論文 - 野田　賀大

Efficacy and moderators of prevention and treatment of delirium with melatonin receptor agonists: A systematic review and meta-analysis of randomized controlled trials

Wada M., Yasuda H., Nakajima S., Etani T., Miura A., Asada S., Yoshida K., Noda Y., Takeuchi H.

General Hospital Psychiatry （General Hospital Psychiatry）  85   71 - 79 2023年11月

査読有り,  ISSN  01638343

　概要を見る

Objective: Delirium is a complex and heterogeneous condition that significantly affects patient outcome. This study aimed to conduct a systematic review and meta-analysis to investigate the effects of melatonin and melatonin receptor agonists (MRAs) on delirium prevention and treatment. Method: Randomized controlled studies, using MRAs as an intervention and placebo as a control were included. We conducted meta-analyses with random-effects model and trial sequential analysis. Results: A total of 33 studies involving 4850 participants were included. The meta-analysis revealed a significant preventive effect of MRAs on delirium (risk ratio = 0.65, p < 0.01), while no significant therapeutic effect was observed. Additionally, MRAs were associated with a significant reduction in mortality rate (risk ratio = 0.90, p = 0.02) in delirium prevention studies. Furthermore, subgroup analyses revealed that assessment scales and the frequency of delirium detection may be significant moderators of the delirium-preventive efficacy of MRAs. Conclusion: This study provides evidence of the potential effects of MRAs in preventing delirium and reducing mortality. Further research is required to elucidate the therapeutic potential of MRAs for delirium and identify specific patient populations that may benefit from this agent.

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Glutamatergic neurometabolite levels in the caudate are associated with the ability of rhythm production.

Honda S, Noda Y, Matsushita K, Tarumi R, Nomiyama N, Tsugawa S, Tobari Y, Hondo N, Saito K, Mimura M, Fujii S, Nakajima S

Frontiers in neuroscience （Frontiers in Neuroscience）  17   1196805 - 1196805 2023年08月

責任著者,  ISSN  1662-4548

　概要を見る

Introduction: Glutamatergic neurometabolites play important roles in the basal ganglia, a hub of the brain networks involved in musical rhythm processing. We aimed to investigate the relationship between rhythm processing abilities and glutamatergic neurometabolites in the caudate. Methods: We aquired Glutamatergic function in healthy individuals employing proton magnetic resonance spectroscopy. We targeted the right caudate and the dorsal anterior cingulate cortex (dACC) as a control region. Rhythm processing ability was assessed by the Harvard Beat Assessment Test (H-BAT). Results: We found negative correlations between the production part of the Beat Saliency Test in the H-BAT and glutamate and glutamine levels in the caudate (r = −0.693, p = 0.002) whereas there was no such association in the dACC. Conclusion: These results suggest that higher glutamatergic neurometabolite levels in the caudate may contribute to rhythm processing, especially the ability to produce meter in music precisely.

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Retrospective study on the trajectories of lower limb volume after outpatient-based complex decongestive therapy in post-operative gynecological cancer patients with lymphedema

Masui A., Harada T., Noda Y., Soeda R., Kida H., Tsuji T.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer （Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer）  31 （ 6 ） 318 - 318 2023年05月

査読有り,  ISSN  0941-4355

　概要を見る

PURPOSE: To determine the effect of outpatient-based complex decongestive therapy in patients with secondary lower limb lymphedema (LLL) after gynecologic cancer surgery using group-based trajectory modeling (GBTM), and to examine factors predictive of the treatment course. METHODS: This retrospective study included participants who underwent surgery for gynecological cancer with pelvic lymph node dissection and subsequently visited the outpatient clinic for the treatment of stage II LLL according to the International Society of Lymphology. The improvement rate of edema at the initial visit and 3, 6, and 12 months later was assessed by calculating the volume of the lower extremity using the circumferential method. For evaluation of the patterns of treatment course, logistic regression analysis was performed after group estimation by the trend of the treatment course using GBTM. RESULTS: A total of 148 women (mean age 60.6 years (standard deviation: 13.4 years)) were analyzed. Three improvement trajectories were identified: (1) no response group, with worsening rather than improvement (n = 26); (2) moderate response group, with a slow improvement rate (n = 89); and (3) high response group, with a high improvement rate (n = 33). In addition, adherence to compression therapy at 3 months post-intervention was found to be a predictor in the no response group. CONCLUSIONS: GBTM estimated that there are three patterns of the treatment course in patients with LLL after gynecologic cancer surgery. Adherence to compression therapy at 3 months post-intervention is a predictor of the treatment effectiveness.

