months, uncontrolled hypertension, heart failure, rhythm or conduction disorders on ECG
  * History of cirrhosis (or ALAT, ASAT or bilirubin greater than 2 N)
  * Severe chronic respiratory insufficiency

Exclusion criteria for control subjects:

* MADRS \<8
* Contraindications to MRI, including refusal to be informed of a clinically significant clinically significant abnormality on MRI

Primary outcomes:
measure: Significant difference in negative emotional bias measured by an image perception task before vs. after esketamine treatment
timeFrame: 1 month
Secondary outcomes:
measure: Measure of the blood oxygenation level with the Blood-Oxygen-Level Dependent (BOLD) signal obtained at the functional magnetic resonance imaging (fMRI) task in depressed patients and in control subjects
timeFrame: patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)
measure: Measure of the functional connectivity obtained at the resting-state functional magnetic resonance imaging (fMRI) in depressed patients and in control subjects
timeFrame: patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)
measure: Measure of the gray matter integrity obtained at the High-resolution anatomical (T1) magnetic resonance imaging (MRI) in depressed patients and in control subjects
timeFrame: Patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)
measure: Measure of the white matter integrity obtained at the diffusion imaging in depressed patients and in control subjects
timeFrame: Patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)
measure: Measure of the depression severity in patients and control subjects thanks to the Montgomery-Åsberg Depression Rating Scale score
timeFrame: Patients: at baseline (Day 0), Day 7, Week 2 (2 times), Week 3 (2 times), Week 4 (2 times), Week 5 (2 times) and at the end-of-study visit (Week 6); control subjects: at baseline (Day 0)
measure: Assessment of the emotional bias measured by an image perception task
timeFrame: Patients: at baseline (Day 0) and at the end-of-study visit (Week 6); control subjects: at baseline (Day 0)
measure: Measure of the suicidality score in depressed patients thanks to the Columbia-Suicide Severity Rating Scale
timeFrame: At baseline (Day 0) and at the end-of-study visit (Week 6)
measure: Measure of anhedonia score in depressed patients thanks to the Snaith-Hamilton Pleasure Scale
timeFrame: At baseline (Day 0) and at the end-of-study visit (Week 6)
measure: Measure of the anxiety score in depressed patients thanks to the Beck anxiety scale
timeFrame: At baseline (Day 0) and at the end-of-study visit (Week 6)
measure: Measure of the emotional reactivity in depressed patients and control subjects thanks to the Multidimensional Assessment of Thymic States scale
timeFrame: Patients: at baseline (Day 0), Day 7, Week 2 (2 times), Week 3 (2 times), Week 4 (2 times), Week 5 (2 times) and at the end-of-study visit (Week 6); control subjects: at baseline (Day 0).
measure: Measure of the mania score in depressed patients and control subjects thanks to the Young Mania Rating Scale
timeFrame: Patients: at baseline (Day 0), Day 7, Week 2 (2 times), Week 3 (2 times), Week 4 (2 times), Week 5 (2 times) and at the end-of-study visit (Week 6); control subjects: at baseline (Day 0)
measure: Assessment of the severity and improvement of the clinical condition using the Clinical Global Impression Severity scale
timeFrame: Patients: at baseline (Day 0), Day 7, Week 2 (2 times), Week 3 (2 times), Week 4 (2 times), Week 5 (2 times) and at the end-of-study visit (Week 6); control subjects: at baseline (Day 0)
measure: Assessment of the moral pain in depressed patients with the Psychological and Physical Pain Visual Analog Scale (PPP-VAS)
timeFrame: At baseline (Day 0) and at the end-of-study visit (Week 6)
measure: Assessment of the present-state dissociative symptoms score in depressed patients with the Clinician Administered Dissociative States Scale (CADSS)
timeFrame: At Day 7, Week 2 (2 times), Week 3 (2 times), Week 4 (2 times) and at Week 5 (2 times)
measure: Measure of the cognitive complaints score with the Cognitive complaints in Bipolar disorder Rating Assessment (COBRA)
timeFrame: Patients: at baseline (Day 0) and at the end-of-study visit (Week 6); control subjects: at baseline (Day 0)
measure: Assessment of the apathy score with the Starkstein Apathy Scale
timeFrame: At baseline (Day 0) and at the end-of-study visit (Week 6)
measure: Analysis of immune-inflammatory markers and RNA editing markers in patients and control subjects
timeFrame: Patients: at baseline (Day 0), Week 2, at the end-of-study visit (Week 10); control subjects: at baseline (Day 0)
Other outcomes:
Locations:
city: Paris
country: France
facility: - Groupe hospitalo-universitaire Paris Psychiatrie et Neurosciences
Study officials:
affiliation: GHU Paris Psychiatry & Neurosciences
name: Chantal Henry, Pr
role: PRINCIPAL_INVESTIGATOR
References: