Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders | Zendy

Daniel C. Javitt | Zendy; Cameron S. Carter | Zendy; John H. Krystal | Zendy; Joshua T. Kantrowitz | Zendy; Ragy R. Girgis | Zendy; Lawrence S. Kegeles | Zendy; J. Daniel Ragland | Zendy; Richard J. Maddock | Zendy; Tyler A. Lesh | Zendy; Costin Tanase | Zendy; Philip R. Corlett | Zendy; Douglas L. Rothman | Zendy; Graeme F. Mason | Zendy; Maolin Qiu | Zendy; James Robinson | Zendy; William Z. Potter | Zendy; Marlene Carlson | Zendy; Melanie M. Wall | Zendy; Tse-Hwei Choo | Zendy; Jack Grinband | Zendy; Jeffrey A. Lieberman | Zendy

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Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders

Author(s) -

Daniel C. Javitt,

Cameron S. Carter,

John H. Krystal,

Joshua T. Kantrowitz,

Ragy R. Girgis,

Lawrence S. Kegeles,

J. Daniel Ragland,

Richard J. Maddock,

Tyler A. Lesh,

Costin Tanase,

Philip R. Corlett,

Douglas L. Rothman,

Graeme F. Mason,

Maolin Qiu,

James Robinson,

William Z. Potter,

Marlene Carlson,

Melanie M. Wall,

Tse-Hwei Choo,

Jack Grinband,

Jeffrey A. Lieberman

Publication year - 2017

Publication title -

jama psychiatry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 7.531

H-Index - 365

eISSN - 2168-6238

pISSN - 2168-622X

DOI - 10.1001/jamapsychiatry.2017.3572

Subject(s) - ketamine , glutamate receptor , medicine , clinical trial , randomized controlled trial , placebo , schizophrenia (object oriented programming) , functional magnetic resonance imaging , psychiatry , psychology , neuroscience , pathology , alternative medicine , receptor

Despite strong theoretical rationale and preclinical evidence, several glutamate-targeted treatments for schizophrenia have failed in recent pivotal trials, prompting questions as to target validity, compound inadequacy, or lack of target engagement. A key limitation for glutamate-based treatment development is the lack of functional target-engagement biomarkers for translation between preclinical and early-stage clinical studies. We evaluated the utility of 3 potential biomarkers-ketamine-evoked changes in the functional magnetic imaging (fMRI) blood oxygen level-dependent response (pharmacoBOLD), glutamate proton magnetic resonance spectroscopy (1H MRS), and task-based fMRI-for detecting ketamine-related alterations in brain glutamate.

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