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There is a growing evidence that serotoninergic systems modulate dopaminergic neurotransmission. We analyzed the association between the variations in the brain tryptophan hydroxylase 2 (TPH2) gene, a rate limiting enzyme for serotonin biosynthesis, and methamphetamine (METH) dependence/psychosis in a Japanese population. We found ten single nucleotide polymorphisms (SNPs) and two polynucleotide polymorphisms in TPH2 gene exons and exon-intron boundaries. A total of 162 patients and 243 controls were used for the association analysis between these polymorphisms and METH dependence/psychosis. No significant differences were observed in either genotypic or allelic frequencies between METH dependent/psychotic patients and controls. A global test of differentiation among samples based on haplotype frequencies showed no significant association. With respect to latency of psychosis, prognosis of psychosis, and spontaneous relapse, we found no significant association with these SNPs. These results suggest that the TPH2 gene variants may not be a factor in vulnerability to METH dependence/psychosis.

Several investigations suggested abnormalities in circadian rhythms are related to the pathophysiology of psychiatric disorders, including drug addiction. Recently, orphan nuclear receptor rev-erb alpha and glycogen synthase kinase-3 β (GSK-3β) were shown to be important circadian components. In addition, the orphan nuclear receptor rev-erb alpha is a key negative feedback regulator of the circadian clock. These evidences indicate that rev-erb alpha gene (NR1D1) is a good candidate gene for the pathogenesis of methamphetamine dependence. To evaluate the association between NR1D1 and methamphetamine dependence, we conducted a case-control study of Japanese samples (215 methamphetamine dependence and 232 controls) with three tagging SNPs selected by HapMap database. Written informed consent was obtained from each subject. This study was approved by the ethics committees at Fujita Health University, Nagoya University Graduate School of Medicine and each participating member of the Institute of the Japanese Genetics Initiative for Drug Abuse (JGIDA). We did not detect an association between NR1D1 and Japanese methamphetamine dependence patients in allele/genotype-wise analysis, or the haplotype analysis. Our findings suggest that NR1D1 does not play a major role in the pathophysiology of methamphetamine dependence in the Japanese population.

Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors in METH abusers. We therefore hypothesized that variations in the A1 adenosine receptor (ADORA1) gene modify genetic susceptibility to METH dependence/psychosis. In this study, we identified 7 single nucleotide polymorphisms (SNPs) in exons and exon-intron boundaries of the ADORA1 gene in a Japanese population. A total of 171 patients and 229 controls were used for an association analysis between these SNPs and METH dependence/psychosis. No significant differences were observed in either the genotypic or allelic frequencies between METH dependent/psychotic patients and controls. A global test of differentiation among samples based on haplotype frequencies showed no significant association. In the clinical feature analyses, no significant associations were observed among latency of psychosis, prognosis of psychosis, and spontaneous relapse. These results suggest that the ADORA1 gene variants may make little or no contribution to vulnerability to METH dependence/psychosis.

Objective: To assess patient-reported efficacy and safety of ramelteon in Japanese patients with chronic insomnia., Methods: Randomized, double-blind, placebo-controlled, multicenter trial. After a placebo lead-in period, 987 adults with chronic insomnia received ramelteon 8 mg or placebo once daily for 2 weeks, followed by a placebo run-out period to monitor rebound insomnia. Patient-reported sleep data were collected using sleep diaries., Results: Ramelteon significantly reduced mean patient-reported sleep latency (primary endpoint) compared with placebo during week 1 (-4.54 min; p=0.001). Ramelteon maintained greater efficacy in sleep latency than placebo at week 2, but the difference did not achieve statistical significance. In a subset of patients who adhered to treatment and completed their diaries as instructed, a statistically significant reduction in subjective sleep latency was sustained through week 2. Compared with placebo, ramelteon also significantly improved mean total sleep time and mean sleep quality during week 1, the number of awakenings during week 2, and overall patient global impression scores. There was no evidence of rebound insomnia. Adverse events were generally mild and transient., Conclusions: In Japanese adults with chronic insomnia, ramelteon 8 mg significantly reduced patient-reported sleep latency, increased total sleep time and improved sleep quality after 1 week of treatment. Ramelteon was generally well tolerated with no rebound insomnia., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: To evaluate the safety of ramelteon, a highly selective MT₁/MT₂ melatonin receptor agonist, during 24 weeks' treatment of Japanese patients with chronic insomnia., Methods: In a single-blind, flexible-titration, multicenter study incorporating placebo run-in and run-out periods, 190 adults with chronic insomnia received ramelteon 4 or 8 mg, titrated up to 16 mg if necessary, for 24 weeks. Primary endpoints included adverse events, residual effects, rebound insomnia, withdrawal symptoms, and dependence. Secondary endpoints included subjective sleep latency and total sleep time., Results: Drug-related adverse events occurred in 11.6% of patients. No clinically important changes occurred in biochemical, hematological or endocrine parameters. There were no signs of next-day residual effect, rebound insomnia, withdrawal symptoms or dependence. Mean subjective sleep latency decreased significantly, and total sleep time increased significantly; both reached a plateau by week 20 and were sustained thereafter (P<0.0001)., Conclusions: Ramelteon was well tolerated in adult Japanese patients with chronic insomnia and did not cause deterioration of efficacy, residual effects, rebound insomnia, withdrawal symptoms, or dependence after 24 weeks' treatment., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of ramelteon 4 and 8 mg in Japanese adults with chronic insomnia. A secondary objective was to evaluate efficacy and safety when doses were uptitrated from placebo, ramelteon 4 and 8 mg to 4, 8 and 16 mg, respectively. Patient-reported sleep data were collected using sleep diaries. There was no statistically significant difference between ramelteon and placebo in the change in subjective sleep latency (sSL) in the full analysis set (n = 1130). Significant improvement was observed in the change in subjective total sleep time with ramelteon 8 mg at week 1. In post hoc analyses, ramelteon 8 mg reduced sSL in individuals with smaller fluctuations (within ±30 min) of sSL at baseline, in those with a shorter (<1 year) history of insomnia and in individuals who had not used benzodiazepines. Ramelteon up to 16 mg nightly was safe and well tolerated.

