Conclusions
depressive symptom reduction, depressed
We present preliminary evidence to support neural complexity measures as biomarkers of rapid and post-rapid effects of ketamine in LL-TRD. Our findings identified ketamine-induced complexity alterations in isolation of depressive symptom reduction. Future work should emphasize the interplay between complexity and properties of oscillations (power and cross-frequency interactions). These limitations notwithstanding, our study is, to our knowledge, the first examination of the effect of ketamine on complexity in a clinically depressed sample. Our findings support the hypothesis that a single sub-anesthetic ketamine infusion has time-varying effects on system-wide contributions to the evoked glutamatergic surge in LL-TRD. Further, changes to complexity were observable outside the time-window previously shown for effects on gamma oscillations. These preliminary results have clinical implications in providing a functional marker of ketamine that is non-linear, amplitude-independent, and represents larger dynamic properties, providing strong advantages over linear measures in highlighting ketamine’s effects. To enhance clinical actionability of complexity as a biomarker, our findings should be replicated in a larger sample with multiple age cohorts and age-matched healthy controls. Conducting a larger study will allow a well-powered multivariate investigation of the physiological properties of ketamine induced MADRS reduction.