Similarities of Aspects of Biological Rhythms between Major Depression and Bipolar II Disorder Compared to Bipolar I Disorder: A Finding from the Early-Onset Mood Disorder Cohort

Article information

Psychiatry Investig. 2019;16(11):829-835
Publication date (electronic) : 2019 October 28
doi :
1Department of Psychiatry, Biomedical Science, Korea University College of Medicine, Seoul, Republic of Korea
2Chronobiology Institute, Korea University, Seoul, Republic of Korea
3Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea
4Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
5Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
6Department of Psychiatry, Gyeongsang National University College of Medicine, Jinju, Republic of Korea
7Department of Psychiatry, Busan National University School of Medicine, Busan, Republic of Korea
8Department of Psychiatry, National Center for Mental Health, Seoul, Republic of Korea
9Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
10Department of Psychiatry, Chonnam National University College of Medicine, Gwangju, Republic of Korea
11Department of Biostatistics, Korea University College of Medicine, Seoul, Republic of Korea
Correspondence: Heon-Jeong Lee, MD, PhD Department of Psychiatry, Korea University Hospital, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea Tel: +82-2-920-6721, Fax: +82-2-6280-5810, E-mail:
Received 2019 September 5; Revised 2019 September 25; Accepted 2019 September 30.



The biological rhythm is closely related to mood symptoms. The purpose of this study was to assess the differences in biological rhythms among subjects with mood disorder [bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD)] and healthy control subjects.


A total of 462 early-onset mood disorder subjects were recruited from nine hospitals. The controls subjects were recruited from the general population of South Korea. Subject groups and control subject were evaluated for the Korean language version of Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN) at the initial evaluation.


The mean K-BRIAN scores were 35.59 [standard deviation (SD)=13.37] for BD I, 43.05 (SD=11.85) for BD II, 43.55 (SD=12.22) for MDD, and 29.1 (SD=8.15) for the control group. In the case of mood disorders, biological rhythm disturbances were greater than that in the control group (p<0.05). A significant difference existed between BD I and BD II (BD I <BD II, p<0.001) and between BD I and MDD (BD I<MDD, p< 0.001) but no difference was observed between BD II and MDD.


BD II and MDD are similar to each other but different from BD I in biological rhythm patterns in early-onset mood disorder cases. Biological rhythm disturbances are similar for early-onset major depression and BD II.


Circadian rhythms exist in lifeforms from microorganisms to mammals and drive circadian cycles (cycles that repeat roughly every 24 hours) to help anticipate and respond to environmental changes [1]. Circadian rhythms help synchronize an organism to periodic fluctuations in the external environment and also facilitate integration of an organism’s internal social environment [2]. Recognition of its importance is growing, and the Nobel Prize in Physiology or Medicine 2017 was awarded to Jeffrey Hall, Michael Rosbash, and Michael Young, who contributed to circadian biology by studying the biological clock and circadian oscillation control through period proteins [3]. The biological rhythm represented by a circadian rhythm is closely related to mood symptoms as well as physiological effects such as sleep patterns, eating behavior, hormone secretion, blood pressure, and body temperature [4]. Previous studies showed that an altered circadian rhythm and sleep disturbances occur in depressive disorders [2], and irregularity of the sleep-wake cycle, eveningness-chronotype, and abnormal melatonin secretion occur in bipolar disorder [5-8]. These studies suggest the changes that occur to biological rhythms (including sleep) in those with mood disorders.

Additionally, integrated insights give an understanding of how biological rhythm disturbances affect a variety of conditions and biological functions such as—monoamine signaling of mood disorders, the immune system, hypothalamic–pituitary–adrenal (HPA) axis regulation, metabolic peptides, cellular processes (redox, mitochondria, apoptosis, neurogenesis) [9], cerebral parenchyma, suprachiasmatic nucleus [10], and regulation of the biological clock through epigenetic control [11]. Researchers have made an effort, through a variety of measurements and actigraphy, to evaluate biological rhythms in subjects with mood disorders objectively [12,13]. In addition, studies show that correction of biological rhythms through light therapy, behavior modification, and pharmacological agents (such as melatonin) reduces the duration of mood-related symptoms and the severity of other symptoms [14,15], improving the overall quality of life [16]. Thus, objective analysis of biological rhythms in the treatment of subjects with early mood disorders may give insights into the diagnosis, treatment, and prognosis of subjects.

The Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) is an assessment that extends to areas including social activity and eating patterns, in contrast to assessments such as the Pittsburgh Sleep Quality Index (PSQI) [17], the Morningness-Eveningness Questionnaire (MEQ) [18], and the Seasonal Pattern Assessment Questionnaire (SPAQ) [19]. BRIAN consists of 21 items divided into five main areas, related to circadian rhythm disturbance in psychiatric subjects. These five domains are sleep, activities, social-rhythm, eating-pattern, and predominant-rhythm [20], and BRIAN’s validity and reliability have been confirmed for Korean population [21].

The purpose of this study was to evaluate sleep, activity, social-activity, eating patterns, and predominant rhythm (chronotype) in early-onset mood disorder subjects and healthy subjects and then verify the biological rhythm differences among bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD) and control subjects.



A total of 467 subjects were recruited. Each subject was less than 35 years old and had a major mood disorder within two years of the treatment; or less than 25 years old and presently diagnosed with a major mood disorder. Subjects with evidence of intellectual disabilities, organic BRIAN injury, or difficulty in reading and understanding Korean characters were excluded [22]. Subjects were recruited from nine different hospitals participating in the Mood Disorder Cohort Research Consortium (MDCRC), including Korea University Hospital, Seoul National University Hospital, Seoul National University Bundang Hospital, Samsung Medical Center, Severance Hospital, Busan National University Hospital, Gyeongsang National University Hospital, Cheonnam National University Hospital, and the National Center for Mental Health [22]. Subjects were diagnosed using the Mini-International Neuropsychiatric Interview (M.I.N.I.) [23], which classified 138 subjects with BD I, 170 subjects with BD II, and 159 subjects with MDD. 40 control subjects were recruited by matching gender and age from the general population of young adults at Korea University Anam Hospital [21].

All subjects and control subjects received informed consent prior to the test, and this study was reviewed by the Institutional Review Boards for all nine participating hospitals (2015 AN0239) [22].


During the initial evaluation, 467 subjects were evaluated for K-BRIAN scores and sociodemographic characteristics. A Korean language version of the mood disorder questionnaire (K-MDQ) [24] was performed to identify bipolarity in the subject. The MDQ is a self-report questionnaire designed to help detect bipolar disorder and focuses on symptoms of hypomania and mania [25]. The K-MDQ was validated in 2009 [24]. Korean language versions of the Montgomery-Asberg Depression Rating Scale (K-MADRS) [26] and the Young Mania Rating Scale (YMRS) [27] were used to evaluate depressive and manic-hypomanic symptoms respectively. Subjects with a K-MADRS score greater than 35 and a YMRS score greater than 25 were classified as severely ill and expected to have low reliability due to mood symptoms [28,29]. In those cases, the K-BRIAN value was used after the mood symptoms improved.

A total of 462 subjects were enrolled. Two subjects with BD II and three with MDD were excluded. The enrolled participants included 138 subjects with BD I, 168 subjects with BD II, and 156 subjects with MDD. The control subjects were administered the M.I.N.I. [23] by a psychiatrist and assessed using the K-BRIAN [21] and the K-MDQ [24]. The K-BRIAN total score used for this study is the sum of the values of four subgroups—sleep, activities, social-rhythm, and eating-patterns. Chronotypes were excluded from the score as in earlier studies [20,21,30-32].

Statistical analyses

First, a normality test of the four groups (BD I, BD II, MDD, and control) was performed. Then, a one-way analysis of variance (ANOVA) for continuous data and a chi-square test for categorical data was performed to analyze statistical differences between the four groups. A Levene’s test for variance and a Welch’s t-test for robustness were performed to test for equal variance. Dunnett’s T3 method was performed post hoc based on a 0.05 p-value significance level. All statistical analyses were performed using SPSS version 21 for windows (IBM, Corp., Armonk, NY, USA).


The mean age of each group was 23.49 (SD 3.48) years for BD I, 23.00 (SD 3.01) years for BD II, 22.67 (SD 3.66) years for MDD, and 24.76 (SD 4.46) years for the control group. There was a statistically significant difference in mean age between MDD and control group (F=3.182, p<0.05). Mean age at onset was 18.34 (SD 4.88) years in BD I, 16.46 (SD 3.76) years in BD II, and 17.89 (SD 4.72) years in MDD; BD I and BD II are statistically different (F=7.675, p<0.001). The gender ratio was 60.14% female in BD I, 59.51% female in BD II, 52.56% female in MDD, and 50% in the control group. There was no statistically significant difference in gender ratio between groups (χ2=4.637, p=0.200). Body-Mass-Index (BMI) was 24.19 (SD 3.58) for BD I, 23.83 (SD 4.52) for BD II, 23.36 (SD 4.01) for MDD.

