Ketamine alters brain activity in people with major depressive disorder, particularly in the anterior cingulate cortex, dorsolateral prefrontal cortex, and amygdala. Most reviewed studies found that these changes in brain activity correlate with improvements in depressive symptoms, involving the prefrontal cortex, ACC, and cortico-cerebellar circuits. The review notes a lack of longitudinal data on lasting effects and a small number of studies. It calls for more research on ketamine's mechanisms, long-term impact, dose-response optimization, and comparisons with other fast-acting antidepressants.
A systematic review of fifteen neuroimaging studies identifies potential brain-based markers that could predict which patients with major depressive disorder will respond to ketamine. The anterior cingulate cortex and amygdala, along with their connections to other brain regions, frequently predicted better response. Higher fractional anisotropy in the cingulum, larger hippocampus volume, and a higher Glx/glutamate ratio in the dorsomedial prefrontal cortex also correlated with response. Task-based imaging showed that anterior cingulate cortex activity predicted antidepressant response. The review notes limitations due to differences in assessments, follow-up times, ketamine doses, and imaging methods across studies.