YANAGI Masaya

Researcher Information

Degree

• Ph.D.（2005 Kobe University）

URL

https://kaken.nii.ac.jp/d/r/10418775.ja.html

J-Global ID

• 201501063383520620

Research Interests

• 統合失調症   死後脳   遺伝子   多型   グルタミン酸作動性ニューロン   マイクロアレイ   神経内分泌   生物学   遺伝子多型   扁桃体   神経画像   遺伝子発現   認知機能   自殺   

Research Areas

• Life sciences / Psychiatry

Academic & Professional Experience

• 2023/04 - Today  Kindai UniversityFaculty of Medicine准教授
• 2014  Kindai UniversityFaculty of Medicine講師
• 2013  Kindai UniversityFaculty of Medicine医学部講師
• 2007  University of Texas Southwestern Medical CenterPostdoctral Researcher
• 2005  Kobe UniversitySchool of Medicine助教

Education

• 2001/04 - 2005/03  Kobe University  大学院  医学研究科
• 1992/04 - 1998/03  Kobe University  School of Medicine

Published Papers

• Evaluating delay of gamma oscillations in patients with schizophrenia using evoked response audiometry system.

  Masaya Yanagi; Aki Tsuchiya; Fumiharu Hosomi; Toru Terada; Satoshi Ozaki; Osamu Shirakawa; Mamoru Hashimoto

  Scientific reports 12 (1) 11327 - 11327 2022/07 

  Impaired gamma oscillations found in a 40-Hz auditory steady-state response (ASSR) in patients with schizophrenia are the robust findings that can be used for future biomarker-based therapeutics. To apply these significant observations into the clinical practice, a clinical system for evoked response audiometry (ERA) may be available. In this study, the delayed 40-Hz ASSR, which was reported as a potent biomarker for schizophrenia, was examined using the ERA system in patients with schizophrenia and its clinical relevance was investigated. The phase of ASSR was significantly delayed in patients with schizophrenia compared with the healthy subjects. The delayed phase was associated with severity of the disease symptoms in the patients. A phase delay with aging was found in healthy subjects, but not in patients with schizophrenia. These findings show availability of the ERA system to identify the delayed 40-Hz ASSR and its clinical implication in patients with schizophrenia. Further applications of the ERA system in clinical psychiatry are warranted in developing biological assessments of schizophrenia with 40-Hz ASSR.
• Application of evoked response audiometry for specifying aberrant gamma oscillations in schizophrenia.

  Masaya Yanagi; Aki Tsuchiya; Fumiharu Hosomi; Satoshi Ozaki; Osamu Shirakawa

  Scientific reports 12 (1) 287 - 287 2022/01 

  Gamma oscillations probed using auditory steady-state response (ASSR) are promising clinical biomarkers that may give rise to novel therapeutic interventions for schizophrenia. Optimizing clinical settings for these biomarker-driven interventions will require a quick and easy assessment system for gamma oscillations in psychiatry. ASSR has been used in clinical otolaryngology for evoked response audiometry (ERA) in order to judge hearing loss by focusing on the phase-locked response detectability via an automated analysis system. Herein, a standard ERA system with 40- and 46-Hz ASSRs was applied to evaluate the brain pathophysiology of patients with schizophrenia. Both ASSRs in the ERA system showed excellent detectability regarding the phase-locked response in healthy subjects and sharply captured the deficits of the phase-locked response caused by aberrant gamma oscillations in individuals with schizophrenia. These findings demonstrate the capability of the ERA system to specify patients who have aberrant gamma oscillations. The ERA system may have a potential to serve as a real-world clinical medium for upcoming biomarker-driven therapeutics in psychiatry.
• 【不安の精神医学】不安症/不安症状を併存した双極性障害の診立てと薬物療法

  山形 祥礼; 安達 融; 柳 雅也; 白川 治

  最新精神医学 (株)世論時報社 26 (2) 133 - 137 1342-4300 2021/03
• Application of Near-Infrared Spectroscopy for Understanding Spontaneous Brain Activity During Resting State in Schizophrenia: A Mini Review.

  Masaya Yanagi; Osamu Shirakawa

  Frontiers in psychiatry 12 704506 - 704506 2021 

  Spontaneous brain activity occurs at rest, as represented by the default mode network. A resting paradigm is suitable for investigating brain function of patients with psychiatric diseases who may have difficulties adhering to goal-oriented tasks. Evidence accumulated in neuroimaging studies using functional magnetic resonance imaging has shown that the resting cerebral blood flow is impaired in psychiatric diseases. Near-infrared spectroscopy (NIRS), a simple neuroimaging modality, is an optimal tool for the resting paradigm, because it can offer a comfortable environment for measurement. Recent NIRS studies have demonstrated some promising data of altered resting activity in the prefrontal cortex of patients with schizophrenia, which may be exploited to develop further applications of NIRS in clinical psychiatry. Based on these findings, we emphasize the benefits of NIRS for assessing the prefrontal pathophysiology during the resting state and some methodological issues to be noted while analyzing cerebral blood flow using NIRS; moreover, we focus on interpreting these changes based on the complex nature of the spontaneous brain activity during resting state.
• 【現代社会における不安の病理と対応】双極性障害における不安症状・不安症とその対応

  安達 融; 柳 雅也; 白川 治

  精神科治療学 (株)星和書店 35 (12) 1335 - 1340 0912-1862 2020/12 

  双極性障害には不安症状がしばしばみられ、不安症を伴うことも少なくない。双極性障害に不安症状・不安症を伴うと、治療抵抗性、自殺リスクの増加、アルコールなどの物質使用障害の併存などにより、臨床経過や予後が不安定・不良になることが指摘されてきた。しかし、双極性障害に伴う不安症状・不安症を標的とした薬物療法に関するエビデンスは、valproate、quetiapine、olanzapine、lurasidoneなどに限定されており、いまだ十分とは言えない。双極性障害に併存する不安症状・不安症の把握と、実臨床で求められる薬物療法および対応のあり方について述べた。(著者抄録)
• A decrease in spontaneous activity in medial prefrontal cortex is associated with sustained hallucinations in chronic schizophrenia: An NIRS study

  Masaya Yanagi; Fumiharu Hosomi; Yoshihiro Kawakubo; Aki Tsuchiya; Satoshi Ozaki; Osamu Shirakawa

  Scientific Reports NATURE PUBLISHING GROUP 10 (1) 9569 - 9569 2045-2322 2020/12 [Refereed]
   

  © 2020, The Author(s). In functional imaging, accumulating evidence suggests that spontaneous activity decreases during the resting state in the core brain regions of the default-mode network [e.g. medial prefrontal cortex (mPFC)] in schizophrenia. However, the significance of this decreased activity has not been clarified in relation to its clinical symptoms. In this study, near-infrared spectroscopy (NIRS), which is a simple imaging modality suitable for resting state paradigm, was used to evaluate the intensity of the spontaneous activity during the resting state in chronic schizophrenia. Consistent with previous findings of fMRI studies, spontaneous activity decreased in the mPFC of patients with schizophrenia. In addition, the decreased spontaneous activity was associated with severe hallucinations in this region where reality monitoring is fundamentally engaged. These results may encourage additional application of NIRS with the resting state paradigm into daily clinical settings for addressing the broad phenotypes and unstable course of schizophrenia.
• Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors

  Amir Segev; Masaya Yanagi; Daniel Scott; Sarah A. Southcott; Jacob M. Lister; Chunfeng Tan; Wei Li; Shari G. Birnbaum; Saïd Kourrich; Carol A. Tamminga

  Molecular Psychiatry 25 (11) 2832 - 2843 1359-4184 2020/11 [Refereed]
   

  © 2018, The Author(s). Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.
• Strategy to simplify antidepressant prescriptions for treating major depressive disorder

  安達 融; 柳 雅也; 白川 治

  臨床精神薬理 (株)星和書店 23 (2) 129 - 136 1343-3474 2020/02 [Refereed]
   

  新規抗うつ薬がうつ病薬物療法の主役となり、重篤な副作用の回避とともに過剰投薬や多剤併用などが問題となる現在、基本に沿った合理的な処方を心がけることの大切さが改めて問われている。うつ病治療では半数近くのうつ病患者は最初に用いられた抗うつ薬に反応しないとされ、抗うつ薬の切り替え(switching)、増強療法(augmentation)、併用療法(combination)が必要となることも少なくない。しかし、増強療法や併用療法についてのエビデンスは限られている。そこで本稿では、うつ病の薬物療法に求められる抗うつ薬の切り替え、増強療法、併用療法の代表的なエビデンスを中心に概説し、投与の実際について述べる。(著者抄録)
• Capturing spontaneous activity in the medial prefrontal cortex using near-infrared spectroscopy and its application to schizophrenia

