Masanori Sekimoto

Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome

Recent progress in biological clock research has facilitated genetic analysis of circadian rhythm sleep disorders, such as delayed sleep phase syndrome (DSPS) and non‐24‐h sleep–wake syndrome (N‐24). We analyzed the human period3 (hPer3) gene, one of the human homologs of the Drosophila clock‐gene period (Per), as a possible candidate for rhythm disorder susceptibility. All of the coding exons in the hPer3 gene were screened for polymorphisms by a PCR‐based strategy using genomic DNA samples from sleep disorder patients and control subjects. We identified six sequence variations with amino acid changes, of which five were common and predicted four haplotypes of the hPer3 gene. One of the haplotypes was significantly associated with DSPS (Bonferronis corrected P = 0.037; odds ratio = 7.79; 95% CI 1.59–38.3) in our study population. Our results suggest that structural polymorphisms in the hPer3 gene may be implicated in the pathogenesis of DSPS.

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.

Association between Delta Waves during Sleep and Negative Symptoms in Schizophrenia

We examined the effects of benzodiazepine (BZD) hypnotics and zopiclone (ZPC), a nonbenzodiazepine hypnotic, on sleep and psychiatric symptoms in schizophrenia, as well as the clinical correlates of these variables. Seven male schizophrenic patients chronically taking neuroleptics together with BZD were studied. We replaced BZD with ZPC and performed polysomnography (PSG) and Brief Psychiatric Rating Scale (BRPS) scoring before and after an 8-week ZPC treatment. The replacement of BZD with ZPC increased the mean amplitude of high-amplitude low-frequency delta waves on the frontal derivation recognized by period-amplitude analysis, and it decreased the BPRS negative-symptom score. Under the BZD treatment, the negative-symptom score correlated inversely with the mean amplitude of high-amplitude low-frequency delta waves. This correlation was weak and not significant under the ZPC treatment. Therefore, delta waves during sleep have a close correlation to negative symptoms in schizophrenia, and such a correlation could be influenced by hypnotics. Although these are preliminary findings, it was suggested that, compared with BZD, ZPC might be a beneficial hypnotic in regard to both sleep and negative symptoms of chronic schizophrenic patients.

Genetic polymorphisms of human melatonin 1b receptor gene in circadian rhythm sleep disorders and controls

Recent studies suggest that melatonin 1b (Mel1b) receptor, as well as melatonin 1a (Mel1a) receptor, is involved in the modulation of circadian rhythms in mammals. Mutational analysis was performed in the entire coding region of the human Mel1b receptor gene using genomic DNA from sleep disorder subjects. We have identified two missense mutations, G24E and L66F. However, neither is likely to be associated with sleep disorders in our study population. One of the subjects with non-24-h sleep-wake syndrome carries missense mutations in both the Mel1a and Mel1b receptor genes.

A polysomnographic study of sleep patterns in normal humans with low- or high-anxiety personality traits

To clarify the effects of anxiety‐related personality traits on sleep patterns, polysomnographic examinations (PSG) were performed over 4 consecutive nights on normal humans who tested within the low‐ or high‐anxiety ranges. The subjects consisted of two groups of six male university students who scored either less than 45 points (low‐anxiety group) or more than 55 points (high‐anxiety group) on the Spielberger’s State Trait Anxiety Inventory. Compared to the levels of sleep change in the high‐anxiety group, the low‐anxiety group exhibited a greater change in REM sleep and stage 2 sleep. The REM sleep in the low‐anxiety group was shorter on the first and second nights compared to the third and fourth nights, and the stage 2 sleep was longer on the first night than on the remaining three nights. Thus, the low‐anxiety group showed a first‐night effect followed by partial recovery on the second night, while the high‐anxiety group exhibited no obvious first‐night effect. These results suggest that there is a difference in sleep patterns, assessed by consecutive PSG, between those with low‐ and high‐anxiety traits, and that anxiety‐related personality traits attenuate the occurrence of the first‐night effect, reflecting a lower adaptability to a novel environment.

Duration of postictal psychotic episodes

Summary:  Purpose: To clarify duration of postictal psychosis (PIP) episodes and identify factors that influence its duration.

Recurrent postictal psychosis after remission of interictal psychosis: further evidence of bimodal psychosis.

