2023/06/30 更新

写真a

ノガミ　ツヨシ
野上　毅
Nogami Tsuyoshi
所属
付属病院 精神神経科 講師
職名
講師
外部リンク

研究分野

  • ライフサイエンス / 精神神経科学

経歴

論文

  • Depression as a Prodromal Symptom of Neurodegenerative Diseases.

    Amane Tateno, Tsuyoshi Nogami, Takeshi Sakayori, Ken Yamamoto, Yoshiro Okubo

    Journal of Nippon Medical School = Nippon Ika Daigaku zasshi   90 ( 2 )   157 - 164   2023年

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Neurodegenerative diseases can manifest as psychiatric symptoms in the prodromal phase, before the onset of core symptoms such as neurological, motor, and cognitive symptoms. Positron emission tomography (PET) has made it possible to detect the pathology of some neurodegenerative diseases in vivo. Many studies have indicated that depression is a preclinical symptom of neurodegenerative diseases. Approximately 10% of non-demented participants with depression developed Alzheimer's disease (AD) during the follow-up period. The prevalence of depression/dysphoria was 42.9% in the preclinical stage of dementia with Lewy bodies. Depression was present in 33.3% of patients with preclinical behavioral-variant frontotemporal lobar degeneration. Approximately 10% of patients had a history of depression at the time of diagnosis with Parkinson's disease. PET studies have revealed the pathology of neurodegenerative diseases in some cases of geriatric depression. Increased brain amyloid-beta deposition in late-onset depression is a possible reflection of prodromal AD. The severity of depression was significantly associated with greater inferior temporal tau and marginally associated with greater entorhinal cortex tau, and depression was associated with significantly greater mean cortical tau deposition. Thus, the presence of depression as a preclinical/prodromal symptom of neurodegenerative diseases has been demonstrated by epidemiological, pathological, and biomarker studies. A growing body of evidence from PET studies indicates that some cases of geriatric depression have pathologies of degenerative neurological disease. In the future, it is expected that PET will be utilized as an imaging biomarker for diagnosis of psychiatric disorders and development of new therapeutic agents.

    DOI： 10.1272/jnms.JNMS.2023_90-216

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  • Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I

    Tsuyoshi Nogami, Ryosuke Arakawa, Takeshi Sakayori, Yumiko Ikeda, Yoshiro Okubo, Amane Tateno

    Frontiers in Psychiatry   13   2022年5月

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    掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

    Rationale

    Since ephedrine has a dopamine transporter (DAT) inhibitory effect similar to amphetamine, dl-methylephedrine, a derivative of ephedrine, is considered to have the characteristics of a central nervous system stimulant due to the DAT inhibitory effect. For example, the World Anti-Doping Agency categorizes dl-methylephedrine as a stimulant in the prohibited list for competitions. Assuming to have the same effect as ephedrine, the urinary concentration of dl-methylephedrine is regulated below 10 μg/mL, as is ephedrine. However, the extent to which dl-methylephedrine affects brain function is not yet fully understood.

    Objectives

    The purpose of this study was to evaluate DAT occupancy by a single oral administration of a daily dose of dl-methylephedrine using positron emission tomography (PET) with [18F]FE-PE2I to characterize its stimulatory effect on the central nervous system.

    Methods

    Nine healthy male volunteers were enrolled in the study. The experiments were designed as a placebo-controlled randomized double-blind crossover comparative study. After the first PET scan in a drug-free state, the second and third PET scans were performed with randomized dosing at 60 mg of dl-methylephedrine or placebo. The plasma and urine concentrations of dl-methylephedrine were measured just before and after the PET scans, respectively.

    Results

    Mean urine and plasma concentrations of dl-methylephedrine were 13.9 μg/mL and 215.2 ng/mL, respectively. Mean DAT occupancy in the caudate was 4.4% for dl-methylephedrine and 1.2% for placebo. Mean DAT occupancy in the putamen was 3.6% for dl-methylephedrine and 0.5% for placebo. There was no significant difference of DAT occupancies between the groups.

    Conclusion

    In this study, the urinary concentration of dl-methylephedrine (13.9 μg/mL) was higher than the prohibited reference value (10.0 μg/mL), and there was no significant difference in DAT occupancy between dl-methylephedrine and placebo. These findings suggest that a clinical daily dose of dl-methylephedrine may exceed the doping regulation value according to urine concentration; however, it was considered that at least the central excitatory effect mediated by DAT inhibition was not observed at the daily dose of dl-methylephedrine.