Shiritori is a popular Japanese word chain game that resembles verbal fluency tasks used in Western countries. Recently, shiritori has been used to determine the dominant hemisphere for language and as a rehabilitation tool. However, there are few reports of neuroimaging during shiritori. We used functional magnetic resonance imaging (fMRI) to conduct a detailed study of brain activities during shiritori and observed activation not only of the left inferior frontal gyrus (including the pars opecularis, the pars triangularis and the pars orbitalis), which is a language-related area, but also of the left superior and middle frontal gyri, the right pars orbitalis (inferior frontal gyrus), and the right cerebellar hemisphere. Shiritori is a useful tool for psychological study and rehabilitation.

The relationship between mother and baby is of fundamental importance in the development of cognitive function and emotion. In this study we investigated the effects of affective photographs of a mother and baby (crying or smiling faces) and other stimuli (neutral mother or baby faces) on visual cognitive function in schizophrenic patents. We recorded exploratory eye movements in 22 healthy controls and 22 age-matched schizophrenic patients. Total number of right and left field gaze points (right TNGP, left TNGP) in the visual fields were determined using an eye-mark recorder as subjects viewed affectively charged or neutral photographs (crying, smiling or neutral faces). Left TNGP for all mother photographs (crying, smiling or neutral) were significantly larger in controls than patients, and right TNGP for neutral mother photographs were significantly larger in controls than in patients. Right TNGP for photographs of smiling babies were significantly larger in controls than patients, and left TNGP for photographs of both smiling and crying babies were significantly larger in controls than patients. Within the patient group, right TNGP were significantly larger than left TNGP for all mother photographs (crying, smiling or neutral). Left TNGP for photographs of mothers and babies correlated negatively with negative symptom scores. These results suggest that exploratory eye movements when viewing emotionally laded twin stimuli such as photographs of a mother and baby are a useful marker of visual cognitive function in both healthy controls and schizophrenic patients.

Background: Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis., Method: Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients., Results: rs6693503 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively., Conclusion: HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population., (Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved.)

Aims: To assess the safety and efficacy of pramipexole in Japanese patients with restless legs syndrome (RLS) and to investigate factors predictive of early treatment response., Methods: Patients with primary RLS and the International Restless Legs Syndrome Study Group rating scale (IRLS) total score of >15 were randomized to receive pramipexole 0.25, 0.5 or 0.75 mg/day for 6 weeks., Results: A total of 154 patients were recruited. Following treatment, the mean adjusted change in IRLS score in the 0.25, 0.5 and 0.75 mg/day groups was -12.3, -12.5 and -11.8, respectively. The proportion of IRLS responders at week 2, when all patients were receiving pramipexole at a dose of 0.25 mg/day, was 34.0-37.7%. At 6 weeks, when the patients were on 0.25, 0.5 or 0.75 mg/day, IRLS responders defined as those having a ≥50% reduction in IRLS score accounted for 60.4, 58.5 and 49.1%, respectively. Older age above the median value (≥55 years) and low IRLS score at baseline (<21.5 points) were significantly associated with early response to low-dose pramipexole therapy. The type and frequency of adverse events were consistent with the known safety profile for dopamine agonists in RLS., Conclusions: Pramipexole at 0.25-0.75 mg/day is efficacious, safe and well tolerated in Japanese patients with primary RLS., (Copyright © 2010 S. Karger AG, Basel.)

Healthy sleep habits entail not only sleeping for a sufficient period (quantity) but also regularity of the sleep cycle and getting sound sleep (quality). University students often have erratic schedules that cause irregular sleep patterns even though sleep durations remain relatively constant. This study compared the physical and mental health of 90 male university students with different sleep habits. We created sleep habit scales using the Tokyo Metropolitan Institute for Neuroscience life habits inventory (TMIN-LHI; Miyashita, 1994) by performing a factor analysis and classifying sleeping habits based on regularity, quality, and quantity. Four types of sleep habits were identified by cluster analysis; good sleep was characterized by regular and high quality sleep but of relatively short sleep duration; long sleep was regular and relatively long but of low quality; short sleep was of high quality but short and irregular, while poor sleep was irregular, of low quality, and relatively long. The good sleep group had a significantly lower average waist circumference, and lower systolic and diastolic blood pressure. The long and poor sleep groups, which both had low quality sleep, scored lower than the national standard on the mental component summary (MCS) calculated from the Social Functioning-36 (SF-36) short-form health survey. Furthermore, the average MCS score of the poor sleep group was significantly lower than that of any other sleep habit group. Subjects with poor sleep also scored lowest on the Self-rating Depression Scale (SDS). In addition, the short and poor sleep groups were prone to glucose or lipid metabolism disorders. Maintaining good physical and mental health without sound sleep and a regular sleep cycle is difficult, even if sleeping hours are kept constant. Therefore, we included the assessment of regularity and quality in addition to hours of sleep in order to develop appropriate sleep guidelines for improved physical and mental health.

