Restoration and Stress in Psychiatry

1980年に卒業して以来,精神科臨床を夢中で学んで きたが,10年目になって学位を取るためとりあえず 2 ~ 3年は研究に専念してみようかと考えるようになっ た.このため,1991年に国立精神・神経センター精神 保健研究所に移り,国の長期出張で 1年あまりドイツと スイスで睡眠障害と概日リズムについて勉強した.当時, 研究生活は博士号を取るための息抜きくらいに考えてい て,再び精神科臨床の一線に戻って活躍したいと思って いた.しかし,研究所生活を始めてみると,これが想像 していたより面白く,睡眠や概日リズムの基盤的研究に 集中し,精神医学についてはやや忘れがちになった. このような中で,当時の国立精神・神経センター高橋 清久総長から,1999年に健康日本 21休養・こころの健 康づくり分科会委員を任ぜられ,国の健康増進プロジェ クト計画を手伝うようになった.ちょうど 1998年から 自殺者が年間 30000人を越え,早急なこころの健康対策 を立てる必要と,これをモニターするシステム作りが 急務とされていた.この時,本学公衆衛生学分野をかつ て主宰されてきた,野崎貞彦名誉教授が中心となって国 で作成した健康づくりのための休養指針(以下,休養指 針)に出会った.休養指針において非常に感銘を受けた のは,休養の大切さと,医学的に整理された休養概念の 明解さだった.しっかりと休むことで得られる心身の 疲労からの生理的な回復を「休(休む)」の要素とし, 積極的な活動を通じて養われる日頃の健康向上を「養 (養う)」とする理解である.受動的な「休」の要素に関 して,こころをしっかり休ませて回復に導くのは精神疾 患の治療に重要であり,自分の行っている睡眠に関する 研究が大きく貢献できると感じた. 休養指針では,休養の「養」をこころの潜在的強さを 養い健康度をダイナミックに向上させるものとしてとら えていた.精神医学においてこころの病,つまり精神疾 患の治療には休養が必要とされながら,実際には休むこ とが主体で,それだけでは予防的側面から不十分だと感 じていた.「養」に近い概念としてその後精神医学にお いても言及され始めたレジリアンスという概念があるが, 「養」 は, より具体的で, 将来の精神科臨床に必要な方向 性と感じた.健康日本 21休養・こころの健康づくりに 関する計画を立てる作業に加わりながら,ストレス対処 戦略を獲得するための指導やこころの糧となる活動の推 進などを「養」と考えて進めて行くことが精神医学にお ける包括的予防戦略につながると考えるようになった. 2002年から,厚生労働科学研究費の「24時問社会に おける睡眠不足 ・睡眠障害による事故および健康被害の 実態と根拠に基づく予防法開発に関する研究班」,この 発展として 2005年より,「健康日本 21こころの健康づ くりの目標達成のための休養・睡眠のあり方に関する根 拠に基づく研究班」を任され,フィールドにおける調査 を班の研究者とまとめる中で,休養とこころの健康につ いて具体的な概念図を作成した.静的なものとしてとら えがちなこころの健康状態をストレスと休養の対立で動 的にとらえる様にした(図 1).図の休養の下にある睡 眠改善は「休」,対処行動は「養」を表すものである. 本稿では,私が関わってきた睡眠や概日リズムの研究 令和元年日本大学医学会 有賀賞受賞記念講演

[1]  M. Uchiyama,et al.  Association between reduced serum BDNF levels and insomnia with short sleep duration among female hospital nurses. , 2019, Sleep medicine.

[2]  H. Kadotani,et al.  A missense variant in PER2 is associated with delayed sleep–wake phase disorder in a Japanese population , 2019, Journal of Human Genetics.

[3]  M. Uchiyama,et al.  Warm Steam Inhalation before Bedtime Improved Sleep Quality in Adult Men , 2019, Evidence-based complementary and alternative medicine : eCAM.

[4]  M. Uchiyama,et al.  Effect of ramelteon on insomnia severity: evaluation of patient characteristics affecting treatment response , 2019, Sleep and Biological Rhythms.

[5]  M. Uchiyama,et al.  Periocular skin warming elevates the distal skin temperature without affecting the proximal or core body temperature , 2019, Scientific Reports.

[6]  M. Uchiyama,et al.  Stressful events and coping strategies associated with symptoms of depression: A Japanese general population survey. , 2018, Journal of affective disorders.

[7]  H. Kadotani,et al.  Lack of association between PER3 variable number tandem repeat and circadian rhythm sleep–wake disorders , 2018, Human Genome Variation.

[8]  F. Benedetti,et al.  Does early response predict subsequent remission in bipolar depression treated with repeated sleep deprivation combined with light therapy and lithium? , 2018, Journal of affective disorders.