  Fumiharu Hosomi; Masaya Yanagi; Yoshihiro Kawakubo; Noa Tsujii; Satoshi Ozaki; Osamu Shirakawa

  Scientific Reports NATURE PUBLISHING GROUP 9 (1) 5283 - 5283 2045-2322 2019/12 [Refereed]
   

  © 2019, The Author(s). Near-infrared spectroscopy (NIRS) is an optimal imaging modality used to examine spontaneous brain activity because it can quietly measure blood flow changes with less physical restriction during the resting state. Here, NIRS was used at rest to measure spontaneous activity in the medial prefrontal cortex (mPFC), a main locus of default mode network. Consistent with previous fMRI studies, magnitude of the spontaneous activity in this region declined with increasing age in healthy subjects. The magnitude reduced in the mPFC of patients with schizophrenia. Additionally, in the mPFC of patients with schizophrenia, the spontaneous activity did not show any age-related decline; the activity was already low in younger patients. Further analysis using fractional amplitude of low-frequency fluctuations confirmed the reduction of spontaneous activity in the mPFC of patients with schizophrenia, consistent with the findings of fMRI studies. Our findings demonstrate the ability of NIRS to evaluate the spontaneous activity in the mPFC of patients with schizophrenia, particularly younger patients. Considering the safety and ease of the NIRS measurements, the current NIRS study of the resting-state activity indicates its utility for clinical applications to schizophrenia, which may facilitate chronological assessment of larger cohorts of patients with schizophrenia in further studies.
• 【精神医学における様々な仮説とモデルの今I】うつ病のモノアミン仮説の現在

  廣瀬 智之; 柳 雅也; 白川 治

  精神科治療学 (株)星和書店 34 (9) 1023 - 1029 0912-1862 2019/09 

  うつ病のモノアミン仮説は、1950年代の抗うつ効果を示す薬物の発見とそれに関連する作用機序解明に始まる。抑うつを引き起こす降圧薬(reserpine)や気分高揚をもたらす抗結核薬(iproniazid)と、抗うつ効果が発見されたimipramineの作用機序解明により、うつ病ではモノアミンが欠乏しているとする仮説が導かれた。薬物の作用機序が解明されるとともに、うつ病の病態でセロトニンとカテコラミンのいずれが重要なのかが課題となった。1980年代に三環系抗うつ薬(TCA)が抗うつ薬の主役となるなか、セロトニン再取り込み阻害を強化する薬物が開発され、選択的セロトニン再取り込み阻害薬(SSRI)の登場に繋がった。SSRIは、TCAの重篤な自律神経系の副作用を回避した抗うつ薬として受け入れられ、後に開発されるSNRIとともに抗うつ薬の第1選択と位置づけられた。現在うつ病診療で用いられているすべての抗うつ薬は、うつ病の病態はモノアミン欠乏にあるとした従来のモノアミン仮説を超えているわけではない。モノアミン仮説は、従来の前シナプスないしはシナプス間隙の病理を重視する考え方から、後シナプス受容体以降の情報伝達系の機能障害に基づく仮説へと変遷し、こうした新しい病態仮説に基づいた創薬も進められてきたが、未だ臨床応用には至っていないのが現状である。(著者抄録)
• Monoamine hypothesis of depression : Current perspective

  廣瀬 智之; 柳 雅也; 白川 治

  精神科治療学 (株)星和書店 34 (9) 1023 - 1029 0912-1862 2019/09 [Refereed]
   

  うつ病のモノアミン仮説は、1950年代の抗うつ効果を示す薬物の発見とそれに関連する作用機序解明に始まる。抑うつを引き起こす降圧薬(reserpine)や気分高揚をもたらす抗結核薬(iproniazid)と、抗うつ効果が発見されたimipramineの作用機序解明により、うつ病ではモノアミンが欠乏しているとする仮説が導かれた。薬物の作用機序が解明されるとともに、うつ病の病態でセロトニンとカテコラミンのいずれが重要なのかが課題となった。1980年代に三環系抗うつ薬(TCA)が抗うつ薬の主役となるなか、セロトニン再取り込み阻害を強化する薬物が開発され、選択的セロトニン再取り込み阻害薬(SSRI)の登場に繋がった。SSRIは、TCAの重篤な自律神経系の副作用を回避した抗うつ薬として受け入れられ、後に開発されるSNRIとともに抗うつ薬の第1選択と位置づけられた。現在うつ病診療で用いられているすべての抗うつ薬は、うつ病の病態はモノアミン欠乏にあるとした従来のモノアミン仮説を超えているわけではない。モノアミン仮説は、従来の前シナプスないしはシナプス間隙の病理を重視する考え方から、後シナプス受容体以降の情報伝達系の機能障害に基づく仮説へと変遷し、こうした新しい病態仮説に基づいた創薬も進められてきたが、未だ臨床応用には至っていないのが現状である。(著者抄録)
• Mitochondrial DNA Copy Number Raises the Potential of Left Frontopolar Hemodynamic Response as a Diagnostic Marker for Distinguishing Bipolar Disorder From Major Depressive Disorder

  Tsujii Noa; Otsuka Ikuo; Okazaki Satoshi; Yanagi Masaya; Numata Shusuke; Yamaki Naruhisa; Kawakubo Yoshihiro; Shirakawa Osamu; Hishimoto Akitoyo

  Frontiers in Psychiatry Frontiers Media 10 (10) 312 - 312 1664-0640 2019/05 [Refereed]
   

  Background: Given a lack of markers, diagnoses of bipolar disorder (BD) and major depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and depressive symptoms of MDD are often difficult to distinguish, which leads to misdiagnoses, which in turn leads to inadequate treatment. Previous studies have shown that the hemodynamic responses of the left frontopolar cortex measured by near-infrared spectroscopy (NIRS) differ between BD and MDD; these hemodynamic responses are associated with altered mitochondrial metabolism; and mitochondrial DNA copy number (mtDNAcn), an index of mitochondrial dysfunction, tends to decrease in BD and increase in MDD patients. In this study, we confirmed that mtDNAcn trends in opposite directions in BD and MDD. We then determined whether mtDNAcn could enhance the utility of NIRS as a diagnostic marker to distinguish between BD and MDD. Methods: We determined mtDNAcn in peripheral blood samples from 58 healthy controls, 79 patients with BD, and 44 patients with MDD. Regional hemodynamic responses during a verbal fluency task (VFT) in 24 BD patients and 44 MDD patients, matched by age and depression severity, were monitored using NIRS. Results: Measurements of mtDNAcn were lower in BD patients and higher in MDD patients than in controls. The left frontopolar region exhibited the most significant differences in mean VFT-related oxy-Hb changes between the BD and MDD groups. Multivariate logistic regression analysis with variables including age, sex, hemodynamic response of the left frontopolar region, and mtDNAcn showed high accuracy for distinguishing BD from MDD (area under the curve = 0.917; 95% confidence interval = 0.849-0.985). For the BD group, we observed a positive correlation between hemodynamic responses in the left frontopolar region and mtDNAcn, while for the MDD group, we observed a negative correlation. Conclusions: Our findings suggest that the association between hemodynamic response and mitochondrial dysfunction in BD or MDD plays an important role in differentiating the pathophysiological mechanisms of BD from those of MDD.
• NIRSを用いた統合失調症前頭葉の安静時脳血流測定

  柳雅也

  日本生物学的精神医学会 AsianBP2019シンポジウム 41st 26  2019
• Medication-induced depressive disorder

  細見 史治; 柳 雅也; 土屋 有希; 白川 治

  臨床精神医学 (株)アークメディア 48 (1) 83 - 89 0300-032X 2019/01
• Mitochondrial DNA copy number of peripheral blood in bipolar disorder: The present study and a meta-analysis

  Naruhisa Yamaki; Ikuo Otsuka; Shusuke Numata; Masaya Yanagi; Kentaro Mouri; Satoshi Okazaki; Shuken Boku; Tadasu Horai; Tetsuro Ohmori; Osamu Shirakawa; Ichiro Sora; Akitoyo Hishimoto

  Psychiatry Research ELSEVIER IRELAND LTD 269 115 - 117 0165-1781 2018/11 [Refereed]
   

