Neuroimaging-Derived Biomarkers of the Antidepressant Effects of Ketamine

Artemis Zavaliangos-Petropulu; Noor B Al-Sharif; Brandon Taraku; Amber M Leaver; Ashish K Sahib; Randall T Espinoza; Katherine L Narr

doi:10.1016/j.bpsc.2022.11.005

Neuroimaging-Derived Biomarkers of the Antidepressant Effects of Ketamine

Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Apr;8(4):361-386. doi: 10.1016/j.bpsc.2022.11.005. Epub 2022 Nov 26.

Authors

Artemis Zavaliangos-Petropulu¹, Noor B Al-Sharif², Brandon Taraku², Amber M Leaver³, Ashish K Sahib², Randall T Espinoza⁴, Katherine L Narr⁵

Affiliations

¹ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: azavalia@g.ucla.edu.
² Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
³ Department of Radiology, Northwestern University, Chicago, Illinois.
⁴ Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
⁵ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.

PMID: 36775711
DOI: 10.1016/j.bpsc.2022.11.005

Abstract

Major depressive disorder is a highly prevalent psychiatric disorder. Despite an extensive range of treatment options, about a third of patients still struggle to respond to available therapies. In the last 20 years, ketamine has gained considerable attention in the psychiatric field as a promising treatment of depression, particularly in patients who are treatment resistant or at high risk for suicide. At a subanesthetic dose, ketamine produces a rapid and pronounced reduction in depressive symptoms and suicidal ideation, and serial treatment appears to produce a greater and more sustained therapeutic response. However, the mechanism driving ketamine's antidepressant effects is not yet well understood. Biomarker discovery may advance knowledge of ketamine's antidepressant action, which could in turn translate to more personalized and effective treatment strategies. At the brain systems level, neuroimaging can be used to identify functional pathways and networks contributing to ketamine's therapeutic effects by studying how it alters brain structure, function, connectivity, and metabolism. In this review, we summarize and appraise recent work in this area, including 51 articles that use resting-state and task-based functional magnetic resonance imaging, arterial spin labeling, positron emission tomography, structural magnetic resonance imaging, diffusion magnetic resonance imaging, or magnetic resonance spectroscopy to study brain and clinical changes 24 hours or longer after ketamine treatment in populations with unipolar or bipolar depression. Though individual studies have included relatively small samples, used different methodological approaches, and reported disparate regional findings, converging evidence supports that ketamine leads to neuroplasticity in structural and functional brain networks that contribute to or are relevant to its antidepressant effects.

Keywords: Connectivity; Depression; Diffusion; Ketamine; MRI; fMRI.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Antidepressive Agents / pharmacology
Antidepressive Agents / therapeutic use
Biomarkers
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Major* / metabolism
Humans
Ketamine* / pharmacology
Ketamine* / therapeutic use
Neuroimaging

Substances

Ketamine
Antidepressive Agents
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding