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

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

Conditions

• Depressive Disorder

Interventions

BEHAVIORAL

fMRI with emotional task and pupillometry

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.

BEHAVIORAL

Behavioral task with emotional facial expressions

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

GENETIC

Biological investigation

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

Sponsors & Collaborators

• Centre Hospitalier St Anne

  lead OTHER

Principal Investigators

• Chantal Henry, Pr · GHU Paris Psychiatry & Neurosciences

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-03-13

Primary Completion

2026-04-13

Completion

2026-04-13

Countries

• France

Study Locations