  © 2018 Elsevier B.V. Numerous evidence indicated mitochondrial abnormalities in the pathophysiology of bipolar disorder (BD); however, it remains unclear whether aberrant mitochondrial DNA (mtDNA) copy number (cn) occur in BD due to the conflicting results in previous studies. Here, peripheral blood mtDNAcn in 69 BD patients and 54 controls were analysed via qPCR. BD patients had significantly lower mtDNAcn compared to controls (regardless of their BD type [BD I or II]). Meta-analysis for all previous BD-mtDNAcn studies combining our results with previously published studies failed to identify any significant association. Meanwhile, Asian-specific meta-analysis remarkably revealed lower mtDNAcn in BD patients.
• Hippocampal Subfield Activity May Mediate Aspects of Psychosis

  Daniel Scott; Chunfeng Tan; Masaya Yanagi; Carol A. Tamminga

  BIOLOGICAL PSYCHIATRY ELSEVIER SCIENCE INC 83 (9) S312 - S313 0006-3223 2018/05
• Repetition of verbal fluency task attenuates the hemodynamic activation in the left prefrontal cortex: Enhancing the clinical usefulness of near-infrared spectroscopy

  Yoshihiro Kawakubo; Masaya Yanagi; Noa Tsujii; Osamu Shirakawa

  PLoS ONE PUBLIC LIBRARY SCIENCE 13 (3) e0193994  1932-6203 2018/03 [Refereed]
   

  © 2018 Kawakubo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In applications of near-infrared spectroscopy (NIRS) in clinical psychiatry settings in Japan, a phonemic verbal fluency test (VFT) that includes “switching” (the ability to shift efficiently to a new word subcategory) to assess phonemic fluency is employed to capture disease-specific hemodynamic changes in the prefrontal cortex (PFC). In this study, to extend the specific features of this test, the VFT was repeated to examine an activation change in NIRS measurements in 20 healthy males. Without task performance change, the hemodynamic activation induced by the VFT was significantly attenuated in the left PFC through repetition of the task. These findings suggest that the left PFC is involved in processing of the VFT. Further, it may be possible to extend the current VFT using this repetition to provide a more sensitive examination of the left PFC, whose dysfunction has been reported in several psychiatric diseases such as major depression, bipolar disorder, and schizophrenia.
• 未服薬統合失調症患者の死後脳前頭前野におけるヘモグロビンタンパク量の変化

  柳 雅也; Tamminga Carol A; 白川 治

  先進医薬研究振興財団研究成果報告集 (公財)先進医薬研究振興財団 2016年度 52 - 53 2189-1303 2017/03
• GABA仮説からみた統合失調症の病態と創薬の展開

  柳雅也

  日本臨床精神神経薬理学会プログラム・抄録集 27th 68  2017
• Mixed features specifier in DSM-5 : its significance and issues to be solved

  白川 治; 柳 雅也; 辻井 農亜

  臨床精神医学 アークメディア 45 (2) 171 - 179 0300-032X 2016/02
• 双極性障害における衝動性・攻撃性と絶望感 自殺傾性との関連

  辻井 農亜; 三川 和歌子; 辻本 江美; 切目 栄司; 川久保 善宏; 阪中 聡一郎; 廣瀬 智之; 高屋 雅彦; 柳 雅也; 小野 久江; 白川 治

  Bipolar Disorder アルタ出版(株) 13 22 - 28 2015/06 

  双極性障害患者を対象に、衝動性、攻撃性、絶望感を評価するとともに、Stop-signal taskによって測定されるStop-signal reaction time(SSRT)で実行機能を評価した。DSM-IVにより双極性障害と診断された患者群60例と健常対照群56例を対象とした。患者群はHAM-D-17スコアが7点以下の寛解群28例と8点以上のうつ状態群32例に分類した。寛解群、うつ状態群、健常対象群の3群で衝動性、攻撃性、絶望感のスコアを比較したところ、衝動性、攻撃性のスコアに関しては、寛解群およびうつ状態群ともに健常対照群と比較して有意に高く、寛解群とうつ状態群の間には有意差はなかった。絶望感スコアでは寛解群、うつ状態群ともに健常群よりも有意に高く、寛解群に比べてうつ状態群が有意に高いことが明らかになった。また自殺企図歴のある双極性障害患者においてSSRTが示す衝動性とBuss-Perry Aggression Questionaire(BAQスコア)が示す攻撃性の間に負の相関が見られた。
• Magnetic resonance spectroscopy and tissue protein concentrations together suggest lower glutamate signaling in dentate gyrus in schizophrenia

  A. D. Stan; S. Ghose; C. Zhao; K. Hulsey; P. Mihalakos; M. Yanagi; S. U. Morris; J. J. Bartko; C. Choi; C. A. Tamminga

  Molecular Psychiatry NATURE PUBLISHING GROUP 20 (4) 433 - 439 1359-4184 2015/04 [Refereed]
   

  © 2015 Macmillan Publishers Limited All rights reserved. Hippocampal dysfunction in schizophrenia is widely acknowledged, yet the mechanism of such dysfunction remains debated. In this study we investigate the excitatory and inhibitory hippocampal neurotransmission using two complementary methodologies, proton magnetic resonance spectroscopy (MRS) and tissue biochemistry, sampling individuals with schizophrenia in vivo and postmortem hippocampal tissue in vitro. The results show significantly lower glutamate concentrations in hippocampus in schizophrenia, an in vivo finding mirrored by lower GluN1 protein levels selectively in the dentate gyrus (DG) in vitro. In a mouse model with a DG knockout of the GRIN1 gene, we further confirmed that a selective decrease in DG GluN1 is sufficient to decrease the glutamate concentrations in the whole hippocampus. Gamma-aminobutyric acid (GABA) concentrations and GAD67 protein were not significantly different in hippocampus in schizophrenia. Similarly, GABA concentrations in the hippocampi of mice with a DG knockout of the GRIN1 gene were not significantly different from wild type. These findings provide strong evidence implicating the excitatory system within hippocampus in the pathophysiology of schizophrenia, particularly indicating the DG as a site of pathology.
• REVERSE TRANSLATION ANIMAL MODEL OF HIPPOCAMPAL DYSFUNCTION IN SCHIZOPHRENIA

  Sarah Southcott; Masaya Yanagi; Jacob Lister; Carol Tamminga

  SCHIZOPHRENIA BULLETIN OXFORD UNIV PRESS 41 S10 - S11 0586-7614 2015/03
• The long-term prognosis of major depressive disorder

  辻井 農亜; 柳 雅也; 白川 治

  臨床精神医学 アークメディア 43 (10) 1421 - 1426 0300-032X 2014/10
• Kv3.1-containing K⁺ channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs

  M. Yanagi; R. H. Joho; S. A. Southcott; A. A. Shukla; S. Ghose; C. A. Tamminga

  Molecular Psychiatry NATURE PUBLISHING GROUP 19 (5) 573 - 579 1359-4184 2014/05 [Refereed]
   

  Neuronal firing is a fundamental element of cerebral function; and, voltage-gated potassium (K+) channels regulate that firing through the repolarization of action potentials. Kv3-type channels (Kv3.1-Kv3.4) represent a family of voltage-gated K + channels that have fast-spiking properties. Kv3.1 channel subunits are predominantly localized to cortical parvalbumin (PV)-positive, inhibitory interneurons. The firing properties of these interneurons participate in establishing the normal gamma oscillations and synchrony of cortical neuronal populations, thought to be the signature of higher information processing in human brain. Schizophrenia (SZ) is associated with abnormalities in cortical gamma synchrony and in information processing, particularly with dysfunction in working memory and executive function. Here, we report the distribution of Kv3.1b and Kv3.2 protein in normal human brain, showing that Kv3.1b is limited to neocortical areas, whereas Kv3.2 is abundantly represented in neo-and subcortical regions. In SZ cases, levels of Kv3.1b protein are decreased in the neocortex, but only in cases without antipsychotic drug (APD) treatment; Kv3.1 levels are normal in antipsychotic-treated cases. Kv3.2 is not different in distribution or in level between normal and SZ cases, nor influenced by APD, in any region tested. The apparent increase in Kv3.1b protein levels by APDs in SZ neocortex was confirmed in laboratory rodents treated with chronic APDs. These findings show a decrease in Kv3.1b channel protein in SZ neocortex, a deficit that is restored by APDs. This alteration could be fundamentally involved in the cortical manifestations of SZ and in the therapeutic response to APDs.
• Right temporal activation differs between melancholia and nonmelancholic depression: A multichannel near-infrared spectroscopy study

  Noa Tsujii; Wakako Mikawa; Hiroyuki Akashi; Emi Tsujimoto; Toru Adachi; Eiji Kirime; Masahiko Takaya; Masaya Yanagi; Osamu Shirakawa

  Journal of Psychiatric Research PERGAMON-ELSEVIER SCIENCE LTD 55 (1) 1 - 7 0022-3956 2014 [Refereed]
   

