Hippocampal volume and the rapid antidepressant effect of ketamine

Accumulating evidence underscores the utility of ketamine in treating severely treatment-resistant depressed patients. We investigated the relationship between the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker of antidepressant treatment outcome. We gave 16 medication-free, major depressive disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5 mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h post-treatment, with the Montgomery-Åsberg Depression Rating Scale (MADRS). Prior to treatment, patients underwent magnetic resonance imaging (MRI) to estimate their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS (post- minus pre-treatment) was significantly correlated with the pre-treatment volumes of the left hippocampus (r = 0.66; p = 0.01), but not the right hippocampus (r = 0.49; p = 0.09). The correlation between delta MADRS and the left hippocampus remained high (r > 0.6; p = 0.13), after controlling for several demographic and clinical variables, although the p value increased due to the reduced degree of freedom (df = 5). Ketamine exerts enhanced antidepressant effects in patients with a relatively smaller hippocampus, a patient population that has been repeatedly shown to be refractory to traditional antidepressants.