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

NCT06630065 | Recruiting

• 1 other identifier: D22-P015
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 4.In depressed patients, early improvement of emotional bias (after a single administration) is predictive of response to treatment at 4 weeks.
5. 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. 6.Depressed subjects have different immunoinflammatory and RNA editing patterns different from control subjects.
7. 7.In depressed patients, clinical improvement correlates with normalization of patients; inflammatory profile and certain mRNA editing
8. 8.Some clinical features of major depressive disorder are associated with greater negative emotional bias significant

Conditions

Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Significant difference in negative emotional bias measured by an image perception task before vs. after esketamine treatment

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

  1 month

Secondary Outcomes (17)

• 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

  patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)

• Measure of the functional connectivity obtained at the resting-state functional magnetic resonance imaging (fMRI) in depressed patients and in control subjects

  patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)

• Measure of the gray matter integrity obtained at the High-resolution anatomical (T1) magnetic resonance imaging (MRI) in depressed patients and in control subjects

  Patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)

• Measure of the white matter integrity obtained at the diffusion imaging in depressed patients and in control subjects

  Patients: at baseline (Day 0) and at the end-of study visit (6 weeks); control subjects: at baseline (Day 0)

• Measure of the depression severity in patients and control subjects thanks to the Montgomery-Åsberg Depression Rating Scale score

  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)

Study Arms (2)

Patients

EXPERIMENTAL

Depressed patients treated with Esketamin

Behavioral: fMRI with emotional task and pupillometry; Behavioral: Behavioral task with emotional facial expressions; Genetic: Biological investigation

healthy volunteers

OTHER

Healthy subjects

Behavioral: fMRI with emotional task and pupillometry; Behavioral: Behavioral task with emotional facial expressions; Genetic: Biological investigation

Interventions

fMRI with emotional task and pupillometry BEHAVIORAL

Anatomical and functional magnetic resonance imaging (fMRI) imaging sequences with pupillometry (\~90 min) A functional sequence - Task (\~20min): * Emotional task in fMRI: Instructions: simply look images, then evaluate the emotions triggered at the end of each block; rating on a valence and intensity scale and intensity (arousal) scale. * Experimental conditions: positive, negative and neutral * Paradigm: block validated image banks: IAPS, GAPED, EMOPICS, OASIS, etc. Pupillometry: In order to collect objective data on emotional bias, we will use pupillometry (or eye-tracking) during functional MRI sequences.

Patients; healthy volunteers

Behavioral task with emotional facial expressions BEHAVIORAL

Description of the recognized emotion joy - sadness. Test to assess the hedonic value of an olfactory stimulus (10 min)

Patients; healthy volunteers

Biological investigation GENETIC

Standard biological assessment, immuno-inflammatory profile and the association of 8 mRNA editing variants

Patients; healthy volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead

Study Sites (1)

- Groupe hospitalo-universitaire Paris Psychiatrie et Neurosciences

Paris, Paris, 75014, France

RECRUITING

MeSH Terms

Conditions

Depressive Disorder

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Chantal Henry, Pr

  GHU Paris Psychiatry & Neurosciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chantal Henry, Pr

CONTACT

0145658452; ch.henry@ghu-paris.fr

Khaoussou Sylla, Dr

CONTACT

0145657728; k.sylla@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: October 8, 2024
• Study Start: March 13, 2023
• Primary Completion: April 13, 2026
• Study Completion: April 13, 2026
• Last Updated: October 8, 2024

Record last verified: 2024-10

Locations

FR (1)