  The aim of this study was to determine whether melancholia differs from nonmelancholic depression in frontotemporal functioning by means of multichannel near-infrared spectroscopy. We recruited 32 major depressive disorder (MDD) patients with melancholic features (MDD-MF), 28 MDD patients with nonmelancholic features (MDD-NMF), and 24 healthy controls. Regional hemodynamic changes induced by a verbal fluency task (VFT) were monitored, and their correlations with depressive symptoms were examined. In comparison with the controls, significant differences were observed in mean oxygenated hemoglobin (oxy-Hb) changes induced by VFT in patients with MDD-MF in 25 channels (p=0.000-0.047) and in those with MDD-NMF in 12 channels (p=0.000-0.023). Moreover, patients with MDD-MF had significantly smaller mean oxy-Hb changes than those with MDD-NMF in 8 channels of the right temporal region (p=0.001-0.048). No significant correlations were observed between mean oxy-Hb changes and the Hamilton rating scale for depression (HAMD) 17 total score in both groups of patients with MDD. On examining each item of HAMD17, psychomotor retardation in patients with MDD-MF showed a significant positive correlation with mean oxy-Hb changes in the right temporal region (ch43; ρ=0.55; p=0.001), whereas that in patients with MDD-NMF showed a significant negative correlation with mean oxy-Hb changes in the frontal and left temporal regions in 3 channels (ρ=-0.60 to-0.53; p=0.000-0.004). In conclusion, our results indicate that melancholia is qualitatively distinct from nonmelancholic depression both clinically and biologically. © 2014 Elsevier Ltd.
• 統合失調症ではカリウムチャネルKv3.1が減少しており、抗精神病薬で回復する 新たな統合失調症治療薬ターゲットの可能性(A potassium channel, Kv3.1, is reduced in schizophrenia and normalized with antipsychotic drugs: a possible new drug target for schizophrenia)

  柳 雅也; ヨーホー・ラルフ; ヘンドリックス・サラ; シュクラ・アベイ; ゴーシュ・スブロートー; タミンガ・キャロル

  日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集 日本臨床精神神経薬理学会・日本神経精神薬理学会 23回・43回 150 - 150 2013/10
• Hippocampal Circuitry and Psychosis

  Subroto Ghose; Wei Li; Masaya Yanagi; Caitlin Meyer; Bryan Potts; Carol Tamminga

  BIOLOGICAL PSYCHIATRY ELSEVIER SCIENCE INC 71 (8) 168S - 168S 0006-3223 2012/04
• Animal models of schizophrenia: Emphasizing construct validity

  Masaya Yanagi; Sarah Southcott; Jacob Lister; Carol A. Tamminga

  Progress in Molecular Biology and Translational Science ELSEVIER ACADEMIC PRESS INC 105 411 - 444 1877-1173 2012 [Refereed]
   

  Achieving animal models of schizophrenia which are representative of clear aspects of the illness is critical to understanding pathophysiology and developing novel treatments for the complex syndrome. This chapter reviews the various approaches that have been used in the past to create animal models of schizophrenia, including pharmacological approaches, environmental risk conditions and schizophrenia risk genes. In addition, we present a new animal model which derives directly from human tissue and brain imaging data used to develop a human schizophrenia model. This chapter emphasizes the crucial need for construct validity and of modeling discrete elements of schizophrenia's illness presentation as the way to successful advances.
• ALTERED LEARNING AND MEMORY PLASTICITY IN SCHIZOPHRENIA: INCREASED P(SER831)-GLUR1 LEVELS IN CA3 IN A MOUSE MODEL AND IN HUMAN CA3 TISSUE

  Masaya Yanagi; B. Potts; Subroto Ghose; C. Tamminga

  SCHIZOPHRENIA BULLETIN OXFORD UNIV PRESS 37 197 - 198 0586-7614 2011/03
• Association of calcineurin A gamma subunit (PPP3CC) and early growth response 3 (EGR3) gene polymorphisms with susceptibility to schizophrenia in a Japanese population

  Chieko Kyogoku; Masaya Yanagi; Kunihiro Nishimura; Daisuke Sugiyama; Akio Morinobu; Masaaki Fukutake; Kiyoshi Maeda; Osamu Shirakawa; Takayoshi Kuno; Shunichi Kumagai

  Psychiatry Research ELSEVIER IRELAND LTD 185 (1-2) 16 - 19 0165-1781 2011/01 [Refereed]
   

  To examine the association of PPP3CC (rs10108011 and rs2461491) and EGR3 (rs3750192) single-nucleotide polymorphisms (SNPs) with Japanese schizophrenia, we performed a case-control association study using 337 patients and 369 healthy controls. As a result, by our moderated cohort-size study, PPP3CC and EGR3 are not genetic risk factors for schizophrenia, whereas meta-analysis showed weak association of rs10108011 with schizophrenia in the Japanese population (odds ratio (OR) = 1.12, P= 0.01). © 2009 Elsevier Ireland Ltd.
• A putative cis-acting polymorphism in the NOS1 gene is associated with schizophrenia and NOS1 immunoreactivity in the postmortem brain

  Huxing Cui; Naoki Nishiguchi; Masaya Yanagi; Masaaki Fukutake; Kentaro Mouri; Noboru Kitamura; Takeshi Hashimoto; Osamu Shirakawa; Akitoyo Hishimoto

  Schizophrenia Research ELSEVIER SCIENCE BV 121 (1-3) 172 - 178 0920-9964 2010/08 [Refereed]
   

  Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. Recent genome-wide scans revealed that rare structural variants disrupted multiple genes in neurodevelopmental pathways, which strongly implicate nitric oxide (NO) signaling in schizophrenia. NO acts as a second messenger of N-methyl-D aspartate receptor activation, which further interacts with both dopaminergic and serotonergic pathways. NO is mainly synthesized by neuronal nitric oxide synthase (NOS1) in the brain, and its gene locus, 12q24.2, has attracted much attention as a major linkage region for schizophrenia. Genetic variations of NOS1 have also been associated with schizophrenia, and differential expression of NOS1 was observed in the postmortem brain of schizophrenic patients. Here, we explored the hypothesis that a putative cis-acting G-84A single nucleotide polymorphism (SNP; rs41279104) in the exon 1c promoter region of the NOS1 gene is associated with the levels of NOS1 immunoreactivity in postmortem prefrontal cortex specimens regardless of disease phenotype. Individuals with the A-allele of this SNP showed significantly lower levels of NOS1 immunoreactivity than did GG homozygotes (p=0.002). Furthermore, a case-control study using 720 individuals in a Japanese population revealed a significant association between the SNP and schizophrenia (genotypic p=0.0013 and allelic p=0.0011). Additionally, the average of onset age in schizophrenic patients with the A-allele was significantly earlier than GG homozygotes (p=0.018). When the analyses took gender into account, this significance was more significant for female. These findings provide further evidences that NOS1 is associated with a biological susceptibility gene to schizophrenia. © 2010 Elsevier B.V.
• New Data to Model the Role of the Hippocampal Formation in Schizophrenia Psychosis

  Carol A. Tamminga; Subroto Ghose; Changho Choi; Hanzhang Lu; Masaya Yanagi

  BIOLOGICAL PSYCHIATRY ELSEVIER SCIENCE INC 67 (9) 189S - 189S 0006-3223 2010/05
• BRAIN REGIONAL EXPRESSION PATTERN OF THE VOLTAGE-GATED POTASSIUM CHANNEL, KV3.2 IN SCHIZOPHRENIA

  Masaya Yanagi; M. Bose; B. W. Potts; A. D. Stan; K. L. Lewis-Amezcua; S. Ghose; R. H. Joho; C. A. Tamminga

  SCHIZOPHRENIA BULLETIN OXFORD UNIV PRESS 35 231 - 231 0586-7614 2009/03
• Association of RGS2 gene polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims

  Huxing Cui; Naoki Nishiguchi; Elena Ivleva; Masaya Yanagi; Masaaki Fukutake; Hideyuki Nushida; Yasuhiro Ueno; Noboru Kitamura; Kiyoshi Maeda; Osamu Shirakawa

  Neuropsychopharmacology NATURE PUBLISHING GROUP 33 (7) 1537 - 1544 0893-133X 2008/06 [Refereed]
   

