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1. Structural aging of human neurons is the opposite of the changes in schizophrenia

Author

Mizutani, Ryuta, Saiga, Rino, Yamamoto, Yoshiro, Uesugi, Masayuki, Takeuchi, Akihisa, Uesugi, Kentaro, Terada, Yasuko, Suzuki, Yoshio, De Andrade, Vincent, De Carlo, Francesco, Takekoshi, Susumu, Inomoto, Chie, Nakamura, Naoya, Torii, Youta, Kushima, Itaru, Iritani, Shuji, Ozaki, Norio, Oshima, Kenichi, Itokawa, Masanari, and Arai, Makoto

Subjects
Quantitative Biology - Neurons and Cognition, Physics - Biological Physics, Physics - Medical Physics, Quantitative Biology - Tissues and Organs
Abstract

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 x 10^(-4)). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 x 10^(-4)), indicating that neurite structure is relevant to brain function. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia. This nano-CT paper is the result of our decade-long analysis and is unprecedented in terms of number of cases., Comment: 24 pages, 5 figures. arXiv admin note: text overlap with arXiv:2007.00212

Published
2022
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2. Structural diverseness of neurons between brain areas and between cases

Author

Mizutani, Ryuta, Saiga, Rino, Yamamoto, Yoshiro, Uesugi, Masayuki, Takeuchi, Akihisa, Uesugi, Kentaro, Terada, Yasuko, Suzuki, Yoshio, De Andrade, Vincent, De Carlo, Francesco, Takekoshi, Susumu, Inomoto, Chie, Nakamura, Naoya, Torii, Youta, Kushima, Itaru, Iritani, Shuji, Ozaki, Norio, Oshima, Kenichi, Itokawa, Masanari, and Arai, Makoto

Subjects
Quantitative Biology - Neurons and Cognition, Physics - Biological Physics
Abstract

The cerebral cortex is composed of multiple cortical areas that exert a wide variety of brain functions. Although human brain neurons are genetically and areally mosaic, the three-dimensional structural differences between neurons in different brain areas or between the neurons of different individuals have not been delineated. Here, we report a nanometer-scale geometric analysis of brain tissues of the superior temporal gyrus of 4 schizophrenia and 4 control cases by using synchrotron radiation nanotomography. The results of the analysis and a comparison with results for the anterior cingulate cortex indicated that 1) neuron structures are dissimilar between brain areas and that 2) the dissimilarity varies from case to case. The structural diverseness was mainly observed in terms of the neurite curvature that inversely correlates with the diameters of the neurites and spines. The analysis also revealed the geometric differences between the neurons of the schizophrenia and control cases, suggesting that neuron structure is associated with brain function. The area dependency of the neuron structure and its diverseness between individuals should represent the individuality of brain functions., Comment: 3 figures

Published
2020

3. Three-dimensional alteration of neurites in schizophrenia

Author

Mizutani, Ryuta, Saiga, Rino, Takeuchi, Akihisa, Uesugi, Kentaro, Terada, Yasuko, Suzuki, Yoshio, De Andrade, Vincent, De Carlo, Francesco, Takekoshi, Susumu, Inomoto, Chie, Nakamura, Naoya, Kushima, Itaru, Iritani, Shuji, Ozaki, Norio, Ide, Soichiro, Ikeda, Kazutaka, Oshima, Kenichi, Itokawa, Masanari, and Arai, Makoto

Subjects
Quantitative Biology - Neurons and Cognition, Physics - Biological Physics
Abstract

This paper reports nano-CT analysis of brain tissues of schizophrenia and control cases. The analysis revealed that: (1) neuronal structures vary between individuals, (2) the mean curvature of distal neurites of the schizophrenia cases was 1.5 times higher than that of the controls, and (3) dendritic spines were categorized into two geometrically distinctive groups, though no structural differences were observed between the disease and control cases. The differences in the neurite curvature result in differences in the spatial trajectory and hence alter neuronal circuits. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia., Comment: 24 pages, 4 figures, and 1 table. Supplementary materials are available from DOI link

Published
2018
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4. Cross-Disorder Analysis of Genic and Regulatory Copy Number Variations in Bipolar Disorder, Schizophrenia, and Autism Spectrum Disorder

