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Review
. 2020:89:195-235.
doi: 10.1016/bs.apha.2020.05.003. Epub 2020 Jun 18.

Neurobiological biomarkers of response to ketamine

Bashkim Kadriu  1 , Elizabeth D Ballard  2 , Ioline D Henter  2 , Stephen Murata  2 , Nimesha Gerlus  2 , Carlos A Zarate Jr  2
Affiliations
Review

Neurobiological biomarkers of response to ketamine

Bashkim Kadriu et al. Adv Pharmacol. 2020.

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.

Keywords: Biomarkers; Depression; Genetic/epigenetic biomarkers; Immunological biomarkers; Ketamine; Neuroimaging biomarkers; Neuroplasticity biomarkers; Sleep biomarkers; Stress/hormonal biomarkers.

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Conflict of interest statement

Conflict of interest statement Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIAMH002857), by a NARSAD Independent Investigator Award to Dr. Zarate, and by a Brain and Behavior Mood Disorders Research Award to Dr. Zarate. Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise.

Figures

Fig. 1
Fig. 1
Schematic diagram of neuroprogression, briefly defined as dynamic changes in the various levels of biological substrates (central and systemic) underlying the chronic, relapsing-remitting clinical course of mental illness.
See this image and copyright information in PMC

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