  Regulators of G-protein signaling are a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors, such as the serotonin receptor. Recent studies have suggested that one of these proteins, the regulator of G-protein signaling 2 (RGS2), plays an important part in anxiety and/or aggressive behavior. To explore the involvement of the RGS2 gene in the vulnerability to suicide, we screened Japanese suicide victims for sequence variations in the RGS2 gene and carried out an association study of RGS2 gene polymorphisms with suicide victims. In the eight identified polymorphisms that were identified by mutation screening, we genotyped four common single-nucleotide polymorphisms (SNPs) in the RGS2 gene, and found significant differences in the distribution of the SNP3 (C+2971G, rs4606) genotypes and alleles of the SNP2 (C-395G, rs2746072) and the SNP3 between completed suicides and the controls. The distribution of the haplotype was also significantly different between the two groups (global p<0.0001). Furthermore, RGS2 immunoreactivity significantly increased in the amygdala and the prefrontal cortex (Brodmann area 9 (BA9)) of the postmortem brain of the suicide subjects. These findings suggest that RGS2 is genetically involved in the biological susceptibility to suicide in the Japanese population. © 2008 Nature Publishing Group All rights reserved.
• Expression of Kruppel-like factor 5 gene in human brain and association of the gene with the susceptibility to schizophrenia

  Masaya Yanagi; Takeshi Hashimoto; Noboru Kitamura; Masaaki Fukutake; Osamu Komure; Naoki Nishiguchi; Toshio Kawamata; Kiyoshi Maeda; Osamu Shirakawa

  Schizophrenia Research ELSEVIER SCIENCE BV 100 (1-3) 291 - 301 0920-9964 2008/03 [Refereed]
   

  Genome-wide gene expression analysis using DNA microarray technology is a potential tool to search for unexpected genes that have a susceptibility to schizophrenia. We carried out a microarray analysis in the postmortem prefrontal cortex and found that the expression of the KLF5 gene, whose locus is on 13q21, was down-regulated in schizophrenia patients. This result was confirmed by a Western blot analysis. In a genetic study, we found that a polymorphism of the KLF5 gene (- 1593T>C) was associated with schizophrenia. We identified neurons in the prefrontal cortex of human brain as sites of KLF5 expression by in situ hybridization and immunohistochemistry. KLF5 was immunohistochemically localized in granular and pyramidal cells in the hippocampus, which are the principal source of glutamatergic neurotransmission. These findings suggest that the KLF5 gene is a novel schizophrenia-susceptibility gene, and that the expression of the gene is involved in the pathophysiology of schizophrenia via glutamatergic neurotransmission. © 2007 Elsevier B.V. All rights reserved.
• 脳画像解析と生物学的指標を用いた精神疾患の診断と治療効果の判定への応用に関する研究 自殺傾性の臨床評価と生物学的指標・神経画像学的評価との関連

  白川治; 河内崇; 西向浩隆; 福武将映; 毛利健太朗; 白岩恭一; CUI H; 柳雅也; 西口直希; 松尾るみ; 前田潔; 小西淳也; 川光秀昭; 藤井正彦; 杉村和朗; 大西隆

  脳画像解析と生物学的指標を用いた精神疾患の診断と治療効果の判定への応用に関する研究 平成17-19年度 総括研究報告書 30 - 31 2008
• 【透析室における精神症状と行動異常】 皮膚を虫がはっていて、気持ちが悪い

  柳 雅也; 白川 治

  臨床透析 (株)日本メディカルセンター 23 (6) 378 - 379 0910-5808 2007/06
• Association between a functional polymorphism in the renin-angiotensin system and completed suicide

  A. Hishimoto; O. Shirakawa; N. Nishiguchi; T. Hashimoto; M. Yanagi; H. Nushida; Y. Ueno; K. Maeda

  Journal of Neural Transmission SPRINGER WIEN 113 (12) 1915 - 1920 0300-9564 2006/12 [Refereed]
   

  Suicide has been suggested to involve disturbances in the stress response system and to be related to genetics. The renin-angiotensin system (RAS) has been shown to affect the stress response, and several functional polymorphisms in RAS-related genes have been predicted to alter protein function. We hypothesized that the dysregulation of RAS was involved in suicide, and examined the association between completed suicides and four functional polymorphisms of RAS-related genes: the angiotensinogen M235T, angiotensin-converting enzyme (ACE) insertion(I)/deletion(D), angiotensin type-1 receptor A1166C, and G-protein-β3 C825T gene polymorphisms. The I allele of the ACE I/D polymorphism was found to be more frequent in completed suicides than in controls (P = 0.014). The I allele was also found to be more frequent in male completed suicides (P = 0.022) than in male controls, while this was not the case in females. These results suggest that the alteration of RAS function caused by the genetic polymorphism is involved in the susceptibility to suicide in males. © 2006 Springer-Verlag.
• Genetic association and postmortem immunoreactivity of RGS2 in suicide victims

  Huxing Cui; Naoki Nishiguchi; Elena Ivleva; Masaya Yanagi; Masaaki Fukutake; Hideyuki Nushida; Yasuhiro Ueno; Noboru Kitamura; Osamu Shirakawa; Kiyoshi Maeda

  AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS WILEY-LISS 141B (7) 758 - 758 1552-4841 2006/10
• Microarray analysis in the prefrontal cortex of schizophrenia

  Masaya Yanagi; Takeshi Hashimoto; Noboru Kitamura; Masaaki Fukutake; Kentarou Mouri; Naoki Nishiguchi; Osamu Shirakawa; Kiyoshi Maeda

  AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS WILEY-LISS 141B (7) 778 - 778 1552-4841 2006/10
• Efficacy of perospirone-paroxetine combination therapy for schizophrenia with obsessive-compulsive disorder

  Takashi Oshimo; Osamu Shirakawa; Masaya Yanagi; Naoki Nisiguti; Masayuki Ohta; Kiyoshi Maeda

  INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LIPPINCOTT WILLIAMS & WILKINS 21 (4) A3 - A3 0268-1315 2006/07
• 【DNAマイクロアレイと脳バンク】統合失調症に関連して

  柳 雅也; 白川 治; 北村 登; 福武 将映; 橋本 健志; 前田 潔

  分子精神医学 (株)先端医学社 6 (3) 251 - 256 1345-9082 2006/07 

  近年の分子遺伝学の急速な発展に伴い,DNAマイクロアレイを用いた大がかりなスクリーニングが可能となった.ヒトゲノム計画が完了し,cDNAに対する情報量も飛躍的に増加している昨今,大規模なヒトゲノム情報をもとにしたマイクロアレイ解析は,統合失調症をはじめとする多因子遺伝疾患のスクリーニング法として,きわめて有用である.一方,死後脳研究は,統合失調症の病因を明らかにするうえで,最も直接的な手法といえる.しかし,そこにはサンプル数の問題をはじめとしたいくつかの課題が存在する.今後,多くの死後脳サンプルが利用可能となる脳バンクの整備は,統合失調症の死後脳研究を再現あるものにしていくうえで重要になると思われる(著者抄録)
• 新規統合失調症候補遺伝子の検索

  柳 雅也; 橋本 健志; 北村 登; 福武 将映; 崔 虎星; 西口 直希; 川又 敏男; 白川 治; 前田 潔

  精神薬療研究年報 (公財)先進医薬研究振興財団 (38) 105 - 108 1346-1702 2006/03 

  新たな統合失調症候補遺伝子の検索を目的として,ヒト死後脳を用いたDNA chip解析を行った.さらにその結果に基づき,血液サンプルを用いた遺伝子相関研究を行った.統合失調症患者および健常対照者の死後剖検脳・前頭前野眼窩部からRNAを抽出し,18Sと28SのリボソーマルRNAの安定性を調べた.SCAM-1遺伝子,ATM遺伝子,CASP1遺伝子,AKAP11遺伝子,UPF3A遺伝子,SLC25A1遺伝子を選び,それらの遺伝子多型について検討した.統合失調症とコントロールあるいは日本人の遺伝子多型データベースと比較検討し,いずれも多型頻度において差をみとめず,統合失調症の病因に大きく関与している可能性が低いことが示唆された
• New therapies and prophylaxis for psychiatric disorders based on molecular pathology. Significance of RGS2 gene in suicide.

