Biomarkers of ketamine's antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology. (May 2021)

• Record Type: Journal Article
• Authors: Alario, Alexandra A.; Niciu, Mark J.
• Is Part Of: Chronic stress. Volume 5(2021)
• Publication Date: 2021-05
• Subjects: ketamine -- glutamate -- major depressive disorder -- treatment resistant depression -- genetics -- functional magnetic resonance imaging -- electroencephalography -- magnetoencephalography; Stress (Psychology) -- Periodicals; Stress (Physiology) -- Periodicals; Stress (Physiology); Stress, Psychological -- therapy; Stress, Physiological; Mental Disorders -- etiology; Electronic journals; Periodicals; Periodicals; 616.89
• DOI: 10.1177/24705470211014210
• Languages: English
• ISSNs: 2470-5470

Abstract

Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.