4.7 Article

Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures

Journal

SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41598-021-91233-z

Keywords

-

Funding

  1. Japan Society for the Promotion of Science [21611009, 25282250, 25610126, 18H04040, 20H03608]
  2. Japan Agency for Medical Research and Development (AMED) [JP20dm0107087, JP20dm0207075, JP20dk0307081, JP20ak0101113, JP18dm0107088, JP19dm0107088, JP20dm0107088, JP19dm0107108]
  3. Grants-in-Aid for Scientific Research [25610126, 18H04040, 25282250, 20H03608] Funding Source: KAKEN

Ask authors/readers for more resources

This study analyzed the three-dimensional structure of cerebral vessels in schizophrenia cases and controls, finding a significant correlation between the mean curvatures of capillary vessels and neurites, while the mean capillary diameter remained constant. The study suggests a volumetric imbalance between neurons and vessels in schizophrenia, potentially related to neurovascular abnormalities.
Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7-9 mu m, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Review Genetics & Heredity

The genetic architecture of schizophrenia: review of large-scale genetic studies

Hidekazu Kato, Hiroki Kimura, Itaru Kushima, Nagahide Takahashi, Branko Aleksic, Norio Ozaki

Summary: Schizophrenia is a complex and chronic psychiatric disorder with a high heritability. Despite the lack of diagnostic tests or biomarkers, genetic research has made significant progress in our understanding of the genetic architecture of schizophrenia, including rare copy number variations (CNVs), rare single-nucleotide variants (SNVs), and common single-nucleotide polymorphisms (SNPs). These genetic variants play crucial roles in the pathogenesis of schizophrenia. New approaches such as CRISPR-based genetics and induced pluripotent stem cell technology can help further study the functional analysis of these variants. These advancements will contribute to the development of pathology-based therapeutics and a better understanding of the pathophysiology of schizophrenia.

JOURNAL OF HUMAN GENETICS (2023)

Article Dentistry, Oral Surgery & Medicine

Comparison of quality of life and psychological distress in patients with tongue cancer undergoing a total/subtotal glossectomy or extended hemiglossectomy and free flap transfer: a prospective evaluation

K. Suzuki, N. Nishio, H. Kimura, T. Tokura, S. Kishi, N. Ozaki, Y. Fujimoto, M. Sone

Summary: The aim of this study was to assess the changes in quality of life and psychological distress in patients with tongue cancer undergoing different surgeries. The results showed that patients who underwent total/subtotal glossectomy (TG) had worse general health and social functioning, as well as higher levels of depression, compared to those who underwent extended hemiglossectomy (HG) with free flap transfer. This suggests that patients in the TG group may experience social isolation and psychological distress even 12 months after surgery, while patients in the HG group had similar outcomes to the general population.

INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY (2023)

Article Pharmacology & Pharmacy

Inhibition of Rho-kinase ameliorates decreased spine density in the medial prefrontal cortex and methamphetamine-induced cognitive dysfunction in mice carrying schizophrenia-associated mutations of the Arhgap10 gene

Rinako Tanaka, Jingzhu Liao, Kazuhiro Hada, Daisuke Mori, Taku Nagai, Tetsuo Matsuzaki, Toshitaka Nabeshima, Kozo Kaibuchi, Norio Ozaki, Hiroyuki Mizoguchi, Kiyofumi Yamada

Summary: Copy-number variations in the ARHGAP10 gene are associated with schizophrenia. Model mice with double-hit mutations in the Arhgap10 gene exhibit schizophrenia-like symptoms, such as altered spine density and cognitive dysfunction. The study found that the activation of the RhoA/Rho-kinase signaling pathway is involved in these symptoms. Fasudil, a Rho-kinase inhibitor, can ameliorate the symptoms in the model mice.