  前田潔; 西口直希; 白川治; 崔虎星; 柳雅也; 福武将映; 山本康二; 櫻井薫; 林祥剛; 主田英之; 上野易弘

  精神疾患の分子病態解明による新しい治療・予防法の開発に関する研究 平成15-17年度 総括・分担研究報告書 70 - 73 2006
• 【術後せん(譫)妄を考える】術後せん妄の薬物療法

  柳 雅也; 松石 邦隆; 北村 登; 福武 将映; 前田 潔

  ICUとCCU 医学図書出版(株) 29 (6) 455 - 460 0389-1194 2005/06 

  せん妄は脳器質性疾患や身体疾患に基づくもの,抗コリン作用を持つ薬物や睡眠薬などの副作用,またアルコールの離脱など様々な要因により起こる.手術後は身体の状態が不安定で,なおかつICU,CCUなど特殊な環境下におかれることが多いため,とりわけせん妄を発症しやすい.せん妄は通常,速やかに改善する病態であるが,ルート抜去,安静保持困難などの問題行動により,原疾患の治療に多大な支障をきたしうる.せん妄に対する治療は原疾患を治療する上においても重要であり,薬物治療はその中で大きな役割を担うと思われる.実際,非定型抗精神病薬を中心とする抗精神病薬や一部の抗うつ薬はせん妄に対する優れた鎮静効果を有し,迅速な治療を可能にする.しかし,薬物治療は心理因子,環境因子へのアプローチを含めた治療戦略の一環として位置づけられるものであり,これらの因子を考慮した上ではじめて薬物治療は奏効することを忘れてはならない(著者抄録)
• Association of 14-3-3 ε gene haplotype with completed suicide in Japanese

  Masaya Yanagi; Osamu Shirakawa; Noboru Kitamura; Kenji Okamura; Kaoru Sakurai; Naoki Nishiguchi; Takeshi Hashimoto; Hideyuki Nushida; Yasuhiro Ueno; Daiji Kanbe; Meiko Kawamura; Kazuaki Araki; Hiroyuki Nawa; Kiyoshi Maeda

  Journal of Human Genetics SPRINGER TOKYO 50 (4) 210 - 216 1434-5161 2005/04 [Refereed]
   

  Genetic factors have been suggested to be involved in suicide. Although some genetic factors, such as serotonergic transduction, have been associated with suicide, the results are inconsistent. There is a possibility that various signaling anomalies are involved in the biological vulnerability to suicide. We carried out a genome-wide gene-expression study in the brains of suicide victims using DNA microarrays;14-3-3 ε, which is related to neurogenesis, was one of the genes upregulated in the brains of suicide victims in the microarray analysis. This was confirmed by Western blot analysis. To examine the possibility of the involvement of 14-3-3 ε in the pathogenesis of suicide, we investigated the association of the 14-3-3 ε gene and completed suicide. We used three high-frequency SNPs (rs1532976, rs3752826, and rs9393) and found a significant association of two alleles (rs1532976 and rs3752826) with completed suicide (p < 0.05). Moreover, the distribution of haplotype revealed a more significant difference between completed suicide and controls (p=0.0005). This finding suggests that 14-3-3 ε is a potential suicide susceptibility gene and implies that dysregulation of neurogenesis may be involved in suicide. © The Japan Society of Human Genetics and Springer-Verlag 2005.
• Therapy development for psychiatric disorders by solving the molecular pathology. Possible suicide-related genes. Correlation between suicide and 14-3-3.EPSILON. gene polymorphism.

  前田潔; 白川治; 柳雅也; 服部晴起; 西口直希; さい虎星; 山本康二; 福武将映; 橋本健志; 桜井薫; 林祥剛; 主田英之; 上野易弘; 那波宏之

  厚生労働省精神・神経疾患研究委託費による研究報告集 平成16年度 (2年度班・初年度班) 127  2005
• Finding a pathophysiology of schizophrenia using postmortem brains

  YANAGI Masaya; HASHIMOTO Takeshi; KITAMURA Noboru; FUKUTAKE Masaaki; SHIRAKAWA Osamu; MAEDA Kiyoshi

  脳と精神の医学 = Brain science and mental disorders 日本生物学的精神医学会 15 (2) 205 - 210 0915-7328 2004/06
• I.統合失調症(精神分裂病)と周縁疾患 接枝分裂病

  白川治; 柳雅也; 服部晴起

  日本臨床 (株)日本臨床社 別冊 (精神医学症候群I) 68 - 70 0047-1852 2003/06
• 自殺と気質規定遺伝子との相関研究

  白川 治; 小野 久江; 青山 慎介; 菱本 明豊; 岡村 健二; 柳 雅也; 服部 晴起; 山本 康二; 主田 英之; 上野 易弘; 前田 潔

  精神薬療研究年報 (公財)先進医薬研究振興財団 (35) 88 - 92 1346-1702 2003/03 

  セロトニントランスポーター(5HTT)遺伝子多型(5HTT-LPR),ドーパミンD4受容体(DRD4)遺伝子多型(-521C/T),A型モノアミン酸化酵素(MAOA)遺伝子多型(MAOA-uVNTR),カテコール-ο-メチルトランスフェラーゼ(COMT)遺伝子多型(158Val/Met)と自殺との相関研究を行った.更に,これら遺伝子多型間の相互作用と自殺との関連についても検討した.その結果,5HTT-LPR,MAOA-uVNTR,DRD4:-521C/T多型では,自殺既遂者群163例(男112例,女51例)と健常対照群169例における遺伝子型ならびに遺伝子頻度の分布に有意差を認めなかったが,COMT:158Val/Met多型では,男性においてのみ遺伝子型の分布に有意差がみられ,遺伝子頻度でも高活性を示すとされるG(Val)アレルが自殺既遂者群で少ない傾向が認められたことから,男性では高COMT活性が自殺に抑制的に働いていることが示唆された.更に,上記多型間の相互作用を検討したところ,男性においてのみ,5HTT-LPRとMAOA-uVNTR及び5HTT-LPRとCOMT:158Val/Met多型で,遺伝子型の組合せの分布に有意差が認められた

Books etc

• エスシタロプラムのすべて

  柳雅也; 白川治 (Contributor2-1.うつ病と不安症におけるシグナル伝達と5-HT受容体機能と選択性)先端医学社 2016/01
• 脳科学辞典

  柳 雅也; 辻井 農亜; 白川 治 (Contributor衝動制御障害)日本神経科学学会 2015/03
• 脳科学辞典

  柳 雅也; 辻井 農亜; 白川 治 (Contributor自殺)日本神経科学学会 2014/10
• デュロキセチンのすべて

  柳雅也; 辻井農亜; 切目栄司; 白川治 (Contributor4-7.他の抗うつ薬からデュロキセチンへの切り替えとそのポイント)先端医学社 2014/07

MISC

• 幻視・幻触から妄想への発展を認めたレビー小体型認知症の1例

  池田真優子; 廣瀬智之; 土屋有希; 谷緑; 柳雅也; 橋本衛  精神神経学雑誌  124-  (3)  2022
• 心不全に多発性脳梗塞を併発した患者が心臓移植をめざす経過へかかわった1例

  西原崇浩; 土屋有希; 細見史治; 廣瀬智之; 柳雅也; 辻井農亜; 白川治  精神神経学雑誌  123-  (10)  2021
• クロザピン導入後に緩徐な症状の改善を認めた治療抵抗性統合失調症の1例

  川久保 善宏; 柳 雅也; 山形 祥礼; 土屋 有希; 池田 真優子; 白川 治  精神神経学雑誌  122-  (1)  66  -66  2020/01
• 練炭自殺企図による間歇型一酸化炭素中毒の1例

  池田真優子; 辻井農亜; 明石浩幸; 柳雅也; 土屋有希; 白川治  精神神経学雑誌  121-  (3)  230  -230  2019/03
• mtDNA copy number raises the potential of left frontopolar hemodynamic responses for distinguishing BD from MDD

  菱本明豊; 辻井農亜; 大塚郁夫; 岡崎賢志; 柳雅也; 沼田周助; 山木愛久; 川久保善宏; 白川治  日本うつ病学会総会プログラム・抄録集  16th-  174  2019
• 双極性うつ病におけるラモトリギン治療反応性と精神病症状の既往との関連

  廣瀬智之; 辻井農亜; 三川和歌子; 細見史治; 森本拓頌; 柳雅也; 白川治  日本うつ病学会総会プログラム・抄録集  16th-  161  2019
• 統合失調症における自発的脳活動のNIRSを用いた検討

  細見史治; 柳雅也; 川久保善宏; 土屋有希; 廣瀬智之; 三川和歌子; 辻井農亜; 尾崎哲; 白川治  日本生物学的精神医学会  41st-  52  2019
• 修正型電気けいれん療法が著効した老年期うつ病の1例

  矢野貴詩; 切目栄司; 山形祥礼; 柳雅也; 丹羽篤; 細見史治; 安達融; 白川治  精神神経学雑誌  121-  (1)  65  -65  2019/01
• Near‐Infrared Spectroscopy(NIRS)を用いた安静時脳血流の解析

  細見史治; 柳雅也; 川久保善宏; 土屋有希; 廣瀬智之; 三川和歌子; 辻井農亜; 白川治  近畿大学医学雑誌  43-  (3-4)  18A  -18A  2018/12
• 精神疲労と身体疲労の客観的評価:加速度脈波と近赤外分光法を用いた研究