[9]  K. Kuriyama,et al.  Effects of bedtime periocular and posterior cervical cutaneous warming on sleep status in adult male subjects: a preliminary study , 2017, Sleep and Biological Rhythms.

[10]  F. Benedetti,et al.  CLOCK gene variants associated with the discrepancy between subjective and objective severity in bipolar depression. , 2017, Journal of affective disorders.

[11]  Stephen F. Smagula,et al.  An Aggregate Measure of Sleep Health Is Associated With Prevalent and Incident Clinically Significant Depression Symptoms Among Community-Dwelling Older Women , 2017, Sleep.

[12]  F. Benedetti,et al.  Discrepancy between subjective and objective severity as a predictor of response to chronotherapeutics in bipolar depression. , 2016, Journal of affective disorders.

[13]  S. Lockley,et al.  Non-24-Hour Sleep-Wake Rhythm Disorder in Sighted and Blind Patients. , 2015, Sleep medicine clinics.

[14]  M. Uchiyama,et al.  Association of short sleep duration and short time in bed with depression: A Japanese general population survey , 2015 .

[15]  H. Kadotani,et al.  Screening of Clock Gene Polymorphisms Demonstrates Association of a PER3 Polymorphism with Morningness–Eveningness Preference and Circadian Rhythm Sleep Disorder , 2014, Scientific Reports.

[16]  H. Kuwahara,et al.  A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia. , 2012, Sleep medicine.

[17]  M. Uchiyama,et al.  The association between sleep problems and perceived health status: a Japanese nationwide general population survey. , 2012, Sleep medicine.

[18]  M. Uchiyama,et al.  Self-help behaviors for sleep and depression: a Japanese nationwide general population survey. , 2011, Journal of affective disorders.

[19]  M. Uchiyama,et al.  Efficacy and safety of ramelteon in Japanese adults with chronic insomnia: a randomized, double-blind, placebo-controlled study , 2011, Expert review of neurotherapeutics.

[20]  M. Uchiyama,et al.  Evaluation of subjective efficacy and safety of ramelteon in Japanese subjects with chronic insomnia. , 2011, Sleep medicine.

[21]  Yasuhiko Saito,et al.  Association between depression and insomnia subtypes: a longitudinal study on the elderly in Japan. , 2010, Sleep.

[22]  Lan Li,et al.  Relationship between late‐life depression and life stressors: Large‐scale cross‐sectional study of a representative sample of the Japanese general population , 2010, Psychiatry and clinical neurosciences.

[23]  M. Uchiyama,et al.  Coping strategies and their correlates with depression in the Japanese general population , 2009, Psychiatry Research.

[24]  M. Matsuura,et al.  Time estimation during sleep relates to the amount of slow wave sleep in humans , 2009, Neuroscience Research.

[25]  D. Neubauer,et al.  An international survey of sleeping problems in the general population , 2008, Current medical research and opinion.

[26]  H. Fukuyama,et al.  Effect of benzodiazepine hypnotic triazolam on relationship of blood pressure and Paco2 to cerebral blood flow during human non-rapid eye movement sleep. , 2006, Journal of neurophysiology.

[27]  Dick F Swaab,et al.  Cutaneous warming promotes sleep onset. , 2005, American journal of physiology. Regulatory, integrative and comparative physiology.

[28]  H. Fukuyama,et al.  Cerebral white matter blood flow is constant during human non-rapid eye movement sleep: a positron emission tomographic study. , 2005, Journal of applied physiology.

[29]  K. Kuriyama,et al.  Dreaming during non-rapid eye movement sleep in the absence of prior rapid eye movement sleep. , 2004, Sleep.

[30]  N. Kajimura,et al.  A Missense Variation in Human Casein Kinase I Epsilon Gene that Induces Functional Alteration and Shows an Inverse Association with Circadian Rhythm Sleep Disorders , 2004, Neuropsychopharmacology.

[31]  K. Kuriyama,et al.  Time estimation during nocturnal sleep in human subjects , 2004, Neuroscience Research.

[32]  M. Uchiyama,et al.  Poor compensatory function for sleep loss in delayed sleep phase syndrome and non-24-hour sleep-wake syndrome , 2004 .

[33]  T. Uema,et al.  Deactivation by benzodiazepine of the basal forebrain and amygdala in normal humans during sleep: a placebo-controlled [15O]H2O PET study. , 2004, The American journal of psychiatry.

[34]  M. Uchiyama,et al.  Circadian rhythms in humans’ delta sleep electroencephalogram , 2003, Neuroscience Letters.

[35]  M. Uchiyama,et al.  Long‐term rectal temperature measurements in a patient with menstrual‐associated sleep disorder , 2002, Psychiatry and Clinical Neurosciences.

