The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression
Using the PET tracer [11C]K-2 to image AMPAR density in vivo, the authors found that lower AMPAR availability correlates with greater illness severity and differs between patients with treatment‑resistant depression and healthy controls. Ketamine produced region‑specific changes in AMPAR density that correlated with clinical improvement and partially restored the abnormal AMPAR phenotype, supporting AMPAR dynamics as a mechanistic substrate of ketamine’s antidepressant effect in TRD.
Authors
- Nakajima, W.
- Hatano, M.
- Ohtani, Y.
Published
Abstract
Abstract Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD. While glutamate α-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, [ 11 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. Thus, AMPAR dynamics underlies the antidepressant effect of ketamine in patients with TRD.
Research Summary of 'The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression'
Study Details
- Study Typeindividual
- Populationhumans
- Journal
- Compound
- Topics