  廣瀬智之; 高屋雅彦; 土屋有希; 川久保善宏; 細見史治; 柳雅也; 辻井農亜; 白川治  日本精神神経学会総会プログラム・抄録集  114th-  (2018特別号)  S389  -S389  2018/06
• 持続性筋注製剤を導入し良好に経過した統合失調症の1例

  川久保 善宏; 柳 雅也; 池田 真優子; 土屋 有希; 高屋 雅彦; 白川 治  精神神経学雑誌  120-  (3)  235  -235  2018/03
• A preliminarily study of near-infrared spectroscopy to measure a resting state activity in prefrontal cortex of schizophrenia

  YANAGI Masaya; HOSOMI Fumiharu; KAWAKUBO Yoshihiro; TSUCHIYA Yuki; HIROSE Tomoyuki; MIKAWA Wakako; TSUJII Noa; OZAKI Tetsuo; SHIRAKAWA Osamu  Asia Pacific Regional Congress of Biological. Psychiatry WFSBP2018KOB  40th-  160  2018
• 自殺企図で救命救急センターに入院した患者に退院後の再企図予防介入を導入した1例

  和田 照平; 明石 浩幸; 柳 雅也; 川久保 善宏; 矢野 貴詩; 丹羽 篤; 辻井 農亜; 白川 治  精神神経学雑誌  119-  (9)  700  -700  2017/09
• Near-Infrared Spectroscopy(NIRS)を用いた安静時脳血流賦活の測定

  細見 史治; 柳 雅也; 川久保 義宏; 土屋 有希; 広瀬 智之; 三川 和歌子; 辻井 農亜; 白川 治  日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集  39回・47回-  195  -195  2017/09
• 言語流暢課題の繰り返しが脳血流の賦活に及ぼす影響

  川久保善宏; 柳雅也; 細見史治; 廣瀬智之; 辻井農亜; 白川治  日本精神神経学会総会プログラム・抄録集  113th-  (2017特別号)  S354  -S354  2017/06
• 経時的な観察により統合失調症の併存が疑われた自閉スペクトラム症の1例

  平野愛佳; 辻井農亜; 三川和歌子; 阪中聡一郎; 安達融; 柳雅也; 白川治  精神神経学雑誌  119-  (4)  274  2017/04
• 定型および非定型抗精神病薬によるKv3.2カリウムイオンチャネルの発現調節

  柳 雅也; 白川 治; Carol Tamminga  精神神経学雑誌  112th-  (2016特別号)  S530  -S530  2016/06
• 双極性障害患者における光トポグラフィー検査を用いた鑑別診断補助に影響を与える因子について

  三川和歌子; 辻井農亜; 辻本江美; 辻本江美; 丹羽篤; 阪中聡一郎; 川久保善宏; 矢野貴詩; 細見史治; 柳雅也; 小野久江; 白川治  日本うつ病学会総会プログラム・抄録集  13th-  167  2016
• 大脳萎縮を認めた神経性無食欲症の1例

  川久保 善宏; 柳 雅也; 池田 真優子; 辻井 農亜; 丹羽 篤; 白川 治  精神神経学雑誌  117-  (8)  682  -682  2015/08
• AYA世代のがん患者に対する心理的サポートについての一考察

  丹羽 篤; 川久保 善宏; 三川 和歌子; 柳 雅也; 辻井 農亜; 白川 治  精神神経学雑誌  117-  (2)  161  -161  2015/02
• メランコリー型うつ病における抑うつ症状とQOL 非メランコリー型うつ病との差異

  川久保 善宏; 辻井 農亜; 切目 栄司; 船津 浩二; 高屋 雅彦; 柳 雅也; 原田 毅; 三川 和歌子; 安達 融; 曽我 愛佳; 阪中 聡一郎; 廣瀬 智之; 丹羽 篤; 和田 照平; 白川 治  精神神経学雑誌  117-  (1)  56  -56  2015/01
• 双極性障害における抑うつ症状とQOL 単極性うつ病との差異

  廣瀬 智之; 辻井 農亜; 高屋 雅彦; 柳 雅也; 明石 浩幸; 三川 和歌子; 安達 融; 阪中 聡一郎; 白川 治  精神神経学雑誌  117-  (1)  64  -64  2015/01
• メランコリー型うつ病と非メランコリー型うつ病の脳機能の差異

  川久保 善宏; 辻井 農亜; 高屋 雅彦; 柳 雅也; 明石 浩幸; 原田 毅; 阪中 聡一郎; 廣瀬 智之; 丹羽 篤; 白川 治  精神神経学雑誌  (2014特別)  S391  -S391  2014/06
• Reduced activation of the temporal cortex in patients with euthymic bipolar disorder during a verbal fluency task: a multi-channel near-infrared spectroscopy study

  N. Tsujii; W. Mikawa; H. Akashi; E. Tsujimoto; E. Kirime; T. Adachi; M. Takaya; H. Ono; M. Yanagi; O. Shirakawa  BIPOLAR DISORDERS  16-  91  -92  2014/03
• Reduction of left temporal cortex activation in suicide attempters with bipolar disorder after a verbal fluency task: a multi-channel near-infrared spectroscopy study

  N. Tsujii; W. Mikawa; E. Tsujimoto; E. Kirime; H. Akashi; M. Takaya; M. Yanagi; T. Adachi; H. Ono; O. Shirakawa  BIPOLAR DISORDERS  16-  92  -92  2014/03
• 双極性障害患者における抑うつ症状と左側頭部機能の関連:a near-infrared spectroscopy study

  三川和歌子; 辻井農亜; 切目栄司; 明石浩幸; 柳雅也; 廣瀬智之; 高屋雅彦; 白川治  日本生物学的精神医学会誌 (Japanese Journal of Biological Psychiatry)  172  2014
• ダラス留学記

  柳 雅也  日本生物学的精神医学会誌 = Japanese journal of biological psychiatry  21-  (4)  279  -279  2010/12
• NOS1の遺伝的変異は統合失調症と脳内のNOS1発現と関連している

  HISHIMOTO Akitoyo; SAI Kosei; NISHIGUCHI Naoki; YANAGI Masaya; FUKUTAKE Masaaki; MOHRI Kentaroh; MOHRI Kentaroh; KITAMURA Noboru; HASHIMOTO Takeshi; SHIRAKAWA Osamu  日本生物学的精神医学会誌 (Japanese Journal of Biological Psychiatry)  21-  95  2010/10
• 自殺とPBR遺伝子多型との相関研究

  毛利健太朗; 白川治; 崔虎星; 福武将映; 柳雅也; 西口直希; 主田英之; 上野易弘; 長崎靖; 前田潔  日本生物学的精神医学会プログラム・講演抄録 (日本生物学的精神医学会プログラム講演抄録)  29th-  (216)  2007
• Glucocorticoid Receptor Gene多型と自殺との相関研究

  福武将映; 柳雅也; 西口直希; 主田英之; 上野易弘; 白川治; 前田潔  日本生物学的精神医学会プログラム・講演抄録 (日本生物学的精神医学会プログラム講演抄録)  29th-  228  2007
• 自殺者におけるP11遺伝子多型

  崔虎星; 西口直希; 柳雅也; 福武将映; 毛利健太朗; 主田英之; 上野易弘; 白川治; 前田潔  日本生物学的精神医学会プログラム・講演抄録 (日本生物学的精神医学会プログラム講演抄録)  29th-  220  2007
• RGS2免疫反応性は統合失調症で変化している(RGS2 immunoreactivity was altered in schizophrenia)

  Nishiguchi Naoki; Cui Huxing; Shirakawa Osamu; Kitamura Noboru; Yanagi Masaya; Fukutake Masaaki; Mouri Kentarou; Maeda Kiyoshi  神経化学  45-  (2-3)  361  -361  2006/08
• 自殺者の剖検におけるRGS2の免疫反応性(postmortem immunoreactivity of RGS2 in suicide victims)

  Cui Huxing; Nishiguchi Naoki; Shirakawa Osamu; Yanagi Masaya; Fuhutake Masaaki; Sakurai Kaoru; Kitamura Noboru; Nushida Hideyuki; Ueno Yasuhiro; Nagasaki Yasusi; Maeda Kiyoshi  神経化学  45-  (2-3)  405  -405  2006/08
• 統合失調症死後脳前頭前野におけるProliferation cell nuclear antigen(PCNA)の検討

  福武 将映; 柳 雅也; 北村 登; 橋本 健志; 毛利 健太郎; 白川 治; 前田 潔  神経化学  45-  (2-3)  361  -361  2006/08
• 日本人における自殺既遂者と14-3-3ε遺伝子ハプロタイプとの関連

