Lower baseline levels of the inflammatory marker interleukin-8 (IL-8) in females, but not males, trended toward predicting a better response to ketamine for depression. In 46 depressed patients receiving a single ketamine infusion, changes in IL-8 over time also differed by sex and treatment response: increasing IL-8 was associated with decreasing depression scores in females, while the opposite pattern appeared in males. Other inflammatory markers showed no significant relationships. These preliminary findings suggest that sex differences in IL-8 may help explain how ketamine works and could guide personalized depression treatment.
In people with treatment-resistant depression, a single low-dose ketamine infusion increased glutamate levels in the dorsal anterior cingulate cortex only in those who responded to treatment, and lower pre-treatment glutamate levels predicted greater improvement in depression scores. GABA levels did not change after treatment. Other brain metabolites linked to neuronal health and metabolism also increased. These findings suggest that ketamine's antidepressant effect involves sustained enhancement of glutamate-related neurotransmission and that baseline glutamate levels may help predict who will benefit from ketamine.