Background: Visual cognitive dysfunction is one of the most important signs indicating the early stage of dementia. Thus, visual testing could be used as an aid to the clinical diagnosis of dementia. In the present study, exploratory eye movement was measured to evaluate visual cognitive function in elderly subjects, including those with dementia., Methods: We analyzed responsive search scores (RSS) from exploratory eye movements of 300 subjects who were examined with an eye mark recorder while viewing S shaped figures. Subjects were divided into three groups (dementia, intermediate, healthy) from the values of the Revised Hasegawa Dementia Scale (HDS-R), the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating. We further divided the intermediate groups into two subgroups, the high score and low score groups, based on RSS. In 202 subjects, Z-scores of voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) were obtained from magnetic resonance imaging (MRI)., Results: RSS of the dementia group were significantly lower than those in the intermediate and healthy groups, in order: dementia < intermediate < healthy groups. RSS of the low score intermediate group was significantly lower than that of the high score intermediate group. There was no significant difference between the low score intermediate and dementia groups, or between the high score intermediate and healthy groups. No significant differences of either HSD-R or MMSE were observed between the low score and the high score intermediate groups. The Z-score of VSRAD using MRI in the low score intermediate group was significantly higher than that in the high score intermediate group., Conclusions: These findings suggest that RSS using an eye mark recorder is a useful psychophysiological marker to evaluate the early stage of dementia as well as at-risk elderly people., (© 2010 The Authors. Psychogeriatrics © 2010 Japanese Psychogeriatric Society.)

Background: Many patients with drug addiction are reported to have comorbid mood disorders. One of the suggested pathophysiological mechanisms for mood disorders is disruption of circadian rhythms. Several animal studies have shown that methamphetamine altered the expression of circadian clock molecules in the brain. Therefore, it is possible that mood disorders and drug addiction have common susceptibility genes. Recently, we reported that the prokineticin 2 receptor gene (PROKR2) was associated with mood disorders including major depressive disorder and bipolar disorder in the Japanese population. In the present study, therefore, we conducted an association analysis of tagging SNPs in PROKR2 with Japanese methamphetamine dependence patients., Methods: Using five tagging SNPs in PROKR2, we conducted a genetic association analysis of case-control samples (199 methamphetamine dependence patients and 337 healthy controls). The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients., Results: We detected a significant association between PROKR2 and methamphetamine dependence patients in allele/genotype-wise and haplotype-wise analysis., Conclusion: Our results suggest that PROKR2 may play a role in the pathophysiology of methamphetamine dependence in the Japanese population. However, because we did not perform a mutation scan of PROKR2, a replication study using a larger sample may be required for conclusive results., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

A phase III, open-label, long-term clinical study was performed to evaluate the safety and efficacy of pramipexole in a cohort of 141 Japanese patients with primary restless legs syndrome (RLS). The patients were started on pramipexole 0.25 mg/day and were subsequently maintained on that dose or switched to 0.125, 0.5, or 0.75 mg/day to achieve optimal efficacy and tolerability. The International Restless Legs Syndrome Study Group Rating Scale for restless legs syndrome (IRLS) score improved from 22.3+/-4.7 at baseline to 11.1+/-7.7 at week 8 and 4.9+/-5.9 at week 52. IRLS responders, defined as patients whose IRLS total score decreased by > or =50% from baseline, accounted for 67.4% at week 12 and 86.6% at week 52. Over 90% of patients were Clinical Global Impression-global improvement (CGI-I) and Patient Global Impression (PGI) responders. The Pittsburgh Sleep Quality Index (PSQI) score decreased from 7.9+/-3.1 at baseline to 4.6+/-2.9 at week 52. Similarly, the Japanese version of the Epworth Sleepiness Scale score decreased from 9.3+/-5.2 to 4.9+/-3.8. Baseline IRLS score < or =20 was significantly associated with a complete IRLS response in this long-term study. Adverse events were typical of nonergot dopamine agonists, mild in intensity, and decreased in frequency as the study progressed. RLS augmentation was not observed. Pramipexole 0.25-0.75 mg/day is efficacious, safe, and well tolerated in patients with RLS. Pramipexole showed good efficacy, particularly in patients with an IRLS total score <20., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Although extensive studies have indicated a relationship between obstructive sleep apnea (OSA) and depressive symptoms, the effect of continuous positive airway pressure (CPAP) treatment on residual depressive symptoms in patients with both major depressive disorder (MDD) and coexisting OSA has not been examined., Methods: Seventeen patients with continued MDD despite pharmacotherapy such as antidepressants and/or benzodiazepines, who also had comorbid OSA, were required to complete the Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HRSD), and Epworth sleepiness scale (ESS) at the commencement of the study and then again after 2 months of CPAP treatment., Results: BDI and HRSD scores decreased from 19.7 to 10.8 and 16.7 to 8.0 after 2 months of CPAP treatment (both p<0.01). We also found significant correlations among the improvement rates in BDI, HRSD and ESS scores (R=0.86 and 0.75, both p<0.01). The mixed effect model demonstrated a significant ESS effect on BDI and HRSD., Conclusions: The results suggest that MDD patients with residual depressive symptoms despite pharmacotherapy who also have symptoms of suspected OSA, such as loud snoring, obesity, and daytime sleepiness, should be evaluated for sleep apnea by polysomnography and treated with an appropriate treatment such as CPAP. CPAP treatment may result in a significant improvement of residual depressive symptoms due to the improvement of daytime sleepiness in these patients., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Abnormalities in glutaminergic neural transmission have been suggested to be involved in the pathogenesis of schizophrenia. A recent study reported that alterations in the 5-HT2A-mGluR2 complex may be involved in neural transmission in the schizophrenic cortex. In addition, methamphetamine-induced psychosis is thought to be similar to schizophrenia. Therefore, we conducted a case-control study with Japanese samples (738 schizophrenia patients, 196 methamphetamine-induced psychosis patients, and 802 controls) to evaluate the association and interaction between GRM2, HTR2A and schizophrenia., Methods: We selected three 'tagging SNPs' in GRM2, and two biologically functional SNPs in HTR2A (T102C and A1438G), for the association analysis., Results: We detected a significant association between methamphetamine-induced psychosis and GRM2 in a haplotype-wise analysis, but not HTR2A. We did not detect an association between GRM2 or HTR2A and schizophrenia. In addition, no interactions of GRM2 and HTR2A were found in methamphetamine-induced psychosis or schizophrenia. We did not detect any novel polymorphisms in GRM2 when we performed a mutation search using methamphetamine-induced psychosis samples., Conclusion: Our results suggested that GRM2 may play a role in the pathophysiology of methamphetamine-induced psychosis but not schizophrenia in the Japanese population. A replication study using larger samples or samples of other populations will be required for conclusive results., (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.)