Socioeconomic status was classified into five categories, taking into account occupation and income [33]. For education level, the percentage of subjects who attended the undergraduate university level or higher were identified. There was a statistically significant difference in socioeconomic status and education level between study groups and the control group (p<0.001). Table 1 shows the sociodemographic characteristics of the study’s subjects.

Sociodemographic characteristics of the study subjects

The value of the K-BRIAN score was 35.59 (SD 13.37) for BD I, 43.05 (SD 11.85) for BD II, 43.55 (SD 12.22) for MDD, and 29.1 (SD 8.15) for the control group. The K-BRIAN values for each subgroup are shown in Table 2. The K-BRIAN scores among the four groups are statistically different (F=24.705, p<0.001). Post hoc analyses of the scores yielded the following statistical differences for BD I vs. BD II (BD I is less than BD II, p<0.001), BD I vs. MDD (BD I is less than MDD, p<0.001). However, no significant difference was found between the BD II and MDD groups (p=0.982)

Biological rhythm assessment in subjects and control subjects

Mean K-MDQ scores were 7.74 (SD 4.77) for BD I, 7.83 (SD 3.87) for BDII, 5.61 (SD 3.42) for MDD, and 3.25 (SD 3.20) for the control group. There are significant differences among the four groups, BD I, BD II, MDD, and the control group (F=21.712, p<0.001). As a result of post hoc analysis, BD I was greater than MDD (p<0.001) and BD II was greater than MDD (p<0.001). However, no significant difference was found between the BD I and BD II groups (p=0.997). The K-MADRS results were 9.20 (SD 8.21) for BD I, 14.72 (SD 9.62) for BD II, and 17.47 (SD 10.04) for MDD, showing statistically significant differences among the three groups, BD I, BD II, MDD (F= 29.263, p<0.001), In post hoc analysis, BD I and MDD (BDI is less than MDD, p<0.001), BD II and MDD (BD II is less than MDD, p<0.001) were statistically different. For the mean YMRS scores, BD I was 3.63 (SD 5.41), BD II was 3.52 (SD 4.60), and MDD was 1.37 (SD 2.41). A significant difference exists among three groups, BD I, BD II, MDD (F=13.631, p<0.001). In post hoc analysis comparison BD I and MDD (BD I is greater than MDD, p<0.001), BD II and MDD (BD II is greater than MDD, p<0.001) with statistical significance. The clinical characteristics of the study subjects are shown in Table 3.

Clinical characteristics of the study subjects


Earlier studies suggest that biological rhythms and physiological functions of the body and the mood influence each other directly and indirectly [5,9,10,34,35]. It is important to control disturbances to biological rhythms in order to reduce the severity of adverse mood-related symptoms, reduce the duration of these symptoms, and increase the overall quality of life [14-16]. According to a prior study examining BD, biological rhythms checked with BRIAN can be used as a subject’s trait marker rather than a static state at only the time of the assessment [36]. In the previous study using BRIAN, the biological rhythm disturbance was greater in BD than in the control group [20]. In drug-naïve, young adult subjects with mood disorders, biological rhythm disturbance was greater than that of the control group and the BD group showed higher BRIAN values than MDD [32]. In a study of 1,023 subjects, those with BD had higher BRIAN values than those with MDD, and when they were classified by mood, subjects showed euthymic MDD–euthymic bipolar–unipolar depression–hypomanic/manic/mixed–bipolar depression in that order, indicating that the most disturbing biological rhythm was found in bipolar depression [31]. However, in a recent study, subjects with MDD tended to have a higher total BRIAN score than those with BD, but there was no statistical difference between the two groups [13].

However, some earlier studies have weaknesses, such as only comparing the BD group and control group [20,37], or only comparing the BD group to those with depressive disorders [31,32]. In addition, only disturbances of biological rhythms according to mood were identified in subjects with BD [30,35,38]. The strength of the present study is that it was designed to analyze BD I and BD II and to compare the biological characteristics of the disease groups in more detail. Furthermore, analyses of study data identified characteristics of each disease group for early-onset mood disorders in young adults.

