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Ketamine has shown antidepressant efficacy for TRD. While glutamate \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) has been demonstrated to play crucial roles in the process of pharmacological action of ketamine in experimental animals, it remains elusive how ketamine exhibits its efficacy through changes in AMPAR dynamics in patients with TRD. In this study, using a positron emission tomography (PET) tracer, [\n                    <jats:sup>11<\/jats:sup>\n                    C]K-2, which depicts AMPAR density in the living human brain, we detected a negative correlation between AMPAR density and illness severity and differences in AMPAR distribution between patients with TRD and healthy participants. Furthermore, we detected brain areas where ketamine administration altered AMPAR density in significant correlations with ketamine-induced antidepressant effect in patients with TRD. AMPAR density alteration in these regions partially rescued AMPAR phenotype in the affected areas. 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Takuya Takahashi and Tetsu Arisawa are the founders and also stockholders of AMPAMETRY, Inc., which holds the exclusive license to use [\n                      11\n                      C]K-2. No other potential conflicts of interest relevant to this article exist.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}