Oral Session

Oral Session 16 一般口演16

O16-1 Trace amine update: in pathophysiology and treatment of mental disorders 微量アミン再考：精神疾患の病態と治療において Ikemoto Keiko（池本桂子） Dept of Psychiatry, Iwaki Kyoritsu General Hospital β‐フェニルエチルアミン（PEA）、チラミンなどの微量アミンと精神疾患の病態の関連については1970年代から関心がもたれていた。その後、D-ニューロン（微量アミン（TA）ニューロン）が哺乳類で報告され、D-ニューロン系はヒト前脳で発達していることがわかった。中脳辺縁ドーパミン（DA）系の投射先である側坐核は、抗精神病薬の作用部位であり、統合失調症の病態との関連が示唆されていた。D-ニューロンはヒトとげっ歯類の側坐核に局在したが、サルの側坐核には確認できず、統合失調症死後脳の側坐核ではD-ニューロンが脱落していた。PEA、チラミンなどのTAの受容体は2001年にクローニングされ、TAAR1（trace amine-associated receptor 1）がヒト内在性TAの唯一の受容体であり、薬理・行動学的解析とTAAR1ノックアウトマウスを用いた研究の結果、中脳腹側被蓋野（VTA）DAニューロンに局在するTAAR1の刺激減弱が、DAニューロンの発火頻度を増加させ、中脳辺縁DA過活動を生じさせることが判明した。側脳室脳室下ゾーン神経幹細胞（NSC）の機能不全は側坐核D-ニューロン脱落の原因と考えられる。側坐核のD-ニューロン減少とTAAR1刺激減弱は、中脳辺縁DAニューロンの過活動を生じさせ、過剰のDAはNSCとD-ニューロンの機能をさらに低下させる。この悪循環を断ち切るのがD2受容体拮抗薬早期投与である。TAAR1は抗精神病薬標的受容体として重要である。D-細胞仮説では、ストレス、加齢、飲酒がNSCの機能を減弱させ、精神病状態を発現させるメカニズムを説明することが可能である。TAAR1は膵β細胞にも局在し、インスリンの分泌を調節し、糖尿病の発症に関わること、TAAR1は、ナルコレプシーのような過眠症やaddictionの病態に関与することが報告された。将来的には、TAAR1のリガンドニューロンであるD-ニューロンを幹細胞から誘導して移植するという、再生医療への応用の可能性も見込まれる。		O16-2 Longitudinal Evaluation of Visual P300 Amplitude in Clinical High Risk Subjects: An ERP Study 統合失調症ハイリスク群における視覚事象関連電位の縦断的研究 Oribe Naoya（織部直弥）^1,2，平野羊嗣^2,3，上野雄文^1,2，神庭重信²，鬼塚俊明²，McCarley Robert³，Niznikiewicz Margaret³ ¹Hizen Psychiatric Center ²Department of Neuropsychiatry Kyushu University ³Laboratory of Neuroscience, VA Boston Healthcare System, Department of Psychiatry, Harvard Medical School Objective: We previously reported abnormal P300 and N200 in a visual oddball task, and progressive P300 amplitude reduction at one-year follow-up in patients with first episode schizophrenia. P300 reduction as well as intact P1/N1 was also observed in clinical high-risk subjects (CHR), but whether or not these components change over time is unknown. This study evaluates, longitudinally, the visual P300, as well as P1, N1, and N200, in CHR.Methods: Visual ERPs were recorded twice, once at baseline and once at one -year follow-up in CHR (n = 19) and healthy comparison subjects (HC; n = 28). Participants silently counted infrequent target stimuli (“x”) among standard stimuli (“y”) presented on the screen while the 64-channel electroencephalogram was recorded.Results: No CHR converted to psychosis from baseline to one-year follow-up in this study. Visual P300 amplitude was reduced and the latency was delayed significantly in CHR at both time points compared with HC. Furthermore, CHR subjects who had more positive symptoms showed more amplitude reduction at both time points. P1, N1 and N200 did not differ between groups.Conclusion: Visual P300 amplitude was found to be reduced in CHR individuals compared with HC. We note that this finding is in subjects who did not convert to psychosis at one-year follow-up. The association between visual P300 amplitude with symptoms suggests that for CHR who often experience clinical symptoms and seek medical care, visual P300 may be an important index that reflects the pathophysiological impairment underlying such clinical states.

O16-3 Accuracy validation of a portable single channel EEG device to record sleep EEG 携帯型脳波計による睡眠脳波測定精度の検討 Kuriyama Kenichi（栗山健一）¹，藤井勇佑¹，尾池祐輝¹，松尾雅博¹，角谷寛²，山田尚登¹ ¹Department of Psychiatry, Shiga University of Medical Science, Otsu, Shiga, Japan ²Department of Sleep and Behavioral Science, Shiga University of Medical Science, Otsu, Shiga, Japan Sixty to 90% of MDD patients suffer sleep disturbances. Polysomnographic (PSG) studies also suggested several sleep-architecture abnormalities in electroencephalogram (EEG) profiles of MDD patients. A meta-analysis revealed that rapid eye movement (REM) density and reduced slow-wave sleep (SWS) are potential candidates for MDD biomarker. In addition, most experts achieved consensus that those EEG parameters could be useful for early detection of MDD at general practioner (GP). However, there is a significant hurdle that PSG can be measured at hospital or sleep laboratories. The traditional PSG requires at least 2 to 4 cortical channels with a reference channel, electromyogram, electrocardiogram, and electro-oculogram for determining sleep stages. Recently, a small portable EEG device has been developed. The device enabled measure patient’s EEG easily at home, but it can measure from just one cortical channel with a reference. If the device could measure EEG without sacrificing quality for determining sleep stages, we will be able to detect MDD earlier at the level of GP. Thus, we validate the accuracy of the portable single channel EEG device to record sleep EEG compared to the traditional PSG system, for developing practical use of sleep EEG for MDD diagnosis. We compared the sleep stages and fast fourier transformed EEG data measured from 26 patients with sleep disorders and 15 healthy volunteers by both the portable EEG and traditional PSG devices. This study was conducted as part of the project of the ‘Practical use of sleep EEG for objective assessment and diagnosis of major depression’, at the Research on Development of New Medical Devices commissioned by the Japan Agency of Medical Research and Development (AMED).