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A Case Series of Continuous Theta Burst Stimulation Treatment for the Supplementary Motor Area Twice a Day in Patients with Obsessive-Compulsive Disorder: A Real World TMS Registry Study in Japan

Noda Y., Fujii K., Tokura F., Nakajima S., Kitahata R.

Journal of Personalized Medicine （Journal of Personalized Medicine）  13 （ 5 ）  2023年05月

筆頭著者, 責任著者, 査読有り,  ISSN  2075-4426

　概要を見る

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by patterns in which unwanted thoughts and fears are evoked as obsessions and furthermore, compulsive behaviors are provoked repeatedly, with a prevalence rate of 2% of the population. These obsessive-compulsive symptoms disrupt daily life and cause great distress to the individual. At present, OCD is treated with antidepressants, mainly selective serotonin reuptake inhibitors, and psychotherapy, including the exposure and response prevention method. However, these approaches may only show a certain level of efficacy, and approximately 50% of patients with OCD show treatment resistance. This situation has led to the research and development of neuromodulation therapies, including transcranial magnetic stimulation treatment, for OCD worldwide in recent years. In this case series, we retrospectively analyzed the TMS registry data of continuous theta burst stimulation (cTBS) therapy targeting the bilateral supplementary motor cortex for six patients with OCD whose obsessive-compulsive symptoms had not improved with pharmacotherapy. The results suggest that treatment with cTBS for the bilateral supplementary motor area may reduce obsessive-compulsive symptoms in patients with OCD, despite the limitations of an open-label preliminary case series. The present findings warrant further validation with a randomized, sham-controlled trial with a larger sample size in the future.

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Identifying Neurophysiological Markers of Intermittent Theta-Burst Stimulation in Treatment-Resistant Depression using Transcranial Magnetic Stimulation- Electroencephalography.

Strafella R, Momi D, Zomorrodi R, Lissemore J, Noda Y, Chen R, Rajji TK, Griffiths JD, Vila-Rodriguez F, Downar J, Daskalakis ZJ, Blumberger DM, Voineskos D

Biological psychiatry （Biological Psychiatry）  94 （ 6 ） 454 - 465 2023年04月

査読有り,  ISSN  0006-3223

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Background: Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation–electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders. Methods: TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for treatment-resistant depression, comparing a separated (54-minute interval) and contiguous (0-minute interval) schedule of 2 × 600-pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the left dorsolateral prefrontal cortex at baseline and posttreatment. One hundred fourteen participants had usable TMS-EEG at baseline, and 98 at posttreatment. TMS-evoked potential components (N45, N100) were examined via global mean field analysis. Results: The N100 amplitude decreased from baseline to posttreatment, regardless of the treatment group (F1,106 = 5.20, p =.02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F1,102 = 11.30, p =.001, pcorrected =.0004). Responders showed higher posttreatment N45 amplitude than nonresponders (F1,94 = 4.11, p =.045, pcorrected =.016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F4,106 = 6.28, p =.00014). Conclusions: These results provide further evidence for an association between the neurophysiological effects of iTBS and treatment efficacy in treatment-resistant depression. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers.

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Dynamics of AMPA receptors regulate epileptogenesis in patients with epilepsy.

Eiro T, Miyazaki T, Hatano M, Nakajima W, Arisawa T, Takada Y, Kimura K, Sano A, Nakano K, Mihara T, Takayama Y, Ikegaya N, Iwasaki M, Hishimoto A, Noda Y, Miyazaki T, Uchida H, Tani H, Nagai N, Koizumi T, Nakajima S, Mimura M, Matsuda N, Kanai K, Takahashi K, Ito H, Hirano Y, Kimura Y, Matsumoto R, Ikeda A, Takahashi T

Cell reports. Medicine （Cell Reports Medicine）  4 （ 5 ） 101020 - 101020 2023年04月

査読有り

　概要を見る

The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.

