What this Trial Is About

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

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