Aims: Emotion-associated sounds have been suggested to exert important effects upon human personal relationships. The present study was aimed to characterize the effects of the sounds of crying or laughing on visual cognitive function in schizophrenia patients., Methods: We recorded exploratory eye movements in 24 schizophrenia patients (mean age, 27.0 +/- 6.1 years; 14 male, 10 female) and age-matched controls. The total eye scanning length (TESL) and total number of gaze points in the left (left TNGP) and right (right TNGP) visual fields of the screen and the number of researching areas (NRA) were determined using eye-mark recording in the presence/absence of emotionally charged sounds., Results: Controls' TESL for smiling pictures was longer than that for crying pictures irrespective of sounds. Patients' TESL for smiling pictures, however, was shorter than for crying pictures irrespective of the sounds. The left TNGP for smiling pictures was lower in patients than controls independent of sound. Importantly, the right TNGP was significantly larger with laughing sounds than in the absence of sound. In controls, the NRA for smiling pictures was significantly greater than for crying pictures irrespective of sound. Patient NRA did not significantly differ between smiling and crying pictures irrespective of sound., Conclusion: Eye movements in schizophrenia patients' left field for smiling pictures associated with laughing sounds particularly differed from those in controls, suggesting impaired visual cognitive function associated with positive emotion, also involving pleasure-related sounds, in schizophrenia.

Background: Several investigations have reported associations the serotonin 1A (5-HT1A) receptor to schizophrenia and psychotic disorders, making 5-HT1A receptor gene (HTR1A) an adequate candidate gene for the pathophysiology of schizophrenia and methamphetamine (METH)-induced psychosis. Huang and colleagues reported that rs6295 in HTR1A was associated with schizophrenia. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. It may indicate that METH-induced psychosis and schizophrenia have common susceptibility genes. In support of this hypothesis, we reported that the V-act murine thymoma viral oncogene homologue 1 (AKT1) gene was associated with METH-induced psychosis and schizophrenia in the Japanese population. Furthermore, we conducted an analysis of the association of HTR1A with METH-induced psychosis., Method: Using one functional SNP (rs6295) and one tagging SNP (rs878567), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients., Results: Rs878567 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this significance remained after Bonferroni correction. In addition, we detected an association between rs6295 and rs878567 in HTR1A and METH-induced psychosis patients in the haplotype-wise analysis. Although we detected an association between rs6295 and METH-induced psychosis patients, this significance disappeared after Bonferroni correction., Conclusion: HTR1A may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population. However, because we did not perform a mutation scan of HTR1A, a replication study using a larger sample may be required for conclusive results., (2009. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS)., Methods: Patients with moderate to severe RLS having periodic limb movements in bed index (PLMI)>or=5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6weeks after starting treatment., Results: The analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p=0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline >or=15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p=0.0005), a significant improvement in both Patient Global Impression (PGI; p<0.0001) and Clinical Global Impressions (CGI-I; p=0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p=0.0016), when compared with those of placebo group at week 6., Conclusions: Pramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder., (Copyright 2009 Elsevier B.V. All rights reserved.)

Using optical topography (near-infrared spectroscopy: NIRS), relative changes in oxidized hemoglobin (oxy-Hb) were measured before and after the introduction of Role lettering. Tasks performed during measurements included antegrade (from the subject to other persons) and retrograde (from other persons to the subject) mental imaging and writing tasks. All subjects were junior high school students. Relative changes in oxy-Hb were measured before and 3, 6, and 12 months after the start of Role lettering. The region of interest (ROI) was determined based upon the motor cortex region of hand movement and upon relative oxy-Hb changes noted before any Role lettering. For antegrade mental tasks, oxy-Hb increased significantly in right-sided ROI after 3 months; this increase persisted at 1 year. For retrograde mental tasks, oxy-Hb significantly increased bilaterally at 3 months, an effect that also persisted at 1 year. With the antegrade writing task, no significant difference was observed throughout the study; with the retrograde writing task, oxy-Hb level decreased significantly in right lateral ROI after 6 months; the decrease persisted at 1 year. The number of words produced after Role lettering increased significantly in both antegrade and retrograde writing tasks at 1 year, compared with the number before Role lettering. Role lettering thus altered mental activity, particularly in the right hemisphere. Retrograde writing tasks, similar to those employed in the actual practice of Role lettering, reduced right hemispheric function; continuation of the task enhanced performance. Role lettering studies using NIRS may provide useful psychophysiologic indices.

