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  • This study was approved by the ethics committee of Tokyo Medical University and conducted after obtaining written informed consent from the subject patients. The consecutive bipolar participants were recruited from patients who visited the outpatient clinic of the Neuropsychiatric Department in Tokyo Medical University Hospital from August 2014 to January 2015. There were 127 patients 18 to 75 years old who met the criteria for bipolar I or II disorder according to DSM-5. Participants were eligible if they were euthymic as defined by the Young Mania Rating Scale (YMRS <7 points) and Montgomery-Åsberg Depression Rating Scale (MADRS <13 points) for at least 8 weeks prior to the investigation [22]. Exclusion criteria included the following: (a) patients were in affective episodes, (b) shift worker, (c) ongoing alcohol or substance abuse, (d) suicidal risk, (e) hospitalized in the previous 8 weeks, or (f) had visual impairments, who were all more likely to have CRSWD [23,24]. Twelve patients refused to participate in the study and 11 patients met the exclusion criteria. As a result, 104 euthymic BD patients were included in the present study. The subjects were asked to answer questionnaires, including demographic variables, clinical descriptive variables of bipolar disorder and circadian rhythm-related sleep problems, and family history of either psychiatric disorders or suicide. The current mood status was assessed using the MADRS [25] and YMRS [26]. Assessment of subjective sleep disturbance was conducted by using the Pittsburgh Sleep Quality Index (PSQI) [27,28]. The diagnoses of CRSWD were made with clinical interview by a board-certified sleep specialist physician together with the results of sleep logs for more than 4 weeks according to the International Classification of Sleep Disorders, third edition (ICSD-3) [18]. The subjects who met the criteria for CRSWD were additionally divided into sub-categories of CRSWD according to the ICSD-3 [18]. The Mann-Whitney U test and chi-square test were used for the comparison of descriptive variables between the subjects who met the criteria for CRSWD (CRSWD group) and those who did not meet the criteria for CRSWD (non-CRSWD group). The chi-square test or Fisher’s exact test was used for the comparison of kinds of medications for the treatment of mood disorders (mood stabilizers, antipsychotics, antidepressants, and benzodiazepines) between the two groups. The Mann-Whitney U test was also used for the comparison of the PSQI score, YMRS score, and MADRS score between the two groups. Thereafter, factors associated with the presence of CRSWD were examined with the aid of a series of logistic regression analyses with independent variables (sex, age at the time of investigation, age at the onset of BD, duration of illness, living alone or not, educational background, being employed or not, type of BD diagnosis, presence or absence of family history of suicide or psychiatric disorders, MADRS score, YMRS score, and PSQI scores). All variables were initially examined in univariate models. To control for confounding factors and to determine the main correlates, we then performed multivariate logistic regression analyses for all variables that showed significant correlations in univariate models. SPSS version 11.5.1J software for Windows (SPSS Inc., Tokyo) was used for the above statistical analyses. A p-value of less than 0.05 was considered to indicate a statistically significant difference.
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