KEIO RESEARCHERS INFORMATION SYSTEM

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression

  Nakajima W., Hatano M., Ohtani Y., Tani H., Yatomi T., Tsuchimoto S., Fujimoto Y., Eiro T., Ichijo S., Nakano K., Arisawa T., Takada Y., Kimura K., Abe H., Sano A., Nomoto-Takahashi K., Yonezawa K., Tomiyama S., Nagai N., Kusudo K., Honda S., Moriyama S., Nakajima S., Yamada T., Iwabuchi Y., Jinzaki M., Yoshimura K., Syed S.A., Tsugawa S., Uchida H., Takahashi T.

  Molecular Psychiatry  2026

  ISSN  13594184

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  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, [¹¹C]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.

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• Impact of Pulmonary Disease on Clinical Outcomes in Patients Undergoing Mitral Valve Edge-to-Edge Repair

  Iwata J., Yamamoto M., Ryuzaki T., Tsuruta H., Yamada T., Shimizu H., Kubo S., Izumi Y., Saji M., Asami M., Enta Y., Shirai S., Izumo M., Mizuno S., Watanabe Y., Amaki M., Kodama K., Otsuki H., Naganuma T., Bota H., Yamawaki M., Ueno H., Nakazawa G., Hachinohe D., Otsuka T., Ohno Y., Ieda M., Hayashida K.

  American Journal of Cardiology 257   263 - 274 2025.12

  ISSN  00029149

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  Background: Pulmonary diseases (PD) are frequently associated with impaired cardiac function and the presence of mitral and tricuspid regurgitation (MR and TR). Objectives: The study aimed to clarify the impact of PD on clinical outcomes following mitral transcatheter edge-to-edge repair (M-TEER). Methods: Of the 3,764 patients who underwent M-TEER, 3,666 were included in the analysis and stratified according to the absence or presence of PD before the procedure. The primary endpoint was all-cause mortality, evaluated using Kaplan-Meier analysis. Cardiovascular and non-cardiovascular mortality and HFH (HFH) were also assessed during a 4-year follow-up. Moreover, the prognostic impact of TR improvement after M-TEER was evaluated in patients with and without PD. Results: Of the 3,666 patients, 580 (15.8%) had PD, included fewer women, and exhibited greater frailty compared with those without PD. Within a median follow-up of 432 [314–826] days, all-cause mortality did not differ significantly between patients with PD and those without (150 [25.9%] vs. 682 [22.1%], Log rank P = 0.331). No significant differences were observed in the incidence of cardiovascular mortality, non-cardiovascular mortality, and HFH between the two groups. When stratified by PD status, residual significant TR after M-TEER was significantly associated with HFH both in patients with PD and without PD. Conclusions: The intermediate-term prognosis after M-TEER was comparable between patients with and without PD. In patients with PD, MR was effectively reduced through minimally invasive M-TEER. However, appropriate management of TR after MTEER may be required to improve outcomes in this population. Clinical trials: OCEAN-Mitral registry (UMIN-ID: UMIN000023653).

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• Exploring the presence of long COVID-like symptoms in patients with chronic pain: a large-scale internet-based cross-sectional study in Japan

  Takaoka S., Saito H., Kawate M., Tanaka C., Wu Y., Kosugi S., Yamada T., Tabuchi T., Wakaizumi K.