Summary:  Purpose: To ascertain whether bimodal psychosis (i.e., independent postictal and interictal psychosis) in patients with epilepsy can be characterized by postictal psychosis that develops after interictal psychosis remits.

A quantitative sleep-EEG study on the effects of benzodiazepine and zopiclone in schizophrenic patients

Polysomnographic examinations (PSG) were performed on 6 male schizophrenic outpatients who were being treated with benzodiazepine (BZD) hypnotics in combination with neuroleptics and 6 healthy male volunteers. In schizophrenic subjects, zopiclone (ZPC), 15 mg/day, was substituted for the BZD hypnotics, and PSGs were recorded again during ZPC therapy. All-night sleep stage scoring was carried out by visual analysis, and computerized period-amplitude analysis of sleep EEG was also performed. The schizophrenics showed marked reduction in the amount of slow-wave sleep (SWS) and in the number of delta half-waves during all-night sleep, especially those with higher amplitude, as compared to the normals. The number of delta half-waves in the patients was markedly reduced during the first sleep cycle. The average amplitude of delta half-waves during all-night sleep in the schizophrenics was significantly lower than that in the normals. The half-wave count of total delta waves in the schizophrenics was higher during treatment with ZPC than with BZDs, although no significant differences were observed in the amount of SWS between the two treatments. Soundness of sleep in the subjective sleep assessment was better evaluated during treatment with ZPC than BZDs. These results suggest that reduction of SWS in schizophrenia may be attributable mainly to the decrease in the number of delta waves with higher amplitude and that ZPC may induce deeper sleep in schizophrenics than BZDs.

Asymmetric interhemispheric delta waves during all-night sleep in humans

OBJECTIVE In order to better understand the asymmetry of brain function during sleep, period-amplitude analysis of delta EEG activity was performed on polysomnograms (PSGs) in normal humans. Twenty healthy, right-handed male volunteers aged 22-35 years (mean age 27.2 years) served as subjects in this study. METHODS EEGs were recorded from disc electrodes placed at bilateral frontal, central, parietal, occipital, anterotemporal and posterotemporal (10-20 electrode system) sites using A1+A2 for reference. Period-amplitude analysis was performed by the zero-crossing method using the Medilog Sleep Analyzing Computer. RESULTS Delta counts in the right frontal and central regions during all-night sleep were significantly greater than in those of the left; total delta counts of the right frontal region were greater than those of the left in 18 of the 20 subjects. There were no significant differences in delta counts between the left and right hemispheres in parietal, occipital, anterotemporal, and postero-temporal regions. CONCLUSIONS These results suggest distinct laterality in the number of delta waves in the frontal and central regions, reflecting functional asymmetry of the brain during sleep.

Cortical regional differences of delta waves during all-night sleep in schizophrenia

BACKGROUND Delta sleep is mediated by thalamocortical circuits and is postulated to be abnormal in schizophrenia. Delta wave deficits during sleep have been observed in patients with schizophrenia. Negative symptoms have been reported to reflect frontal lobe dysfunction and to be associated with decreased delta wave sleep. This investigation was undertaken to identify cortical functional abnormalities in patients with schizophrenia shown on the electroencephalogram. METHODS We compared seventeen male, medically treated or neuroleptic-naive outpatients with schizophrenia and 18 healthy male volunteers by all-night polysomnography and investigated cortical regional differences of delta waves. All-night sleep data was evaluated by period amplitude analyses. Delta waves during sleep were investigated in bilateral frontal, central, parietal, and occipital regions by computer analysis. The associations between delta waves in all regions and measures of clinical variables were also estimated. RESULTS Patients with schizophrenia showed lower total delta wave counts during all-night sleep than did control subjects in all regions. Control subjects showed significantly higher delta wave counts in the right frontal and central region than in the left, which was not observed in patients with schizophrenia. Significant inverse correlations were observed between negative symptom scores and delta wave counts in all regions. Control subjects showed significant inverse correlations between delta wave counts and age, which were not identified in patients with schizophrenia. CONCLUSIONS Delta wave deficits in all regions may reflect thalamocortical dysfunction in schizophrenia. Reduced right frontal and central delta wave dominance is suggested to be involved in the pathophysiology of schizophrenia.