According to the result of present study, the disturbance of biological rhythms for those with BD II and MDD is statistically significant compared to subjects with BD I. This differs from previous studies [31,32,39] which proposed that BD is more disturbing to biological rhythms than MDD. Therefore, it is important to note that BD I and BD II, and MDD show different biological rhythm patterns in early mood disorders.

First, when comparing the K-MDQ score, both BD I and BD II groups scored higher than the MDD group. However, the BD I and BD II groups could not be distinguished. The results of this study show that the disturbance of the biological rhythms for BD II is greater in all subgroups (sleep, activities, social rhythm, eating pattern, chronotype) compared to BD I. In the case of BD II, the general clinician considers BD II to be a simple and milder form of a manic-depressive illness [40], and often BD II goes underdiagnosed or misdiagnosed as unipolar disorder or personality disorder [41]. Many studies have confirmed that BD I and BD II have different pathophysiological characteristics, and BD II is known to have more clinically complex characteristics [42]. In particular, BD II subjects are known to have depressive predominant polarity [43,44], suffer from a longer depressive duration (compared to BD I), and experience more persistent residual depression [45]. In addition, subjects with BD II have a higher incidence of premenstrual symptoms compared to subjects with BD I [46]. Combining this evidence, we hypothesize that BD I and BD II have different characteristics in terms of the long-term disease course and pathophysiology. In view of earlier results, the distinction between BD I and BD II, which are bound by the same bipolar spectrum, is important and reveals the limitations of an assessment focused on symptoms (such as K-MDQ). Thus, BRIAN, which is known to reflect a subject’s traits [36], may be used as a tool to distinguish bipolar disorder’s endophenotype if subsequent studies strengthen the evidence.

Second, Subjects with early-onset MDD showed similar levels of disturbances in biological rhythms as those with BD II. However, using the results of K-MADRS, MDD subjects had a significantly higher value than BD subjects. According to some studies, 40–50% of subjects with depressive episodes in the out-subject and in-subject setting were diagnosed with BD during the course of the disease [47-50], and the risk factor of diagnostic change was related to these factors—onset at a young age, high number of depressive episodes, bipolar family history, female gender, psychosis, depressive mixed episodes with mood lability, psychomotor agitation, and crowded thoughts [48,51,52].

Studies have shown that the onset of first depression in BD subjects is faster than that of subjects with MDD [52-56] and the first episode of BD is known to begin primarily with depression [57]. Therefore, progression from early-onset major depression to BD is an important consideration for prognosis, course of disease, and choice of medication. Early-onset major depression showed a disturbance of biological rhythms similar to BD I and BD II. Hence, for subjects with early-onset major depression, the hallmarks of BD II should be noted throughout the disease such as more chronicity [58], lower probability of returning to a premorbid level of function between episodes [59], higher rate of rapid cycling [60], and shorter well periods [59]. With further research comparing biological rhythm disturbances to long-term MDD subjects, BRIAN will yield new criterion for suggesting bipolarity in early-onset major depression.

This current study also has limitations. The first is that the number of subjects in the control group was smaller than that of the subject groups, and most of the control group were college students. However, the goal of this study was to compare each subject group to each other. It is well known from previous studies that disturbances in biological rhythms are higher in the mood disorder groups than in the control group [20,31,32], Thus, a small control group population should not affect the validity of the study. In addition, the analysis of sociodemographic characteristics (education, tobacco) showed significant differences in the control group compared to the subject groups and should be considered due to the characteristics of the control subjects. The second limitation is that BRIAN itself has limitations such as recall-bias and answer-reliability problems [61], but it is meaningful in that it is not invasive and can easily obtain information serially. Finally, although biological rhythms identified through BRIAN are known to reflect the subject’s traits [36], circadian rhythm [62] and mood change with the seasons [63]. Follow-up studies are needed to determine the relationship between seasonality and biological rhythms.

This study is a large-scale examination of subjects with early-onset mood disorders in South Korea, and it takes an important step to separate BD I and BD II and analyze early-onset MDD. This study suggests a new approach to the characteristics of early-onset mood disorders through the assessment of biological rhythms. Existing assessments related to mood disorders can distinguish BD and MDD because they focus on symptoms, but there are limitations in actually distinguishing endophenotype of BD or diagnosing early-onset major depression. Assessments (such as BRIAN) that reflect the subject’s traits in terms of biological rhythms may provide additional information to the current diagnostic systems with further research. It is also realistic to believe that new tools for classifying diseases will arise from further research which could change the current practice of simply classifying overlapping diseases as degrees of severity.