    DOI： 10.3389/fpsyt.2022.799319

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  • A positron emission tomography study of the serotonin1B receptor effect of electroconvulsive therapy for severe major depressive episodes. 国際誌

    Mikael Tiger, Martin Gärde, Amane Tateno, Granville J Matheson, Takeshi Sakayori, Tsuyoshi Nogami, Hiroki Moriya, Katarina Varnäs, Ryosuke Arakawa, Yoshiro Okubo

    Journal of affective disorders   294   645 - 651   2021年11月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders, although its molecular mechanism of action is unknown. The serotonin 1B (5-HT1B) receptor is a potential target for treatment of depression and low 5-HT1B receptor binding in limbic regions has been reported in previous positron emission tomography (PET) studies of depression. METHODS: The objective of this longitudinal PET study was to examine the effect of ECT for depression on 5-HT1B receptor binding. Fifteen hospitalized patients with major depressive episodes were examined with PET and the 5-HT1B receptor selective radioligand [11C]AZ10419369, before and after ECT. Fifteen controls matched for age and sex were examined. Limbic regions with previously reported low 5-HT1B receptor binding in depression and a dorsal brain stem region were selected. RESULTS: Thirteen patients completed the study according to protocol. Eleven out of thirteen patients responded to ECT. 5-HT1B receptor binding in hippocampus increased with 30 % after ECT (p=0.021). Using linear mixed effects modelling, we observed increases in 5-HT1B receptor binding following ECT with a moderate to large effect size, which did not differ significantly between regions. In an exploratory analysis, strong correlations between changes in 5-HT1B receptor binding and agitation scores on the Hamilton Depression Rating Scale after ECT were observed. LIMITATIONS: Albeit representative of a PET study, the sample size is still small and there are potential confounding effects of medication. CONCLUSIONS: Increased 5-HT1B receptor binding was observed following ECT for depression, corresponding to previous findings of increased 5-HT1B receptor binding in hippocampus after rapid acting ketamine for treatment resistant depression.

    DOI： 10.1016/j.jad.2021.07.060

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  • Potential for imaging the high-affinity state of the 5-HT receptor: a comparison of three PET radioligands with differing intrinsic activity.

    Lindberg Anton, Arakawa Ryosuke, Nogami Tsuyoshi, Nag Sangram, Schou Magnus, Elmore Charles S, Farde Lars, Pike Victor W, Halldin Christer

    EJNMMI research   9 ( 1 )   100   2019年11月

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    記述言語：英語  

    Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT receptors. The 5-HT receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity C-labeled 5-HT PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release.A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [C]3. The most antagonistic radioligand show

    DOI： 10.1186/s13550-019-0570-1

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  • Development of a F-labeled PET radioligand for imaging 5-HT receptors: [F]AZ10419096.

    Lindberg Anton, Nag Sangram, Schou Magnus, Arakawa Ryosuke, Nogami Tsuyoshi, Moein Mohammad Mahdi, Elmore Charles S, Pike Victor W, Halldin Christer

    Nuclear medicine and biology   78-79   11 - 16   2019年

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    記述言語：英語  

    DOI： 10.1016/j.nucmedbio.2019.10.003

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  • 救急患者精神科継続支援開始後の院内体制整備の取り組みに関する報告

    大高 靖史, 成重 竜一郎, 肥田 道彦, 野上 毅, 坂寄 健, 朝山 健太郎, 高野 亜希子, 高橋 馨, 金 禹瑣, 増岡 孝浩, 西川 律子, 飯田 謙司, 大久保 善朗

    総合病院精神医学   29 ( Suppl. )   S - 137   2017年11月

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    記述言語：日本語   出版者・発行元：(一社)日本総合病院精神医学会  

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  • 精神保健福祉法改正の要点と精神科救急医療に関する行政の取り組み (第23回日本精神科救急学会総会 シンポジウム) -- (特集 精神科救急医療と精神保健福祉法)

    野上 毅

    精神科救急 : 日本精神科救急学会誌   19 ( 19 )   2 - 6   2016年11月

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    記述言語：日本語   出版者・発行元：日本精神科救急学会  

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  • わが国の精神保健医療の現状と身体合併症 (総合医学会報告 シンポジウム 精神科身体合併症医療における地域連携)

    野上 毅

    医療 = Japanese journal of National Medical Services : 国立医療学会誌   70 ( 10 )   413 - 417   2016年10月

