Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

Total sleep deprivation study in delayed sleep-phase syndrome.

Delayed sleep-phase syndrome (DSPS) is characterized by delayed sleep onset against the desired clock time. It often presents with symptoms of sleep-onset insomnia or difficulty in awakening at the desired time. We report the finding of sleep studies after 24 h total sleep deprivation (TSD) in a 28-year-old DSPS male patient. He had characteristics of mild chronic DSPS, which may have been precipitated by his frequent night shift assignments. The TSD improved the patients sleep latency and efficiency but all other sleep variables showed marked differences.

Effect of Dawn Simulation on Difficulty Awakening in the Morning and Daytime Sleepiness in Adolescents with Delayed Sleep Phase Syndrome / 신경정신의학

OBJECTIVES: Delayed sleep phase syndrome (DSPS) is characterized by difficulties in falling asleep and waking up at a desired time. Dawn simulation is a technique using a light that gradually increases in intensity before awakening in the morning, to imitate a natural sunrise. It has been found to be effective in decreasing both morning drowsiness and difficulty in awakening as well as treating symptoms of seasonal affective disorder. The aim of this study was to determine whether dawn simulation is helpful in decreasing difficulty in morning awakening and daytime sleepiness in adolescents with DSPS. METHODS: Twelve adolescents with DSPS participated in a 2-week dawn simulation trial. Each subject self-assessed level of difficulty in awakening, morning drowsiness and daytime sleepiness during a 2-week baseline period and a following 2-week trial period with dawn simulator. Subjects used Stanford Sleepiness Scale (SSS) for measuring morning drowsiness and Epworth Sleepiness Scale (ESS) for measuring daytime sleepiness. Difficulty in awakening was assessed by a single-item questionnaire. RESULTS: Dawn simulation trial decreased morning drowsiness (p=0.016) and daytime sleepiness (p=0.013) significantly compared to baseline. It also seemed to improve difficulty in awakening, but the effect was not statistically significant (p=0.092). CONCLUSION: Dawn simulation may help waking up in the morning and may improve daytime functioning by deceasing both morning drowsiness and daytime sleepiness in adolescents with DSPS.