This study was supported by the Korea Health 21 R&D Project funded by the Ministry of Health & Welfare (HM14C2606) and the National Research Foundation of Korea (2017M3A9F1031220), Republic of Korea.


The authors have no potential conflicts of interest to disclose.

Author Contributions

Conceptualization: Heon-Jeong Lee, Su Cheol Kim. Data curation: Heon-Jeong Lee, Chul-Hyun Cho, Yong-Min Ahn, Se Joo Kim, Tae Hyon Ha, Boseok Cha, Eunsoo Moon, Dong Yeon Park, Ji Hyun Baek, Hee-Ju Kang, Hyonggin An. Formal analysis: All author. Funding acquisition: Heon-Jeong Lee. Investigation: All author. Methodology: Heon-Jeong Lee, Su Cheol Kim, Chul-Hyun Cho, Yujin Lee, Ju Yeon Seo. Project administration: Heon-Jeong Lee, Su Cheol Kim. Resources: All author. Software: Su Cheol Kim, Chul-Hyun Cho. Supervision: Heon-Jeong Lee. Visualization: Su Cheol Kim, Chul-Hyun Cho, Yujin Lee. Writing—original draft: Su Cheol Kim. Writing—review& editing: Heon-Jeong Lee, Chul-Hyun Cho, Yujin Lee.