Author

Kushima, Itaru, Nakatochi, Masahiro, Aleksic, Branko, Okada, Takashi, Kimura, Hiroki, Kato, Hidekazu, Morikawa, Mako, Inada, Toshiya, Ishizuka, Kanako, Torii, Youta, Nakamura, Yukako, Tanaka, Satoshi, Imaeda, Miho, Takahashi, Nagahide, Yamamoto, Maeri, Iwamoto, Kunihiro, Nawa, Yoshihiro, Ogawa, Nanayo, Iritani, Shuji, Hayashi, Yu, Lo, Tzuyao, Otgonbayar, Gantsooj, Furuta, Sho, Iwata, Nakao, Ikeda, Masashi, Saito, Takeo, Ninomiya, Kohei, Okochi, Tomo, Hashimoto, Ryota, Yamamori, Hidenaga, Yasuda, Yuka, Fujimoto, Michiko, Miura, Kenichiro, Itokawa, Masanari, Arai, Makoto, Miyashita, Mitsuhiro, Toriumi, Kazuya, Ohi, Kazutaka, Shioiri, Toshiki, Kitaichi, Kiyoyuki, Someya, Toshiyuki, Watanabe, Yuichiro, Egawa, Jun, Takahashi, Tsutomu, Suzuki, Michio, Sasaki, Tsukasa, Tochigi, Mamoru, Nishimura, Fumichika, Yamasue, Hidenori, Kuwabara, Hitoshi, Wakuda, Tomoyasu, Kato, Takahiro A., Kanba, Shigenobu, Horikawa, Hideki, Usami, Masahide, Kodaira, Masaki, Watanabe, Kyota, Yoshikawa, Takeo, Toyota, Tomoko, Yokoyama, Shigeru, Munesue, Toshio, Kimura, Ryo, Funabiki, Yasuko, Kosaka, Hirotaka, Jung, Minyoung, Kasai, Kiyoto, Ikegame, Tempei, Jinde, Seiichiro, Numata, Shusuke, Kinoshita, Makoto, Kato, Tadafumi, Kakiuchi, Chihiro, Yamakawa, Kazuhiro, Suzuki, Toshimitsu, Hashimoto, Naoki, Ishikawa, Shuhei, Yamagata, Bun, Nio, Shintaro, Murai, Toshiya, Son, Shuraku, Kunii, Yasuto, Yabe, Hirooki, Inagaki, Masumi, Goto, Yu-ichi, Okumura, Yuto, Ito, Tomoya, Arioka, Yuko, Mori, Daisuke, and Ozaki, Norio

Published
2022
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5. Copy number variations in RNF216 and postsynaptic membrane–associated genes are associated with bipolar disorder: a case‐control study in the Japanese population.

Author

Nakatochi, Masahiro, Kushima, Itaru, Aleksic, Branko, Kimura, Hiroki, Kato, Hidekazu, Inada, Toshiya, Torii, Youta, Takahashi, Nagahide, Yamamoto, Maeri, Iwamoto, Kunihiro, Nawa, Yoshihiro, Iritani, Shuji, Iwata, Nakao, Saito, Takeo, Ninomiya, Kohei, Okochi, Tomo, Hashimoto, Ryota, Yamamori, Hidenaga, Yasuda, Yuka, and Fujimoto, Michiko

Subjects
JAPANESE people, BIPOLAR disorder, GENE ontology, ODDS ratio, DATABASES
Abstract

Aim: Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population. Methods: Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene‐based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%. Results: The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66–14.89], false discovery rate < 10%). The BD‐associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05). Conclusion: We provide evidence that CNVs in RNF216 and postsynaptic membrane–related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

Published
2025
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8. Pathological alterations of chondroitin sulfate moiety in postmortem hippocampus of patients with schizophrenia

Author

Yukawa, Takayuki, Iwakura, Yuriko, Takei, Nobuyuki, Saito, Mami, Watanabe, Yuichiro, Toyooka, Kazuhiko, Igarashi, Michihiro, Niizato, Kazuhiro, Oshima, Kenichi, Kunii, Yasuto, Yabe, Hirooki, Matsumoto, Junya, Wada, Akira, Hino, Mizuki, Iritani, Shuji, Niwa, Shin-ichi, Takeuchi, Ryoko, Takahashi, Hitoshi, Kakita, Akiyoshi, Someya, Toshiyuki, and Nawa, Hiroyuki

Published
2018
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9. Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights

Author

Kushima, Itaru, Aleksic, Branko, Nakatochi, Masahiro, Shimamura, Teppei, Okada, Takashi, Uno, Yota, Morikawa, Mako, Ishizuka, Kanako, Shiino, Tomoko, Kimura, Hiroki, Arioka, Yuko, Yoshimi, Akira, Takasaki, Yuto, Yu, Yanjie, Nakamura, Yukako, Yamamoto, Maeri, Iidaka, Tetsuya, Iritani, Shuji, Inada, Toshiya, Ogawa, Nanayo, Shishido, Emiko, Torii, Youta, Kawano, Naoko, Omura, Yutaka, Yoshikawa, Toru, Uchiyama, Tokio, Yamamoto, Toshimichi, Ikeda, Masashi, Hashimoto, Ryota, Yamamori, Hidenaga, Yasuda, Yuka, Someya, Toshiyuki, Watanabe, Yuichiro, Egawa, Jun, Nunokawa, Ayako, Itokawa, Masanari, Arai, Makoto, Miyashita, Mitsuhiro, Kobori, Akiko, Suzuki, Michio, Takahashi, Tsutomu, Usami, Masahide, Kodaira, Masaki, Watanabe, Kyota, Sasaki, Tsukasa, Kuwabara, Hitoshi, Tochigi, Mamoru, Nishimura, Fumichika, Yamasue, Hidenori, Eriguchi, Yosuke, Benner, Seico, Kojima, Masaki, Yassin, Walid, Munesue, Toshio, Yokoyama, Shigeru, Kimura, Ryo, Funabiki, Yasuko, Kosaka, Hirotaka, Ishitobi, Makoto, Ohmori, Tetsuro, Numata, Shusuke, Yoshikawa, Takeo, Toyota, Tomoko, Yamakawa, Kazuhiro, Suzuki, Toshimitsu, Inoue, Yushi, Nakaoka, Kentaro, Goto, Yu-ichi, Inagaki, Masumi, Hashimoto, Naoki, Kusumi, Ichiro, Son, Shuraku, Murai, Toshiya, Ikegame, Tempei, Okada, Naohiro, Kasai, Kiyoto, Kunimoto, Shohko, Mori, Daisuke, Iwata, Nakao, and Ozaki, Norio

Published
2018
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10. Structural diverseness of neurons between brain areas and between cases

Author

Mizutani, Ryuta, Saiga, Rino, Yamamoto, Yoshiro, Uesugi, Masayuki, Takeuchi, Akihisa, Uesugi, Kentaro, Terada, Yasuko, Suzuki, Yoshio, De Andrade, Vincent, De Carlo, Francesco, Takekoshi, Susumu, Inomoto, Chie, Nakamura, Naoya, Torii, Youta, Kushima, Itaru, Iritani, Shuji, Ozaki, Norio, Oshima, Kenichi, Itokawa, Masanari, and Arai, Makoto

Published
2021
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15. Structural aging of human neurons is opposite of the changes in schizophrenia

Author

Mizutani, Ryuta, primary, Saiga, Rino, additional, Yamamoto, Yoshiro, additional, Uesugi, Masayuki, additional, Takeuchi, Akihisa, additional, Uesugi, Kentaro, additional, Terada, Yasuko, additional, Suzuki, Yoshio, additional, De Andrade, Vincent, additional, De Carlo, Francesco, additional, Takekoshi, Susumu, additional, Inomoto, Chie, additional, Nakamura, Naoya, additional, Torii, Youta, additional, Kushima, Itaru, additional, Iritani, Shuji, additional, Ozaki, Norio, additional, Oshima, Kenichi, additional, Itokawa, Masanari, additional, and Arai, Makoto, additional

Published
2023
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16. Neuropathological substrate of incident dementia in older patients with schizophrenia: A clinicopathological study.

Author

Arafuka, Shusei, Fujishiro, Hiroshige, Torii, Youta, Sekiguchi, Hirotaka, Habuchi, Chikako, Miwa, Ayako, Yoshida, Mari, Iritani, Shuji, Iwasaki, Yasushi, Ikeda, Masashi, and Ozaki, Norio

Subjects
OLDER patients, PROGRESSIVE supranuclear palsy, DEMENTIA patients, LEWY body dementia, PEOPLE with schizophrenia, ALZHEIMER'S disease
Abstract

