Yoshikazu Takaesu

Melatonin profile and its relation to circadian rhythm sleep disorders in Angelman syndrome patients

BACKGROUND Sleep problems are known to be common in Angelman syndrome (AS), a neurodevelopmental disorder which is associated with an abnormality of chromosome 15q11-q13. However, the circadian aspect of sleep disorders in AS and an effective treatment for the disorder have yet to be established. METHODS We elucidated the sleep-wake patterns of AS patients and its relationship to the serum melatonin levels. The serum melatonin levels of 15 AS patients were measured every 4h for one day and the values were compared with those of age-matched controls. We also examined the effectiveness of the oral administration of melatonin on AS patients with circadian rhythm sleep disorders (CRSD). RESULTS A total of eight of the 15 AS patients had CRSD (irregular sleep-wake type, n=4; free-running type n=2; delayed sleep phase type, n=2). The nighttime serum melatonin levels of the AS patients were significantly lower than those of the controls at the measured time points during the night. The nocturnal melatonin levels were comparably low both in AS patients with and without CRSD except for the cases with delayed sleep phase type, which showed normal but delayed peak melatonin level. Six out of eight CRSD cases were given a daily dose of 1mg of melatonin between 18:00 and 19:00 regularly for three months. After receiving the treatment, the sleep patterns improved in four cases. CONCLUSION This study revealed a high prevalence of CRSD in AS patients, which may be related to abnormal serum melatonin profiles.

Effects of nasal continuous positive airway pressure on panic disorder comorbid with obstructive sleep apnea syndrome

BACKGROUNDS Both obstructive sleep apnea syndrome (OSAS) and panic disorder (PD) are common disorders that often coexist. Continuous positive airway pressure (CPAP) has been established as the first-line treatment for OSAS. In this study, we examined the efficacy of CPAP on PD comorbid with OSAS by conducting a randomized crossover study using sham CPAP as control. METHODS PD patients (n=12) with an apnea hypopnea index (AHI) of 20/h or higher completed the study. At baseline, the subjects were asked to write their own records pertaining to the frequency of attacks and their score on the panic disorder severity scale (PDSS), and then they participated in the randomized crossover trial period, which measured optimal CPAP and sham CPAP set at 4cmH(2)O during nighttime sleep for each 4-week assignment. RESULTS The frequency of panic attacks, total PDSS score, and the frequency of alprazolam use for alleviating the attack symptoms were significantly decreased during the optimal CPAP period than during the baseline period and the sham CPAP period. Among the PDSS subitems, the frequency of attacks, panic distress, work impairment, and social impairment showed significant improvements during the optimal pressure period. CONCLUSION Our results suggest that OSAS contributes to PD aggravation, and a combination of pharmaceutical treatment for PD and OSAS-specific treatments such as CPAP could be recommended for patients with PD comorbid with OSAS.

Prevalence of Circadian Rhythm Sleep-Wake Disorders and Associated Factors in Euthymic Patients with Bipolar Disorder

Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients.

Factors Associated with Long-Term Use of Hypnotics among Patients with Chronic Insomnia

This study investigated factors associated with long-term use of benzodiazepines (BZDs) or benzodiazepine receptor agonists (BzRAs) as hypnotics in patients with chronic insomnia. Consecutive patients (n = 140) with chronic insomnia were enrolled in this study (68 men and 72 women; mean age, 53.8±10.8 years). All patients filled out a self-assessment questionnaire asking clinical descriptive variables at the baseline of the treatment period; patients received the usual dose of a single type of BZD or BzRA. The Pittsburgh Sleep Quality Index (PSQI) and the Zung Self-Rating Depression Scale were self-assessed at the baseline, and the former was re-evaluated at the time of cessation of medication or at the end of the 6-month treatment period. The PSQI included the following sub-items: evaluating sleep quality (C1), sleep latency (C2), sleep duration (C3), habitual sleep efficiency (C4), frequency of sleep disturbance (C5), use of sleeping medication (C6), and daytime dysfunction (C7). Among the patients, 54.6% needed to continue hypnotics for a 6-month treatment period. Logistic regression analysis revealed that, among descriptive variables, only the PSQI score appeared as a significant factor associated with long-term use {odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.0–4.0}. The receiver operating curve (ROC) analysis identified that the cut-off PSQI total score at the baseline for predicting long-term use was estimated at 13.5 points (area under the curve = 0.86, 95% CI = 0.8–0.92). Among the sub-items of PSQI, the increases in C1: (OR = 8.4, 95% CI = 2.4–30.0), C3: (OR = 3.6, 95% CI = 1.1–11.5), C4: (OR = 11.1, 95% CI = 3.6–33.9), and C6: (OR = 3.4, 95% CI = 1.9–6.2) scores were associated with long-term use. This study revealed that a high PSQI score at the baseline, particularly in the sub-items relating to sleep maintenance disturbance, is predictive of long-term hypnotic treatment. Our results imply the limitation of the effectiveness of hypnotic treatment alone for chronic insomnia.