1. Kim J, Jang S, Choe HK, Chung S, Son GH, Kim K. Implications of circadian rhythm in dopamine and mood regulation. Mol Cells 2017;40:450–456.
2. Rusak B, Zucker I. Neural regulation of circadian rhythms. Physiol Rev 1979;59:449–526.
3. Burki T. Nobel Prize awarded for discoveries in circadian rhythm. Lancet 2017;390e25.
4. Armitage R. Sleep and circadian rhythms in mood disorders. Acta Psychiatr Scand Suppl 2007;433:104–115.
5. Germain A, Kupfer DJ. Circadian rhythm disturbances in depression. Hum Psychopharmacol 2008;23:571–585.
6. Takaesu Y. Circadian rhythm in bipolar disorder: a review of the literature. Psychiatry Clin Neurosci 2018;72:673–682.
7. Moon JH, Cho CH, Son GH, Geum D, Chung S, Kim H, et al. Advanced circadian phase in mania and delayed circadian phase in mixed mania and depression returned to normal after treatment of bipolar disorder. EBioMedicine 2016;11:285–295.
8. Lee HJ. Is the Circadian rhythm dysregulation a core pathogenetic mechanism of bipolar disorder? J Korean Neuropsychiatr Assoc 2018;57:276–286.
9. McClung CA. How might circadian rhythms control mood? Let me count the ways. Biol Psychiatry 2013;74:242–249.
10. Vadnie CA, McClung CA. Circadian rhythm disturbances in mood disorders: Insights into the role of the suprachiasmatic nucleus. Neural Plast 2017;2017:1504507.
11. Sahar S, Sassone-Corsi P. The epigenetic language of circadian clocks. Handb Exp Pharmacol 2013;217:29–44.
12. Allega OR, Leng X, Vaccarino A, Skelly M, Lanzini M, Hidalgo MP, et al. Performance of the biological rhythms interview for assessment in neuropsychiatry: an item response theory and actigraphy analysis. J Affect Disord 2018;225:54–63.
13. Slyepchenko A, Allega OR, Leng X, Minuzzi L, Eltayebani MM, Skelly M, et al. Association of functioning and quality of life with objective and subjective measures of sleep and biological rhythms in major depressive and bipolar disorder. Aust N Z J Psychiatry 2019;53:683–696.
14. Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry 2005;162:656–662.
15. Dodson ER, Zee PC. Therapeutics for circadian rhythm sleep disorders. Sleep Med Clin 2010;5:701–715.
16. Cudney LE, Frey BN, Streiner DL, Minuzzi L, Sassi RB. Biological rhythms are independently associated with quality of life in bipolar disorder. Int J Bipolar Disord 2016;4:9.
17. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193–213.
18. Lee JH, Kim SJ, Lee SY, Jang KH, Kim IS, Duffy JF. Reliability and validity of the Korean version of Morningness-Eveningness Questionnaire in adults aged 20-39 years. Chronobiol Int 2014;31:479–486.
19. Magnusson A. Validation of the Seasonal Pattern Assessment Questionnaire (SPAQ). J Affect Disord 1996;40:121–129.
20. Giglio LM, Magalhaes PV, Andreazza AC, Walz JC, Jakobson L, Rucci P, et al. Development and use of a biological rhythm interview. J Affect Disord 2009;118:161–165.
21. Cho CH, Jung SY, Kapczinski F, Rosa AR, Lee HJ. Validation of the Korean version of the biological rhythms interview of assessment in neuropsychiatry. Psychiatry Investig 2018;15:1115–1120.
22. Cho CH, Ahn YM, Kim SJ, Ha TH, Jeon HJ, Cha B, et al. Design and methods of the Mood Disorder Cohort Research Consortium (MDCRC) Study. Psychiatry Investig 2017;14:100–106.
23. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(Suppl 20):22–33. quiz 34-57.
24. Jon DI, Hong N, Yoon BH, Jung HY, Ha K, Shin YC, et al. Validity and reliability of the Korean version of the Mood Disorder Questionnaire. Compr Psychiatry 2009;50:286–291.
25. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry 2000;157:1873–1875.
26. Ahn YM, Yi JS, Kang MH, Kim DH, Kim JL, Lee KY, et al. A validation study of the Korean-version of the Montgomery-Asberg depression rating scale. J Korean Neuropsychiatr Assoc 2005;44:466–476.
27. Jung HY, Cho HS, Joo YH, Shin HK, Yi JS, Hwang S. A validation study of the Korean-Version of the Young Mania Rating Scale. J Korean Neuropsychiatr Assoc 2003;42:263–269.
28. Herrmann N, Black SE, Lawrence J, Szekely C, Szalai JP. The Sunnybrook Stroke Study: a prospective study of depressive symptoms and functional outcome. Stroke 1998;29:618–624.
29. Lukasiewicz M, Gerard S, Besnard A, Falissard B, Perrin E, Sapin H, et al. Young Mania Rating Scale: how to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort. Int J Methods Psychiatr Res 2013;22:46–58.
30. Pinho M, Sehmbi M, Cudney LE, Kauer-Sant’anna M, Magalhaes PV, Reinares M, et al. The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study. Acta Psychiatr Scand 2016;133:102–108.
31. Mondin TC, Cardoso TA, Souza LDM, Jansen K, da Silva Magalhaes PV, Kapczinski F, et al. Mood disorders and biological rhythms in young adults: a large population-based study. J Psychiatr Res 2017;84:98–104.
32. Duarte Faria A, Cardoso Tde A, Campos Mondin T, Souza LD, Magalhaes PV, Patrick Zeni C, et al. Biological rhythms in bipolar and depressive disorders: a community study with drug-naive young adults. J Affect Disord 2015;186:145–148.
