Suicidal ideation in treatment-resistant major depression is linked to activity in the infralimbic cortex (Brodmann area 25). In 19 medication-free patients, higher baseline metabolism in this brain region correlated with more severe suicidal thoughts, but not with overall mood. A single ketamine infusion (0.5 mg/kg) reduced both suicidal ideation and metabolism in the infralimbic cortex, and the degree of metabolic decrease matched the degree of symptom improvement. Other brain areas examined—the amygdala and subgenual anterior cingulate cortex—showed no significant association with suicidal ideation or depression. The infralimbic cortex may be a specific neural substrate for suicidal thinking, distinct from general mood.
A single low-dose infusion of the anesthetic ketamine produces rapid antidepressant effects in people with treatment-resistant major depressive disorder. In this trial, depressed individuals with a family history of alcohol use disorder showed a longer-lasting antidepressant response to ketamine compared to those without such a family history. Adding the drug riluzole did not extend or enhance ketamine's antidepressant durability. The findings suggest that family history of alcohol use disorder may predict a more durable ketamine response, which should be accounted for in future ketamine depression studies.
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.