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    記述言語：日本語   出版者・発行元：国立医療学会  

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  • Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer ¹¹C-AZD2184. 国際誌

    Ito Hiroshi, Shimada Hitoshi, Shinotoh Hitoshi, Takano Harumasa, Sasaki Takeshi, Nogami Tsuyoshi, Suzuki Masayuki, Nagashima Tomohisa, Takahata Keisuke, Seki Chie, Kodaka Fumitoshi, Eguchi Yoko, Fujiwara Hironobu, Kimura Yasuyuki, Hirano Shigeki, Ikoma Yoko, Higuchi Makoto, Kawamura Kazunori, Fukumura Toshimitsu, Böö Éva Lindström, Farde Lars, Suhara Tetsuya

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine   55 ( 6 )   932 - 8   2014年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-β deposits and neurofibrillary tangles. Recently, a new radioligand for amyloid senile plaques, (11)C-labeled 5-(6-{[tert-butyl(dimethyl)silyl]oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine ((11)C-AZD2184), was developed, and it was reported to show rapid brain uptake followed by rapid washout. In this study, (11)C-AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods using a reference brain region was also evaluated.After intravenous bolus injection of (11)C-AZD2184, a dynamic PET scan was obtained for 90 min in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and high-performance liquid chromatography analysis were performed.Time-activity curves in all brain regions could be described using the standard 2-tissue-compartment model. The total distribution volume ratios to reference region (DVR) in cerebral cortical regions were significantly higher in AD patients than in control subjects. Although there

    DOI： 10.2967/jnumed.113.133793

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  • Quantitative Analysis of Amyloid Deposition in Alzheimer Disease Using PET and the Radiotracer 11C-AZD2184. 査読

    Ito H, Shimada H, Shinotoh H, Takano H, Sasaki T, Nogami T, Suzuki M, Nagashima T, Takahata K, Seki C, Kodaka F, Eguchi Y, Fujiwara H, Kimura Y, Hirano S, Ikoma Y, Higuchi M, Kawamura K, Fukumura T, Böö EL, Farde L, Suhara T

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine   55 ( 6 )   932 - 938   2014年4月

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  • Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[¹⁸F]FMeNER-D₂. 国際誌

    Takano Harumasa, Arakawa Ryosuke, Nogami Tsuyoshi, Suzuki Masayuki, Nagashima Tomohisa, Fujiwara Hironobu, Kimura Yasuyuki, Kodaka Fumitoshi, Takahata Keisuke, Shimada Hitoshi, Murakami Yoshitaka, Tateno Amane, Yamada Makiko, Ito Hiroshi, Kawamura Kazunori, Zhang Ming-Rong, Takahashi Hidehiko, Kato Motoichiro, Okubo Yoshiro, Suhara Tetsuya

    The international journal of neuropsychopharmacology   17 ( 4 )   553 - 60   2014年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies in the brain as a result of the administration of 75-200 mg/d of nortriptyline. The estimated effective dose (ED₅₀) and concentration (EC₅₀) required to induce 50% occupancy was 65.9 mg/d a

    DOI： 10.1017/S1461145713001521

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  • Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[¹⁸F]FMeNER-D₂. 査読

    Takano H, Arakawa R, Nogami T, Suzuki M, Nagashima T, Fujiwara H, Kimura Y, Kodaka F, Takahata K, Shimada H, Murakami Y, Tateno A, Yamada M, Ito H, Kawamura K, Zhang MR, Takahashi H, Kato M, Okubo Y, Suhara T

    The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)   17 ( 4 )   553 - 560   2014年4月

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  • Reproducibility of PET measurement for presynaptic dopaminergic functions using L-[β-(11)C]DOPA and [(18)F]FE-PE2I in humans. 査読

    Suzuki M, Ito H, Kodaka F, Takano H, Kimura Y, Fujiwara H, Sasaki T, Takahata K, Nogami T, Nagashima T, Nengaki N, Kawamura K, Zhang MR, Varrone A, Halldin C, Okubo Y, Suhara T

    Nuclear medicine communications   35 ( 3 )   231 - 237   2014年3月

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  • Reproducibility of PET measurement for presynaptic dopaminergic functions using L-[β-(11)C]DOPA and [(18)F]FE-PE2I in humans. 国際誌