Aim: Clinical studies reported that patients with schizophrenia are at a higher risk of developing dementia than people without schizophrenia. However, early neuropathological studies have shown that the incidence of Alzheimer's disease (AD) in schizophrenia patients does not differ from that in controls. These inconsistent results may be attributable to the inclusion of non‐AD dementia, but there have been few clinicopathological studies in older patients with schizophrenia based on the current neuropathological classification. This study aimed to investigate the neuropathological basis of incident dementia in older patients with schizophrenia. Methods: We systematically examined 32 brains of old patients with schizophrenia using standardized pathological methods. The severity of dementia‐related neuropathologies was analyzed using standardized semiquantitative assessments. After excluding patients who fulfilled the neuropathological criteria, clinicopathological variables were compared between patients with and without incident dementia to identify potential differences. Results: Seven patients fulfilled the pathological criteria for AD (n = 3), argyrophilic grain disease (AGD) (n = 2), dementia with Lewy bodies (n = 1), and AGD/progressive supranuclear palsy (n = 1). Among 25 patients for whom a neuropathological diagnosis was not obtained, 10 had dementia, but the clinicopathological findings did not differ from the remaining 15 patients without dementia. Conclusion: Two types of older schizophrenia patient present dementia: patients with co‐existing neurodegenerative disease and patients who do not meet pathological criteria based on the current classification. To understand the neurobiological aspects of incident dementia in older patients with schizophrenia, further clinicopathological studies are needed that do not simply analyze incident dementia as a comorbidity of conventional dementia‐related neuropathologies. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Striatal123I‐2β‐carbomethoxy‐3b‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane single‐photon emission computed tomography demonstrates nigral degeneration in the early stage of behavioural variant frontotemporal dementia: an autopsy case with frontotemporal lobar degeneration with trans‐activation response DNA protein 43 type B

Author

Arafuka, Shusei, primary, Fujishiro, Hiroshige, additional, Iritani, Shuji, additional, Torii, Youta, additional, Miwa, Ayako, additional, Yabata, Hiroyuki, additional, Sekiguchi, Hirotaka, additional, Habuchi, Chikako, additional, Kawashima, Kunihiro, additional, Yoshida, Mari, additional, Iwasaki, Yasushi, additional, and Ozaki, Norio, additional

Published
2022
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32. Temporal trajectories of proposed biomarkers in psychiatric‐onset prodromal dementia with Lewy bodies: a case report.

Author

Fujishiro, Hiroshige, Arafuka, Shusei, Ogasawara, Kazuyoshi, Iwamoto, Kunihiro, Miyata, Seiko, Torii, Youta, Iritani, Shuji, and Ozaki, Norio

Subjects
BIOMARKERS, APATHY, LEWY body dementia, AGITATION (Psychology), ACTIVITIES of daily living, MAGNETIC resonance imaging, POLYSOMNOGRAPHY, RAPID eye movement sleep, DYSPNEA, NEUROPSYCHOLOGICAL tests, DISEASE relapse, RADIONUCLIDE imaging, MENTAL depression, ATTENTION, SINGLE-photon emission computed tomography, DISEASE duration, ANOREXIA nervosa, INSOMNIA, FATIGUE (Physiology), ELECTROMYOGRAPHY, DISEASE risk factors, SYMPTOMS, OLD age
Abstract

A case study of a 69-year-old woman developed depressive mood with appetite loss, apathy, insomnia, agitation, decreased ability of concentration, fatigue, dyspnea, and thoughts of suicide, is presented. Topics include clinical profiles during two depressive episodes at hospitalization and discuss the potential predictors of higher risk of developing dementia with Lewy bodies (DLB); and dimer brain perfusion single-photon emission computed tomography showed localised occipital hypoperfusion.

Published
2023
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34. Schizophrenia-Like Behavioral Impairments in Mice with Suppressed Expression of Piccolo in the Medial Prefrontal Cortex

Author

Nitta, Atsumi, primary, Izuo, Naotaka, additional, Hamatani, Kohei, additional, Inagaki, Ryo, additional, Kusui, Yuka, additional, Fu, Kequan, additional, Asano, Takashi, additional, Torii, Youta, additional, Habuchi, Chikako, additional, Sekiguchi, Hirotaka, additional, Iritani, Shuji, additional, Muramatsu, Shin-ichi, additional, Ozaki, Norio, additional, and Miyamoto, Yoshiaki, additional

Published
2021
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35. Brain research and clinical psychiatry : establishment of a psychiatry brain bank in Japan

Author

Iritani, Shuji, Habuchi, Chikako, Sekiguchi, Hirotaka, and Torii, Youta

Subjects
neuropathology, clinical psychiatry, psychiatric disease, brain bank, brain research
Abstract

The Japan Agency of Medical Research and Development (AMED) has approved the budget for the 5-year project called Establishment of the JAPAN Brain Bank Network, which commenced in 2016. This project was established with the aim of storing brain tissue samples to enable research on the etiologies and mechanisms of psychiatric diseases, which would eventually improve standards of clinical treatment for these diseases. Japanese researchers in the field of biological psychiatry have historically depended on Western brain banks, particularly from Europe and the United States, which is regrettable. To remedy this situation and improve the Japanese research standards, attempts for establishing an autonomous Japanese brain bank are ongoing. Reviews of the previous attempts on elucidating the etiopathology of neuropsychiatric diseases reveal that rapid advances result from studies on tissue samples from diseased brains. For example, in the Kraepelin era, i.e. in 1900 years before and after, long-term, resolute research on diseased brain specimens ultimately led to the discoveries of entities such as Alzheimer disease and Lewy body disease. The recent advances in techniques of neuroimaging and molecular biology have resulted in a shift of interest from brain tissue analysis. However, the integration of findings of all these techniques is recommended going forward, with a shift in focus back to brain tissue analysis. The JAPAN Brain Bank Network project was launched under this setting. The success of this project largely depends on the will of patients and family members (for donating samples) as well as cooperation among many clinicians. In this paper, we provide a brief overview of the history of biological psychiatric research and related perspectives, which will hopefully encourage further studies that will help bridge the gap between clinical and biological research on psychiatric diseases.

