Symposium

Symposium 25 Neuroimaging findings in psychiatric disorders シンポジウム25 本邦における精神疾患の脳画像研究up-to-date

SY25-1 Enhanced carbonyl stress and white matter disruption in schizophrenia 統合失調症におけるカルボニルストレスと白質統合性について Son Shuraku（孫樹洛）¹，新井誠²，鳥海和也²，水田弘人¹，宮田淳¹，林拓也³，浦山慎一⁴，麻生俊彦^1,4，福山秀直⁴，糸川昌也²，村井俊哉¹ ¹Department of Psychiatry, Kyoto University Graduate School of Medicine ²Project for Schizophrenia and Affective Disorders Research, Tokyo Metropolitan Institute of Medical Science ³RIKEN Center for Biosystems Dynamics Research (BDR) Brain Connectomics Imaging Team ⁴Human Brain Research Center, Kyoto University Graduate School of Medicine Carbonyl stress is a state featuring rich reactive carbonyl compounds (RCOs). Enhanced carbonyl stress accumulates advanced glycation end products (AGEs) including pentosidine, resulting in such as arteriosclerosis. Pyridoxal, one kind of vitamin B6, is known to detoxify RCOs and AGEs. Recently, some studies have reported that schizophrenia, especially treatment-resistant type, is related with enhanced carbonyl stress. Additionally, one in vitro study reports that circumstance with less pyridoxal induces decreased myelination simultaneously with increased AGEs. We therefore investigated relationships between carbonyl stress and white matter disruption in schizophrenia using diffusion tensor imaging. Twenty-eight patients with schizophrenia and 42 age and gender matched healthy controls were recruited. Diffusion-weighted data were acquired on a 3-Tesla MRI unit. We preprocessed all data using the program of FSL version 5.0.9. We calculated mean values of fractional anisotropy (FA) and mean diffusivity (MD) of white matter areas within the skeleton image using Tract-Based Spatial Statistics (TBSS). We investigated group differences in plasma pentosidine and serum pyridoxal as carbonyl stress markers and relationships of these markers with mean FA and MD values. Significance level were set at 0.05. In schizophrenia, plasma pentosidine was not significantly increased whereas serum pyridoxal was significantly decreased. By correlation analyses, we found significant negative correlation of plasma pentosidine with mean FA values and positive correlation with mean MD values only in schizophrenia. Although further studies are needed, this is the first study suggesting that increased carbonyl stress could be one factor related with white matter disruption in schizophrenia.		SY25-2 Subcortical association with cognitive and social function in schizophrenia: a structural magnetic resonance imaging study 統合失調症の皮質下体積と認知・社会機能の相関解析 Koshiyama Daisuke（越山太輔）¹，福永雅喜²，岡田直大¹，山下典生³，山森英長⁴，安田由華⁴，藤本美智子⁴，大井一高⁴，藤野陽生⁵，渡邉嘉之⁶，笠井清登¹，橋本亮太^4,7,8 ¹Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo ²Division of Cerebral Integration, National Institute for Physiological Sciences, Aichi, Japan ³Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan ⁴Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan ⁵Graduate School of Human Sciences, Osaka University, Osaka, Japan ⁶Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan ⁷Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan ⁸Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders. Although previous studies focused on the neurocognitive and socio-functional consequences of prefrontal and tempolo-limbic abnormalities in psychiatric disorders, those of subcortical structures remain largely unknown. Recently, MRI volume alterations in subcortical structures in patients with schizophrenia have been replicated in large-scale meta-analytic studies. Here we investigated the relationship between volumes of subcortical structures and neurocognitive and socio-functional indices in a large sample of patients with schizophrenia. First, we replicated the results of meta-analyses: the regional volumes of the bilateral hippocampus, amygdala, thalamus and nucleus accumbens were significantly smaller for patients (N=174) than for healthy controls (HCs, N=638). Second, in the patient group, the nucleus accumbens volume was significantly correlated with the Digit Symbol Coding score, which is known as a distinctive characteristic index of cognitive deficits in schizophrenia. The thalamic volume was significantly correlated with social function scores. Furthermore, verbal immediate recall/delayed recall scores in patients with schizophrenia were significantly correlated not only with hippocampal volume, but also with nucleus accumbens volume. In HCs, no significant correlation was found. The results from this large-scale investigation shed light upon the role of specific subcortical nuclei on cognitive and social functioning in schizophrenia.

