Neurobiological biomarkers of response to ketamine.

Psychiatry is moving toward early identification and intervention to reduce the burden and duration of severe mental illnesses. The rapid-acting antidepressant ketamine has transformed understanding of antidepressant response and expanded treatment options for treatment-resistant depression. Efforts to characterize biomarkers of ketamine response aim to identify biologically enriched subgroups more likely to benefit. This chapter reviews translational biomarkers from imaging, electrophysiology, sleep, circadian rhythms, HPA axis function, metabolism, immune, (epi)genetic, and neurotrophic systems. Ketamine's properties may model new rapid-acting treatments. However, most studies focus on acute effects, and no biomarkers are ready for clinical use.

Study at a glance

Abstract

As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatly expanded the pharmacologic armamentarium for treatment-resistant depression. Efforts to characterize biomarkers of ketamine response support a growing emphasis on early identification, which would allow clinicians to identify biologically enriched subgroups with treatment-resistant depression who are more likely to benefit from ketamine therapy. This chapter presents a broad overview of a range of translational biomarkers, including those drawn from imaging and electrophysiological studies, sleep and circadian rhythms, and HPA axis/endocrine function as well as metabolic, immune, (epi)genetic, and neurotrophic biomarkers related to ketamine response. Ketamine's unique, rapid-acting properties may serve as a model to explore a whole new class of novel rapid-acting treatments with the potential to revolutionize drug development and discovery. However, it should be noted that although several of the biomarkers reviewed here provide promising insights into ketamine's mechanism of action, most studies have focused on acute rather than longer-term antidepressant effects and, at present, none of the biomarkers are ready for clinical use.