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Ketamine and Other Glutamate Receptor Antagonists As Fast-Actin

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Translational Research Methods for Major Depressive Disorder

Part of the book series: Neuromethods ((NM,volume 179))

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Abstract

The glutamate hypothesis of depression was prominently emerging in this decade. Evidence has shown that low-dose ketamine infusion or intranasal S-ketamine spray exhibited a prominent and rapid antidepressant and antisuicidal effect. A single infusion of 0.5 mg/kg ketamine may achieve up to 70% treatment response in Caucasian patients with treatment-resistant depression (TRD), but only approximately 50% in Taiwanese patients with TRD. The BDNF release and AMPA receptor upregulation via the blockade of NMDA receptor by low-dose ketamine result in the synaptogenesis and neuroplasticity modulation, which may explain the rapid antidepressant effect of low-dose ketamine. Clinical and biological markers, such as depression severity, body mass index, subjective feeling during infusion, and prefrontal cortex (PFC) and anterior cingulate cortex (ACC) functioning, may predict the treatment response of low-dose ketamine infusion. The 18F-FDG-PET studies found that a short activation in the PFC engendered by ketamine infusion may work as a kindler, facilitating the persistent increase in glucose metabolism in the dorsal ACC, which may further explain the outcome that the antidepressant effects of a single infusion of ketamine may be approximately 2 weeks. In recent years, whether several potential glutamate receptor antagonists/modulators, including R-ketamine, ketamine metabolites (i.e., hydroxynorketamine), lanicemine, and D-cycloserine, may also have a fast-acting antidepressant effect is still being studied. However, the exact neuromechanisms of the rapid antidepressant and antisuicidal effects of low-dose ketamine and intranasal S-ketamine spray in the TRD may go beyond the current evidence, which needs further investigation.

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Acknowledgements

The authors thank Mr I-Fan Hu, MA (Courtauld Institute of Art, University of London; National Taiwan University) for his friendship and support. Mr Hu declares no conflicts of interest. Funding source: The study was supported by grant from Taipei Veterans General Hospital (V106B-020, V107B-010, V107C-181, V108B-012), Yen Tjing Ling Medical Foundation (CI-110-30), and the Ministry of Science and Technology, Taiwan (107-2314-B-075-063-MY3, 108-2314-B-075 -037). The funding source had no role in any process of our study.

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Authors and Affiliations

  1. Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

    Mu-Hong Chen, Tung-Ping Su & Shih-Jen Tsai

  2. Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Mu-Hong Chen, Tung-Ping Su & Shih-Jen Tsai

  3. Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Mu-Hong Chen, Tung-Ping Su & Shih-Jen Tsai

  4. Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan

    Tung-Ping Su

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  1. Mu-Hong Chen
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  2. Tung-Ping Su
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  3. Shih-Jen Tsai
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Editors and Affiliations

  1. Department of Psychiatry, Korea University Ansan Hospital, Ansan, Korea (Republic of)

    Yong-Ku Kim

  2. Deptartment of Speech Therapy, Isfahan University of Medical Sciences, Isfahan, Iran

    Meysam Amidfar

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Chen, MH., Su, TP., Tsai, SJ. (2022). Ketamine and Other Glutamate Receptor Antagonists As Fast-Actin. In: Kim, YK., Amidfar, M. (eds) Translational Research Methods for Major Depressive Disorder. Neuromethods, vol 179. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2083-0_19

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  • DOI: https://doi.org/10.1007/978-1-0716-2083-0_19

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  • Publisher Name: Humana, New York, NY

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