Nakajima, Shinichiro



School of Medicine, Department of Neuropsychiatry (Shinanomachi)


Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)


Papers 【 Display / hide

  • Transcranial magnetic stimulation neurophysiology of patients with major depressive disorder: A systematic review and meta-analysis

    Kinjo M., Wada M., Nakajima S., Tsugawa S., Nakahara T., Blumberger D.M., Mimura M., Noda Y.

    Psychological Medicine (Psychological Medicine)  51 ( 1 ) 1 - 10 2021.01

    ISSN  00332917

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    Major depressive disorder (MDD) is a mental illness with high socio-economic burden, but its pathophysiology has not been fully elucidated. Recently, the cortical excitatory and inhibitory imbalance hypothesis and neuroplasticity hypothesis have been proposed for MDD. Although several studies have examined the neurophysiological profiles in MDD using transcranial magnetic stimulation (TMS), a meta-analysis of TMS neurophysiology has not been performed. The objective of this study was to compare TMS-electromyogram (TMS-EMG) findings between patients with MDD and healthy controls (HCs). To this end, we examined whether patients with MDD have lower short-interval cortical inhibition (SICI) which reflects gamma-aminobutyric acid (GABA)A receptor-mediated activity, lower cortical silent period (CSP) which represents GABAB receptor-mediated activity, higher intracortical facilitation (ICF) which reflects glutamate N-methyl-D-aspartate receptor-mediated activity, and the lower result of paired associative stimulation (PAS) paradigm which shows the level of neuroplasticity in comparison with HC. Further, we explored the effect of clinical and demographic factors that may influence TMS neurophysiological indices. We first searched and identified research articles that conducted single- or paired-pulse TMS-EMG on patients with MDD and HC. Subsequently, we extracted the data from the included studies and meta-analyzed the data with the comprehensive meta-analysis software. Patients with MDD were associated with lower SICI, lower CSP, potentially higher ICF, and lower PAS compared with HC. Our results confirmed the proposed hypotheses, suggesting the usefulness of TMS neurophysiology as potential diagnostic markers of MDD.

  • Increased blood COASY DNA methylation levels a potential biomarker for early pathology of Alzheimer’s disease

    Kobayashi N., Shinagawa S., Niimura H., Kida H., Nagata T., Tagai K., Shimada K., Oka N., Shikimoto R., Noda Y., Nakajima S., Mimura M., Shigeta M., Kondo K.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    Early diagnosis of dementia including Alzheimer’s disease (AD) is an urgent medical and welfare issue. However, to date, no simple biometrics have been available. We reported that blood DNA methylation levels of the COASY gene, which encodes coenzyme A synthase, were increased in individuals with AD and amnestic mild cognitive impairment (aMCI). The present study sought to replicate these findings with larger numbers of samples. Another objective was to clarify whether COASY methylation is associated with neurodegeneration through a comparison of AD, AD with cardiovascular disease (CVD), and vascular dementia (VaD). We measured blood COASY methylation levels in normal controls (NCs) (n = 200), and individuals with aMCI (n = 22), AD (n = 151), and VaD (n = 21). Compared with NCs, they were significantly higher in individuals with aMCI and AD. Further, they were significantly higher in AD patients without cardiovascular diseases compared to AD patients with them. These findings suggest that COASY methylation levels may be related to neurodegeneration in AD.

  • Resting-state isolated effective connectivity of the cingulate cortex as a neurophysiological biomarker in patients with severe treatment-resistant schizophrenia

    Wada M., Nakajima S., Tarumi R., Masuda F., Miyazaki T., Tsugawa S., Ogyu K., Honda S., Matsushita K., Kikuchi Y., Fujii S., Blumberger D.M., Daskalakis Z.J., Mimura M., Noda Y.

    Journal of Personalized Medicine (Journal of Personalized Medicine)  10 ( 3 ) 1 - 12 2020.09

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    Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t = 7.659, p = 0.008) and theta (t = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance. 45 45

  • Treatment effects on neurometabolite levels in schizophrenia: A systematic review and meta-analysis of proton magnetic resonance spectroscopy studies

    Kubota M., Moriguchi S., Takahata K., Nakajima S., Horita N.

