日本生物学的精神医学会誌 27 巻 4 号 177 特集 1 栄養学から見た精神疾患の予防 治療の可能性 1. 緑茶成分テアニンの向精神作用について 抄録 : L theanine N ethyl L glutamine prepulse inhibition PPI 200

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1 177 特集 1 栄養学から見た精神疾患の予防 治療の可能性 1. 緑茶成分テアニンの向精神作用について 抄録 : L theanine N ethyl L glutamine prepulse inhibition PPI 2mg 4mg PPI (4): , 216 Key words L theanine glutamate green tea depression schizophrenia prepulse inhibition PPI psychotropic effects はじめに L theanine N ethyl L glutamine Thea sinensis Camellia sinensis 図 12 Psychotropic effects of a green tea ingredient, L theaine Hiroshi Kunugi, Miho Ota, Chisato Wakabayashi, Shinsuke Hidese Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry , Ogawa Higashi, Kodaira, Tokyo , Japan Hayato Ozawa, Tsutomu Okubo Department of Research and Development, Nutrition Division, Taiyo Kagaku Co., Ltd. 1 3, Takaramachi, Yokkaichi, Mie , Japan E mail hkunugi@ncnp.go.jp

2 178 Japanese Journal of Biological Psychiatry Vol.27, No.4, 216 NH 2 CH-CH 2-CH 2-CO-NH-CH 2CH 2 COOH テアニン NH 2 CH-CH 2-CH 2-COOH 2 COOH グルタミン酸 図 1 テアニンとグルタミン酸の構造 1. マウスにおける前臨床的検討 13 MK 81 NMDA prepulse inhibition PPI MK 81 PPI 3 MK 81 PPI 図 BDNF MK 81 NMDA AP 5 NMDA PPI NMDA BDNF Time(s) Immobilization Vehicle Fluoxetine 1 mg/kg L theanine.4 mg/kg L theanine 2 mg/kg 図 2 強制水泳テストにおけるテアニン持続的投与 (3 週間 ) の効果 ( 文献 13より引用 ) テアニン (.4,2mg/kg) またはフルオキセチン (1 mg/kg) を隔日に3 週間腹腔内注射したところ, テアニンはフルオキセチンとともにvehicle 投与と比較して無動時間 (immobility time) が有意に減少した 感覚運動ゲイティングや統合失調症患者への効果 PPI 14 mg 2mg 4mg 6mg PPI 2mg 4mg PPI 図 6 PPI 3 PPI 4mg/

3 179 1 Prepulse inhibition(%).5 Baseline 2mg 4mg 6mg 6ms 86dB 6ms 9dB 12ms 86dB 12ms 9dB 図 3 健常者 (N=14) のプレパルスインヒビション (PPI) に対するテアニン単回投与 (,2,4,6mg) の効果 ( 文献 6より引用 ) パルス (115dB) とプレパルス (86dBまたは 9dB) との間隔が 6msと 12msの条件について検討した p<.5( 補正後の検定 ) mg 8 MRS PSQI 7 MRS 3. うつ病患者に対する効果 mg/ 8 HAMD 21 score n.s. 4 Weeks unremitted remitted 図 4 2 名の大うつ病患者に対するテアニンのアドオン療法の効果 ( 文献 1より引用 ) 21 項目ハミルトンうつ病尺度 (HAMD 21) で評価した 非寛解患者 (13 名 ) は有意に改善し, 寛解患者 (7 名 ) は有意な変化がみられなかった :p< GRID HAMD 21 STAI PSQI 8

4 18 Japanese Journal of Biological Psychiatry Vol.27, No.4, 216 BACS HAMD 21 HAMD 21 8 図 STAI PSQI BACS 図 おわりに 文献 1 Hidese S, Ota M, Wakabayashi C, et al in press Effects of chronic L theanine administration in patients with major depressive disorder an open label study. Acta Neuropsychiatr New Diet Therapy, Kunugi H, Tanaka M, Hori H, et al 27 Prepulse inhibition of acoustic startle in Japanese patients with chronic schizophrenia. Neurosci Res, Niu K, Hozawa A, Kuriyama S, et al 29 Green tea consumption is associated with depressive symptoms in the elderly. Am J Clin Nutr, Noguchi Shinohara M, Yuki S, Dohmoto C, et al 214 Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One, 9 e Ota M, Wakabayashi C, Matsuo J, et al 214 Effect of L theanine on sensorimotor gating in healthy human subjects. Psychiatry Clin Neurosci, Ota M, Wakabayashi C, Sato N, et al 215 Effect of L theanine on glutamatergic function in patients with schizophrenia. Acta Neuropsychiatr, Pham NM, Nanri A, Kochi T, et al 214 Coffee and green tea consumption is associated with insulin resistance in Japanese adults. Metabolism, Ritsner MS, Miodownik C, Ratner Y, et al 211 L theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder an 8 week, randomized, double blind, placebo controlled, 2 center study. J Clin Psychiatry, Amide Theanine , Unno K, Fujitani K, Takamori N, et al 211 Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic Res, Vuong QV, Bowyer MC and Roach PD 211 L Theanine properties, synthesis and isolation from tea. J Sci Food Agric, Wakabayashi C, Numakawa T, Ninomiya M, et al 212 Behavioral and molecular evidence for psychotropic effects in L theanine. Psychopharmacology Berl, Yin C, Gou L, Liu Y, et al 211 Antidepressant like effects of L theanine in the forced swim and tail suspension tests in mice. Phytother Res,

5 181 ABSTRACT Psychotropic effects of a green tea ingredient, L theaine Hiroshi Kunugi 1 Miho Ota 1 Chisato Wakabayashi 1 Shinsuke Hidese 1 Hayato Ozawa 2 Tsutomu Okubo 2 1 Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry 2 Department of Research and Development, Nutrition Division, Taiyo Kagaku Co., Ltd Recent evidence suggests that greater green tea consumption is associated with a reduced risk of psychiatric diseases such as depressive disorder. Theanine L theanine or L glutamylethylamide, an amino acid uniquely contained in green tea, is known as a relaxing agent which has a chemical structure similar to glutamate. In our animal experiments, theanine improved sensorimotor gating as assessed with prepulse inhibition [PPI] and showed an antidepressant like effect such as shortening the immobility time in the forced swimming test and upregulation of brain derived neurotrophic factor in the hippocampus. We found that single administration of theanine 2 or 4 mg increased PPI in healthy individuals. Administration of theanine for 8 weeks mitigated positive symptoms and sleep quality in chronic schizophrenia patients. In an 8 week open label study on major depressive disorder, theanine improved depressed mood, anxiety, sleep and cognitive function. These findings suggest that theanine has various psychotropic effects and is useful in the treatment of psychiatric disorders including schizophrenia and depressive disorder. Japanese Journal of Biological Psychiatry , 216

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