PHARMACOLOGICAL RESEARCH (2023)

Letter Clinical Neurology

Late-onset panic disorder as the initial presentation in autopsy-confirmed dementia with Lewy bodies

Shusei Arafuka, Hirotaka Sekiguchi, Hiroshige Fujishiro, Shuji Iritani, Youta Torii, Chikako Habuchi, Mari Yoshida, Yasushi Iwasaki, Norio Ozaki, Kiyoshi Fujita

PSYCHIATRY AND CLINICAL NEUROSCIENCES (2023)

Article Psychiatry

Sensory evaluation of the bitterness of asenapine using D-sorbitol pretreatment: single-blind, placebo-controlled, crossover trial

Shuhei Wada, Kunihiro Iwamoto, Hiroki Okumura, Hirotake Hida, Shuichi Hiraoka, Aya Kamei, Daisuke Mori, Kiyofumi Yamada, Norio Ozaki

Summary: This study aims to evaluate the effect of D-sorbitol on the bitter taste of asenapine in patients with schizophrenia. Participants will rinse their mouths with different liquids and complete questionnaires to assess taste changes and willingness to continue asenapine. The findings will provide evidence on the efficacy of D-sorbitol in improving adherence to asenapine.

BMC PSYCHIATRY (2023)

Article Biochemistry & Molecular Biology

Molecular diagnosis of 405 individuals with autism spectrum disorder

Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Itaru Kushima, Nobuhiko Okamoto, Kei Ohashi, Kazuhiko Nakamura, Ryota Hashimoto, Yoko Hiraki, Shuraku Son, Mitsuhiro Kato, Yasunari Sakai, Hitoshi Osaka, Kimiko Deguchi, Toyojiro Matsuishi, Saoko Takeshita, Aviva Fattal-Valevski, Nina Ekhilevitch, Jun Tohyama, Patrick Yap, Wee Teik Keng, Hiroshi Kobayashi, Keiyo Takubo, Takashi Okada, Shinji Saitoh, Yuka Yasuda, Toshiya Murai, Kazuyuki Nakamura, Shouichi Ohga, Ayumi Matsumoto, Ken Inoue, Tomoko Saikusa, Tova Hershkovitz, Yu Kobayashi, Mako Morikawa, Aiko Ito, Toshiro Hara, Yota Uno, Chizuru Seiwa, Kanako Ishizuka, Emi Shirahata, Atsushi Fujita, Eriko Koshimizu, Satoko Miyatake, Atsushi Takata, Takeshi Mizuguchi, Norio Ozaki, Naomichi Matsumoto

Summary: Autism spectrum disorder (ASD) is caused by a combination of genetic and environmental factors. By analyzing 405 ASD patients, researchers identified disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses. They achieved a molecular diagnosis in 16.3% of the patients and found a higher diagnostic rate in females and in simplex cases compared to multiplex families.

EUROPEAN JOURNAL OF HUMAN GENETICS (2023)

Article Biochemistry & Molecular Biology

Astrotactin 2 (ASTN2) regulates emotional and cognitive functions by affecting neuronal morphogenesis and monoaminergic systems

Takahiro Ito, Mikio Yoshida, Tomomi Aida, Itaru Kushima, Yuka Hiramatsu, Maiko Ono, Akira Yoshimi, Kohichi Tanaka, Norio Ozaki, Yukihiro Noda

Summary: Astrotactin2 (ASTN2) regulates neuronal migration and synaptic strength through the trafficking and degradation of surface proteins. Deletion of ASTN2 has been found in patients with schizophrenia, bipolar disorder, and autism spectrum disorder. ASTN2-deficient mice showed increased exploratory activity and social behavior, or decreased despair-, anxiety-like behaviors. These behavioral abnormalities were partially attenuated by risperidone, but not by haloperidol. Dopamine contents were decreased in the striatum, and serotonin or dopamine turnover were increased in multiple brain regions of Astn2 KO mice. Morphological analyses revealed thinning of neural cell layers in the hippocampus, reduction of neural cell bodies in the prefrontal cortex, and decrease in spine density and PSD95 protein in both tissues. ASTN2 deficiency may contribute to the pathogenic mechanism and symptom onset of mental disorders.