[36]  N. Kajimura,et al.  Mutation screening of the human Clock gene in circadian rhythm sleep disorders , 2002, Psychiatry Research.

[37]  M. Uchiyama,et al.  Somatic and Psychological Complaints and Their Correlates With Insomnia in the Japanese General Population , 2001, Psychosomatic medicine.

[38]  Yuichi Inoue,et al.  Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome , 2001, EMBO reports.

[39]  Makoto Uchiyama,et al.  Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects , 2000, Psychiatry Research.

[40]  M. Uchiyama,et al.  Diurnal fluctuation of sleep propensity and hormonal secretion across the menstrual cycle , 2000, Biological Psychiatry.

[41]  M. Uchiyama,et al.  Altered phase relation between sleep timing and core body temperature rhythm in delayed sleep phase syndrome and non-24-hour sleep–wake syndrome in humans , 2000, Neuroscience Letters.

[42]  M. Uchiyama,et al.  Poor compensatory function for sleep loss as a pathogenic factor in patients with delayed sleep phase syndrome. , 2000, Sleep.

[43]  M. Uchiyama,et al.  Menstrual changes in sleep, rectal temperature and melatonin rhythms in a subject with premenstrual syndrome , 2000, Neuroscience Letters.

[44]  M. Uchiyama,et al.  Diurnal preference, sleep habits, circadian sleep propensity and melatonin rhythm in healthy human subjects , 2000, Neuroscience Letters.

[45]  N. Kajimura,et al.  Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls , 2000, Neuroscience Letters.

[46]  M. Uchiyama,et al.  An epidemiological study of insomnia among the Japanese general population. , 2000, Sleep.

[47]  Masanori Sekimoto,et al.  Activity of Midbrain Reticular Formation and Neocortex during the Progression of Human Non-Rapid Eye Movement Sleep , 1999, The Journal of Neuroscience.

[48]  N. Kajimura,et al.  Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders. , 1999, Biochemical and biophysical research communications.

[49]  Anna Wirz-Justice,et al.  Physiology: Warm feet promote the rapid onset of sleep , 1999, Nature.

[50]  M. Uchiyama,et al.  Lifestyles and sleep disorders among the Japanese adult population , 1999, Psychiatry and clinical neurosciences.

[51]  M. Uchiyama,et al.  Diurnal fluctuation of sleep propensity across the menstrual cycle , 1999, Psychiatry and clinical neurosciences.

[52]  M. Uchiyama,et al.  Poor recovery sleep after sleep deprivation in delayed sleep phase syndrome , 1999, Psychiatry and clinical neurosciences.

[53]  M. Uchiyama,et al.  Twenty‐four hour profiles of four hormones under constant routine , 1998, Psychiatry and clinical neurosciences.

[54]  M. Uchiyama,et al.  Continuous measurement of temperature in non‐24 hour sleep‐wake syndrome , 1998, Psychiatry and Clinical Neurosciences.

[55]  M. Uchiyama,et al.  Delayed phase jumps of sleep onset in a patient with non-24-hour sleep-wake syndrome. , 1996, Sleep.

[56]  M. Uchiyama,et al.  The relationship between sleep-wake rhythm and body temperature rhythm in delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake rhythm , 1994 .

[57]  M. Uchiyama,et al.  A Polysomnographic Study on Patients with Delayed Sleep Phase Syndrome (DSPS) , 1992, The Japanese journal of psychiatry and neurology.

[58]  S. Lockley,et al.  Non-24-h Sleep–Wake Disorder (Free-running Type, Nonentrained Type, Hypernychthemeral Syndrome) in Sighted and Blind Patients* , 2013 .

[59]  D. Léger,et al.  Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey. , 2012, Sleep medicine.

[60]  M. Uchiyama,et al.  Stress coping behaviors and sleep hygiene practices in a sample of Japanese adults with insomnia , 2011 .

[61]  H. Yamadera.  [Non-24-hour sleep-wake syndrome]. , 2003, Ryōikibetsu shōkōgun shirīzu.

[62]  T. Ebisawa,et al.  Larger phase angle between sleep propensity and melatonin rhythms in sighted humans with non-24-hour sleep-wake syndrome. , 2002, Sleep.

[63]  土井 由利子.  Prevalence of sleep disturbance and hypnotic medication use in relation to sociodemographic factors in the general Japanese adult population , 2001 .

[64]  M. Uchiyama,et al.  Prolonged interval from body temperature nadir to sleep offset in patients with delayed sleep phase syndrome. , 1996, Sleep.

[65]  尾崎茂.  Prolonged Interval from Body Temperature Nadir to Sleep Offset in Patients with Delayed Sleep Phase Syndrome(睡眠相後退症候群における体温リズムの最低点から覚醒までの延長所見について) , 1996 .