    Suzuki Masayuki, Ito Hiroshi, Kodaka Fumitoshi, Takano Harumasa, Kimura Yasuyuki, Fujiwara Hironobu, Sasaki Takeshi, Takahata Keisuke, Nogami Tsuyoshi, Nagashima Tomohisa, Nengaki Nobuki, Kawamura Kazunori, Zhang Ming-Rong,Varrone Andrea,Halldin Christer, Okubo Yoshiro, Suhara Tetsuya

    Nuclear medicine communications   35 ( 3 )   231 - 7   2014年3月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Recent PET studies have indicated altered presynaptic function and relation with psychotic symptoms in patients with schizophrenia. The L-[β-(11)C]DOPA uptake rate reflects the dopamine synthesis capacity (kref), whereas the nondisplaceable binding potential (BPND) of [(18)F]FE-PE2I reflects the dopamine transporter availability. Although the kref values of L-[β-(11)C]DOPA and the BPND of [(18)F]FE-PE2I can be potential markers for evaluating the severity of positive symptoms, test-retest reproducibility has not been confirmed. The purpose of this study was to investigate the test-retest reproducibility of kref values of L-[β-(11)C]DOPA and that of BPND of [(18)F]FE-PE2I in the striatum and midbrain in healthy humans.Twelve healthy male volunteers underwent two PET studies on separate days. Each PET study comprised two PET scans, one with L-[β-(11)C]DOPA and the other with [(18)F]FE-PE2I. Volumes of interest were defined for the caudate, putamen, midbrain, and thalamus. Test-retest reproducibility was assessed in terms of intrasubject variability (absolute variability) and reliability [intraclass correlation coefficient (ICC)].The absolute variability values of kref and BPND we

    DOI： 10.1097/MNM.0000000000000052

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  • Relation between Dopamine Synthesis Capacity and Cell-Level Structure in Human Striatum: A Multi-Modal Study with Positron Emission Tomography and Diffusion Tensor Imaging

    Hiroshi Kawaguchi, Takayuki Obata, Harumasa Takano, Tsuyoshi Nogami, Tetsuya Suhara, Hiroshi Ito

    PLOS ONE   9 ( 1 )   e87886   2014年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

    Positron emission tomography (PET) study has shown that dopamine synthesis capacity varied among healthy individuals. This interindividual difference might be due to a difference in the cell-level structure of presynaptic dopaminergic neurons, i.e., cellular density and/or number. In this study, the relations between the dopamine synthesis capacity measured by PET and the parameter estimates in diffusion tensor imaging (DTI) in striatal subregions were investigated in healthy human subjects. DTI and PET studies with carbon-11 labeled L-DOPA were performed in ten healthy subjects. Age-related changes in the above parameters were also considered. Fractional anisotropy showed a significant positive correlation with age in the posterior caudate. There was significant negative correlation between dopamine synthesis capacity and mean diffusivity in the posterior caudate and putamen. Assuming that mean diffusivity reflects the density of wide-spreading axonal terminals in the striatum, the result suggests that dopamine synthesis may be related to the density of dopaminergic neuronal fibers. It is evident that PET/DTI combined measurements can contribute to investigations of the pathophysiology of neuropsychiatric diseases involving malfunction of dopaminergic neurons.

    DOI： 10.1371/journal.pone.0087886

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  • Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2). 国際誌

    Tsuyoshi Nogami, Harumasa Takano, Ryosuke Arakawa, Tetsuya Ichimiya, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Takeshi Sasaki, Keisuke Takahata, Masayuki Suzuki, Tomohisa Nagashima, Takaaki Mori, Hitoshi Shimada, Hajime Fukuda, Mizuho Sekine, Amane Tateno, Hidehiko Takahashi, Hiroshi Ito, Yoshiro Okubo, Tetsuya Suhara

    The international journal of neuropsychopharmacology   16 ( 5 )   937 - 43   2013年6月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported >80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2), in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED(50) was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupancies were observed in a dose-dependent manner. Both 5-HTT and NET occupancies were about 40% by milnacipran at 100 mg, the dose most commonly administered to MDD patients.

