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Biomedical subjects

Kiyohisa Takahashi

Publications and source records attributed to Kiyohisa Takahashi.

At least 19 recordsLinked to original sources

Reduced frontal asymmetry of delta waves during all-night sleep in schizophrenia.

Delta wave deficits during sleep have been observed in patients with schizophrenia. Decreased slow-wave sleep is reported to be associated with negative symptoms. Frontal lobe dysfunction is also believed to underlie negative symptoms of schizophrenia. This study was designed to identify functional abnormalities in schizophrenia manifested on patients' electroencephalograms. Polysomnograph examinations were performed in 12 healthy male volunteers and 11 male outpatients with schizophrenia. We investigated the laterality of frontal cortical delta waves in patients with schizophrenia and in healthy control subjects. Laterality of frontal cortex delta wave counts during all-night sleep was investigated by computer analysis. Total delta wave counts were lower in patients with schizophrenia than in control subjects. Control subjects showed significantly higher delta wave counts in the right frontal cortex than in the left. This asymmetry was not observed in patients with schizophrenia. These findings suggest that reduced right frontal delta wave dominance is involved in the pathophysiology of schizophrenia.

Adolescent↗

Effect of benzodiazepine hypnotic triazolam on relationship of blood pressure and Paco2 to cerebral blood flow during human non-rapid eye movement sleep.

We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (Paco2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (non-REM) sleep. Nine young normal volunteers were treated in a randomized, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow wave (stages 3 and 4) sleep, we measured mean arterial blood pressure (MAP), Paco2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, Paco2 increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain decreased more during stage 2 than slow wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During triazolam-induced stage 2 sleep, absolute CBF of the cerebral white matter correlated more strongly to both MAP and Paco2 than during placebo sleep and also correlated more strongly to both MAP and Paco2 than absolute CBF of the occipital cortex. In the frontal white matter, during triazolam-induced stage 2 sleep compared to wakefulness, absolute CBF was significantly better correlated to MAP, but not to Paco2. During triazolam-induced stage 2, the cerebral white matter may receive a modulated CBF regulation having the strengthened relationship of Paco2 to CBF and, more locally, the frontal white matter may depend precariously on CBF regulation.

Adult↗

Clinical analyses of sighted patients with non-24-hour sleep-wake syndrome: a study of 57 consecutively diagnosed cases.

STUDY OBJECTIVES: The objective of this study was to clarify the clinical features of sighted patients with non-24-hour sleep-wake syndrome. DESIGN: Clinical analyses of consecutive patients suffering from non-24-hour sleep-wake syndrome. SETTING: The sleep disorders clinic at Kohnodai Hospital, National Center of Neurology and Psychiatry, Japan. PATIENTS: Fifty-seven patients who were diagnosed consecutively as having non-24-hour sleep-wake syndrome between 1991 and 2001 were included in the study. MEASUREMENTS AND RESULTS: The clinical features and sleep characteristics of the patients were analyzed. A semistructured psychiatric interview that included the criteria for Axis I or II disorders of Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised was conducted, and relationships between psychiatric problems and non-24-hour sleep-wake syndrome were analyzed. The patient cohort included 41 (72%) men and 16 (28%) women. The onset of non-24-hour sleep-wake syndrome had occurred during the teenage years in 63% of the cohort, and the mean ( +/-SD) period of the sleep-wake cycle was 24.9 +/- 0.4 hours (range 24.4-26.5 hours). The mean sleep length of the patients was 9.3 +/- 1.3 hours, and 44% of them had a sleep length of between 9 and 10 hours. Psychiatric disorders had preceded the onset of non-24-hour sleep-wake syndrome in 16 patients (28%); of the remaining 41 patients, 14 (34%) developed major depression after the onset of non-24-hour sleep-wake syndrome. CONCLUSIONS: These results represent the first detailed clinical review of a relatively large number of sighted patients with non-24-hour sleep-wake syndrome.

Adult↗

Diurnal fluctuation of time perception under 30-h sustained wakefulness.

Previous studies have reported that time perception in humans fluctuates over a 24-h period. Behavioral changes seem to affect human time perception, so that the fluctuation in human time perception may be the result of such changes due to self-determined activities. Recently, we carried out a study in which a healthy human cohort was asked to perform simultaneously loaded cognitive tasks under controlled conditions, and found that time perception decreased linearly from morning to evening. In addition, the variations in time perception were not a consequence of behavioral changes. It remains to be elucidated whether diurnal variations in time perception are a consequence of circadian rhythm or of some homeostatic changes that are attributable to accumulated wake time. The effects of circadian rhythm on time perception were investigated in eight healthy young male volunteers by conducting 10-s time production tasks under 30-h constant-routine conditions. Core body temperature and serum melatonin and cortisol levels were measured during the course of the study. Produced time exhibited a diurnal variation and was strongly correlated with circadian variations in core body temperature and serum melatonin levels. These results suggest that human short-term time perception is under the influence of the circadian pacemaker.

Adult↗

Difference in the characteristics of subjective and objective sleepiness between narcolepsy and essential hypersomnia.

