Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

• Published in: Chronic Stress Vol. 5; p. 24705470211014210
• Main Authors: Alario, Alexandra A., Niciu, Mark J.
• Format: Book Review Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 2021; Sage Publications Ltd; SAGE Publishing
• Subjects: Antidepressants; Biomarkers; Electroconvulsive therapy; Ketamine; Review; electroencephalography; genetics; major depressive disorder; ketamine; treatment resistant depression; magnetoencephalography; glutamate; functional magnetic resonance imaging
• ISSN: 2470-5470; 2470-5470
• DOI: 10.1177/24705470211014210

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.