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Real world research on transcranial magnetic stimulation treatment strategies for neuropsychiatric symptoms with long-COVID in Japan

Noda Y., Sato A., Shichi M., Sato A., Fujii K., Iwasa M., Nagano Y., Kitahata R., Osawa R.

Asian Journal of Psychiatry （Asian Journal of Psychiatry）  81   103438 - 103438 2023年03月

筆頭著者, 責任著者, 査読有り,  ISSN  18762018

　概要を見る

The number of patients suffering from long-COVID is currently increasing rapidly, even after the acute symptoms of COVID-19 have improved. The objective of this study was to investigate the effects of a pilot transcranial magnetic stimulation (TMS) treatment on neuropsychiatric symptoms caused by long-COVID. In this study, we examined the efficacy of the TMS treatment protocol, which has been established to be effective in refractory depression, by applying it to patients who sought TMS treatment for neuropsychiatric symptoms caused by long-COVID at TMS clinics in Tokyo, Japan in the context of the real world TMS registry study in Japan. Of the 23 patients (13 females) with long-COVID included in this case series, the main neuropsychiatric symptoms were chronic fatigue (n = 12) and cognitive dysfunction (n = 11), but most patients also showed mild depressive symptoms. The mean score on the Montgomery-Åsberg Depression Rating Scale before TMS treatment was 21.2, which improved to 9.8 after treatment. Similarly, the score on the Performance Status, which assesses the degree of fatigue, improved from 5.4 to 4.2, and the score on the Perceived Deficits Questionnaire–Depression 5-item, which reflects cognitive function, improved from 10.0 to 6.3. Although a few patients complained of pain at the stimulation site during the TMS as a side effect, there were no serious adverse events. Despite the limitations of this open-label pilot study, the TMS protocol implemented in this study may have beneficial effects on neuropsychiatric symptoms caused by long-COVID, including depressive symptoms, chronic fatigue, and cognitive impairment. These preliminary findings warrant further validation in randomized controlled trials.

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Decrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia

Ogyu K., Matsushita K., Honda S., Wada M., Tamura S., Takenouchi K., Tobari Y., Kusudo K., Kato H., Koizumi T., Arai N., Koreki A., Matsui M., Uchida H., Fujii S., Onaya M., Hirano Y., Mimura M., Nakajima S., Noda Y.

Schizophrenia Research （Schizophrenia Research）  252   129 - 137 2023年02月

最終著者, 責任著者, 査読有り,  ISSN  09209964

　概要を見る

Background: Thirty percent of patients with schizophrenia do not respond to non-clozapine antipsychotics and are termed treatment-resistant schizophrenia (TRS). The 40-Hz auditory steady-state response (ASSR) is a well-known to be reduced in patients with schizophrenia compared to healthy controls (HCs), suggesting impaired gamma oscillation in schizophrenia. Given no ASSR study on TRS, we aimed to examine the neurophysiological basis of TRS employing 40-Hz ASSR paradigm. Method: We compared ASSR measures among HCs, patients with non-TRS, and patients with TRS. TRS criteria were defined by a score of 4 or higher on two items of the Positive and Negative Syndrome Scale (PANSS) positive symptoms despite standard antipsychotic treatment. Participants were examined for ASSR with 40-Hz click-train stimulus, and then time-frequency analysis was performed to calculate evoked power and phase-locking factor (PLF) of 40-Hz ASSR. Results: A total of 79 participants were included: 27 patients with TRS (PANSS = 92.6 ± 15.8); 27 patients with non-TRS (PANSS = 63.3 ± 14.7); and 25 HCs. Evoked power in 40-Hz ASSR was lower in the TRS group than in the HC group (F2,79 = 8.37, p = 0.015; TRS vs. HCs: p = 0.012, d = 1.1) while no differences in PLF were found between the groups. Conclusion: These results suggest that glutamatergic and GABAergic neurophysiological dysfunctions are involved in the pathophysiology of TRS. Our findings warrant more comprehensive and longitudinal studies for deep phenotyping of TRS.