The present study was conducted to investigate the difference in the characteristics of daytime sleepiness between narcolepsy and essential hypersomnia and to identify the relationship between the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT) in patients with these two disorders. Subjects consisted of 34 patients with essential hypersomnia (32.4 +/- 11.0 years old), 52 patients with narcolepsy (29.0 +/- 13.8 years old), and 45 control subjects (33.3 +/- 6.6 years old). The subjects completed the ESS and underwent MSLT following a regular sleep-wake schedule for over 2 weeks. The ESS scores were pathologically high and mean sleep latency on MSLT was short, not only in narcolepsy but also in essential hypersomnia. With respect to sleep latencies on each MSLT session, both essential hypersomnia and control subjects had the smallest value at 14:00, while narcolepsy lacked any statistical change at this time period. The correlation between ESS and mean sleep latency on MSLT was higher in essential hypersomnia than in narcolepsy, and the correlation was strongest for the session performed at 14:00. Based on the ESS and MSLT results, the severity of excessive daytime sleepiness was significantly milder in essential hypersomnia compared with that in narcolepsy. The results also indicate that diurnal variation of sleepiness was maintained, and the correlation between subjective and objective sleepiness was relatively maintained in essential hypersomnia compared to narcolepsy. It is suggested that the mild disease severity of essential hypersomnia contributed to the formation of these characteristics.

Adult↗

Cerebral white matter blood flow is constant during human non-rapid eye movement sleep: a positron emission tomographic study.

This study aimed to identify brain regions with the least decreased cerebral blood flow (CBF) and their relationship to physiological parameters during human non-rapid eye movement (NREM) sleep. Using [(15)O]H(2)O positron emission tomography, CBF was measured for nine normal young adults during nighttime. As NREM sleep progressed, mean arterial blood pressure and whole brain mean CBF decreased significantly; arterial partial pressure of CO(2) and, selectively, relative CBF of the cerebral white matter increased significantly. Absolute CBF remained constant in the cerebral white matter, registering 25.9 +/- 3.8 during wakefulness, 25.8 +/- 3.3 during light NREM sleep, and 26.9 +/- 3.0 (ml.100 g(-1).min(-1)) during deep NREM sleep (P = 0.592), and in the occipital cortex (P = 0.611). The regression slope of the absolute CBF significantly differed with respect to arterial partial pressure of CO(2) between the cerebral white matter (slope 0.054, R = - 0.04) and frontoparietal association cortex (slope - 0.776, R = - 0.31) (P = 0.005) or thalamus (slope - 1.933, R = - 0.47) (P = 0.004) and between the occipital cortex (slope 0.084, R = 0.06) and frontoparietal association cortex (P = 0.021) or thalamus (P < 0.001), and, with respect to mean arterial blood pressure, between the cerebral white matter (slope - 0.067, R = - 0.10) and thalamus (slope 0.637, R = 0.31) (P = 0.044). The cerebral white matter CBF keeps constant during NREM sleep as well as the occipital cortical CBF, and may be specifically regulated by both CO(2) vasoreactivity and pressure autoregulation.

Adult↗

Effective components of a nationwide case management program in Japan for individuals with severe mental illness.

This study identified effective components in a case management program based on the Japan Case Management Guidelines (JCM-GL). Subjects (n = 295) with severe mental illness were enrolled throughout Japan. Four outcome scales were utilized. The independent variable, "Fidelity to the JCM-GL" was the subject of interest. Case management components comprised three factors, extracted from factor analysis to fidelity scales, with the "needs-oriented approach" factor displaying the highest score. Subjects demonstrating high fidelity on this factor showed significantly higher quality of life and service satisfaction than low scorers. This component should be established first in countries where community care is underdeveloped.

Adolescent↗

Time estimation during nocturnal sleep in human subjects.

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.

Adolescent↗

A missense variation in human casein kinase I epsilon gene that induces functional alteration and shows an inverse association with circadian rhythm sleep disorders.

Recent studies have shown that functional variations in clock genes, which generate circadian rhythms through interactive positive/negative feedback loops, contribute to the development of circadian rhythm sleep disorders in humans. Another potential candidate for rhythm disorder susceptibility is casein kinase I epsilon (CKIepsilon), which phosphorylates clock proteins and plays a pivotal role in the circadian clock. To determine whether variations in CKIepsilon induce vulnerability to human circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (N-24), we analyzed all of the coding exons of the human CKIepsilon gene. One of the variants identified encoded an amino-acid substitution S408N, eliminating one of the putative autophosphorylation sites in the carboxyl-terminal extension of CKIepsilon. The N408 allele was less common in both DSPS (p = 0.028) and N-24 patients (p = 0.035) compared to controls. When DSPS and N-24 subjects were combined, based on an a priori prediction of a common mechanism underlying both DSPS and N-24, the inverse association between the N408 allele and rhythm disorders was highly significant (p = 0.0067, odds ratio = 0.42, 95% confidence interval: 0.22-0.79). In vitro kinase assay revealed that CKIepsilon with the S408N variation was approximately 1.8-fold more active than wild-type CKIepsilon. These results indicate that the N408 allele in CKIepsilon plays a protective role in the development of DSPS and N-24 through alteration of the enzyme activity.