    Schizophrenia Research (Schizophrenia Research)  222   122 - 132 2020.08

    ISSN  09209964

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    Background: Although there is growing evidence of alterations in the neurometabolite status associated with the pathophysiology of schizophrenia, how treatments influence these metabolite levels in patients with schizophrenia remains poorly studied. Methods: We conducted a literature search using Embase, Medline, and PsycINFO to identify proton magnetic resonance spectroscopy studies that compared neurometabolite levels before and after treatment in patients with schizophrenia. Six neurometabolites (glutamate, glutamine, glutamate + glutamine, gamma-aminobutyric acid, N-acetylaspartate, myo-inositol) and six regions of interest (frontal cortex, temporal cortex, parieto-occipital cortex, thalamus, basal ganglia, hippocampus) were investigated. Results: Thirty-two studies (n = 773 at follow-up) were included in our meta-analysis. Our results demonstrated that the frontal glutamate + glutamine level was significantly decreased (14 groups; n = 292 at follow-up; effect size = −0.35, P = 0.0003; I = 22%) and the thalamic N-acetylaspartate level was significantly increased (7 groups; n = 184 at follow-up; effect size = 0.47, P < 0.00001; I = 0%) after treatment in schizophrenia patients. No significant associations were found between neurometabolite changes and age, gender, duration of illness, duration of treatment, or baseline symptom severity. Conclusions: The current results suggest that glutamatergic neurometabolite levels in the frontal cortex and neuronal integrity in the thalamus in schizophrenia might be modified following treatment. 2 2

  • Pharmacological management of behavioral disturbances in patients with Alzheimer’s disease

    Nagata T., Shinagawa S., Nakajima S., Noda Y., Mimura M.

    Expert Opinion on Pharmacotherapy (Expert Opinion on Pharmacotherapy)  21 ( 9 ) 1093 - 1102 2020.06

    ISSN  14656566

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    Neuropsychiatric symptoms (NPS) inevitably occur during the course of Alzheimer’s disease (AD) including psychosis, aggression, and depression. The effectiveness of pharmacological treatments for NPS has been limited because of their lack of efficacy, discontinuation due to undesirable adverse events, or poor adherence. In recent consensus guidelines, non-pharmacological treatments for NPS have been prioritized as first-line management strategies. Pharmacological treatments for severe NPS should be administrated as a second-line approach, and have been suggested to be started at a lower dosage followed by titration to a minimum effective dosage and for a limited time period. However, recent studies have shown that some patients receiving pharmacological treatments do not exhibit treatment efficacy in comparison with placebo. The concurrence of several sub-symptoms in NPS makes it difficult to target one symptom exclusively. Therefore, the current review focuses on a strategy for such refractory NPS in patients with AD. Recent randomized controlled trials have shown that the severity of NPS gradually reduces in a time-dependent manner regardless of active treatments. Therefore, clinicians should consider potential causes of NPS sub-symptoms from multifactorial aspects and select alternative treatments (e.g. neuromodulation or relocation into specialized care units) during the long-term disease course.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

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

  • 治療抵抗性統合失調症における興奮抑制バランスの破綻:TMS-EEG/MRS研究


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 中島 振一郎, Grant-in-Aid for Scientific Research (B), Principal Investigator

  • グルタミン酸機能障害仮説に基く1H-MRSによる治療抵抗性統合失調症の病態の解明


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 中島 振一郎, Grant-in-Aid for Young Scientists (A), Principal Investigator

Awards 【 Display / hide

  • Schizophrenia International Research Society Conference’s travel award


  • University of Toronto Department of Psychiatry’s Travel Award


  • SOBP's best poster award (As a Co-Investigator of Mr. Jun Ku Chung)


  • 慶應義塾大学医学部三四会奨励賞


  • International Congress on Schizophrenia Research’s Young Investigator Travel Award


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