    DOI： 10.1017/S1461145712001009

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  • Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2). 査読

    Nogami T, Takano H, Arakawa R, Ichimiya T, Fujiwara H, Kimura Y, Kodaka F, Sasaki T, Takahata K, Suzuki M, Nagashima T, Mori T, Shimada H, Fukuda H, Sekine M, Tateno A, Takahashi H, Ito H, Okubo Y, Suhara T

    The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)   16 ( 5 )   937 - 943   2013年6月

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  • Effects of menopause on brain structural changes in schizophrenia

    Hajime Fukuta, Itsuo Ito, Amane Tateno, Tsuyoshi Nogami, Yasutomo Taiji, Ryosuke Arakawa, Tetsuya Suhara, Kunihiko Asai, Yoshiro Okubo

    Psychiatry and Clinical Neurosciences   67 ( 1 )   3 - 11   2013年1月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Aim The aim of this study was to investigate the influences of menopause on brain morphological changes in schizophrenia using magnetic resonance imaging (MRI). Methods Forty female schizophrenia patients, 20 premenopausal and 20 postmenopausal, and 50 female controls underwent cerebral MRI. Optimized voxel-based morphometry was performed with Statistical Parametric Mapping version 5. Results Compared with controls, regional gray matter reductions in schizophrenia patients were observed in the insula, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, and thalamus. Direct comparison between the patient groups showed that the gray matter of postmenopausal patients was significantly smaller when compared with premenopausal patients in the left middle frontal gyrus, and no region had significantly lower gray matter volume in premenopausal patients relative to postmenopausal patients. Significant negative correlation between gray matter volume and the interval after menopause was found in the right superior frontal gyrus in the postmenopause patient group. Conclusion Differential morphological alterations between postmenopausal and premenopausal schizophrenia patients were observed, suggesting that the female hormone plays a protective role against schizophrenia. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

    DOI： 10.1111/pcn.12003

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  • Effects of menopause on brain structural changes in schizophrenia. 査読

    Fukuta H, Ito I, Tateno A, Nogami T, Taiji Y, Arakawa R, Suhara T, Asai K, Okubo Y

    Psychiatry and clinical neurosciences   67 ( 1 )   3 - 11   2013年1月

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  • [Effect of menopause on morphological changes of the brain in schizophrenia]. 査読

    Fukuta H, Ito I, Tateno A, Nogami T, Taiji Y, Arakawa R, Suhara T, Asai K, Okubo Y

    Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica   115 ( 12 )   1178 - 1185   2013年

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  • Effects of dopamine D2 receptor partial agonist antipsychotic aripiprazole on dopamine synthesis in human brain measured by PET with L-[β-11C]DOPA.

    Ito Hiroshi, Takano Harumasa, Arakawa Ryosuke, Takahashi Hidehiko, Kodaka Fumitoshi, Takahata Keisuke, Nogami Tsuyoshi, Suzuki Masayuki, Suhara Tetsuya

    PloS one   7 ( 9 )   e46488   2012年9月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Dopamine D(2) receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2) receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11)C]raclopride and L-[β-(11)C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2) receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2) receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamin

    DOI： 10.1371/journal.pone.0046488

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  • Striatal and extrastriatal dopamine D₂ receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [¹¹C]raclopride and [¹¹C]FLB457. 査読

    Takahata K, Ito H, Takano H, Arakawa R, Fujiwara H, Kimura Y, Kodaka F, Sasaki T, Nogami T, Suzuki M, Nagashima T, Shimada H, Kato M, Mimura M, Suhara T

    Psychopharmacology   222 ( 1 )   165 - 172   2012年7月

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  • Quantification of dopamine transporter in human brain using PET with 18F-FE-PE2I. 国際誌

    Takeshi Sasaki, Hiroshi Ito, Yasuyuki Kimura, Ryosuke Arakawa, Harumasa Takano, Chie Seki, Fumitoshi Kodaka, Saori Fujie, Keisuke Takahata, Tsuyoshi Nogami, Masayuki Suzuki, Hironobu Fujiwara, Hidehiko Takahashi, Ryuji Nakao, Toshimitsu Fukumura, Andrea Varrone, Christer Halldin, Toru Nishikawa, Tetsuya Suhara