SY25-3 The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: A prospective mega study 抗精神病薬が海馬、扁桃体体積に与える影響　国内大規模多施設共同研究から Hashimoto Naoki（橋本直樹） The Department of Psychiatry, Graduate School of Medicine, Hokkaido University 背景統合失調症患者の皮質下体積に対する抗精神病薬および罹病期間の影響について、先行研究の結果は一致しない。Prospective meta-studyは、一定の要件をみたす条件で撮像された脳画像データを、同一の手法で処理し、解析する新しい研究手法であり、この手法を用いた研究から統合失調症患者と健常者の皮質下脳体積の差異について重要な知見が得られている。しかし脳画像データと背景因子の関連の検討については、これまでどおりmega-regiressionの手法が取られていた。我々は、国内で行われたprospective meta-analysisについて、個々の背景因子データをプールし、直接にその影響を計算するprospective mega-analysisの手法を用い、抗精神病薬が皮質下体積に及ぼす影響を検討した。方法国内のCOCOROネットワークにて行われたprospective meta-analysisで得られた統合失調症患者778名の脳画像データを用いた。個々の皮質下構造物の体積を従属変数、撮像日の抗精神病薬投与量（クロルプロマジン換算）、罹病期間、年齢、性別、頭蓋内体積を独立変数とした。また撮像プロトコルを切片の変量効果とし、混合線形効果モデルを作成した。このモデルにおいて抗精神病薬投与量、罹病期間の係数の有意性についてt検定、bootstrap法の双方を用いて検討した。結果抗精神病薬投与量は左淡蒼球体積と有意な正の相関、右海馬体積と有意な負の相関を示した。抗精神病薬投与量は淡蒼球のLaterality Indexと有意な正の相関を示した。罹病期間は左右淡蒼球体積と有意な正の相関を示した。抗精神病薬のタイプ（定型vs非定型）は皮質下体積に影響しなかった。考察本研究は、皮質下体積に対する罹病期間、抗精神病薬投与量の影響を多数症例のデータを直接に用いて検討した初めての研究である。本研究の結果は、抗精神病薬の脳組織に対する何らかの影響の存在を示唆するものであり、今後の生物学的な基盤の検討が待たれる。		SY25-4 Up-to-date structural MRI studies in mood disorders 気分障害における脳構造MRI研究up-to-date Matsuo Koji（松尾幸治） Div. Neuropsychiatry, Dpt. Neurosci. Yamaguchi Univ. Grad. Shol. Med. Evidence of structured brain abnormalities in mood disorders has been accumulated in MRI studies, yet it remains inconclusive. Small gray matter volume (GMV) is observed in patients with mood disorders in dorsolateral prefrontal cortex, anterior medical frontal region, and medial temporal region including hippocampus and amygdala. These structures are presumed to be involved in the neural circuit of mood regulation. Abnormal white matter (WM) integrities of fronto-temporal regions are also seen in patients with mood disorders in diffusion tensor imaging studies. Cross-sectional and longitudinal studies suggest that the structured abnormalities are associated with clinical variables; e.g., age of onset illness, duration of illness, the number of episode, and a history of psychotic episode and suicide attempt. Very recent structured MRI studies of mood disorders were conducted in the form of multi-site, resulting in the usage of machine learning methods to analyze immense MRI data. Further, multi-modal studies combined with GMV, and structured and functional connectivity has been increasingly reported. For primary outcomes, most of structured studies of mood disorders are to seek the differences of GMV and WM integrity in a case-control manner and some are to compare these differences between bipolar disorder and major depressive disorder. The comparison of the two disorders can shed light on elucidation of neural mechanism for depression within the bipolar/major depressive disorder continuum. Here we review up-to-date evidence of structured abnormalities and discuss future directions of MRI studies in mood disorders.

SY25-5 Establish the learning environment of neuroimaging analysis 脳画像解析学習環境の構築 Nemoto Kiyotaka（根本清貴） Department of Neuropsychiatry, Faculty of Medicine, University of Tsukuba Learning neuroimaging analysis requires understanding principles of analysis and how to use software packages. A variety of neuroimaging software packages have been available from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We have developed a cusomized Linux distribution named "Lin4Neuro." This system includes popular neuroimaging analysis tools and the user interface is customized so that even novice users can use it intuitively.Nowadays it is available as virtual machine, which enables anyone to run the system on any operating system (OS). We found several benefits of using this system for hands-on tutorials. First, we can get an uniform environment, which helps participants to understand exactly what they need to do since appearance of the system is the same. Second, it has made teachers and tutors possible to replicate the tutorial easily, which resulted in the easiness of verification. Lastly, all materials can be distributed using the Internet service, which reduces various cost for running tutorial. This system also provides a practical means of sharing analysis environments across sites.