Re-analysis of the association of temperature or sunshine with hyperthymic temperament using lithium levels of drinking water

BACKGROUND The Japanese archipelago stretches over 4000km from north to south and has four large islands: Hokkaido, Honshu, Shikoku, and Kyushu. Previously, using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A), we compared the hyperthymic scores of residents in Sapporo, Obihiro, Takaoka, Koshigaya, and Oita cities (which are located at latitudes of 43°N, 42°N, 36°N, 36°N and 33°N with various combinations of ambient temperament and sunshine in Japan, respectively). We found that latitude predicted significant variance in hyperthymic temperament, and that ambient temperature, but not sunshine, significantly affected hyperthymic temperament scores. However, the analysis failed to consider the effects of naturally occurring low-dose lithium on temperament. METHODS In addition to the TEMPS-A data previously collected, we measured lithium levels of the five cities. The effect of temperature, sunshine, and lithium levels on hyperthymic temperament was analyzed for the five cities. RESULTS A stepwise multiple regression analysis revealed that lithium levels as well as latitude, but not temperature or sunshine, predicted significant variance in hyperthymic temperament scores. Hyperthymic temperament scores were significantly and positively associated with lithium levels whereas they were significantly and negatively associated with latitude. LIMITATIONS The light, temperature, lithium exposure that residents actually received was not measured. The number of regions studied was limited. The findings might not be generalized to residents across Japan or other countries. CONCLUSIONS The present findings suggest that lithium in drinking water may positively maintain hyperthymic temperament, and that latitude may negatively maintain it.

Factors associated with discontinuation of aripiprazole treatment after switching from other antipsychotics in patients with chronic schizophrenia: A prospective observational study

The purpose of the study was to identify factors associated with discontinuation of aripiprazole after switching from other antipsychotics in patients with schizophrenia in real world clinical settings. From January 2011 to December 2012, a prospective, 48-week open-label study was undertaken. Thirty-eight subjects on antipsychotic monotherapy were switched to aripiprazole. Patients who discontinued aripiprazole were compared to those who continued with regards to demographic characteristics as well as treatment factors. Multiple regression analysis was conducted to identify predictors for aripiprazole discontinuation. Thirteen out of 38 patients (34.2%) discontinued aripiprazole during the follow up period. Nine patients (23.7%) discontinued aripiprazole due to worsening of psychotic symptoms. Multiple logistic regression analysis revealed that only the duration of previous antipsychotic treatment was associated with aripiprazole discontinuation after switching to aripiprazole. The receiver operating curve (ROC) analysis identified that the cut-off length for duration of illness to predict aripiprazole discontinuation was 10.5 years. Longer duration of illness was associated with aripiprazole discontinuation. Greater caution may be required when treating such patients with aripiprazole.