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine   53 ( 7 )   1065 - 73   2012年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    UNLABELLED: (18)F-(E)-N-(3-iodoprop-2E-enyl)-2β-carbofluoroethoxy-3β-(4-methylphenyl)nortropane ((18)F-FE-PE2I) is a new PET radioligand with a high affinity and selectivity for the dopamine transporter (DAT). In nonhuman primates, (18)F-FE-PE2I showed faster kinetics and less production of radiometabolites that could potentially permeate the blood-brain barrier than did (11)C-PE2I. The aims of this study were to examine the quantification of DAT using (18)F-FE-PE2I and to assess the effect of radiometabolites of (18)F-FE-PE2I on the quantification in healthy humans. METHODS: A 90-min dynamic PET scan was obtained for 10 healthy men after intravenous injection of (18)F-FE-PE2I. Kinetic compartment model analysis with a metabolite-corrected arterial input function was performed. The effect of radiometabolites on the quantification was evaluated by time-stability analyses. The simplified reference tissue model (SRTM) method with the cerebellum as a reference region was evaluated as a noninvasive method of quantification. RESULTS: After the injection of (18)F-FE-PE2I, the whole-brain radioactivity showed a high peak (∼3-5 standardized uptake value) and fast washout. The radioactive uptake of (18)F-FE-PE2I in the brain was according to the relative density of the DAT (striatum > midbrain > thalamus). The cerebellum showed the lowest uptake. Tissue time-activity curves were well described by the 2-tissue-compartment model (TCM), as compared with the 1-TCM, for all subjects in all regions. Time stability analysis showed stable estimation of total distribution volume with 60-min or longer scan durations, indicating the small effect of radiometabolites. Binding potentials in the striatum and midbrain were well estimated by the SRTM method, with modest intersubject variability. Although the SRTM method yielded a slight underestimation and overestimation in regions with high and low DAT densities, respectively, binding potentials by the SRTM method were well correlated to the estimates by the indirect kinetic method with 2-TCM. CONCLUSION: (18)F-FE-PE2I is a promising PET radioligand for quantifying DAT. The binding potentials could be reliably estimated in both the striatum and midbrain using both the indirect kinetic and SRTM methods with a scan duration of 60 min. Although radiometabolites of (18)F-FE-PE2I in plasma possibly introduced some effects on the radioactivity in the brain, the effects on estimated binding potential were likely to be small.

    DOI： 10.2967/jnumed.111.101626

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  • Quantification of dopamine transporter in human brain using PET with 18F-FE-PE2I. 査読

    Sasaki T, Ito H, Kimura Y, Arakawa R, Takano H, Seki C, Kodaka F, Fujie S, Takahata K, Nogami T, Suzuki M, Fujiwara H, Takahashi H, Nakao R, Fukumura T, Varrone A, Halldin C, Nishikawa T, Suhara T

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine   53 ( 7 )   1065 - 1073   2012年7月

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  • Striatal and extrastriatal dopamine D₂ receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [¹¹C]raclopride and [¹¹C]FLB457. 国際誌

    Takahata Keisuke, Ito Hiroshi, Takano Harumasa, Arakawa Ryosuke, Fujiwara Hironobu, Kimura Yasuyuki, Kodaka Fumitoshi, Sasaki Takeshi, Nogami Tsuyoshi, Suzuki Masayuki, Nagashima Tomohisa, Shimada Hitoshi, Kato Motoichiro, Mimura Masaru, Suhara Tetsuya

    Psychopharmacology   222 ( 1 )   165 - 72   2012年7月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D₂ receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D₂ receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D₂ receptors have reported inconsistent results regarding regional differences of dopamine D₂ receptor occupancy by aripiprazole.To test the hypothesis of preferential binding to extrastriatal dopamine D₂ receptors by aripiprazole, we investigated its regional dopamine D₂ receptor occupancies in healthy young subjects.Using PET and two radioligands with different affinities for dopamine D₂ receptors, [¹¹C]raclopride and [¹¹C]FLB457, striatal and extrastriatal dopamine D₂ receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy

    DOI： 10.1007/s00213-011-2633-5

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  • Central nervous system drug evaluation using positron emission tomography. 国際誌

    Mizuho Sekine, Jun Maeda, Hitoshi Shimada, Tsuyoshi Nogami, Ryosuke Arakawa, Harumasa Takano, Makoto Higuchi, Hiroshi Ito, Yoshiro Okubo, Tetsuya Suhara

    Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology   9 ( 1 )   9 - 16   2011年4月

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    記述言語：英語   掲載種別：研究論文（学術雑誌）  

    In conventional pharmacological research in the field of mental disorders, pharmacological effect and dose have been estimated by ethological approach and in vitro data of affinity to the site of action. In addition, the frequency of administration has been estimated from drug kinetics in blood. However, there is a problem regarding an objective index of drug effects in the living body. Furthermore, the possibility that the concentration of drug in blood does not necessarily reflect the drug kinetics in target organs has been pointed out. Positron emission tomography (PET) techniques have made progress for more than 20 years, and made it possible to measure the distribution and kinetics of small molecule components in living brain. In this article, we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs in the drug development process using PET.