Adult↗

In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine concentration without alterations in mitochondrial function in the prefrontal cortex of medicated schizophrenic patients at rest.

The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms.

Adult↗

Deactivation by benzodiazepine of the basal forebrain and amygdala in normal humans during sleep: a placebo-controlled [15O]H2O PET study.

OBJECTIVE: The authors' goal was to identify differences in regional brain activity between physiological and benzodiazepine-induced sleep to clarify the brain structures involved in the drug's hypnotic effect. METHOD: Using positron emission tomography, they compared regional cerebral blood flow during non-REM sleep in nine volunteers treated with placebo or triazolam, a short-acting benzodiazepine, in a double-blind, crossover design. RESULTS: Blood flow in the basal forebrain and amygdaloid complexes was lower during non-REM sleep when subjects were given triazolam than when they were given placebo. CONCLUSIONS: The hypnotic effect of the benzodiazepines may be mediated mainly by deactivation of the forebrain control system for wakefulness and also by the anxiolytic effect induced by deactivation of the emotional center.

Adult↗

Circadian rhythms in humans' delta sleep electroencephalogram.

Eight healthy young male volunteers entered a 20-40 min ultrashort sleep-wake schedule for 78 h in the time-isolation facility. Rectal temperature was continuously recorded. Sleep electroencephalograms (EEGs) obtained during 20 min nap trials were stored in the computer and later analyzed by fast Fourier transform. A two-way repeated-measures ANOVA (with day and time-of-day as the repeated measures) revealed significant circadian rhythms in the powers of sigma and delta sleep EEGs, and in rectal temperature. These results obtained under conditions in which behavioral confounding factors of retiring and rising were experimentally minimized suggest that the circadian pacemaker contributes to determining the hours of day when one can sleep deeply.

Adult↗

Circadian fluctuation of time perception in healthy human subjects.

Previous studies suggested that various psychophysiological factors have influences on human time perception. In particular, working memory loads, time of day, body temperature, and mood were known as important modifiers of time perception. The purpose of this study is to elucidate factors affecting the short-term time perception under controlled condition. Fourteen healthy young male adults participated in this study. Time perception sessions (TPS) were conducted 4 times at 0900, 1300, 1700 and 2100 h. The TPS consisted of five 10-s time production trials under five different conditions (control trial, those with reward, and 3 different dual-load working memory tasks). Subjective status was assessed using visual analogue scales (VAS). To verify a participant's vigilance state, an alpha attenuation coefficient (AAC) was calculated. Two-way repeated measures ANOVA for produced time revealed a significant main effect of session, but no effect of task or interaction. Although produced time was not correlated with AACs or VAS scores, there was a significant negative correlation between produced time and core body temperature. These results suggest that human short-term time perception may be more influenced by circadian rhythm than working memory load or psychophysiological status.

Adult↗

The psychological aspects of patients with delayed sleep phase syndrome (DSPS).

OBJECTIVE: The current study attempts to define the psychological features of patients with delayed sleep-phase syndrome (DSPS). METHOD: We administered the Yatabe-Guilford test (Y-G test), Minnesota Multiphasic Personality Inventory (MMPI), Picture-Frustration study (P-F study) and Rorschach test to two groups, one of patients with DSPS (case group) and the other of people without psychiatric symptoms or insomnia (control group). RESULTS: Overall, the results of the tests indicate that patients with DSPS showed emotional features such as nervousness, depression and lack of control of emotional expression. Specific personality traits included introspection, defensiveness, aspiration for intellectual attainment with compulsivity, overly abstract thinking, unawareness of impulsivity to immediate gratification, perseverance and reduced cognitive ability. In addition, the patients with DSPS showed psychopathological features similar to those of neurosis, hypochondriasis, depression, conversion hysteria and psychopathic deviate. CONCLUSIONS: There seems to exist a definite psychological profile for patients with DSPS. (1) an excessive defense mechanism that increases nervousness and develops neurosis; (2) a high level of intellectual aspiration with compulsivity that makes the patients feel self-defeated, powerless and disappointed; (3) a tendency to egocentric emotion, inhibition and perseverance. These characteristics may worsen social withdrawal, causing a loss of social cues in synchronizing their circadian rhythm. Thus, the phase shift becomes more difficult and a vicious circle is constituted.

Adult↗

Childhood parental separation experiences and depressive symptomatology in acute major depression.

The aim of this study was to examine the pathoplastic effects of childhood parental separation experiences on depressive symptoms. Patients with acute major depression were identified in a large 31-center study of affective disorders in Japan. Information regarding the patients' childhood losses was collected using a semistructured interview, and their depressive symptomatology was assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). Patients reported significantly higher CES-D total scores when they had experienced early object loss of the same-sex parent. In terms of the CES-D subscores derived by factor analysis, early object loss significantly aggravated symptoms that people normally could cope with but could no longer cope with when depressed (e.g. 'poor appetite', 'cannot shake off the blues' and 'everything an effort.'). Once depression develops, early object loss may act as a pathoplastic factor by making it severer especially by rendering people less able to perform what they normally could do.

Acute Disease↗