JOURNAL OF NEUROCHEMISTRY (2023)

Review Clinical Neurology

Shedding light on latent pathogenesis and pathophysiology of mental disorders: the potential of iPS cell technology

Yuko Arioka, Hiroki Okumura, Hideya Sakaguchi, Norio Ozaki

Summary: Mental disorders have a significant impact on patients' quality of life and cause serious social burdens. Induced pluripotent stem cell (iPSC) technology has emerged as a novel tool for research on mental disorders, addressing the limitations of other research approaches. This review discusses the history, current trends, potential, and future of iPSC technology in the field of mental disorders.

PSYCHIATRY AND CLINICAL NEUROSCIENCES (2023)

Editorial Material Clinical Neurology

Neuropsychopharmacology renaissance in Japan: A new era after the crisis

Norio Ozaki, Teiji Kimura, Tetsuro Kikuchi, Takeo Ishiyama

PSYCHIATRY AND CLINICAL NEUROSCIENCES (2023)

Article Clinical Neurology

Exploratory Validation of Sleep-Tracking Devices in Patients with Psychiatric Disorders

Masaya Ogasawara, Masahiro Takeshima, Shumpei Kosaka, Aya Imanishi, Yu Itoh, Dai Fujiwara, Kazuhisa Yoshizawa, Norio Ozaki, Kazuyuki Nakagome, Kazuo Mishima

Summary: This study tested the performance of three sleep-tracking devices against polysomnography (PSG) in patients with psychiatric disorders. The results showed that the portable EEG device (Sleepgraph) had the best sleep stage-tracking performance, while the consumer sleep device (Fitbit Sense) exhibited poor sleep stage-tracking performance in patients with psychiatric disorders.

NATURE AND SCIENCE OF SLEEP (2023)

Article Biochemistry & Molecular Biology

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder

Azmeraw T. Amare, Anbupalam Thalamuthu, Klaus Oliver Schubert, Janice M. Fullerton, Muktar Ahmed, Simon Hartmann, Sergi Papiol, Urs Heilbronner, Franziska Degenhardt, Fasil Tekola-Ayele, Liping Hou, Yi-Hsiang Hsu, Tatyana Shekhtman, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Barbara Arias, Jean-Michel Aubry, Roland Hasler, Helene Richard-Lepouriel, Nader Perroud, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Cynthia Marie-Claire, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Maria Del Zompo, J. Raymond DePaulo, Bruno etain, Stephane Jamain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Sebastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Andreas J. Fallgatter, Sophia Stegmaier, Thomas Ethofer, Silvia Biere, Kristiyana Petrova, Ceylan Schuster, Kristina Adorjan, Monika Budde, Maria Heilbronner, Janos L. Kalman, Mojtaba Oraki Kohshour, Daniela Reich-Erkelenz, Sabrina K. Schaupp, Eva C. Schulte, Fanny Senner, Thomas Vogl, Ion-George Anghelescu, Volker Arolt, Udo Dannlowski, Detlef Dietrich, Christian Figge, Markus Jaeger, Fabian U. Lang, Georg Juckel, Carsten Konrad, Jens Reimer, Max Schmauss, Andrea Schmitt, Carsten Spitzer, Martin von Hagen, Jens Wiltfang, Joerg Zimmermann, Till F. M. Andlauer, Andre Fischer, Felix Bermpohl, Philipp Ritter, Silke Matura, Anna Gryaznova, Irina Falkenberg, Cueneyt Yildiz, Tilo Kircher, Julia Schmidt, Marius Koch, Kathrin Gade, Sarah Trost, Ida S. Haussleiter, Martin Lambert, Anja C. Rohenkohl, Vivien Kraft, Paul Grof, Ryota Hashimoto, Joanna Hauser, Stefan Herms, Per Hoffmann, Esther Jimenez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Ewa Ferensztajn-Rochowiak, Barbara Koenig, Ichiro Kusumi, Gonzalo Laje, Mikael Landen, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Alfonso Tortorella, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Vincent Millischer, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Noethen, Tomas Novak, Claire O'Donovan, Norio Ozaki, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Mario Maj, Gustavo Turecki, Eduard Vieta, Julia Veeh, Stephanie H. Witt, Adam Wright, Peter P. Zandi, Philip B. Mitchell, Michael Bauer, Martin Alda, Marcella Rietschel, Francis J. McMahon, Thomas G. Schulze, Scott R. Clark, Bernhard T. Baune

Summary: A polygenic score (Li-PGS(+)) for lithium treatment response in bipolar disorder patients was developed in this study. Li-PGS(+) was found to be positively associated with lithium treatment response. Gene-based analysis also identified 36 candidate genes related to lithium's molecular mechanism.