Methamphetamine psychosis is considered as one of the pharmacological models of schizophrenia, and a hyperdopaminergic one. However, many lines of experimental evidence indicate that glutamatergic signaling is also involved in development of methamphetamine psychosis. Several genes related to glutamate function, e.g. the DTNBP1, G72, and GRM3 genes, were shown to be associated with schizophrenia susceptibility. Recently, we found significant association of the DTNBP1 gene with methamphetamine psychosis. This finding prompted us to examine the G72 gene encoding the d-amino acid oxidase activator (DAOA), which metabolizes d-serine, an NMDA co-agonist, in methamphetamine psychosis. Six SNPs of the G72 gene, which previously showed significant association with schizophrenia, were analyzed in 209 patients with methamphetamine psychosis and 291 age- and sex-matched normal controls. One SNP of M22 (rs778293) showed a significant association with methamphetamine psychosis (genotype: p=0.00016, allele: p=0.0015). Two haplotypes G-A of M12 (rs3916965)-M15 (rs2391191) (p=0.00024) and T-T of M23 (rs947267)-M24 (rs1421292) (p=0.00085) also showed associations with methamphetamine psychosis. The present findings suggest that the G72 gene may contribute to a predisposition to not only schizophrenia but also to methamphetamine psychosis.

n-Decanoyl ghrelin (D-ghrelin), a member of ghrelin-derived peptides, is found in plasma and the stomach; however, there have so far been no studies describing its dynamics. A D-ghrelin-specific radioimmunoassay was established to examine the tissue distribution and the kinetics of D-ghrelin in mice. The effect of D-ghrelin on food intake was also examined and compared to n-octanoyl ghrelin (O-ghrelin). D-ghrelin was detected throughout the gastrointestinal tissue and plasma with highest level in the stomach. An immunofluorescent study revealed the co-localization of D- and O-ghrelin in the same stomach cells. Upon fasting, the levels of D-ghrelin in the stomach and plasma significantly increased, while that of O-ghrelin in the stomach declined. D-ghrelin increased the 2 h food consumption in mice as O-ghrelin does. These findings indicate that D-ghrelin is mainly produced in the stomach to work in concert with O-ghrelin. The different kinetics of D- and O-ghrelin in the stomach upon fasting implies the possibility of D-ghrelin-specific bioregulation.

Sleepiness, the mood state, and quality of life (QOL) were compared in patients with insufficient sleep syndrome (ISS), between before and after treatment. Concerning the profile of mood states(POMS), the score of the V scale for "vigor" was significantly low, and the score of the C scale for "confusion" was significantly high. The primary treatment was life guidance. After treatment, the sleep time was significantly prolonged due primarily to going to bed earlier, and while the score on the Epworth sleepiness scale(ESS) decreased significantly. The scores of the V and C scales of the POMS were significantly improved after treatment but were still lower than in the control group. On the QOL26, significant improvements were observed in all items after treatment.

The neuregulin 1 gene (NRG1) has been identified as a candidate gene for schizophrenia in a linkage study in the Icelandic population. Recent evidence also suggested that it might be related to the neurodevelopmental hypothesis and glutamate hypothesis for schizophrenia. Because the symptomatology of methamphetamine (METH) use disorder with accompanying psychosis is similar to that of patients with schizophrenia, NRG1 is an appropriate candidate gene for METH-induced psychosis. We conducted a case-control association study between NRG1 and METH-induced psychosis in a Japanese population (184 subjects with METH-induced psychosis and 534 controls). Written informed consent was obtained from each subject. We selected four SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177, and rs3924999) in NRG1 from previous reports. No significant association was found between NRG1 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion, NRG1 might not contribute to the risk of METH-induced psychosis in the Japanese population.

Background: A recent study reported an association between rs2234693, which influences enhancer activity levels in estrogen receptor alpha gene (ESR1), and schizophrenia. This study reported that schizophrenic patients with the CC genotype have significantly lower ESR1 mRNA levels in the prefrontal cortex than patients with other genotypes. The symptoms of methamphetamine induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an association analysis of rs2234693 with Japanese methamphetamine induced psychosis patients., Method: Using rs2234693, we conducted a genetic association analysis of case-control samples (197 methamphetamine induced psychosis patients and 197 healthy controls). The age and sex of the control subjects did not differ from those of the methamphetamine induced psychosis patients., Results: We detected a significant association between ESR1 and methamphetamine induced psychosis patients in allele/genotype-wise analysis. For further interpretation of these associations, we performed single marker analysis of subjects divided by sex. Rs2234693 was associated with male methamphetamine induced psychosis., Discussion: Our results suggest that rs2234693 in ESR1 may play a role in the pathophysiology of Japanese methamphetamine induced psychosis patients.

D2-like receptors are key targets for methamphetamine in the CNS, and their activation is an initial and indispensable effect in the induction of dependence and psychosis. It is possible that genetic variants of D2-like receptors may affect individual susceptibility to methamphetamine dependence and psychosis. To test this hypothesis, 6 putatively functional polymorphisms of D2-like receptors, -141C Ins/Del, Ser311Cys and TaqIA of the DRD2 gene, Ser9Gly of the DRD3 gene, and -521C>T and a variable number of tandem repeats in exon 3 of the DRD4 gene, were analyzed in 202 patients with methamphetamine dependence and/or psychosis and 243 healthy controls in a Japanese population. No polymorphism examined showed significant association with methamphetamine dependence, but two polymorphisms of DRD2 were associated with the clinical course and prognosis of methamphetamine psychosis. The A1/A1 homozygote of DRD2 was a negative risk factor for a poorer prognosis of psychosis that continues for more than 1 month after the discontinuance of methamphetamine abuse and the beginning of treatment with neuroleptics (p=0.04, odds ratio (OR)=0.42, 95% CI; 0.27-0.65) and the complication of spontaneous relapse of methamphetamine psychosis after remission (p=0.014, OR=0.34, 95% CI; 0.22-0.54). The genotype of -141C Del positive (Del/Del and Del/Ins) was at risk for rapid onset of methamphetamine psychosis that develops into a psychotic state within 3 years after initiation of methamphetamine abuse (p=0.00037, OR=3.62, 95% CI 2.48-5.28). These findings revealed that genetic variants of DRD2, but not DRD3 or DRD4, confer individual risks for rapid onset, prolonged duration, and spontaneous relapse of methamphetamine psychosis.