Affective temperaments play an important role in the relationship between childhood abuse and depressive symptoms in major depressive disorder

Previous studies have shown that various factors, such as genetic and environmental factors, contribute to the development of major depressive disorder (MDD). The aim of this study is to clarify how multiple factors, including affective temperaments, childhood abuse and adult life events, are involved in the severity of depressive symptoms in MDD. A total of 98 participants with MDD were studied using the following self-administered questionnaire surveys: Patient Health Questionnaire-9 measuring the severity of depressive symptoms; Life Experiences Survey (LES) measuring negative and positive adult life events; Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A) measuring affective temperaments; and the Child Abuse and Trauma Scale (CATS) measuring childhood abuse. The data were analyzed using single and multiple regression analyses and structural equation modeling (SEM). The neglect score reported by CATS indirectly predicted the severity of depressive symptoms through affective temperaments measured by TEMPS-A in SEM. Four temperaments (depressive, cyclothymic, irritable, and anxious) directly predicted the severity of depressive symptoms. The negative change in the LES score also directly predicted severity. This study suggests that childhood abuse, especially neglect, indirectly increases the severity of depressive symptoms through increased scores of affective temperaments in MDD.

A preliminary study on the relationships between diurnal melatonin secretion profile and sleep variables in patients emergently admitted to the coronary care unit

To clarify the significance of melatonin secretion under intensive care conditions, we investigated melatonin secretion profiles and sleep parameters of 23 patients just after admission to the coronary care unit (CCU) and 19 age-matched controls. Sleep parameters were evaluated by actigraphy, and melatonin secretion was assessed by measuring the urinary 6-sulphatoxy melatonin (6-SMT). 6-SMT secretion was lower and nocturnal sleep parameters were less satisfactory in the subjects than those in the controls, and there were positive correlations between these variables, particularly in the subject patients. The lowered melatonin secretion might be involved in the mechanism of insomnia in CCU patients.

Impact of hypnotics use on daytime function and factors associated with usage by female shift work nurses

OBJECTIVE We investigated quality of life (QOL) and work performance of hypnotics users, and explored the factors associated with multiple hypnotics usage in shift work nurses. METHODS We conducted a questionnaire-based, cross-sectional survey on nurses in university hospitals. We analyzed responses from 1202 nurses; 997 were female shift work nurses (82.9%), including 696 and 281 two- and three-shift workers, respectively. RESULTS The rate of hypnotics use was 10% (6.9% were single hypnotic users and 3.1% were multiple hypnotics users). The rate of insomnia did not differ between the single and multiple hypnotics users. However, multiple hypnotics users showed lower QOL, more severe depressive symptoms, and greater frequencies of work-related errors than those using a single hypnotic. A multiple logistic regression analysis revealed that age ≥27 years, presence of depression, eveningness chronotype, and presence of insomnia symptoms were significantly associated with hypnotics use. On the other hand, only the existence of shift work disorder (SWD) was significantly associated with usage of multiple hypnotics. CONCLUSIONS The present study suggested that usage of multiple hypnotics is not beneficial for relieving insomnia or for keeping better QOL in shift work nurses. It would be desirable to explore the causal relationship between SWD and multiple hypnotics use in a future longitudinal study.

Associations among depressive symptoms, childhood abuse, neuroticism, and adult stressful life events in the general adult population

Background Recent studies have suggested that the interactions among several factors affect the onset, progression, and prognosis of major depressive disorder. This study investigated how childhood abuse, neuroticism, and adult stressful life events interact with one another and affect depressive symptoms in the general adult population. Subjects and methods A total of 413 participants from the nonclinical general adult population completed the Patient Health Questionnaire-9, the Child Abuse and Trauma Scale, the neuroticism subscale of the shortened Eysenck Personality Questionnaire – Revised, and the Life Experiences Survey, which are self-report scales. Structural equation modeling (Mplus version 7.3) and single and multiple regressions were used to analyze the data. Results Childhood abuse, neuroticism, and negative evaluation of life events increased the severity of the depressive symptoms directly. Childhood abuse also indirectly increased the negative appraisal of life events and the severity of the depressive symptoms through enhanced neuroticism in the structural equation modeling. Limitations There was recall bias in this study. The causal relationship was not clear because this study was conducted using a cross-sectional design. Conclusion This study suggested that neuroticism is the mediating factor for the two effects of childhood abuse on adulthood depressive symptoms and negative evaluation of life events. Childhood abuse directly and indirectly predicted the severity of depressive symptoms.