  福武将映; 柳雅也; 橋本健志; 大下隆司; 西口直希; 白川治; 前田潔  日本生物学的精神医学会プログラム・講演抄録 (日本生物学的精神医学会プログラム講演抄録)  27th-  303  2005
• 自殺既遂者へん桃体における14‐3‐3εタンパクの発現変化

  柳雅也; 橋本健志; 北村登; 西口直希; 白川治; 前田潔  日本生物学的精神医学会プログラム・講演抄録  27th-  303  2005
• Chlorpromazineが原因と考えられた赤芽球癆の1例

  大川 伸一; 柳 雅也; 田中 究; 橋本 健志; 山本 泰司; 柿木 達也; 大川 慎吾; 前田 潔  九州神経精神医学  47-  (2)  114  -114  2001/08
• 逆耐性形成ラット線条体におけるDARPP‐32を介する情報伝達系の変化

  林賢浩; 橋本健志; 北村登; 柳雅也; 村上直也; 白川治; 前田潔  日本生物学的精神医学会プログラム・講演抄録  23rd-  246  2001/04
• シクロスポリン併用中にステロイド精神病を発症したネフローゼ症候群の1症例

  柳 雅也; 大西 俊子; 福島 春子; 橋本 健志; 田中 究; 白川 治; 前田 潔  九州神経精神医学  45-  (3〜4)  206  -206  1999/12

Awards & Honors

• 2015 先進医薬研究振興財団 精神薬療研究助成
  
• 2006 日本臨床精神神経学会 海外研修員
  

Research Grants & Projects

• 病態バイオマーカーを新機軸とした心理社会的療法の共創

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2023/06 -2028/03 

  Author : 柳 雅也
• Application of gamma entrainment to patients with schizophrenia and its effect on hippocampal pathology

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2022/04 -2026/03 

  Author : 柳 雅也; 橋本 衛; 石井 一成; 難波 寿明
• Identification of a biomarker for pathophysiology of schizophrenia using Kv3.1/3.2 gene mutations

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2017/04 -2020/03 

  Author : YANAGI Masaya

   

  We measured the auditory steady state response (ASSR) using electroencephalography (EEG) and the cerebral blood flow at rest using near-infrared spectroscopy（NIRS）to identify a biomarker for the pathophysiology of the prefrontal cortex in schizophrenia. In the analysis of the cerebral blood flow during resting-state, we applied the methods of the amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF), which have been used in fMRI studies to quantify the resting-state blood flow, to the NIRS data. We found that both ALFF and fALFF were decreased in the medial prefrontal cortex of the chronic patients with schizophrenia, and that the ALFF was negatively associated with the symptoms of auditory hallucinations in the patients.
• Development of the objective evaluation system of the depressive state in mood disorders by the near-infrared spectroscopy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2016/04 -2019/03 

  Author : SHIRAKAWA Osamu

   

  For an objective evaluation of symptoms particularly such as suicidality in major depressive disorder (MDD) and bipolar disorder(BD), near-infrared spectroscopy (NIRS) was used. MDD with a history of suicidal behavior showed smaller hemodynamic response in the left precentral gyrus. the reduced response in the left inferior frontal gyrus was negatively correlated with impulsivity level and hemodynamic responses in the right middle frontal gyrus were negatively associated with hopelessness and aggression in MDD with a history of suicidal behavior. BD with a history of suicidal behavior exhibits reduced activation in frontotemporal region and delayed activation timing of the NIRS signal in the prefrontal region. BD showed characteristic inactivation pattern of the right superior temporal gyri during an inhibitory control task.
• Searching for mechanism of antipsychotic action; modulation of Kv3 channel family

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2014/04 -2017/03 

  Author : YANAGI Masaya; TAMMINGA CA

   

  In this study, we found that haloperidol, a typical APD and risperidone, an atypical APD differentially modulated cortical Kv3.1 and Kv3.2 channels. While both haloperidol and risperidone significantly increased Kv3.1 protein levels in rat prefrontal cortex, Kv3.2 protein levels showed an increase and a decrease in the same region by haloperidol and risperidone, respectively. A similar pattern of Kv3.2 change was found in cerebellum, however, no significant changes were found in Kv3.2 protein levels in hippocampus, thalamus and striatum. These result were reported in Annual Meeting of the Japanese Society of Psychiatry and Neurology.
• Evaluation of Lithium responsiveness and suicidality in mood disorders by near-infrared spectroscopy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

  Date (from‐to) : 2013/04 -2016/03 

  Author : SHIRAKAWA Osamu; TSUJII Noa; KIRIME Eiji; YANAGI Masaya

   

  We investigated the factors associated with lithium responsiveness and suicidality in mood disorders (bipolar disorder, depression) by brain function evaluated by the near-infrared spectroscopy and various clinical data. The small number of cases with lithium responsiveness do not reach the statistical significance. On the other hand, we obtained significant results about suicidality as follows. 1) Discrepancies between self- and observer-rated depression severities are associated with vulnerability to suicide in patients with major depressive disorder, and prefrontal cortex activation is associated with these discrepancies. 2) Right temporal activation differs between melancholia and nonmelancholic depression. 3) Patients with bipolar disorders have persistent hypofunction of the frontotemporal cortical regions and the hemodynamic response in the left temporal regions is associated with symptom severity.
• 死後脳DNA chip解析に基づいた神経新生関連統合失調症候補遺伝子の同定

  日本学術振興会：科学研究費助成事業 若手研究(B)

  Date (from‐to) : 2006 -2007 

  Author : 柳 雅也

   

  DNA chip解析により、13qに位置し、転写因子をコードするKLF5遺伝子の発現量が、統合失調症死後脳前頭前野においてコントロール群よりも減少していることを見出した。さらに、その結果に基づき、378名の健常者および328名の統合失調症患者の血液サンプルを用いてKLF5遺伝子と統合失調症との相関研究をおこなったころ、KLF5遺伝子プロモーター上のSNPと統合失調症との有意な相関をみとめた。また、その相関をみとめた-1593T/C SNPについて統合失調症死後脳における発現量を検討したところ、-1593T/C SNPはKLF5遺伝子の発現量に影響を及ぼしていることを見出した。さらに統合失調症の血液サンプルを用いた遺伝子配列解析をおこなったところ、一つの一塩基変異はコントロール群においてはみられず、統合失調症においてのみみられた。 さらにKLF5遺伝子の脳における発現分布について免疫組織学的な検討をおこなったところ、グルタミン酸ニューロンに多く発現していることを見出した。これまでにKLF5遺伝子は、MAPキナーゼカスケートに位置することが報告されており、MAPキナーゼカスケードは脳においてはシナプス可塑性に重要であることが知られている。これらのことは、KLF5遺伝子がグルタミン酸ニューロンのシナプス可塑性にかかわる可能性を示している。本研究において、KLF5遺伝子が統合失調症と相関したことは、統合失調症においてはグルタミン酸神経伝達に障害があるのではないかというグルタミン酸神経伝達仮説を支持するものであり、その障害にKLF5遺伝子が関わっていることを示唆するものである。以上の結果は、現在欧文雑誌に掲載予定である。
• Identification of suicide candidate genes in amygdala and its application to neuroimaging studies

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

  Date (from‐to) : 2005 -2007 

  Author : SHIRAKAWA Osamu; MAEDA Kiyoshi; NISHIGUCHI Naoki; YANAGI Masaya; UENO Yasuhiro; NUSHIDA Hideyuki

   

  1. We studied the clinical and psychological characteristics associated with suicidality based on the history of lethal suicide attempt in 76 patients mainly with mood disorders. Hopelessness rather than depression, aggression in less than 40 years old patients and neuroticism were associated with suicidality. The perspectives on death were not associated with suicidality. 2. We performed the profiling of mRNA expressions in amygdala of suicide brains. The 21 increased and the 9 decreased expressions of genes were identified. Among the genes with increased expressions, the polymorphisms of 14-3-3 ε gene were associated with suicide. Any polymorphisms in genes with the decreased expressions were not associated with suicide. 3. Among the functional gene polymorphisms which affect a hypothalamic-pituitary-adrenal system (HPA system), we found the significant associations of OPRM1 Asn40Asp, ACE I/D and ADEA2A C-1291G polymorphism with suicide. 4. For functional MRI, we made a neuropsychological task which activates emotion. A stronger activation in amygdala and posterior cingulate gyrus was shown in case of recognition in emotionally negative words, compared with emotionally neutral words. We made the tasks comprising the recall of past negative or positive episodes and the imagination of future negative or positive episodes. The activations were found in the medial frontal cortex, dorsolateral prefrontal cortex posterior cingulate gyrus.

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