    DOI： 10.9758/cpn.2011.9.1.9

    PubMed

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  • 統合失調症とうつ病の分子イメージング (特集 脳疾患の分子イメージング)

    野上 毅, 荒川 亮介, 須原 哲也

    PET journal   ( 10 )   31 - 33   2010年

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    記述言語：日本語   出版者・発行元：寺田国際事務所先端医療技術研究所  

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MISC

  • PETイメージングを用いたうつ病におけるセロトニン1B受容体評価研究

    野上 毅, 守屋 洋紀, 増岡 孝浩, 坂寄 健, 舘野 周, 大久保 善朗

    先進医薬研究振興財団研究成果報告集   2017年度   24 - 25   2018年3月

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    記述言語：日本語  

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  • 若年性統合失調症に対し、アリピプラゾール持続型注射剤が奏功した一例

    藤本 泰樹, 野上 毅, 肥田 道彦, 成重 竜一郎, 舘野 周, 大久保 善朗

    精神神経学雑誌   119 ( 10 )   802 - 802   2017年10月

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    記述言語：日本語  

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  • 高齢者うつ病に対する運動療法の試み

    永田 恵理香, 秋山 友美, 太田 杏奈, 大和田 陽代, 松本 早栄子, 山本 憲, 小泉 公平, 野上 毅, 池森 紀夫, 下田 健吾, 木村 真人

    心身医学   54 ( 6 )   631 - 631   2014年6月

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    記述言語：日本語   出版者・発行元：(一社)日本心身医学会  

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  • 当院におけるうつ病に対する運動療法の試み

    永田 恵理香, 秋山 友美, 太田 杏奈, 大和田 陽代, 松本 早栄子, 山本 憲, 小泉 公平, 野上 毅, 池森 紀夫, 下田 健吾, 木村 真人

    総合病院精神医学   26 ( 2 )   203 - 203   2014年4月

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    記述言語：日本語   出版者・発行元：(一社)日本総合病院精神医学会  

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  • 光トポグラフィー検査で双極性障害パターンと評価された患者の特徴

    永田恵理香, 秋山友美, 太田杏奈, 大和田陽代, 増岡孝治, 山本憲, 松本早栄子, 野上毅, 大森中, 池森紀夫, 下田健吾, 木村真人

    日本うつ病学会総会プログラム・抄録集   11th   2014年

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  • 精神医学のフロンティア 統合失調症の脳形態変化における閉経の影響について

    福田 一, 伊藤 逸生, 舘野 周

    精神神経学雑誌   115 ( 12 )   1178 - 1185   2013年12月

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    記述言語：日本語   出版者・発行元：日本精神神経学会  

    統合失調症の脳形態変化における閉経の影響について、患者群を閉経患者と非閉経患者の2群に分けMRIを用いて調査した。最終月経からMRI撮像までの期間が12ヵ月以上である統合失調症女性患者20名と同時期が12ヵ月未満であり閉経患者群と年齢を一致させた統合失調症女性患者20名(平均41.8±9.0歳)を対象とした。分析の結果、非閉経患者群と比較し、閉経患者群において左中前頭回の灰白質に有意な体積減少を認めた。一方、非閉経患者群が閉経患者群と比較して有意に体積減少している部位は認められなかった。閉経患者20名において、閉経後経過年数と脳体積の相関を調べた結果、右上前頭回の灰白質体積と閉経後経過年数に負の相関が認められた。健常者が閉経する平均年齢は50から52歳の間であるとされるが、今回の閉経患者群においては、若年期に最終月経がきており、原因の一つに抗精神薬の副作用であることが考えられた。

    CiNii Books

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  • ドーパミン生成能およびドーパミントランスポーター結合能の測定再現性に関する研究

    鈴木 雅之, 伊藤 浩, 高野 晴成, 藤原 広臨, 木村 泰之, 小高 文聰, 高畑 圭輔, 佐々木 健至, 野上 毅, 大久保 喜朗, 須原 哲也

    核医学   49 ( 3 )   S235 - S235   2012年8月

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    記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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共同研究・競争的資金等の研究課題

  • PETを用いたうつ病のECT後の効果維持に関する予測因子の解明

    研究課題/領域番号：20K16656  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    野上 毅

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    配分額：4160000円 （ 直接経費：3200000円 、 間接経費：960000円 ）