  Pain  2025

  ISSN  03043959

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  Individuals with chronic pain not only endure the direct burden of pain but also experience various symptoms, including sleep disturbances and fatigue, which deteriorate their quality of life. Notably, these symptoms closely resemble those observed in "long COVID,"a prolonged health complication that can arise after coronavirus disease 2019 (COVID-19) infection. Because the similarities between chronic pain and long COVID remain unexplored, this study aimed to investigate their relationship using Japanese epidemiological data. Using the Japan COVID-19 and Society Internet Survey in 2022, which included 32,000 participants, we analyzed data on the presence of chronic pain, history of COVID-19 infection, and presence of 17 long COVID-like symptoms, including gastrointestinal upset, back pain, limb/joint pain, headache, chest pain, shortness of breath, dizziness, sleep disorder, hearing disorder, taste disorder, smell disorder, memory impairment, poor concentration, hair loss, decreased libido, fatigue, and cough. Individuals with history of COVID-19 experienced a significantly greater number of long COVID-like symptoms (median: 5) compared with those with neither COVID-19 nor chronic pain (median: 4, P < 0.001). Individuals with chronic pain alone and those with both COVID-19 and chronic pain exhibited an even greater number of symptoms (median: 8 and 9, respectively). In addition, individuals with chronic pain exhibited greater prevalence odds for 15 of the 17 symptoms than those with neither COVID-19 nor chronic pain (P < 0.001). Our findings indicate that long COVID-like symptoms are not specifically associated with COVID-19. Instead, the data suggest that chronic pain contributes as an independent risk factor for these symptoms.

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• Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial

  Ohtani Y., Tani H., Nomoto-Takahashi K., Yatomi T., Yonezawa K., Tomiyama S., Nagai N., Kusudo K., Honda S., Moriyama S., Nakajima S., Yamada T., Morisaki H., Iwabuchi Y., Jinzaki M., Yoshimura K., Eiro T., Tsugawa S., Ichijo S., Fujimoto Y., Miyazaki T., Takahashi T., Uchida H.

  Psychiatry and Clinical Neurosciences 78 ( 12 ) 765 - 775 2024.12

  ISSN  13231316

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  Aim: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. Methods: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. Results: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (−8.1 ± 10.0 vs −2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (−9.1 ± 10.2 vs −2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. Conclusion: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

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• Neuraxial anesthesia for patients with severe pulmonary arterial hypertension undergoing urgent open abdominal surgeries: two case reports

  Yamada S., Takise Y., Sekiya Y., Masuda Y., Misonoo Y., Wakaizumi K., Suhara T., Morisaki H., Kato J., Yamada T.

  Ja Clinical Reports 10 ( 1 )  2024.12

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  Background: There is no consensus regarding the choice of anesthetic method for patients with pulmonary hypertension (PH). We report two cases in which neuraxial anesthesia was safely performed without general anesthesia during open abdominal surgery in patients with severe PH. Case presentation: Case 1: A 59-year-old woman had an atrial septal defect and a huge abdominal tumor with a mean pulmonary arterial pressure (PAP) of 39 mmHg and pulmonary vascular resistance (PVR) of 3.5 Wood units. Case 2: A 23-year-old woman who had hereditary pulmonary artery hypertension (mean PAP, 65 mmHg; PVR, 16.45 Wood units). Both patients underwent open abdominal surgery under neuraxial anesthesia without circulatory collapse with intraoperative administration of vasoconstrictors. Conclusion: Although anesthetic care must be personalized depending on the pathology and severity of PH, neuraxial anesthesia may be an option for patients with severe PH undergoing abdominal surgery.

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• 硬膜外麻酔の癌再発抑制機序の解明

  2013.04

  -

  2015.03

  Grant-in-Aid for Scientific Research, Principal investigator

• 菌の鉄獲得機構阻害による静菌効果と臨床応用に向けた試み

  2012.04

  -

  2014.03

  Grant-in-Aid for Scientific Research, Coinvestigator(s)

• 肝虚血再灌流障害における環状グアノシン一リン酸の関与

  2007.04

  -

  2009.03

  Grant-in-Aid for Scientific Research, Principal investigator

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• PAIN CONTROL: PRACTICE

  2026

• LECTURE SERIES, ANESTHESIOLOGY AND PALLIATIVE CARE

  2026

• PAIN CONTROL: SEMINAR

  2026

• CLINICAL ANESTHESIOLOGY

  2026

• CLINICAL CLERKSHIP IN ANESTHESIOLOGY AND PALLIATIVE CARE

  2026

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