Ketamine, an antidepressant, can alter activity in brain reward areas within two hours of a single infusion, even in people who are not currently depressed. In a study of 37 remitted depression patients, ketamine increased brain responses in the nucleus accumbens and putamen during anticipation and receipt of small rewards, and the level of a ketamine metabolite (2R,6R)-HNK correlated with activation in the ventral tegmental area. These changes occurred without any changes in mood symptoms, suggesting ketamine may improve anhedonia by directly modulating how the brain processes reward feedback.
In depersonalization disorder (DPD), a condition marked by a diminished sense of self and dampened emotional experience, functional MRI revealed that emotional processing is altered. Before treatment, patients showed reduced brain activity in the insula—a region linked to interoceptive awareness and feeling states—along with attenuated autonomic responses to emotional visual stimuli. After pharmacological treatment, clinical improvement in DPD symptoms was associated with increased insula activity. A right ventrolateral prefrontal cortex area also appeared to be involved in top-down inhibition of emotional responses. These findings connect emotional numbing in DPD to disrupted interoception and self-related processes.