AUTHOR=Smith Donald F. TITLE=Quest for Biomarkers of Treatment-Resistant Depression: Shifting the Paradigm Toward Risk JOURNAL=Frontiers in Psychiatry VOLUME=Volume 4 - 2013 YEAR=2013 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2013.00057 DOI=10.3389/fpsyt.2013.00057 ISSN=1664-0640 ABSTRACT=The search for potential biomarkers of psychiatric disorders is a central topic in biological psychiatry. This review concerns published studies on potential biomarkers of treatment-resistant depression (TRD). The search for biomarkers of TRD in the bloodstream has focused on cytokines and steroids as well as brain-derived neurotropic factor. Additional approaches to identifying biomarkers of TRD have dealt with cerebrospinal fluid analysis, magnetic resonance imaging, and positron emission tomography. Some studies have also investigated potential genetic and epigenetic factors in TRD. Most studies have, however, used a post hoc experimental design that failed to determine the association between biomarkers and the initial risk of TRD. Particular attention in future studies should be on shifting the experimental paradigm towards procedures that can determine the risk for developing treatment resistance in untreated depressed individuals.