    電気けいれん療法(electroconvulsive therapy: ECT)は、うつ病において最も効果のある治療法の一つであり、特に薬剤抵抗性のうつ病や重症のうつ病に対して行われている。一方で、ECTは終了後に薬物療法等の維持療法を行わないと3カ月以内に6割の患者が再燃するとの報告がある。過去の我々のPET研究からECT治療直後の評価でドーパミン神経伝達が重要な役割を持つことを示唆している。一方で、これまでECT治療の経過を経時的に評価したPET研究はない。今回[18F]FE-PE2Iを用いてECT治療後のドーパミントランスポーター機能をPETにより経時的に評価し、うつ病の症状の変化との関連を調べることにより、ECTの作用機序やうつ病の治療効果に対する病態解明に寄与することが出来ると考える。
    当初の計画においては最初の2年において12名のECT治療による治療に同意したうつ病患者を対象としてMRIによる形態画像検査、ハミルトンうつ病評価尺度(HAM-D)などの神経心理学的検査、初回ECT開始前にDAT機能を評価するための[18F]FE-PE2Iを用いたPET撮像を行い、更にECT治療後数日以内に[18F]FE-PE2Iを用いたPET撮像を行う予定であった。また、それらの被検者をそれぞれECT治療1カ月後、3か月後、6か月後、1年後に振り分けて経時的なDAT機能の評価を行う予定であった。
    しかし、被検者の選定や検査スケジュールなどの調整を行ったものの、COVID-19の影響により病院から敷地外のPETセンターへの移動の制限が解除されておらず、なかなか研究を進めることが出来きていない状況である。

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  • タウ蛋白PETイメージングからみた老年期うつ病の治療反応性の解明

    研究課題/領域番号：20K07981  2020年4月 - 2023年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    荒川 亮介, 大久保 善朗, 舘野 周, 野上 毅, 坂寄 健

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    配分額：4290000円 （ 直接経費：3300000円 、 間接経費：990000円 ）

    高齢者のうつ病治療においては、通常の薬物療法に反応が乏しいことがしばしば見受けられる。その背景に、アルツハイマー型認知症をはじめとする器質性疾患の前駆症状としてのうつ状態、もしくはその合併があるとする報告があるが、臨床症状からの判断だけでは、その鑑別や確認を行うのは困難であることが多い。アルツハイマー型認知症の病態生理の代表的なものとして、老人斑（アミロイドβ）と神経原繊維変化（タウ蛋白）があげられる。アミロイドβについては、PETにより生体内において脳内集積を評価出来るようになっており、アルツハイマー型認知症で認められる病理が高齢者のうつ病発症に関与している可能性が報告されている。一方、アルツハイマー型認知症の認知機能障害の程度は、タウ蛋白の局所集積と関連するという報告があり、タウ蛋白による局所神経細胞脱落が精神・神経症状の出現、進行に強く関与していることが示唆されている。近年、タウ蛋白を対象としたPETリガンドの開発が盛んに行われているが、従来の[11C]PBB3等のPETリガンドについては、脳内のタウ蛋白の定量に一定の制限があることが指摘されている。これらの問題点を改良した[18F]PM-PBB3が開発され、臨床応用が進められているところである。
    本年度は、6名の寛解期にあるうつ病患者に対して、[18F]PM-PBB3を用いたPET測定を行い、６名全てでタウ蛋白の集積は認められなかった。昨年度の結果と合わせると、１名のみが陽性で、残り７名は陰性と判断された。このことから、同様の寛解期にあるうつ病患者においても、その脳内のタウ蛋白の集積に大きな差があることが判明した。

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  • うつ病におけるセロトニン１B受容体のPETイメージングを用いた評価研究

    研究課題/領域番号：17K16400  2017年4月 - 2020年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    野上 毅

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    配分額：4160000円 （ 直接経費：3200000円 、 間接経費：960000円 ）

    寛解のうつ病患者群は男性6名、女性6名、平均年齢53歳、HAM-D4.4点、難治性のうつ病患者群は男性5名、女性7名、平均年齢59歳、HAM-D22.9点、健常対象群は男性6名、女性6名、平均年齢53歳を対象とした。線条体におけるセロトニン1B受容体結合能の平均は、健常対象群、寛解の患者群、難治性の患者群の順で2.53、2.29、2.56、後頭皮質での平均は、1.67、1.43、1.32であった。明らかな群間差は認めなかったものの、後頭皮質では健常対象群、寛解群、難治群でセロトニン1B受容体結合能が低下する傾向が認められた。

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