33. Edwards-Hewitt T, Gray JJ. Comparison of measures of socioeconomic status between ethnic groups. Psychol Rep 1995;77:699–702.
34. Cho CH, Moon JH, Yoon HK, Kang SG, Geum D, Son GH, et al. Molecular circadian rhythm shift due to bright light exposure before bedtime is related to subthreshold bipolarity. Sci Rep 2016;6:31846.
35. Rosa AR, Comes M, Torrent C, Sole B, Reinares M, Pachiarotti I, et al. Biological rhythm disturbance in remitted bipolar patients. Int J Bipolar Disord 2013;1:6.
36. Kuppili PP, Menon V, Chandrasekaran V, Navin K. Biological rhythm impairment in bipolar disorder: a state or trait marker? Indian J psychiatr 2018;60:404–409.
37. Giglio LM, Magalhaes PV, Kapczinski NS, Walz JC, Kapczinski F. Functional impact of biological rhythm disturbance in bipolar disorder. J Psychiatr Res 2010;44:220–223.
38. Dopierala E, Chrobak A, Kapczinski F, Michalak M, Tereszko A, Ferensztajn-Rochowiak E, et al. A study of biological rhythm disturbances in Polish remitted bipolar patients using the BRIAN, CSM, and SWPAQ Scales. Neuropsychobiology 2016;74:125–130.
39. Moro MF, Carta MG, Pintus M, Pintus E, Melis R, Kapczinski F, et al. Validation of the Italian version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN): Some Considerations on its screening usefulness. Clin Pract Epidemiol Ment Health 2014;10:48–52.
40. Vieta E, Suppes T. Bipolar II disorder: arguments for and against a distinct diagnostic entity. Bipolar Disord 2008;10:163–178.
41. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry 2000;61:804–808.
42. Chung JK, Lee KY, Kim SH, Kim EJ, Jeong SH, Jung HY, et al. Circadian rhythm characteristics in mood disorders: comparison among bipolar I disorder, bipolar II disorder and recurrent major depressive disorder. Clin Psychopharmacol Neurosci 2012;10:110–116.
43. Quitkin FM, Rabkin JG, Prien RF. Bipolar disorder: are there manicprone and depressive-prone forms? J Clin Psychopharmacol 1986;6:167–172.
44. Perlis RH, Delbello MP, Miyahara S, Wisniewski SR, Sachs GS, Nierenberg AA. Revisiting depressive-prone bipolar disorder: polarity of initial mood episode and disease course among bipolar I systematic treatment enhancement program for bipolar disorder participants. Biol Psychiatry 2005;58:549–553.
45. Benazzi F. Course and outcome of Bipolar II disorder: a retrospective study. Psychiatry Clin Neurosci 2001;55:67–70.
46. Choi J, Baek JH, Noh J, Kim JS, Choi JS, Ha K, et al. Association of seasonality and premenstrual symptoms in bipolar I and bipolar II disorders. J Affect Disord 2011;129:313–316.
47. Benazzi F. Prevalence of bipolar II disorder in outpatient depression: a 203-case study in private practice. J Affect Disord 1997;43:163–166.
48. Goldberg JF, Harrow M, Whiteside JE. Risk for bipolar illness in patients initially hospitalized for unipolar depression. Am J Psychiatry 2001;158:1265–1270.
49. Angst J, Gamma A, Lewinsohn P. The evolving epidemiology of bipolar disorder. World Psychiatr 2002;1:146–148.
50. Hantouche EG, Akiskal HS, Lancrenon S, Allilaire JF, Sechter D, Azorin JM, et al. Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP). J Affect Disord 1998;50:163–173.
51. Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Keller M, et al. Switching from ‘unipolar’ to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995;52:114–123.
52. Angst J, Sellaro R, Stassen HH, Gamma A. Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions. J Affect Disord 2005;84:149–157.
53. Kim WW, Kwon YJ, Shim SH, Jeong HY, Kwon WJ, Lee HY. The association study between mood disorder questionnaire and bipolar spectrum disorder in major depressive disorder. J Korean Neuropsychiatr Assoc 2012;51:291–299.
54. Geller B, Zimerman B, Williams M, Bolhofner K, Craney JL. Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry 2001;158:125–127.
55. Hillegers MH, Reichart CG, Wals M, Verhulst FC, Ormel J, Nolen WA. Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents. Bipolar Disord 2005;7:344–350.
56. Grof P, Alda M. Discrepancies in the efficacy of lithium. Arch Gen Psychiatry 2000;57:191.
57. Baldessarini RJ, Tondo L, Visioli C. First-episode types in bipolar disorder: predictive associations with later illness. Acta Psychiatr Scand 2014;129:383–392.
58. Vieta E, Benabarre A, Colom F, Gastó C, Nieto E, Otero A, et al. Suicidal behavior in bipolar I and bipolar II disorder. J Nerv Ment Dis 1997;185:407–409.
59. Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003;60:261–269.
60. Akiskal HS, Hantouche E-G, Allilaire J-F, Sechter D, Bourgeois ML, Azorin JM, et al. Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II). J Affect Disord 2003;73:65–74.
61. Van de Mortel. Faking it: social desirability response bias in self-report research. Aust J Adv Nurs 2008;25:40–48.
62. Honma K, Honma S, Kohsaka M, Fukuda N. Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm. Am J Physiol 1992;262:R885–R891.
63. Wirz-Justice A. Seasonality in affective disorders. Gen Comp Endocrinol 2018;258:244–249.