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Music rhythm perception and production relate to treatment response in schizophrenia

Honda S., Matsushita K., Noda Y., Tarumi R., Nomiyama N., Tsugawa S., Nakajima S., Mimura M., Fujii S.

Schizophrenia Research （Schizophrenia Research）  252   69 - 76 2023年02月

責任著者, 査読有り,  ISSN  09209964

　概要を見る

Accumulating evidence indicates that pathophysiology of schizophrenia involves abnormalities in the dopamine and glutamatergic neuronal systems. Antipsychotic medications are currently used to normalize dopaminergic function for schizophrenia. However, approximately 30 % of the patients have no response to antipsychotic medications, which is classified as treatment-resistant schizophrenia (TRS). Furthermore, dopamine and glutamate levels in the neural basis have been reported to differ between TRS and non-TRS. In this study, we assumed that these differences may affect music rhythm perception and production abilities between the two groups. We examined fifty-seven schizophrenia (26 TRS, 31 non-TRS) and thirty-one healthy controls (HCs) by using the Harvard Beat Assessment Test (H-BAT). As a result, we found that rhythm production was worse in patients with TRS compared to patients with non-TRS and HCs, while no difference was observed between patients with non-TRS and HCs. In addition, rhythm perception and production abilities were impaired in the whole patient group compared with HCs. Furthermore, in the patient group, the deficits were correlated with cognitive impairments. Collectively, these results suggest that patients with schizophrenia may have rhythm processing deficits, with particular a rhythm production problem in the TRS group.

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A Case Series of Intermittent Theta Burst Stimulation Treatment for Depressive Symptoms in Individuals with Autistic Spectrum Disorder: Real World TMS Study in the Tokyo Metropolitan Area.

Noda Y, Fujii K, Mimura Y, Taniguchi K, Nakajima S, Kitahata R

Journal of personalized medicine （Journal of Personalized Medicine）  13 （ 1 ）  2023年01月

筆頭著者, 責任著者, 査読有り,  ISSN  2075-4426

　概要を見る

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. While the symptoms of ASD are present from early childhood, there has been an increase in the number of adults with ASD in recent years who visit healthcare professionals to seek the treatment of depression due to maladjustment resulting from the core symptoms and are eventually diagnosed with ASD. Currently, no treatment is available for the core symptoms of ASD, and pharmacotherapy and psychotherapy are often provided mainly for secondary disorders such as depression and anxiety. However, the effectiveness of these therapies is often limited in individuals with ASD compared to those with major depression. In this context, neuromodulation therapies such as transcranial magnetic stimulation (TMS) have gained increasing attention as potential treatments. In this case series, we retrospectively analyzed 18 cases with ASD from the TMS registry data who had failed to improve depressive symptoms with pharmacotherapy and were treated with intermittent theta burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). We also explored the relationship between treatment efficacy and clinical epidemiological profile. Our results indicated that, despite the limitations of an open-label preliminary case series, TMS therapy in the form of iTBS may have some beneficial therapeutic effects on depressive symptoms in individuals with ASD. The present findings warrant further validation through randomized, sham-controlled trials with larger sample sizes.

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A pilot study on the effect of transcranial magnetic stimulation treatment on cognitive dysfunction associated with long-COVID.

Noda Y, Sato A, Fujii K, Nagano Y, Iwasa M, Hirahata K, Kitahata R, Osawa R

Psychiatry and clinical neurosciences 77 （ 4 ） 241 - 242 2023年01月

筆頭著者, 責任著者, 査読有り,  ISSN  1323-1316

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Impaired neuroplasticity in the dorsolateral prefrontal cortex of patients with treatment-resistant depression indexed by paired associative stimulation paradigm and a combined TMS-EEG measurements

Naotsugu Kaneko, Masakata Wada, Mayuko Takano, Keita Taniguchi, Shiori Honda, Shinichiro Nakajima, Masaru Mimura, Yoshihiro Noda

Brain Stimulation （Elsevier BV）  16 （ 1 ） 240 - 240 2023年01月

ISSN  1935-861X

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When the brain goes quiet: cortical silence inhibition in schizophrenia

M Mikail, R Zomorrodi, Y Noda, J Daskalakis

Royal College of Surgeons in Ireland 2023年

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia

S Koike, S Shibukawa, H Kan, S Honda, M Wada, R Tarumi, S Tsugawa, ...

