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Investigator

Carlos A. Zarate, M.D.

Experimental Therapeutics and Pathophysiology Branch
10 Center Drive, CRC
Bethesda MD 20892-

Dr. Zarate earned his medical degree from the Catholic University of Cordoba in Argentina. He completed a clinical psychopharmacology fellowship at McLean Hospital in 1993, after which he remained on staff until 1998. In 1998, Dr. Zarate joined the faculty at the University of Massachusetts Medical School. In 2001, Dr. Zarate joined the Mood and Anxiety Disorders program at the NIMH and, in 2009, formed the Experimental Therapeutics and Pathophysiology Branch.


His achievements and awards include the Ethel-DuPont Warren Award and Livingston Awards, Consolidated Department of Psychiatry, Harvard Medical School; Outstanding Psychiatrist Research Award, Massachusetts Psychiatric Association; Program for Minority Research Training in Psychiatry, APA; the National Alliance for Research on Schizophrenia and Depression Young Investigator Award; National Alliance for Research on Schizophrenia and Depression Independent Investigator Award; the National Institutes of Health Director’s Award Scientific/Medical, the 2011 Brain & Behavior Research Foundation Award for Bipolar Mood Disorder Research, the 2013 National Institute of Health Director’s Award—Scientific/Medical Achievement and Mogens Schou Research Award: Bipolar Disorder and the Simon-Bolivar Award American Psychiatric Association; 2015 Ruth L. Kirschtein Mentoring Award NIH and the Astute Clinician Lecture Award, NIH.


Dr. Zarate’s research focuses on the development of novel medications for treatment-resistant depression and bipolar disorder. His branch conducts proof-of-concept studies utilizing novel compounds and biomarkers to identify potentially relevant drug targets and biosignatures of treatment response.



The Experimental Therapeutics & Pathophysiology Branch (ETPB) has been dedicated to developing and implementing novel, and much-needed, treatments for mood disorders. The ETPB research focuses on developing innovative and ground-breaking therapeutics for treatment resistant depression and bipolar disorder, identifying biomarkers that predict treatment response, and understanding the neurobiology of treatment response in patients with severe, recurrent mood disorders. The research program is truly translational in nature. The ETPB conducts proof-of-concept studies using novel compounds and biomarkers (magnetoencephalography [MEG] and polysomnography [PSG], positron emission tomography [PET], functional magnetic resonance imaging [fMRI] and magnetic resonance spectroscopy [MRS]) to identify potentially relevant drug targets and biosignatures of treatment response. The Branch’s long-term goal is to develop the next generation of antidepressant agents, thereby significantly improving the treatment of severe treatment-resistant depression. In addition, the Branch provides thoughtful, supportive training to develop the next generation of clinical translational researchers.



Clinical Protocols:

  • Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder, 17-M-0060

  • Neurobiology of Suicide, 15-M-0188

  • An Investigation of the Antidepressant Effects of the Glycine Receptor Antagonist AV-101 (4-chlorokynurenine) in Major Depressive Disorder, 15-M-0151

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  • 1) Nugent AC, Ballard E, Gould TD, Park LT, Moaddel R, Brutsche NE, Zarate CA Jr (2018)
  • Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects
  • Mol Psychiatry, [Epub ahead of print]. PMID:29487402
  • 2) Evans JW, Szczepanik J, Brutsche N, Park LT, Nugent AC, Zarate CA Jr. (2018)
  • Default mode connectivity in major depressive disorder measured up to 10 days after ketamine administration
  • Biol Psychiatry 2018, [Epub ahead of print]. PMID:29580569
  • 3) Vande Voort JL, Ballard ED, Luckenbaugh DA, Bernert RA, Richards EM, Niciu MJ, Park L, Machado-Vieira R, Duncan WC Jr, Zarate CA Jr (2017)
  • Antisuicidal response after ketamine infusion is associated with increased nighttime wakefulness in treatment-resistant depression
  • J Clin Psychiatry , 78:1068-1074. PMMID: PMID:27929610
  • 4) Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, Alkondon M, Yuan P, Pribut HJ, Singh NS, Dossou KS, Fang Y, Huang X-P, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas CJ, Zarate CA Jr, Gould TD (2016)
  • NMDA-independent antidepressant actions of ketamine metabolite (2R,6R)-hydroxynorketamine
  • Nature, 533(7604):481-6. , PMID:27144355
  • 5) Zarate CA, Jr., Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I, Jolkovsky L, Brutsche NE, Smith MA, Luckenbaugh DA (2013)
  • A randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression
  • Biol Psychiatry, 74:257-264, PMID: 23206319
  • 6) Cornwell BR, Salvadore G, Furey M, Marquardt CA, Brutsche NE, Grillon C, Zarate CA Jr. (2012)
  • Synaptic potentiation is critical for rapid antidepressant response to ketamine
  • Biological Psychiatry , 72:555-561 , PMID: 22521148
  • 7) Salvadore G, Cornwell BR, Sambataro F, Latov D, Colon-Rosario V, Carver F, Holroyd T, Machado-Vieira R, Grillon C, Drevets WC, Zarate CA Jr (2010)
  • Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine
  • Neuropsychopharmacology, 35, 1415-1422
  • 8) Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr (2010)
  • A randomized add-on trial of an N-methyl-D-aspartate (NMDA) antagonist in treatment-resistant bipolar depression
  • Arch Gen Psychiatry, 67, 793-802
  • 9) Diazgranados N, Ibrahim L, Brutsche N, Ameli R, Henter I, Luckenbaugh D, Machado-Vieira R, Zarate CA Jr (2010)
  • Rapid resolution of suicidal ideation after a single ketamine infusion in patients with treatment-resistant major depression
  • J Clin Psychiatry, 71, 1605-11
  • 10) Zarate CA, Jr, Singh J, Carlson P, Brutsche N, Ameli R, Luckenbaugh D, Charney DS, Manji HK (2006)
  • A Randomized Trial of an NMDA Antagonist in Treatment-Resistant Major Depression
  • Arch Gen Psychiatry, 63, 856-64
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