Aims: The aim of the present study was to investigate social attitudes toward schizophrenia in Japan and China in view of social distance and knowledge of psychiatry, as well as sociocultural aspects., Methods: Two self-rating scales were used to compare social distance and knowledge regarding schizophrenia in 352 Japanese subjects and 347 Chinese subjects. The Social Distance Scale-Japanese version was used to measure social distance from schizophrenia subjects in Japan. This scale consists of eight questions graded using a 4-point Likert scale (0-3 points), with higher scores representing increased social distance. A translation of the SDSJ into Chinese was used to assess social distance in China. The Knowledge of Illness and Drugs Inventory was used to determine participant knowledge of mental illness and its treatment (medication) through 20 questions (responses are graded as correct or incorrect, with higher scores indicating greater knowledge). A Chinese version of this questionnaire was also created., Results: Total scores of both scales were significantly higher in Japanese subjects than in Chinese subjects., Conclusions: Social distance associated with schizophrenia is large in both Beijing and Fukuoka, but the features of social distance differ between countries. It is important to determine the features of stigma associated with schizophrenia and develop anti-stigma programs based on trans-cultural considerations.

Purpose: To understand influencing factors for late bedtime of infants having nocturnal life, with respect to each development age and sleep behavior of parents and children. We researched on sleep-awake behaviors and ten-day sleep logs of 277 subjects, who registered for a three-year cohort survey. The cohort is recruited at the time of routine examinations for 4 month, 1.5 years, and 3 years, held at three Health and Welfare centers in Fukuoka city in September and October, 2007. We conducted two-way analysis of variance and post-hoc test of Turkey's multiple comparative tests. The independent variables are three age groups (infants, 1.5 years, and 3 years) and three bedtime categories (late: after 22 o'clock, normal: between 21 and 22 o'clock, and early: before 21 o'clock), and the dependent variables are background date, sleep parameter of parents and children, and factors of sleep behavior and so on. The qualitative data including physical conditions, growth status, frequencies of each life activity are analyzed by tabulation, and fulfillment in child raring is analyzed by stepwise multiple linear regression analysis with 15 objective variables, to bring out factors to induce nocturnal life., Results: Children's bedtime had significant effect for bedtime variables. The bedtime difference was about 40 minutes between the early bedtime group and the late bedtime group. The early bedtime group had the earliest wake-up time among the all age groups, followed by the normal, and then the late bedtime group. Efforts to keep regular sleep and wake-up times were made greatly in the early bedtime group, and the normal and then the late bedtime group followed after. The mothers in the late bedtime group considened an ideal bedtime was around 21h although they were not able to realize it. The lengths of TV viewing and daytime nap had also significant effects for children's bedtimes. As a result of multiple comparisons, there were significant differences between the early and the late bedtime groups and between the normal and the late bedtime groups. For the bedtime of children, only mothers' total sleep hours on weekdays had a significant negative correlation, while all the other parameters were significantly and positively correlated., Discussion: The study showed influencing factors for bedtime of children were mothers' routine duties in daily life, especially wake-up time, total sleep hours, daytime napping hours of children, and the length of TV viewing. This suggests that further effort on education for sleep environment management is needed.

Background: Frizzled 3 (Fzd3) is a receptor required for the Wnt-signaling pathway, which has been implicated in the development of the central nervous system, including synaptogenesis and structural plasticity. We previously found a significant association between the FZD3 gene and susceptibility to schizophrenia, but subsequent studies showed inconsistent findings. To understand the roles of the FZD3 gene in psychotic disorders further, it should be useful to examine FZD3 in patients with methamphetamine psychosis because the clinical features of methamphetamine psychosis are similar to those of schizophrenia., Methods: Six SNPs of FZD3, rs3757888 in the 3' flanking region, rs960914 in the intron 3, rs2241802, a synonymous SNP in the exon5, rs2323019 and rs352203 in the intron 5, and rs880481 in the intron 7, were selected based on the previous schizophrenic studies and analyzed in 188 patients with methamphetamine psychosis and 240 age- and gender-matched controls., Results: A case-control association analyses revealed that two kinds of FZD3 haplotypes showed strong associations with methamphetamine psychosis (p < 0.00001). Having the G-A-T-G or A-G-C-A haplotype of rs2241802-rs2323019-rs352203-rs880481 was a potent negative risk factor (odds ratios were 0.13 and 0.086, respectively) for methamphetamine psychosis., Conclusion: Our present and previous findings indicate that genetic variants of the FZD3 gene affect susceptibility to two analogous but distinct dopamine-related psychoses, endogenous and substance-induced psychosis.

We examined the general health and psychological symptoms among survivors of the 1996 Garuda Indonesia air disaster in Japan. We conducted a prospective study 6 months and 1 year (Study 1) after the disaster. A retrospective follow-up study was performed ten years after the disaster (Study 2). The mean score on the 28-Item General Health Questionnaire was 6.5 (SD=6.9) 1 year after the disaster. Those who witnessed the death of an acquaintance in the disaster were classified into the high risk group. In Study 2, more than one-third of respondents complained of a flying phobia. These findings indicate that the psychological burdens of air disasters may last as long as 10 years.