Translational psychiatry （Translational Psychiatry）  14 （ 1 ） 164 - 164 2023年

査読有り

　概要を見る

Quantitative susceptibility mapping is a magnetic resonance imaging technique that measures brain tissues’ magnetic susceptibility, including iron deposition and myelination. This study examines the relationship between subcortical volume and magnetic susceptibility and determines specific differences in these measures among patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls (HCs). This was a cross-sectional study. Sex- and age- matched patients with MDD (n = 49), patients with schizophrenia (n = 24), and HCs (n = 50) were included. Magnetic resonance imaging was conducted using quantitative susceptibility mapping and T1-weighted imaging to measure subcortical susceptibility and volume. The acquired brain measurements were compared among groups using analyses of variance and post hoc comparisons. Finally, a general linear model examined the susceptibility–volume relationship. Significant group-level differences were found in the magnetic susceptibility of the nucleus accumbens and amygdala (p = 0.045). Post-hoc analyses indicated that the magnetic susceptibility of the nucleus accumbens and amygdala for the MDD group was significantly higher than that for the HC group (p = 0.0054, p = 0.0065, respectively). However, no significant differences in subcortical volume were found between the groups. The general linear model indicated a significant interaction between group and volume for the nucleus accumbens in MDD group but not schizophrenia or HC groups. This study showed susceptibility alterations in the nucleus accumbens and amygdala in MDD patients. A significant relationship was observed between subcortical susceptibility and volume in the MDD group’s nucleus accumbens, which indicated abnormalities in myelination and the dopaminergic system related to iron deposition.

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A pilot study of the effect of transcranial magnetic stimulation treatment on cognitive dysfunction associated with post COVID‐19 condition

Y Noda, A Sato, K Fujii, Y Nagano, M Iwasa, K Hirahata, R Kitahata, ...

Psychiatry and Clinical Neurosciences 77 (4), 241-242 2023年

Reduced signal propagation from the left dorsolateral prefrontal cortex to the salience network associated with oligodendrocyte abnormalities in treatment-resistant depression

M Wada, S Nakajima, S Honda, M Takano, K Taniguchi, S Tsugawa, ...

Brain Stimulation: Basic, Translational, and Clinical Research in … 2023年

A pilot study on the effect of transcranial magnetic stimulation treatment on cognitive dysfunction associated with long‐COVID

Y Noda, A Sato, K Fujii, Y Nagano, M Iwasa, K Hirahata, R Kitahata, ...

Psychiatry and Clinical Neurosciences 2023年

A Case Series of Intermittent Theta Burst Stimulation Treatment for Depressive Symptoms in Individuals with Autistic Spectrum Disorder: Real World TMS Study in the Tokyo …

Y Noda, K Fujii, Y Mimura, K Taniguchi, S Nakajima, R Kitahata

Journal of Personalized Medicine 13 (1), 145 2023年

Decreased cholinergic function in the dorsolateral prefrontal cortex of amnestic mild cognitive impairment assessed by TMS-evoked potentials in the short-latency afferent …

Y Mimura, Y Tobari, M Takano, M Wada, S Honda, S Bun, H Tabuchi, ...

Brain Stimulation: Basic, Translational, and Clinical Research in … 2023年

Disease progression patterns of brain morphology in schizophrenia: More progressed stages in treatment-resistance

D Sone, A Young, S Shinagawa, S Tsugawa, Y Iwata, R Tarumi, K Ogyu, ...

Schizophrenia bulletin （Schizophrenia Bulletin）  50 （ 2 ） 393 - 402 2023年

査読有り,  ISSN  0586-7614

　概要を見る

Background and Hypothesis: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. Study Design: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machinelearning analysis. Study Results: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). Conclusions: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.

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