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.
Before serial ketamine infusion, brain structure, function, and connectivity measures predicted how much depressive symptoms changed afterward. In 60 patients with depression, machine learning models using pretreatment MRI scans explained 19% of variance in core mood and anhedonia symptoms, 27% in a depression subscale, and 1% in rumination reflection. Greater connectivity in the right medial prefrontal cortex, anterior cingulate, and posterior insula, along with lower kurtosis of a white-matter tract, predicted larger symptom reductions. Connectivity of the left posterior cingulate, left insula, and right superior parietal lobule predicted changes in rumination. These findings suggest that anterior default mode network and posterior insula connectivity may serve as biomarkers for antidepressant response.