MOLECULAR PSYCHIATRY (2023)

Article Biochemistry & Molecular Biology

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification

Naohiro Okada, Masaki Fukunaga, Kenichiro Miura, Kiyotaka Nemoto, Junya Matsumoto, Naoki Hashimoto, Masahiro Kiyota, Kentaro Morita, Daisuke Koshiyama, Kazutaka Ohi, Tsutomu Takahashi, Michihiko Koeda, Hidenaga Yamamori, Michiko Fujimoto, Yuka Yasuda, Naomi Hasegawa, Hisashi Narita, Satoshi Yokoyama, Ryo Mishima, Takahiko Kawashima, Yuko Kobayashi, Daiki Sasabayashi, Kenichiro Harada, Maeri Yamamoto, Yoji Hirano, Takashi Itahashi, Masahito Nakataki, Ryu-ichiro Hashimoto, Khin K. Tha, Shinsuke Koike, Toshio Matsubara, Go Okada, Theo G. M. van Erp, Neda Jahanshad, Reiji Yoshimura, Osamu Abe, Toshiaki Onitsuka, Yoshiyuki Watanabe, Koji Matsuo, Hidenori Yamasue, Yasumasa Okamoto, Michio Suzuki, Jessica A. Turner, Paul M. Thompson, Norio Ozaki, Kiyoto Kasai, Ryota Hashimoto

Summary: This article discusses the difficulties in differential diagnosis in practical psychiatric settings and the prospect of creating a novel diagnostic system using objective biomarkers. Neuroimaging studies have shown that subcortical brain structures are associated with various psycho-behavioral functions, but there are currently no neuroimaging data-driven clinical criteria that can overcome the limitations of the current diagnostic system in reflecting cognitive/social functioning. The authors conducted a large-scale study and found volumetric and lateralization alterations in several psychiatric disorders, which were associated with cognitive/social functioning.

MOLECULAR PSYCHIATRY (2023)

Editorial Material Clinical Neurology

Evaluating sleep-wake rhythm using a wearable device in patients with mental disorders

Seiko Miyata, Kunihiro Iwamoto, Norio Ozaki

PSYCHIATRY AND CLINICAL NEUROSCIENCES (2023)

Meeting Abstract Clinical Neurology

LONG-TERM EFFICACY OF LEMBOREXANT ON OBJECTIVE SLEEP MEASURES IN CLINICAL PRACTICE

Seiko Miyata, Kunihiro Iwamoto, Ippei Okada, Akihiro Fujimoto, Yuki Kogo, Manabu Amano, Nao Matsuyama, Norio Ozaki

SLEEP (2023)

Article Optics

Multibeam laser-plasma interaction at the Gekko XII laser facility in conditions relevant for direct-drive inertial confinement fusion

G. Cristoforetti, P. Koester, S. Atzeni, D. Batani, S. Fujioka, Y. Hironaka, S. Huller, T. Idesaka, K. Katagiri, K. Kawasaki, R. Kodama, D. Mancelli, Ph. Nicolai, N. Ozaki, A. Schiavi, K. Shigemori, R. Takizawa, T. Tamagawa, D. Tanaka, A. Tentori, Y. Umeda, A. Yogo, L. A. Gizzi

Summary: The interaction between laser and plasma as well as the generation of hot electrons were studied in an experiment relevant to direct-drive inertial confinement fusion. High-energy electrons with temperatures of 20-50 keV were mainly produced by the damping of electron plasma waves driven by two-plasmon decay (TPD). Stimulated Raman scattering (SRS) was observed in a near-threshold growth regime and described by an analytical model, indicating a more vigorous growth driven by multiple beams compared to single-beam laser intensity.

HIGH POWER LASER SCIENCE AND ENGINEERING (2023)

No Data Available