Article information Continued

Table 1.

Sociodemographic characteristics of the study subjects

BD I (N=138) BD II (N=168) MDD (N=156) Control (N=40) Statistic p
Age 23.49 (SD 3.48) 23.00 (SD 3.01) 22.67 (SD 3.66) 24.3 (SD 2.89) F=3.182 0.024 (MDD<control)*
Age at onset 18.34 (SD 4.88) 16.46 (SD 3.76) 17.89 (SD 4.72) (-) F=7.675 <0.001 (BD I-BD II)*
Gender female 83 (60.14%) 100 (59.52%) 82 (52.56%) 20 (50%) χ2=4.637 0.200
BMI 24.19 (SD 3.58) 23.83 (SD 4.52) 23.36 (SD 4.01) 22.59 (SD 3.89) F=2.051 0.106
Socioeconomic status (%) χ2=39.591 <0.001
 Upper 4 (2.89) 6 (3.57) 3 (1.92) 3 (7.5)
 Upper middle 20 (14.49) 36 (21.42) 19 (12.17) 2 (5)
 Lower middle 66 (47.82) 76 (45.23) 75 (48.07) 16 (40)
 Upper lower 42 (30.43) 37 (22.02) 45 (28.84) 19 (47.5)
 Lower 6 (4.34) 13 (7.73) 14 (8.97) 0 (0) <0.001
Education (%) χ2=25.988
 University degree 99 (71.73) 116 (69.04) 93 (59.61) 40 (100) 0.790
Marriage (%) χ2=3.145
 Single 128 (92.75) 161 (95.83) 148 (94.87) 40 (100)
 Married 7 (5.07) 5 (2.97) 5 (3.20) 0 (0)
 Separate 3 (2.17) 2 (1.19) 3 (1.92) 0 (0)
Tobacco 45 (32.60) 62 (36.90) 49 (31.41) 1 (2.5) χ2=18.582 <0.001

“Age at onset” means the age at which the disease first developed, Categorical data were analyzed by chi-square test, and continuous data were analyzed by ANOVA.


there is a statistically significant difference between the two groups in post hoc analysis.

BD: bipolar disorder, MDD: major depressive disorder

Table 2.

Biological rhythm assessment in subjects and control subjects

F statistic p Post hoc (Dunnett T3)
BD I (N=138) BD II (N=168) MDD (N=156) Control (N=40)
K-BRIAN score 35.59 (SD 13.37) 43.05 (SD 11.85) 43.55 (SD 12.22) 29.1 (SD 8.15) 24.705 <0.001 Control<BD I<MDD, BD II
Sleep 10.79 (SD 4.14) 12.82 (SD 3.71) 13.16 (SD 4.00) 9.28 (SD 2.61) 18.403 <0.001 Control<BD I<BD II, MDD
Activities 9.53 (SD 4.45) 11.23 (SD 4.20) 11.18 (SD 4.28) 7.17 (SD 2.36) 13.926 <0.001 Control<BD I<BD II, MDD
Social rhythms 7.31 (SD 3.43) 8.64 (SD 3.29) 8.89 (SD 3.40) 5.62 (SD 1.93) 14.792 <0.001 Control<BD I<BD II, MDD
Eating pattern 7.94 (SD 3.32) 10.34 (SD 3.28) 10.32 (SD 3.55) 7.05 (SD 2.59) 23.808 <0.001 Control, BD I<BD II, MDD
Chronotype 6.50 (SD 1.63) 7.08 (SD 1.53) 6.96 (SD 1.54) 5.90 (SD 1.42) 8.587 <0.001 Control<BD II, MDD BD I<BD II

The K-BRIAN total score is the sum of sleep, activities, social rhythms, and eating pattern. Values are presented as means. K-BRIAN: Korean version of the biological rhythms interview of assessment in neuropsychiatry, BD: bipolar disorder, MDD: major depressive disorder

Table 3.

Clinical characteristics of the study subjects

F statistic p Post hoc (Dunnett T3)
BD I (N=138) BD II (N=168) MDD (N = 156) Control (N=40)
K-MDQ 7.74 (SD 4.77) 7.83 (SD 3.87) 5.61 (SD 3.42) 3.25 (SD 3.20) 21.712 <0.001 Control<MDD<BD I, BD II
K-MADRS 9.20 (SD 8.21) 14.72 (SD 9.62) 17.47 (SD 10.04) (-) 29.263 <0.001 BD I<BD II<MDD
YMRS 3.63 (SD 5.41) 3.52 (SD 4.60) 1.37 (SD 2.41) (-) 13.631 <0.001 MDD<BD I, BD II

K-MDQ were compared between the BD I, BD II, MDD, and control subject. The other items were compared between BD I, BD II, and MDD because there was no value for control subject. Values are presented as means. BD: bipolar disorder, MDD: major depressive disorder, K-MDQ: Korean version of the mood disorder questionnaire, K-MADRS: Korean version of the Montgomery-Asberg Depression Rating Scale, YMRS: Young Mania Rating Scale