Correlation among clock gene expression rhythms, sleep quality, and meal conditions in delayed sleep-wake phase disorder and night eating syndrome

ABSTRACT

Clock genes that comprise the circadian clock system control various physiological functions. Delayed sleep-wake phase disorder (DSWPD) and night eating syndrome (NES) are characterized by delayed sleep and meal timing, respectively. We estimated that clock gene expression rhythms in DSWPD patients may be delayed in comparison with the healthy subjects due to delayed melatonin secretion rhythms, producing eveningness chronotype in these individuals. However, it was difficult to estimate which clock gene expression rhythms were delayed or not in NES patients, because previous studies revealed that melatonin secretion rhythm was a little delayed compared with healthy individuals and that chronotype of NES patients depended on the individuals. Therefore, we examined expression rhythms of clock genes such as Period3 (Per3), nuclear receptor subfamily 1, group D, member 1 (Nr1d1) and Nr1d2 in these patients. Further, we expected sleep and meal patterns in DSWPD and NES patients may be more diverse than patterns observed in healthy subjects, and thus analyzed relationships among clock gene expression rhythms, sleep quality, sleep midpoint time, and meal times. We enrolled healthy male participants along with DSWPD and NES male patients, and asked all participants to answer questionnaires and to keep diaries to record information on their sleep and meals. Further, we asked them to collect 5–10 beard follicle samples, 6 times every 4 h. We measured clock gene expression rhythms using total RNA extracted from beard follicle cells. Peak time of clock gene expression in the NES group showed more diversity than the other groups, and that in the DSWPD group was delayed compared with the control group. In addition, the peak time of clock gene expression was negatively correlated with sleep quality and positively correlated with meal time after a long fast. Amplitudes of clock gene expression, especially Per3, positively responded to better mental and physical conditions as well as with better sleep quality. Results of this study suggest that peak times of clock gene expression in NES patients depended on the individuals; some patients with NES showed similar clock gene expression rhythm to healthy subjects, and other patients with NES showed similar to DSWPD patients. Moreover, this study suggests that meal time after a long fast may influence more determination in clock gene expression rhythms than the time of breakfast. Therefore, this study also indicates that Per3 clock gene may be one of the parameters that will help us understand sleep and meal rhythm disturbances.

KEYWORDS:

• Clock gene expression rhythm
• delayed sleep-wake phase disorder
• night eating syndrome
• sleep quality
• sleep midpoint time
• meal time after a long fast

Acknowledgments

We thank Dr. Akira Usui, Dr. Yoshikazu Takaesu, Dr. Kentaro Matsui, Dr. Wakako Ito, Dr. Kunihiro Futenma, and Dr. Moeko Sato who helped make this research possible.

Declaration of interest

We have no declaration of interest for this study.

Additional information

Funding

This work was supported in part by the Leading Graduate Program in Science and Engineering, Waseda University from MEXT, Japan (A.H.); a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Number 22700781) (Y.K); Sapporo Bioscience Foundation (Y.K), MSD K.K, and Otsuka Pharmaceutical Co., Ltd (Y.K); clinical fees (Y.I),  lecture fees and research funding from Nippon Boehringer Ingelheim (Y.I), Takeda Pharmaceutical (Y.I), Astellas Pharma (Y.I), Philips Respironics (Y.I), Alfresa Pharma (Y.I), MSD (Y.I), Pacific Medico (Y.I), Otsuka Pharmaceutical (Y.I), Eisai (Y.I), Yoshitomiyakuhin (Y.I), and Hisamitsu Pharmaceutical (Y.I); and a Grant-in-Aid for Scientific Research (S) (26220201) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (S.S).