Published
2018

39. Striatal 123I‐2β‐carbomethoxy‐3b‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane single‐photon emission computed tomography demonstrates nigral degeneration in the early stage of behavioural variant frontotemporal dementia: an autopsy case with frontotemporal lobar degeneration with trans‐activation response DNA protein 43 type B

Author

Arafuka, Shusei, Fujishiro, Hiroshige, Iritani, Shuji, Torii, Youta, Miwa, Ayako, Yabata, Hiroyuki, Sekiguchi, Hirotaka, Habuchi, Chikako, Kawashima, Kunihiro, Yoshida, Mari, Iwasaki, Yasushi, and Ozaki, Norio

Subjects
APATHY, FRONTAL lobe, DISEASE progression, DNA, RESPIRATORY insufficiency, ALKALOIDS, IMPULSIVE personality, AUTOPSY, MICROSCOPY, IMMUNOHISTOCHEMISTRY, FRONTOTEMPORAL lobar degeneration, MAGNETIC resonance imaging, DIFFERENTIAL diagnosis, DEGLUTITION disorders, ASPIRATION pneumonia, ATROPHY, DOPAMINE, SINGLE-photon emission computed tomography, INTERPERSONAL relations, MEMBRANE transport proteins, SOCIAL skills, NEURODEGENERATION, FRONTOTEMPORAL dementia
Abstract

The article presents a case report of a 52-year-old man with socially inappropriate and apathetic behaviours. Examinations showed bilateral frontal lobes with atrophy and hypoperfusion and he was diagnosed with behavioural variant frontotemporal dementia (bvFTD). He developed dysphagia at age 55 and ten months hence, died of repeated aspiration pneumonia. Also noted is the detection of abnormal dopamine transporter (DAT) findings in frontotemporal lobar degeneration (FTLD)-TDP type B patients.

Published
2022
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41. Association of SNPs linked to increased expression of SLC1A1 with schizophrenia

Author

Horiuchi, Yasue, Iida, Syuhei, Koga, Minori, Ishiguro, Hiroki, Iijima, Yoshimi, Inada, Toshiya, Watanabe, Yuichiro, Someya, Toshiyuki, Ujike, Hiroshi, Iwata, Nakao, Ozaki, Norio, Kunugi, Hiroshi, Tochigi, Mamoru, Itokawa, Masanari, Arai, Makoto, Niizato, Kazuhiro, Iritani, Shuji, Kakita, Akiyoshi, Takahashi, Hitoshi, Nawa, Hiroyuki, and Arinami, Tadao

Published
2012
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49. The accumulation of advanced glycation end-products in a schizophrenic patient with a glyoxalase 1 frameshift mutation: An autopsy study

Author

Torii, Youta, primary, Iritani, Shuji, additional, Sekiguchi, Hirotaka, additional, Habuchi, Chikako, additional, Fujishiro, Hiroshige, additional, Kushima, Itaru, additional, Kawakami, Ito, additional, Itokawa, Masanari, additional, Arai, Makoto, additional, Hayashida, Shotaro, additional, Masaki, Katsuhisa, additional, Kira, Jun-ichi, additional, Kawashima, Kunihiro, additional, and Ozaki, Norio, additional

Published
2020
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50. Morphological alteration of myelin-oligodendrocytes in a schizophrenic patient with 22q11.2 deletion syndrome: An autopsy study

Author

Torii, Youta, primary, Iritani, Shuji, additional, Marui, Tomoyasu, additional, Sekiguchi, Hirotaka, additional, Habuchi, Chikako, additional, Fujishiro, Hiroshige, additional, Kushima, Itaru, additional, Oshima, Kenichi, additional, Niizato, Kazuhiro, additional, Hayashida, Shotaro, additional, Masaki, Katsuhisa, additional, Kira, Jun-ichi, additional, Yoshida, Mari, additional, and Ozaki, Norio, additional

Published
2020
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