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Authors

Jones, Gregory H.

Gilbert, Jessica R. https://orcid.org/0000-0002-4194-6172

Johnston, Jenessa N. https://orcid.org/0000-0003-2986-3179

Akula, Nirmala

Schulmann, Anton https://orcid.org/0000-0002-6323-4969

Arakelian, Miranda https://orcid.org/0000-0003-0193-318X

Peng, Shiyong

Yuan, Peixiong

Winful, Ewurakua A.

Yavi, Mani

Quintanilla, Brandi

Elkahloun, Abdel

Moaddel, Ruin

Henter, Ioline D.

Greenstein, Dede

Machado-Vieira, Rodrigo https://orcid.org/0000-0002-4830-1190

Bartley, Christopher M. https://orcid.org/0000-0002-1391-4130

Kadriu, Bashkim https://orcid.org/0000-0002-3809-9451

Amit, Moran

Rezvani, Katy

Kvarta, Mark D. https://orcid.org/0000-0002-1093-1648

McMahon, Francis J. https://orcid.org/0000-0002-9469-305X

Zarate, Carlos A. Jr.

Funding

Funding for this research was provided by:

U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (ZIAMH002857; ZIAMH002844)

U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NCTMH002857; NCTMH002844)

U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (ZIAMH002857; ZIAMH002844)

U.S. Department of Health & Human Services | NIH | National Institute on Aging (Z01-AG00029)

License Information

Text and Data Mining valid from 2026-07-28

Version of Record valid from 2026-07-28

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Article History

Received: 7 October 2025

Revised: 19 June 2026

Accepted: 15 July 2026

First Online: 28 July 2026

Ethics

Competing interests: Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; Dr. Zarate and Dr. Moaddel are listed as co-inventors on a patent for the use of (2 R ,6 R )-hydroxynorketamine, ( S )-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of ( R,S )-ketamine in the treatment of depression and neuropathic pain; and as co-inventors on a patent application for the use of (2 R ,6 R )-hydroxynorketamine and (2 S ,6 S )-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. They have assigned their patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. Dr. Machado-Vieira has received consulting fees from Eurofarma Pharmaceuticals, Abbott, and the BioStrategies Group, and has a research contract for trials with Janssen and Boehringer-Ingelheim Pharmaceuticals. Dr. Machado-Vieira has also received speaker fees from Otsuka, Lundbeck, EMS, and Cristalia, and is a member of the scientific board of Symbinas Pharmaceuticals and Allergan. Dr. Kvarta holds and receives royalties from a patent for the use of negative modulators of GABA receptors containing α5 subunits as rapid-acting antidepressants, with rights assigned to the University of Maryland, Baltimore. Dr. Kadriu is presently employed full-time and holds shares in Bristol Myers Squibb. He was previously employed by Johnson & Johnson and Jazz Pharmaceuticals, where he maintains share ownership. All other authors have no conflict of interest to disclose, financial or otherwise.

Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the National Institutes of Health under protocol numbers 01-M-0254 and 15-M-0151 (iPSC-based studies) and 04-M-0222 (ketamine clinical trial and associated biomarker data. All methods were performed in accordance with the relevant guidelines and regulations, and all participants provided written informed consent.

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