Background: Laboratory sleep studies in posttraumatic stress disorder (PTSD) have not provided consistent evidence of sleep disturbance, despite apparent sleep complaints. Most of these studies have investigated middle-aged chronic PTSD subjects with a high prevalence of comorbidities such as substance dependence and/or personality disorder., Methods: Ten young adult PTSD patients (aged 23.4 +/- 6.1 years) without comorbidities of substance dependence and/or personality disorder underwent 2-night polysomnographic recordings. These sleep measures were compared with those of normal control subjects and were correlated with PTSD symptoms., Results: Posttraumatic stress disorder patients demonstrated significantly poorer sleep, reduced sleep efficiency caused by increased wake time after sleep onset, and increased awakening from rapid eye movement (REM) sleep (REM interruption). We found significant positive correlations between the severity of trauma-related nightmare complaints and the percentage of REM interruption, as well as wake time after sleep onset., Conclusions: The results indicate that trauma-related nightmares are an important factor resulting in increased REM interruptions and wake time after sleep onset in PTSD.

Phenserine (PS) was designed as a selective acetylcholinesterase (AChE) inhibitor, with a tartrate form (PST) for oral administration in mild to moderate Alzheimer's disease (AD). Recent phase 3 trials of PST in Europe indicate that any clinically relevant activity of PST may be limited by its duration of action. Like many oral drugs, bioavailability and plasma concentrations of PST are regulated by hepatic and gastrointestinal first-pass effects. To minimize the kinetic limitations of first-pass metabolism, transdermal formulations of PS and PST (ointment/patch) were developed and characterized in vitro and in vivo. Initial in vitro kinetic characterization of PS or PST formulations used a diffusion cell chamber and skin samples isolated from hairless mice. Liquid paraffin and fatty alcohol/propylene glycol (FAPG) were found to be suitable vehicles for ointment formulation. Addition of a penetration enhancer, 1-[2-(decylthio)ethyl]-azacyclopentane-2-one (HPE-101), improved stratum corneum permeability. Application of the optimal formulation of PS/HPE-101/FAPG to the shaved back of rats resulted in significantly lowered plasma and brain AChE activities and improved cognitive performance in animals with scopolamine-induced cognitive impairment. These results suggest that the transdermal application of AChE inhibitors may represent an effective therapeutic strategy for AD. Particular benefits over oral therapies might include avoiding first-pass metabolic effects and improved dosing compliance.

Background: Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of type A gamma-aminobutyric acid (GABA(A)) receptor beta2 subunit gene (GABRB2) were initially found to be associated with schizophrenia in Chinese. This finding was subjected to cross-validation in this study with Japanese (JP) and German Caucasian (GE) subjects., Methods: Single nucleotide polymorphisms discovery and genotyping were carried out through resequencing of a 1839 base pair (bp) region in GABRB2. Tagging SNPs (tSNPs) were selected based on linkage disequilibrium (LD), combinations of which were analyzed with Bonferroni correction and permutation for disease association. Random resampling was applied to generate size- and gender-balanced cases and control subjects., Results: Out of the 17 SNPs (9.2/kilobase [kb]) revealed, 6 were population-specific. Population variations in LD were observable, and at least two low LD points were identified in both populations. Although disease association at single SNP level was only shown in GE, strong association was demonstrated in both JP (p = .0002 - .0191) and GE (p = .0033 - .0410) subjects, centering on haplotypes containing rs1816072 and rs1816071. Among different clinical subtypes, the most significant association was exhibited by systematic schizophrenia., Conclusions: Cross-population validation of GABRB2 association with schizophrenia has been obtained with JP and GE subjects, with the genotype-disease correlations being strongest in systematic schizophrenia, the most severe subtype of the disease.

Gibberellin (GA) is considered an important growth regulator involved in many aspects of plant development. However, little is known about the relationship between GA and lignification. In this study, we analyzed the role of GA in tracheary element (TE) differentiation and lignification using a Zinnia elegans xylogenic culture. When gibberellic acid-3 (GA3) was exogenously supplied, a slight increase in the frequency of TE differentiation and a remarkable increase in lignin content were observed. Computer image analysis of individual TEs showed that the lignification level of each TE was significantly increased in the culture treated with GA3 compared with those of the control. In contrast, suppression of TE differentiation and lignification was observed when GA biosynthesis was inhibited by ancymidol, paclobutrazol, or uniconazole. This suppression was restored by the addition of GA3. These results suggest that GA plays an important role in TE differentiation, and even more so in lignification. When conditioned medium obtained after 120 h of control culture was analyzed by high-performance liquid chromatography, many lignin precursors were detected. However, these lignin precursors were greatly reduced in the GA-treated culture. This result suggests that GA promotes lignification by activating the polymerization of lignin precursors.

This study was conducted to determine the effect of zolpidem (ZOL) 10 mg orally on the sleep architecture and the next-morning residual effect in patients with non-organic insomnia (ICD-10) as compared to the effect of brotizolam (BTM) 0.25 mg orally, a widely used short-acting benzodiazepine (BZD) hypnotic in Japan, in a randomized, crossover comparative study. Fourteen patients with non-organic insomnia (3 males and 11 females; mean age of 54.9+/-S.D. 8.9 years). First three nights with placebo, middle three nights with either ZOL 10 mg or BTM 0.25 mg, and last three nights again with placebo in each session (a total of two sessions). Primary endpoints were polysomnography findings of sleep stages, sleep parameters, and sleep latency (SL) in the morning to examine calculable sleepiness as a residual effect. Secondary endpoint was sleep quality assessed by self-assessment questionnaire. At 150 min after Tmax, both ZOL and BTM significantly increased stage 2 (S2), and ZOL showed significantly longer slow wave sleep (SWS; stage 3+4) as compared to BTM. Stage wake was significantly increased by ZOL at the first withdrawal night and by BTM at the second withdrawal night. ZOL did not affect SL after rising, whereas BTM showed significantly shorter SL. Both drugs reduced the number of nocturnal awakenings and improved subjective sleep quality. The common adverse drug reaction (ADR) was sleepiness (3 patients) in each treatment. All events were mild. No serious adverse events occurred. ZOL is as effective as BTM in improving subjective sleep quality in patients with psychophysiological insomnia (PPI). ZOL has advantages over BTM in having a unique profile of increasing SWS with less next-morning residual effect.

Long-term oral anticoagulant therapy is required for recipients of mechanical heart valves. In our hospital, the international normalized ratio of prothrombin time (PT-INR) has been set in the range 1.5-2.5 since October 2001. To evaluate whether coagulant activity is fully suppressed by this target range, coagulant activity was evaluated by measuring thrombin-antithrombin III complex (TAT) levels and valve-related complications were investigated retrospectively. Two hundred twenty-three patients who underwent mechanical valve replacement were enrolled in this study. PT-INR and TAT were measured at our outpatient clinic in March 2005 and valve-related complications since October 2001, when we started to control PT-INR in the range 1.5-2.5, were investigated. Under adequate warfarin control, there was no significant correlation between PT-INR and TAT, however nine patients who exhibited a PT-INR of less than 2.0 had high levels of TAT. And in atrial fibrillation (AF) patients after mitral valve replacement (MVR), the level of TAT was significantly high compared with sinus rhythm patients after atrial valve replacement. Valve-related complications were bleeding events at 2.75% per patient year and thromboembolism at 0.32% per patient year. Attention to complications of thromboembolism is necessary when the PT-INR is less than 2.0, especially in AF patients after MVR and in those with a thrombotic past history or high levels of TAT. The monitoring of TAT is useful in detecting potential coagulation factors and to determine the therapeutic range of warfarin that can normalize coagulant activity.

The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.

Myointimal hyperplasia (MIH) after vascular intervention is a major problem. Recent reports describing elimination of within-stent restenosis by means of rapamycin-eluting stents prompted us to examine the effect of systemic oral rapamycin on MIH induced by arterial trauma. We studied the effect of oral rapamycin on MIH after rabbit aorta balloon injury. Thirty-five New Zealand white rabbits (2.5-3 kg) had aortic injury and were given either no rapamycin (control), 0.1 (low dose) rapamycin mg/kg/day, or 0.4 mg/kg/day (high dose). Rapamycin was started 1 week before injury and continued for 3 (4 weeks total) or 6 weeks (7 weeks total) post-injury. Sections were analyzed to measure aortic intima/media area ratios (I:M) at either 3 or 6 weeks. At 3 weeks, the I:M (mean +/- SD) for controls was 0.53 +/- 0.1; for low dose, 0.17 +/- 0.13; and for high dose, 0.24 +/- 0.07 (p < 0.001 vs. control). At 6 weeks, the I:M for controls was 0.52 +/- 0.12; for low dose-4 weeks, 0.29 +/- 0.15; low dose-7 weeks, 0.33 +/- 0.07; and high dose-4 weeks, 0.47 +/- 0.16. At 6 weeks only the difference between the low dose-4 weeks and control I:M ratios was significant (p = 0.018). The results confirm earlier studies showing that systemic rapamycin inhibits MIH after arterial injury when drug therapy is started before injury. Therapy for 3 or 6 weeks after injury yields similar inhibition, indicating that exposure to the drug early in the response to injury is more important than prolonged exposure. We observed a paradoxical relation between dose and degree of MIH inhibition, with the low dose being more effective than the high dose at both time intervals studied. Overall, the results suggest that oral rapamycin therapy might be a useful adjunct to clinical interventions at risk for development of MIH.

Current research has been evaluating morphological modifications and density of Langerhans' cells in women with histopathological HPV lesions of the uterine cervix. Fourteen women with subclinical HPV infections underwent clinical, colpocytological colposcopy examinations, and paired biopsies of the uterine cervix. Histopathological, HPV hybrid capture and S-100 immunohistochemical examinations were performed in biopsy specimens. Groupings of viral lesions and normal tissue were analyzed by the Wilcoxon rank-sum test. Langerhans' cells in the specimens were frequently located in the intermediate and basal layers of the epithelium. A significant reduction of cytoplasmic profiles occurred in viral lesions (144.08 profiles/mm2) when compared to normal tissue (256.27 profiles/mm2) of the epithelium. An inverse modulation occurred in the cytoplasmatic profiles/nuclei ratio with 2.80 in viral lesions and 4.89 in normal tissue of the stroma. A local immunodeficiency based on cytoplasmic changes of Langerhans' cells has been postulated as a mechanism by which HPV could be involved in the genesis of neoplasia.

A 24-year-old male with recurrent hypersomnia associated with decreased blood flow in the thalamus on single photon emission computed tomography (SPECT) is reported. In the hypersomnolent period, the decrease of blood flow in the left thalamus was revealed in the SPECT and slow waves appeared sporadically or sometimes as a burst on the electroencephalogram (EEG). In a phase of insomnia in the convalescent period there were almost no slow waves in the resting EEG but many slow waves appeared on hyperventilation EEG and the power spectrum at this hyperventilation resembled the power spectrum at the resting EEG in the hypersomnolent period. In the remission period there was no abnormal data in these testings.

The polysomnogram (PSG), blood melatonin concentration, rectal temperature, and answers to a self-evaluation questionnaire about the effects of agarwood (jinkoh in Japanese), which has been reported to have sleep-promoting effects were examined. The subjects tested were male medical students, who were free of otorhinolaryngological diseases and were non-smokers. The results of sleep stage and other sleep variables, and those of rectal temperature rhythm and blood melatonin concentrations showed no significant differences between the baseline nights, experimental nights, and recovery nights.